,text,label 678,"Effects of milk, prostaglandin, and antacid on experimentally induced duodenitis in the rat. Use of myeloperoxidase as an index of inflammation. Ulcerogenesis of the duodenal mucosa frequently involves an inflammatory reaction with infiltration of leukocytes. Measurement of neutrophil myeloperoxidase activity might thus be a sensitive indicator of damage, before visible lesions occur. To test this possibility, a rat model for duodenal injury was used where fasted animals were treated with indomethacin and histamine-diHCl. Twenty-four hours after indomethacin treatment, duodenal tissues were collected for histochemical staining and biochemical assay for myeloperoxidase activity. Indomethacin- and histamine-challenged rats had significantly elevated myeloperoxidase activity compared to unchallenged controls (P less than 0.05) for both histochemistry and biochemistry. There was also a significant correlation between these two parameters (r = 0.68, P less than 0.001). The duodenal injury model then was used to test the effectiveness of known gastric protective agents. Results indicated that milk and buttermilk did not aggravate or protect against duodenal injury, while antacid and prostaglandin did significantly protect against inflammation (P less than 0.02). We concluded that measurement of myeloperoxidase activity is a sensitive and potentially useful estimate of duodenal injury that can be valuable in assessing ulcerogenesis and healing. ",5 1495,"Maternal mortality in the United States, 1979-1986. To understand better the epidemiology and to describe the causes of maternal death, we reviewed all identified maternal deaths in the United States and Puerto Rico for 1979-1986. The overall maternal mortality ratio for the period was 9.1 deaths per 100,000 live births. The ratios increased with age and were higher among women of black and other minority races than among white women for all age groups. The causes of death varied for different outcomes of pregnancy; pulmonary embolism was the leading cause of death after a live birth. Unmarried women had a higher risk of death than married women. The risk of death increased with increasing live-birth order, except for primiparas. In order to develop strategies to reduce the risk of maternal death in the United States, future studies should include expanded information about each death, which will allow better understanding of factors associated with maternal mortality. ",12 2106,"Hemopump ventricular support for patients undergoing high risk coronary angioplasty. Prophylactic implantation of a Hemopump (Johnson and Johnson, Skillman, NJ) has been evaluated in nine patients selected for high risk coronary angioplasty. They were unstable patients, refractory to maximal pharmacology, with indications for revascularization, but contraindications for surgery such as low ejection fraction and lack of material for bypass. In all, the target lesion was located on the last patent vessel. The pump was inserted under local anesthesia, without any graft. A specially designed occluder permitted avoidance of retrograde bleeding during implantation. The bypass flow ranged from 2.5 to 3.2 L/min, and permitted a rise in cardiac index from 2.05 to 2.55 L/min/m2, with a drop in capillary wedge pressure from 13 (7-18) to 10 (7-13) mmHg. During balloon inflation, no electrocardiographic changes were observed, because only minor ventricular arrhythmias occurred. No significant hemolysis was seen (plasma free hemoglobin less than 10 mg/dl in all) after 2 hr of pumping. The only limitation of the technique appears to be difficulty at the time of implantation from narrow, stenosed, or tortuous iliofemoral arteries (3 patients). This experience strongly supports the benefit of temporary left ventricular Hemopump support in high-risk situations and clearly shows the need for a smaller pump. ",13 2320,"Spontaneous rheumatoid-like arthritis in a line of mice sensitive to collagen-induced arthritis. Twenty-eight percent of 13-month-old male mice of the high antibody responder line of Biozzi's selection I (HI) spontaneously developed a long-lasting inflammatory arthritis. This disease was clinically and histologically similar to human rheumatoid arthritis. The synovium of joints and some tendons was hypertrophied, with thickening of the synovial cell layer and infiltration by polymorphonuclear and mononuclear leukocytes. In some cases, synovial pannus formation led to destructive damage of articular cartilage and bone. Rheumatoid factor and antinuclear, anti-DNA, and anti-type II collagen (CII) antibodies were often found in the sera of both arthritic mice and clinically normal littermates. The presence of CII autoantibodies in this line of mice suggests that a potentially harmful anti-CII T cell autoimmunity can also develop spontaneously and lead to joint damage. Moreover, HI mice are also susceptible to collagen-induced arthritis, while a closely related mouse line (HII) is resistant to both diseases. These data support the hypothesis that collagen-induced arthritis is pathogenetically related both to this spontaneous arthritis and to rheumatoid arthritis. ",16 2240,"Intraoperative echocardiography in infants and children with congenital cardiac shunt lesions: transesophageal versus epicardial echocardiography. To determine the utility and limitations of intraoperative transesophageal echocardiography in infants and children with congenital intracardiac shunts, intraoperative transesophageal (n = 50) and epicardial (n = 49) echocardiograms were performed before and after cardiopulmonary bypass in children from 4 days to 16 years old and 3 to 45 kg in body weight. A miniaturized transesophageal probe (6.9 mm maximal diameter) was used in 36 patients weighting less than or equal to 20 kg. Epicardial imaging was performed with a 5 MHz precordial probe. The intraoperative transesophageal echocardiographic findings before and after cardiopulmonary bypass were correct and complete in 94% of patients. Transesophageal echocardiography correctly identified atrial septal defects, most types of ventricular septal defects, anomalous pulmonary veins, atrioventricular septal defects, tetralogy of Fallot, truncus arteriosus and double inlet ventricles. It failed to provide a correct diagnosis in only three patients, all of whom had doubly committed subarterial ventricular septal defects. Epicardial echocardiography identified all cases that had a doubly committed subarterial ventricular septal defect. A correct and complete intraoperative diagnosis was obtained with the use of epicardial imaging in 92% before and after cardiopulmonary bypass, but this technique required interruption of surgery and could not be completed in three patients because of induced arrhythmias and hypotension. These results demonstrated that intraoperative transesophageal echocardiography consistently defined important morphologic, color and pulsed Doppler ultrasound features of most congenital shunt lesions. Lesions that involved the right ventricular outflow tract are sometimes difficult to image with uniplane transesophageal echocardiography. There were no complications in any of the 50 subjects. ",15 2241,"Increased birth prevalence of cardiac defects in Yuma, Arizona A systematic study was undertaken to estimate the birth prevalence of congenital heart disease because there was a clinical impression that a disproportionate number of cases occurred in Yuma, Arizona. Control data were obtained from Sierra Vista, Arizona, a region with similar demographic characteristics, and from the Baltimore-Washington Infant Study. Patients with chromosomal or syndromal associations were excluded. In the Baltimore-Washington Infant Study only echocardiographic and invasively documented cases were included. From 1983 to 1988 the birth prevalence was significantly higher in Yuma (10.5/1,000) than in Sierra Vista (5.4/1,000, p less than 0.0001). As assessed only by invasive or echocardiographic diagnosis, there was a higher birth prevalence of congenital heart disease in the study population (6.7/1,000) compared with both the Baltimore-Washington Infant Study (3.7/1,000, p = 0.0008) and Sierra Vista (4.6/1,000, p = 0.04). Families were interviewed to exclude cases in which the mother did not spend the month before conception and the first trimester in Yuma or Sierra Vista. The birth prevalence for Yuma (6.0/1,000) remained significantly greater than that for Sierra Vista (3.8/1,000, p = 0.03). The exclusion of cases in which the mother resided elsewhere suggests, but does not prove, that an environmental influence may have played a role in the increased birth prevalence of congenital heart disease in this community. ",15 1658,"Experimental studies of the physiologic properties of technetium-99m isonitriles. Recently, efforts have been directed at the development of technetium-99m (Tc-99m)-labeled isonitrile compounds for assessment of regional perfusion and viability after experimental myocardial infarction or ischemia. One of the most promising of these agents, Tc-99m sestamibi, has undergone rather extensive laboratory investigation. Like thallium-201 (Tl-201), the uptake of Tc-99m sestamibi in myocardial tissue is proportional to myocardial blood flow after intravenous injection. Similar to other diffusible indicators, Tc-99m sestamibi underestimates blood flow at high flow rates. In low flow regions, the myocardial uptake of this agent is higher relative to nonischemic uptake than is microsphere-determined blood flow. This is attributed to increased extraction at low flows. This first-pass myocardial extraction fraction for Tc-99m sestamibi is less than that for Tl-201. However, Tc-99m sestamibi has a higher parenchymal cell permeability and higher volume of distribution than T;-201. Tc-99m sestamibi shows minimal ""delayed redistribution"" after initial intravenous administration. Uptake of Tc-99m sestamibi is not altered by myocardial ""stunning"" or with ischemic dysfunction produced by sustained low coronary flow. The uptake of the isonitrile is still proportional to blood flow in these situations. In intact animal models, myocardial uptake of Tc-99m sestamibi during coronary occlusion delineates the in vivo area at risk. When Tc-99m sestamibi is administered after reperfusion following variable periods of preceding coronary occlusion, Tc-99m sestamibi uptake delineates the area of viable myocardium that is salvaged and not simply the degree of reflow. This suggests that serial Tc-99m sestamibi imaging might be useful in assessing the efficacy of coronary reperfusion after thrombolytic therapy. ",13 2787,"Penetrating injuries of the abdominal aorta. The charts of 56 consecutive patients with penetrating injuries to the abdominal aorta were reviewed in an attempt to identify prognostic factors. Mechanism of injury was gunshot wound (GSW), 82 per cent (.22 cal: 15.2%; greater than .38 cal: 84.8%); shotgun wound (SGW), 5 per cent; and stab wound (SW), 13 per cent. Overall mortality was 73 per cent, with GSW 78 per cent (.22 cal: 0%; greater than .38 cal: 92%), 67 per cent with SGW, and 43 per cent with SW. Average initial systolic blood pressure (ISBP) was 53 (0-130); 87 (0-120) in survivors; and 40 (0-130) in nonsurvivors (NS). Eighteen patients (32%) had no ISBP, with one survivor. Thirty (54%) patients had ISBP less than 70, with three survivors. Six Emergency Department (ED) thoracotomies were performed, with five patients surviving to reach the operating room (OR), and none surviving long-term. Ten patients died in the ED, 18 during surgical intervention, six within 24 hr, and seven greater than 24 hr postop. Average time from injury to OR was 75 minutes, with 122 minutes in survivors, and 53 minutes in nonsurvivors (P less than 0.05); 49 minutes in those dying in the OR; and 58 minutes in those surviving the OR but dying postop (NS). At surgery, six patients had thoracotomy before celiotomy for control of the thoracic aorta, with three surviving the OR and two surviving long-term. Survivors had 2.53 associated injuries; nonsurvivors had 2.89 (NS). No significant difference was noted in number or location of associated injuries between survivors and nonsurvivors. ",20 2890,"Submersion in The Netherlands: prognostic indicators and results of resuscitation. STUDY OBJECTIVES: To analyze prognostic indicators and the outcome of resuscitation in submersion victims (drowning and near drowning). DESIGN: Retrospective study. SETTING: Intensive and Respiratory Care Unit. Between January 1, 1979, and December 31, 1985, 87 submersion victims were admitted. The files of 83 victims were available for statistical analysis. There were 66 male victims and 17 female victims; the average age was 31.4 +/- 25.8 years. There were ten salt water and 73 fresh water submersions. MEASUREMENTS AND MAIN RESULTS: Predictors for better survival potentials were a young age, submersion of less than ten minutes, no signs of aspiration, and a central body temperature of less than 35 C at admission. We did not detect factors that accelerated a decrease in core body temperature at admission and assume that lethal hypoxia had preceded protective hypothermia in our submersion victims. The Orlowski score had a predictive value but at the same time we found nonindependent indicators in this score. Neurologic outcome in our patients, who were not treated according to a brain protection protocol, was not worse than the outcome published by authors who have used such a protocol. Thirty-three percent of the victims with a cardioventilatory arrest (15) and all victims with a ventilatory arrest (11) survived resuscitation and were discharged. Five nonarrest victims died due to late complications. CONCLUSION: This study shows that no indicator at the rescue site and in the hospital is absolutely reliable with respect to death or survival. ",20 2796,"Estimation of the amount of alcohol ingested from a single blood alcohol concentration. Capillary blood alcohol concentrations (BAL) measured in 22 young adult male volunteers each of whom received three different treatments of alcohol (total N = 66) have been related quantitatively to the dose of alcohol ingested. Linear regression with reasonably homogeneous variances have been found when the BAL at 2, 2.5 and 3 hr are divided by the person's body weight and plotted versus the g/kg (D/W) dose. Error analysis indicated that the least error in the predicted dose (D/W) was obtained for BAL measured at 2 hr post dosing. In the latter case the mean absolute error was 6.23%, 59% of the errors were within +/- 5% and 88% of the errors were within +/- 10%. ",20 1919,"Predictive value of lipoprotein (a) and other serum lipoproteins in the angiographic diagnosis of coronary artery disease. To determine the relation among lipids in predicting coronary artery disease (CAD), 213 patients undergoing diagnostic angiography for suspected CAD were prospectively studied. Twenty-one patients had normal coronary arteries and 192 had CAD in 1 to 3 arteries at arteriography with measurements obtained with digital calipers. Lipoproteins were measured and lipoprotein (a) [Lp(a)] was also assayed in a subset of 98 patients with CAD. Statistical analysis was performed using uni- and multivariate techniques to test the association among age, gender, systemic hypertension, diabetes mellitus, cigarette smoking, family history, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein cholesterol, apolipoproteins (apo) A-I and apo B, ratio of apo A-I to apo B, and ratio of HDL cholesterol to total cholesterol, to Lp(a) and to CAD. All factors except gender, systemic hypertension, diabetes mellitus and cigarette smoking were univariate predictors of CAD. Multivariate predictors were, in decreasing order of significance, family history, age, HDL/total cholesterol ratio and apo B. When Lp(a) was included, multivariate predictors were age, family history, apo B and Lp(a), in that order. Lipid parameters alone showed that the HDL/total cholesterol ratio and that Lp(a) provide the best predictive tests for the detection of CAD in this referral population and may ultimately become important screening tests for CAD. ",13 2761,"Alcohol and trauma. An endemic syndrome. Injuries are a pervasive and costly problem, and alcohol use appears to be an important risk factor for injury. We examined the blood alcohol levels and selected demographic and epidemiologic variables recorded on trauma patients by 1 trauma center for a 28-month period. A total of 2,262 trauma patients were admitted to the trauma center during this period, of whom 75% were male and 72% were injured in vehicle-related incidents. Blood alcohol levels of 2,095 patients (93%) were measured, and alcohol was present in the blood of 855 (41%). Of those patients with a blood alcohol level done, 32% had a level higher than 100 mg per dl. We conclude that the level of alcohol involvement in trauma is high and that this involvement must be addressed by the medical community and the health care system. ",20 67,"Percutaneous central venous catheterization. Three years' experience in a neonatal intensive care unit. Prolonged venous access is desirable in very-low-birth-weight infants and infants for whom feedings are contraindicated. We prospectively evaluated 481 small-diameter venous catheters placed percutaneously in 317 patients over 3 years. Of 478 catheters, 241 (50%) were placed in infants weighing 1 kg or less. Mean catheter stay was 13 days (range, less than 1 to 77 days). Almost half (49%) of the central and thoracic catheters (91% of placements) were removed nonelectively: 43% due to problems such as leaking or clotting and 6% to suspicion of sepsis or venous occlusion. Of the 23 episodes of possible sepsis in the 478 catheter stays, six (1.3%) were confirmed catheter-related sepsis; 12 (2.5%) were confirmed alternate locus sepsis. Three factors specific to percutaneous central venous catheter-related sepsis were prolonged catheter stay (3 to 5 weeks), Staphylococcus epidermidis, and weight less than or equal to 1 kg. Four factors specific to alternate locus sepsis were presence of an alternate infection site, earlier infection (1 to 2 weeks), extremely low birth weight, and prolonged clinical instability. Percutaneous central venous catheterizations reduced the need for the stress of repeated venipuncture, resulting in lower complication rates than those reported with surgically placed central venous catheters, and leading to identification of risk factors specific to catheter sepsis and alternate locus sepsis. ",0 334,"Alternating cisplatinum and VAC ineffective in end stage squamous cell carcinoma of the head and neck. Sixteen patients with end stage squamous cell carcinoma of the head and neck were admitted to a phase II study of alternating courses of cisplatinum (100 mg/m2) and VAC (vincristine 1.4 mg/m2, adriamycin 50 mg/m2, cyclophosphamide 750 mg/m2) given at three weekly intervals. Only two patients achieved a response (12 per cent). The median survival time was 62 days which is much the same as that of a similar group of patients who received no chemotherapy in a previous trial (70 days). ",3 39,"Bioaerosols: prevalence and health effects in the indoor environment. Assessing the role of bioaerosols in residence-related symptoms involves (1) determining that symptoms are related to the residence by medical examination and careful questioning, (2) connecting reported symptoms with known or hypothesized effects of bioaerosols, (3) examining the residence for bioaerosol risk factors such as overcrowding/poor ventilation, inappropriate outdoor air intrusion, and dampness/standing water, (4) and finally, if no obvious risk factors are present, air sampling. Air sampling should always be a last resort and should use a reliable volumetric method. Particulate samplers, such as the Burkard personal spore trap, are inexpensive alternatives to viable particle samplers and will provide data on most organisms implicated in hypersensitivity diseases. Interpretation of residential bioaerosol sample data requires both qualitative and quantitative comparison with adjacent outdoor air and examination of aerosol changes related to domestic activities. Recommendations that should lead to a decrease in indoor bioaerosols include the use of air conditioning to allow limitation of outdoor aerosols, prevention of dampness or moisture intrusion, and discouraging the use of humidifying devices other than steam. Bioaerosol assessment in the workplace is often more complex than for residences. Because the symptomatic subjects are not in charge of the environment, such situations often lead to difficult employee/management relations and occasionally to litigation. It is essential that each step in workplace bioaerosol assessment be defensible and that the best possible methods are used. The approach is similar to the approach used for residences, but on a larger scale. Symptom assessment must include stress and ergonomic factors. Air sampling, if this is necessary, must usually be extensive with controls for ventilation rates, occupancy, and spatial variation. ",0 1312,"Digital rectal examination in the early detection of prostate cancer. Screening using digital rectal examination improves the clinical stage distribution of prostate cancer and prolongs survival. Unfortunately, digital rectal examination may not be sensitive enough to detect the small-volume tumors that are most amenable to cure. In several studies, approximately 50 per cent of cancers detected through screening had already spread beyond the prostate. Regardless, the key to demonstrating overall benefit from screening is a diminished disease-specific mortality rate. To date, this has not been shown. Lower mortality rates from prostate cancer can be demonstrated only through a randomized study comparing screened and unscreened populations. Such a study, which has recently been approved and funded by the National Institutes of Health, will require 10 to 15 years to complete. Until that time, the value of screening for prostate cancer by digital rectal examination or any other method will be unknown. Beyond a lack of proved benefit, screening for prostate cancer may be harmful because of the variable natural history of the disease and the morbidity and mortality rates associated with treatment. There exists a large population of patients with pathologically detectable prostate cancer who will never have clinical disease. The detection of some of these tumors may expose those patients to the risks of unnecessary treatment. Large-scale prostate cancer screening studies may ultimately be shown to be advantageous. The sooner this occurs, the earlier aggressive screening can be advocated, similar to screening for breast cancer. However, the temptation to embark on such screening programs without first demonstrating clear benefit should be resisted. ",11 3281,"Hemorrhage in mice produces alterations in pulmonary B cell repertoires. Nosocomial pneumonia occurs frequently after hemorrhage and trauma and contributes to the increased incidence of morbidity and mortality after severe injury. The production of secretory antibodies by mucosally associated B cells is an important component of pulmonary host defense mechanisms. To determine the effects of hemorrhage on pulmonary B cell function, we examined hemorrhage induced alterations in pulmonary B cell repertoires. There were no changes in the relative distribution of T or B cells among intraparenchymal pulmonary lymphocytes after blood loss. Hemorrhage induced decreases of between 5- and 10-fold in the frequencies and numbers of pulmonary B cell clonal precursors specific for the bacterial Ag levan and Pseudomonas aeruginosa polysaccharide. These decreases in numbers and frequencies of bacterial Ag-specific pulmonary B cell clonal precursors were present between 3 and 10 days after blood loss. Similar decreases in numbers and frequencies were found among pulmonary clonal precursors specific for the autoantigen mouse transferrin, but not for the autoantigen dsDNA or the external antigens OVA and keyhole limpet hemocyanin. These results demonstrate that hemorrhage produces marked alterations in pulmonary B cell repertoires, which may contribute to postinjury abnormalities in host defenses. ",22 1779,"Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p less than 0.05), aldosterone (p = 0.003), noradrenaline (p less than 0.001), adrenaline (p = 0.001), and atrial natriuretic factor (p = 0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular. ",13 1407,"Transrectal sonographic cystourethrography: studies in stress urinary incontinence. Transrectal ultrasonic sagittal transducer is an excellent modality to image the bladder and urethra in dynamic change. In female patients, we found it is also helpful for the diagnosis of urinary stress incontinence. The posterior urethrovesical (PUV) angle is measured with the transrectal sonoprobe under strain and non-strain conditions. We compared the results of sonographic cystourethrogram with the radiographic chain cystourethrogram. The sonographic cystourethrography is superior to the radiography. The former may estimate the PUV angle accurately and differentiate between the patients with and without stress urinary incontinence. Furthermore, we also use the transrectal sagittal probe intraoperatively to adjust the suspension force as well as PUV angle in patients who underwent vesical neck suspension for stress urinary incontinence (SUI). ",11 2194,"Right ventricular growth after transventricular pulmonary valvotomy and central aortopulmonary shunt for pulmonary atresia and intact ventricular septum. We performed transventricular pulmonary valvotomy as initial surgery in 22 consecutive patients with pulmonary atresia and intact ventricular septum who had a patent infundibulum. Nineteen patients also had placement of a central aortopulmonary shunt. All patients survived surgery, and 16 patients have had preoperative and later postoperative catheterizations. The purpose of this study was to determine the response of the right ventricle to transventricular pulmonary valvotomy with regard to relief of right ventricular hypertension and growth of the entire right ventricle, including tricuspid valve, right ventricular volume, and right ventricular outflow tract. Right ventricular systolic pressure decreased from 111.3 +/- 31.7 mm Hg before initial surgery to 65.6 +/- 26.2 mm Hg. Right ventricular end-diastolic volume increased from 59.1 +/- 39.3% of predicted normal before initial surgery to 114.6 +/- 63.2% at late follow-up catheterization. Tricuspid valve anulus circumference also increased in size from 73.2 +/- 21.3% of predicted normal before initial surgery to 90.4 +/- 22.8% at late follow-up catheterization. Only one patient (6%) required a transanular right ventricular outflow tract patch at the time of biventricular repair. Twenty of 22 patients (91%) either have had or are awaiting biventricular repair. We conclude that transventricular pulmonary valvotomy and central aortopulmonary shunt can be performed safely in newborn infants with pulmonary atresia and intact ventricular septum who have a patent infundibulum. Effective valvotomy relieves right ventricular hypertension, allows for excellent right ventricular and tricuspid valve growth, and optimizes potential for biventricular repair. ",15 2122,"Hemodynamic efficacy of rapid saline infusion and dobutamine versus saline infusion alone in a model of cardiac rupture. Despite recent reports describing survival after cardiac rupture, the effectiveness of circulatory support while awaiting definitive surgical treatment is controversial. To assess the efficacy of volume expansion and pharmacologic support in cardiac tamponade due to cardiac rupture, a model of hemorrhagic cardiac tamponade was developed and treatment with rapid saline infusion and dobutamine was compared with rapid saline infusion alone in 15 closed chest dogs. A right ventricular wound of reproducible size was produced by deflating an aortic valvuloplasty balloon that had previously been passed by way of the internal jugular vein into the pericardial space and through a stab wound in the right ventricular free wall. Hemodynamic values were compared at baseline, during tamponade and after a rapid infusion (1 liter at 100 ml/min) of either saline solution alone or saline solution plus dobutamine (20 micrograms/kg per min). Atrial and pericardial pressures increased significantly in both groups. Mean arterial pressure, cardiac output and stroke volume increased with combined saline and dobutamine infusion to values similar to those at baseline (91 +/- 19%, 114 +/- 43% and 94 +/- 37% of baseline, respectively). In contrast, saline infusion alone caused a small increase in cardiac output but failed to significantly increase mean arterial pressure or stroke volume (76.8 +/- 14.2%, 55 +/- 18% and 51 +/- 17% of baseline, respectively). Combined rapid infusion of saline solution and dobutamine infusion has a more beneficial hemodynamic effect and may be more effective than rapid saline infusion alone in resuscitating patients with hemorrhagic cardiac tamponade due to cardiac rupture. ",13 1395,"Adult minimal change glomerulopathy with acute renal failure. Oliguric acute renal failure occurs in some adult patients with minimal change glomerulopathy. To look for clinical and pathologic factors that increase the risk for developing acute renal failure, 21 adults with minimal change glomerulopathy and a serum creatinine greater than 177 mumol/L (mean, 486 mumol/L; range, 194 to 1,344 mumol/L) (greater than 2.0 mg/dL [mean, 5.5 mg/dL; range, 2.2 to 15.2 mg/dL]) were compared with 50 adults with minimal change glomerulopathy and a serum creatinine less than 133 mumol/L (mean, 88 mumol/L; range, 53 to 124 mumol/L) (less than 1.5 mg/dL [mean, 1.0 mg/dL; range, 0.6 to 1.4 mg/dL]). Minimal change glomerulopathy patients with acute renal failure were older (59.5 v 40.3 years, P less than 0.001), and had higher systolic blood pressure (158 v 138 mm Hg, P = 0.001), more proteinuria (13.5 v 7.9 g/24 h, P = 0.01), and more arteriosclerosis in the renal biopsy specimen (1.7 + v 0.7 + on a scale of 0 to 4+, P = 0.005). Tubular epithelial simplification identical to that observed with ischemic acute renal failure (acute tubular necrosis) was observed in 71% of the patients with serum creatinine greater than 177 mumol/L (greater than 2.0 mg/dL) and 0% of those with less than 133 mumol/L (less than 1.5 mg/dL). All 18 patients with renal failure for whom follow-up data were available had recovery of function (mean creatinine, 539 +/- 301 mumol/L [6.1 +/- 3.4 mg/dL] at the time of biopsy and 106 +/- 27 mumol/L [1.2 +/- 0.3 mg/dL] at last follow-up), but sometimes only after weeks of dialysis support. ",11 3202,"Mechanisms of edema formation in experimental autoimmune encephalomyelitis. The contribution of inflammatory cells. Most of the central nervous system (CNS) endothelium regulates the passage of solutes and functions as a blood-brain barrier (BBB). During experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, loss of BBB function occurs. The authors have previously shown an increase in endothelial transcytotic activity associated with decreased mitochondrial content as evidence of BBB dysfunction in EAE. These changes occurred in the capillary bed and correlated with CNS edema and clinical signs. In the present report, a fixation procedure before infusion of the intravascular tracer horseradish peroxidase (HRP) in rats at the height of clinical EAE has been used. In these animals, tracer leakage was only noted in inflamed venules with diameters of 12 to 19 mu. The authors detected several mechanisms of passive leakage: 1) increased junctional permeability; 2) increased interendothelial space; 3) leakage alongside migrating inflammatory cells. Some small capillaries showed necrotic changes with minimal tracer leakage. This report demonstrates that BBB disruption also occurs via nonendocytic mechanisms that may be induced by inflammatory cells. ",22 464,"Rhabdomyosarcomas in the head and neck: MR imaging evaluation. To determine the typical magnetic resonance (MR) signal intensity characteristics of rhabdomyosarcomas, short repetition time (TR)/short echo time (TE) (T1-weighted) and long TR (proton density and T2-weighted) images of 13 patients with rhabdomyosarcomas of the head and neck were retrospectively reviewed. Seven patients received gadopentetate dimeglumine injections. The most common MR appearance was that of a homogeneous mass, hyperintense to both muscle and fat on long TR/long TE images and isointense or minimally hyperintense to muscle on short TR/short TE images. All lesions of the patients who received gadopentetate dimeglumine enhanced markedly. Two lesions had intratumoral hemorrhage, and six were markedly heterogeneous in signal intensity. Similar MR signal intensity patterns have been described for lymphomas and nasopharyngeal carcinomas. The forte of MR imaging lies in its ability to delineate precisely the extent of the rhabdomyosarcoma. ",3 2859,"Agreement between two dietary methods in the measurement of alcohol consumption. This study compares estimates of alcohol consumption from two dietary methods: a self-reported diet diary and a quantitative food frequency questionnaire. In the 1984-85 University of Michigan Food Frequency Study, 228 black and white, male and female respondents, ages 23-51 years, kept diet diaries covering 16 days during a 1-year period. At the end of the year, the same respondents completed a dietary quantity-frequency questionnaire that included alcoholic beverages. The two methods showed excellent agreement in estimated group mean ethanol consumption and good agreement in the ranking of individual respondents. Respondents described alcohol consumption in abstract terms on the questionnaire in a way that was consistent with the consumption recorded in the diary. However, the two methods showed only poor to moderate agreement in classifying individuals as infrequent, moderate or heavier drinkers, suggesting that such classifications should be used cautiously. These results suggest that in general population studies a dietary quantity-frequency questionnaire and a diet diary covering several weeks can measure moderate levels of alcohol consumption similarly. The degree of consistency suggests that, for moderate levels of intake, measures of alcohol consumption derived from the two methods are equally valid. ",20 494,"Abnormal vitamin B6 status in childhood leukemia. Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status. ",3 1731,"Studies of salt intake in hypertension. What can epidemiology teach us? It has been suggested that small changes in population blood pressure will have a major impact upon the incidence of cardiovascular disease caused by blood pressure elevation. Early reports indicated a close correlation between intercultural differences in salt intake and blood pressure. Before such epidemiological associations can be translated into population advice, certain conditions have to be met. The association has to be validated scientifically, and persuasive evidence has to be produced that the relationship is causal and reversible by changes in salt intake. Further, risk-benefit analysis should indicate that net harm is unlikely. Finally it has to be demonstrated that the population measures being advocated will produce an adequate change in dietary salt intake. The small individual effects upon blood pressure being examined, and the prevailing changes in blood pressure and cardiovascular mortality suggest that data will always fall short of the ideal and therefore that extrapolation will always be necessary. Nevertheless, a review of the present evidence indicates the inadequacies of the available data as a basis for population advice. ",13 1691,"Digitalis-like activity in human plasma: relation to blood pressure and sodium balance. PURPOSE: On the assumption that renal tubular cells are more important as the target cells for a natriuretic factor than blood cells, we used a well-characterized cultured renal tubular cell line, Madin-Darby canine kidney (MDCK), cells to monitor the circulating digitalis-like factor in human plasma and examine its role in the regulation of blood pressure and sodium balance. SUBJECTS AND METHODS: We investigated the effects of plasma on binding of radioactive ouabain to monolayered MDCK cells in order to determine the level of a circulating digitalis-like factor. First, we measured specific 3H-ouabain binding to MDCK cells in the presence of plasma from 71 outpatients (34 normotensive subjects and 37 hypertensive patients) after incubation for 4 hours. Second, we measured specific 3H-ouabain binding after incubation of cells with plasma from 16 hospitalized subjects (eight normotensive subjects and eight hypertensive patients) receiving low and high sodium diets. RESULTS: In Study 1, ouabain binding was lower by 30% with plasma from hypertensive patients than with plasma from normotensive subjects (p less than 0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = -0.34, p less than 0.01 or r = -0.29, p less than 0.01). In Study 2, ouabain binding was also significantly reduced by 25% in the presence of plasma from hypertensive subjects as compared with plasma from normotensive subjects irrespective of sodium intake (p less than 0.01). A significant negative correlation was also found for all subjects between either systolic, diastolic, or mean blood pressure and ouabain binding (r = -0.58, p less than 0.01, r = -0.51, p less than 0.01, or r = -0.55, p less than 0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p less than 0.01) and an increase in sodium excretion (p less than 0.01). A significant negative correlation was observed between these two parameters (r = -0.47, p less than 0.05). CONCLUSIONS: These findings suggest that a circulating digitalis-like factor, which may act on renal tubular cells as the ouabain-displacing compound, is increased in patients with essential hypertension and also demonstrate that plasma levels may be influenced by changes in dietary sodium intake. ",13 2186,"Chromosomal region of the cystic fibrosis gene in yeast artificial chromosomes: a model for human genome mapping. A general strategy for cloning and mapping large regions of human DNA with yeast artificial chromosomes (YAC's) is described. It relies on the use of the polymerase chain reaction to detect DNA landmarks called sequence-tagged sites (STS's) within YAC clones. The method was applied to the region of human chromosome 7 containing the cystic fibrosis (CF) gene. Thirty YAC clones from this region were analyzed, and a contig map that spans more than 1,500,000 base pairs was assembled. Individual YAC's as large as 790 kilobase pairs and containing the entire CF gene were constructed in vivo by meiotic recombination in yeast between pairs of overlapping YAC's. ",15 1500,"Serum estradiol as an aid in the diagnosis of ectopic pregnancy. The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis. ",12 919,"Mortality from pulmonary embolism in the United States: 1962 to 1984. To examine the effect of advances in the prevention of and therapy for PE, we reviewed mortality for PE in the United States from 1962 to 1984. Age-adjusted PE mortality increased by 67 to 100 percent between 1962 and 1974 for white and non-white men and women. From 1975 to 1984, these rates declined by 20 to 28 percent. Non-white PE mortality was greater than white PE mortality; men had a greater risk of PE death than women. Age-specific patterns (more than 40 years of age) of PE mortality followed those of the age-adjusted death rates, with increases noted in all groups between 1962 and 1974 and declines during the 1975-1984 period. These patterns might reflect improved ascertainment of cases and better prevention of disease. The magnitude of the rates suggests that the list of indications for prophylactic anticoagulation should be re-examined for possible expansion. ",7 1257,"Cytopathology of adenovirus keratitis by replica technique. Corneal replicas were made from the severely affected eyes of 12 patients presenting with typical signs and symptoms of epidemic keratoconjunctivitis. Adenovirus was isolated from the eyes. Histopathological study of the replicas and cytology of diseased cells removed with the replica showed diffuse mild oedema of the epithelium, with scattered moderately swollen and deformed cells. The clinically observed punctate lesions histologically consisted of markedly swollen cells that had become oval or rounded. Fusion of these cells led to small syncytial formations, and the development of pseudopodia-like processes was occasionally observed. Loss of cell contents resulted in the formation of plicae on the surface of many cells. Two types of inclusion bodies were detected in the epithelial cells. The first type, intranuclear vacuolar inclusions, contained homogeneous material. The second type of inclusions were round, dense bodies, that developed in the homogeneous material of intranuclear vacuolar inclusions. The dense bodies contained the replicating and maturing virus particles. After cell degeneration the dense bodies become extracellular. Making a corneal replica had a beneficial effect on the clinical course of adenovirus keratitis. ",10 352,"Radioimmunoscintigraphy using iodine-131-anti-CEA monoclonal antibodies and thallium-201 scintigraphy in medullary thyroid carcinoma: a case report. This case report demonstrates the use of thallium-201 (201Tl) scans versus iodine-131- (131l) anti-CEA F(ab')2 scans in a patient with high serum CEA levels due to metastases of medullary thyroid carcinoma in the suprarenal region and sacroiliacal region. Scintigraphy using monoclonal antibodies directed against CEA showed a higher tumor uptake (0.26% dose and 0.64% dose, respectively) than a thallium scan and is believed to be promising for future radiotherapeutic applications. ",3 2680,"Effect of procaterol on arterial blood gas in asthmatic children. We determined changes in arterial blood gas after the inhalation of procaterol, a highly beta 2-selective and long-acting adrenergic agonist, in 11 asthmatic children. Seven of the patients, with a maximum fall of 14 mmHg (63.6%), showed a decrease in PaO2 (mean +/- SD = -7.1 +/- 4.0 mmHg) and had poorer pulmonary function with a lower initial PaO2 than four subjects who had an increase in PaO2 after inhalation. There was a statistically significant correlation between values of the PaO2 before and after inhalation (P less than .05). ",19 2654,"Hodgkin's disease and CD30-positive anaplastic large cell lymphomas--a continuous spectrum of malignant disorders. A quantitative morphometric and immunohistologic study. The authors have examined cellular areas of lymphoma tissue in 28 cases of Hodgkin's disease (HD) or anaplastic large cell lymphoma (ALCL, 'Ki-1 cell lymphoma') to evaluate the boundaries between the two entities. Methods applied included conventional histology; test point analysis; semiautomated morphometry of nuclear profile features of Reed-Sternberg and other atypical large cells (RSALCs); and immunohistochemistry of these elements on all paraffin sections and, in 15 cases, on frozen sections. Mean nuclear profile morphotypes of RSALCs per case varied independently of immunophenotype and histologic diagnosis. Conversely, immunohistochemistry demonstrated significant, although not consistent, preferential positivities of these CD30+ elements for CD15 in HD, and for epithelial membrane antigen (EMA) and CD43 in ALCLs. In the latter, RSALCs also exhibited a tendency for CD45 and CD45RO positivity and for the expression of T-cell-associated antigens. However, there were considerable overlaps. This continuous spectrum of RSALC nuclear profile morphotypes and immunophenotypes, ranging from HD over questionable cases, intermediate between HD and ALCL, to ALCLs, was paralleled by differences in the reactive component of lymphomas. Lymphocytes and granulocytes were significantly deficient in ALCLs. ",19 3062,"Percutaneous transluminal coronary angioplasty of gastroepiploic artery graft. The right gastroepiploic artery is being used as a third arterial conduit for coronary artery bypass surgery. Presented here is a case demonstrating successful percutaneous transluminal coronary angioplasty of the gastroepiploic artery graft. This successful accomplishment may avoid repeat surgical revascularization in case of failure of the gastroepiploic artery graft, hence may encourage people to use it more often. ",22 887,"Mechanical disruption of pulmonary emboli in dogs with a flexible rotating-tip catheter (Kensey catheter). Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day-old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kensey catheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism. ",7 998,"An adherent subline of a unique small-cell lung cancer cell line downregulates antigens of the neural cell adhesion molecule. Small-cell lung cancer (SCLC) lines are distinguished from non-small-cell lung cancer (NSCLC) lines by their growth in floating aggregates, in contrast to the adherent monolayers formed by NSCLC cells in culture. Of 50 well-characterized SCLC lines recently described by the National Cancer Institute (NCI)-Navy Medical Oncology Branch, only four variant cell lines (SCLC-v) grew as adherent monolayers. One line, NCI-H446, was unique in growing long-term with coexisting floating and surface adherent subpopulations. We have physically segregated these two populations over many passages in vitro to enrich for relatively pure cultures of floating and adherent cells. No differences in c-myc expression, keratin pattern, or cytogenetic appearance were found between the adherent and floating sublines. However, expression of the neuroendocrine marker neuron-specific enolase in the floating cells was three times that found in the adherent cells. The floating subline also had much greater surface expression of neuroendocrine tumor antigens detected by monoclonal antibodies UJ13A and HNK-1, which have been recently shown to detect the neural cell adhesion molecule (NCAM) on SCLC cells. Two other adherent SCLC-v lines were also found to be unreactive with UJ13A and HNK-1, generalizing the association between NCAM expression and the growth of most SCLC cultures as floating aggregates. In conclusion, we have an interesting model to study expression of NCAM as related to the adhesive properties of SCLC cells. ",7 2081,"Spectrum of hemodynamic changes in cardiac tamponade. To investigate the pathophysiology of cardiac tamponade, the hemodynamics of 77 consecutive patients with greater than 150 ml of pericardial effusion were studied. Patients were classified into 3 groups based on the equilibration of intrapericardial with right atrial and pulmonary arterial wedge pressures (mm Hg): group I (n = 16), intrapericardial pressure was less than right atrial and pulmonary arterial wedge pressures; group II (n = 13), intrapericardial pressure was equilibrated with right atrial but not pulmonary arterial wedge pressures; group III (n = 48), intrapericardial pressure was equilibrated with right atrial and pulmonary arterial wedge pressures. Pericardiocentesis produced the following changes: group I--significant (p less than 0.03) decreases in intrapericardial pressure (7 +/- 2 mm Hg), right atrial pressure (3 +/- 2 mm Hg), pulmonary arterial wedge pressure (2 +/- 2 mm Hg), and the inspiratory decrease in arterial systolic pressure (3 +/- 4 mm Hg) but no significant change in cardiac output; group II--significant (p less than 0.02) decreases in intrapericardial pressure (11 +/- 5 mm Hg), right atrial pressure (6 +/- 4 mm Hg), pulmonary arterial wedge pressure (4 +/- 5 mm Hg), and inspiratory decrease in arterial systolic pressure (8 +/- 7 mm Hg), and increase in cardiac output (1.1 +/- 1.2 liters/min); group III--significant (p less than 0.001) decreases in intrapericardial pressure (16 +/- 7 mm Hg), right atrial pressure (9 +/- 4 mm Hg), pulmonary arterial wedge pressure (8 +/- 5 mm Hg), inspiratory decrease in arterial systolic pressure (17 +/- 11 mm Hg), and increase in cardiac output (2.8 +/- 1.5 liters/min). The changes after pericardiocentesis in all parameters were significantly (p less than 0.05) greater in group III than in groups I or II except for the change in right atrial pressure, which was not significantly different in groups II versus III. The changes after pericardiocentesis indicate pericardial effusion caused the greatest abnormalities in group III but also caused significant abnormalities of pressure and flow in group II and of pressure alone in group I. ",13 1988,"Inferior vena caval filter thrombi: evaluation with intravascular US. A 20-MHz intravascular ultrasound (US) transducer inside a percutaneously inserted catheter was used to evaluate inferior vena caval (IVC) filters for thrombi in vitro and in vivo. Six different IVC filters were studied with intravascular US in a saline-filled model. Each filter had a characteristic, recognizable US pattern. Experimental thrombi as small as 0.5 cm3 were easily detected. Intravascular US was used clinically 25 times to evaluate the IVC in 23 patients with 24 IVC filters. Positive-contrast cavograms were available for comparison in all 25 cases. In 13 cases, no thrombi were identified in the filter or IVC with either intravascular US or cavography; in five of 12 cases with thrombi, intravascular US and cavography demonstrated the thrombi equally well. In six cases, intravascular US was superior to cavography in detection or delineation of thrombus in the IVC or filter. Intravascular US was considered superior to external duplex US in evaluation of caval thrombi in all 21 cases available for comparison. No complications from intravascular US were noted. ",13 2029,"Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects. A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102, blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45 +/- 10 years old and 52% female; normotensive group, 44 +/- 9 years old and 55% female) and similar body mass index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2, p = 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected by Taq I/Hind III was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050), but the difference was not statistically significant. In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study. ",13 1949,"Effect of intravenous streptokinase on early mortality in patients with suspected acute myocardial infarction. A meta-analysis by anatomic location of infarction [published erratum appears in Ann Intern Med 1991 Mar 15;114(6):522] PURPOSE: To determine the effect of intravenous streptokinase on early mortality in patients with suspected acute anterior and acute inferior myocardial infarctions. DATA IDENTIFICATION: A literature search of English-language studies on the use of intravenous streptokinase in the treatment of suspected acute myocardial infarction for the period 1966 to 1989 using Medlars II and the bibliographies of relevant articles. In a number of instances, additional details on early mortality by location of myocardial infarction were provided by the authors. STUDY SELECTION: Of 140 originally identified articles, 6 that specifically met our inclusion criteria were selected: randomized trials that used intravenous streptokinase in a dose of 1.5 million units, with or without additional agents, compared with a group that differed only by the absence of streptokinase. Trials were selected by review of the methods section without regard for the results. DATA EXTRACTION: Data were extracted independently by two observers using specific methodologic criteria for infarct location and early mortality. After they conferred, the observers agreed completely on the data. RESULTS OF DATA SYNTHESIS: Among the 9155 patients with suspected acute anterior myocardial infarction, the mortality rate in the control group was 17.4%. In contrast, patients treated with streptokinase had a 12.5% mortality. The mean risk difference was -4.8% (95% CI, -7.5% to -2.1%) and the summary risk ratio was 0.72 (CI, 0.65 to 0.79). A total of 9650 patients with suspected inferior infarction had a mortality rate in the control group of 7.6% [corrected]. The mortality for streptokinase-treated patients was 6.6%. The mean risk difference was -0.8% (CI, -1.8% to 0.2%) and the summary risk ratio was 0.87 (CI, 0.76 to 1.01). CONCLUSIONS: Intravenous streptokinase clearly confers a protective effect against early mortality in patients with suspected acute anterior myocardial infarction. The magnitude of this effect is on the order of a 5% absolute reduction in risk of death by 21 to 35 days. For these patients, 21 need to be treated to save 1 additional life. For patients with suspected acute inferior infarction, the benefit of treatment on reducing early mortality is of smaller magnitude and less certain. These patients have an estimated absolute reduction of early mortality of approximately 1%, which would require treating 125 patients to save 1 additional life. ",13 1836,"Dynamic positron tomographic imaging with nitrogen-13 glutamate in patients with coronary artery disease: comparison with nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose imaging. This study was designed to test the usefulness of nitrogen-13 (N-13) glutamate imaging with positron emission tomography in defining myocardial ischemia in humans. Seventeen patients who had undergone coronary arteriography were studied with N-13 glutamate at peak supine exercise using a bicycle ergometer, as well as with the flow tracer N-13 ammonia at peak exercise during a second similar exercise test. Six of the patients also underwent imaging with N-13 glutamate at rest before exercise testing; in the remaining 11 patients imaging with fluorine-18 (F-18) fluorodeoxyglucose was performed to assess glucose metabolism after the second exercise test. Seven patients had classic metabolism-flow mismatches consistent with ischemia (that is, decreased N-13 ammonia uptake in a region with relatively increased F-18 fluorodeoxyglucose uptake). There was no evidence of increased N-13 glutamate uptake in the ischemic mismatched regions in any of these patients. In all 17 patients, the uptake of N-13 glutamate during exercise paralleled the uptake of N-13 ammonia during exercise, suggesting that N-13 glutamate behaves as a flow tracer rather than as a metabolic marker of ischemia in humans. ",13 1884,"Regression of intracardiac thrombus after embolic stroke. Using two-dimensional echocardiography, we studied the pathophysiology of intracardiac thrombus regression accompanied by anticoagulant therapy in 82 consecutive patients with acute cardiogenic cerebral embolism. We noted intracardiac thrombus in 15 patients; nine of the 15 were started on anticoagulant therapy with warfarin potassium to maintain the prothrombin time between 2.5 and 3.5 (international normalized ratio). Serial two-dimensional echocardiograms were obtained for these nine patients before and after anticoagulation, with the plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, and D-dimer measured at the same time. In eight of the nine patients the intracardiac thrombi gradually decreased in size while the plasma level of fibrinopeptide A fell to within the normal range and the plasma levels of fibrinopeptide B beta 15-42 and D-dimer remained above the normal ranges. In the other patient the thrombus disappeared, with embolization to the right arm immediately after starting anticoagulant therapy. Mobile or small thrombi regressed earlier than nonmobile or large ones. We conclude that regression of intracardiac thrombi after anticoagulation may be based on the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin activity. ",13 1915,"Reduction of mortality, sudden death and non-fatal reinfarction with beta-adrenergic blockers in survivors of acute myocardial infarction: a new hypothesis regarding the cardioprotective action of beta-adrenergic blockade. Beta-adrenergic blockers have been shown definitely to reduce the incidence of total mortality, cardiovascular mortality, sudden death and nonfatal reinfarction in survivors of an acute myocardial infarction. The mechanisms to explain this protective action of beta blockers have never been elucidated conclusively, and include the antiarrhythmic and myocardial oxygen demand-reducing effects of the drugs. An antithrombotic mechanism has also been suggested. However, beta blockers have relatively weak antiplatelet activity, suggesting that their antithrombotic effects may be related to prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than direct anticoagulant action. The therapeutic ability of beta blockers to attenuate the hemodynamic consequences of catecholamine surges, may protect a vulnerable atherosclerotic plaque from fracture, thereby reducing risk of coronary thrombosis, myocardial infarction and death. ",13 2568,"Modulation of interleukin-1 beta RNA in monocytic cells infected with human immunodeficiency virus-1. The effect of HIV-1 infection on cytokine levels was studied in monocytic cells by using Northern blotting analysis. Monoblasts (THP-1, U937) did not express IL-1 beta RNA even if the cells were infected with HIV-1. After exposure to LPS (10 micrograms/ml) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 100 nM) for 12 h, these HIV-1-infected monoblasts accumulated 8-15-fold greater levels of IL-1 beta RNA as compared with their HIV-1-uninfected counterparts that were similarly stimulated. In contrast, levels of RNAs coding for monocyte-colony-stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF alpha) were elevated less than twofold in the HIV-1-infected cells as compared with HIV-1-uninfected cells after their stimulation with LPS and TPA. Inhibition of new protein synthesis did not block the marked accumulation of IL-1 beta RNA produced by exposure to LPS and TPA in the HIV-1-infected cells. Time-course experiments showed that the maximal levels of IL-1 beta RNA occurred at 12 and 24 h after LPS and TPA stimulation of the HIV-1-infected and uninfected U937 cells, respectively. Studies of stability of RNA using actinomycin D showed that IL-1 beta RNA was equally stable in infected and uninfected U937 cells after their stimulation with TPA and LPS. Taken together, our data show that HIV-1 infection markedly augments IL-1 beta RNA accumulation in stimulated monocytic cells, probably through increasing rate of transcription of IL-1 beta. ",19 1612,"Evolution of deep venous thrombosis: a prospective evaluation with US. Forty-six patients with a diagnosis of acute deep venous thrombosis (DVT) established by means of duplex ultrasound (US) were prospectively followed up with serial duplex US examinations during a 6-month period to assess the persistence of venous abnormalities. All patients were asymptomatic. Isolated popliteal DVT was found to be more likely to revert to normal at duplex compression US than thrombosis involving both the femoral and popliteal systems (P less than .05). Increased venous diameter was a sign of acute clot (P less than .005). Clot echogenicity did not help to enable distinction of acute DVT and chronic DVT. At compression US, 10 of 21 patients (48%) who initially had occlusive thrombosis had persistent abnormalities that mimicked findings consistent with acute DVT. Chronic venous changes that persisted after 6 months consisted of either lumen recanalization (with resultant intimal thickening) or persistent venous occlusion. Both of these conditions can result in incomplete compression, the major US indication of acute DVT. This appearance should not be confused with that of acute DVT. Follow-up examinations to establish a baseline appearance can be obtained as early as 6 months after an acute episode of DVT. ",13 2175,"A constitutive antibody in normal human serum directed against rabbit bone marrow cells: lack in parturients, neonates, and hematologic disorders. Normal human serum effectively inhibits a bioassay for erythropoietin based on DNA synthesis by rabbit erythroid precursors. This heat-sensitive inhibitory activity is readily lost on dilution of serum, revealing the presence of erythropoietin-potentiating activity. Inhibitory activity is caused by a rapid cytotoxic effect on rabbit bone marrow cells; mouse cells are less sensitive. Cytotoxic activity is removed from serum by adsorption to protein A, is not expressed at 4 degrees C, and is neutralized by anti-C3c complement antibody. Cytotoxicity is inhibited by EGTA; the effect of EGTA is reversed by addition of Ca2+ ions. These findings show that cytotoxicity is exerted through an antibody via the classical pathway of complement-dependent cell lysis. Although serum from healthy, adult human donors consistently contains cytotoxic activity, no such activity is observed in most serum samples from neonates, parturients, and patients with severe anemia. Patients with polycythemia or chronic renal failure occasionally lack cytotoxic activity in their serum. Serum samples lacking cytotoxic activity were found to be deficient in the antibody component in 34 out of 35 cases examined. These results show that an antibody directed against rabbit cells is constitutively present in normal human serum but is absent in a number of pathologic situations as well as being absent in neonates and parturients. ",14 3279,"Cup containment and orientation in cemented total hip arthroplasties. We reviewed the radiographs of 864 Charnley and STH (Zimmer) cemented total hip arthroplasties with a mean follow-up of seven years (maximum 16 years). Survivorship analysis was used to assess the correlation between radiographic performance and the bony containment or the coronal orientation of the acetabular cup. The cup orientation and containment were interrelated; all vertically oriented cups were completely contained, whereas 25% of more horizontal cups were only partially contained. Completely contained cups had significantly lower incidences of complete cement-bone radiolucency (p = 0.02) and of wear (p = 0.09). Vertically oriented cups had a lower incidence of continuous radiolucency than neutrally oriented cups, but this was not statistically significant (p = 0.25). Our results confirm the importance of complete bony containment, and also indicate that it is better to accept vertical orientation and obtain full bony coverage than to have a more horizontal orientation with partial containment. ",22 1954,"Tension pneumopericardium as a complication of single-lung transplantation. Tension pneumopericardium is distinctly uncommon in the adult population. We present a case of tension pneumopericardium as a complication of lung transplantation in a 54-year-old woman with thromboembolic pulmonary hypertension who underwent single-lung transplantation. ",13 2987,"Influence of postmortem time and temperature on osteoinductive activity of demineralized microperforated ethylene oxide-sterilized syngeneic bone implant in the rat. Bone morphogenetic protein is labile and easily inactivated by many extracorporeal factors. It is crucial to establish whether delay in retrieval of donor bone and ambient holding temperature of the donor body influence osteoinductivity of bone left in situ. Of ten adult rats that were killed, five were kept at 4 degrees and five at room temperature. Femurs were harvested at 24, 36, 48, 72, and 168 hours. After processing, segments were implanted in 20 four-week-old syngeneic rats for 14 days. The level of osteoinduction was evaluated histologically. It was excellent in the 4 degrees group in the 24-, 36-, and 48-hour specimens but less advanced at 72 hours. Bone taken from the room temperature group showed findings identical to those kept at 4 degrees through 36 hours, but osteoinduction was less advanced at 48 hours and absent at 72 hours. No bone formed at 168 hours in either temperature group. The following observations were made. (1) Osteoinductivity of demineralized bone left in situ after death was unexpectedly stable. (2) Retrieval time was extended by donor cooling. (3) Microperforated demineralized bone actively induced new bone formation. (4) Ethylene oxide does not inhibit osteoinduction when correctly applied for sterilization. If confirmed in humans, retrieval of bone to be used for osteoinduction could be delayed for some hours, particularly if the donor was immediately refrigerated. This would increase the effective number of bone tissue donors and utilize an undeveloped resource. ",22 2827,"The osteogenic response to distant skeletal injury. We tested the hypothesis that when one bone of the skeleton is injured, others experience an osteogenic response. Although similar or related phenomena have been observed previously, the purposes of the study were to determine if this response was reproducible, to characterize it in terms of its magnitude and duration, and to show how it is related to the type of injury sustained. To obtain this information, a model was used in which an intramedullary nail was implanted in the femur and a standard closed fracture was subsequently produced. The osteogenic response was measured by histomorphometry. Eight-four nine-week-old male Sprague-Dawley rats were divided into seven groups of twelve animals each. Groups I and II consisted of control animals in which no injury was produced. In Group-III rats, cortical drilling of the intercondylar notch and piriformis fossa of the right femur was performed, without intramedullary nailing. In Groups IV through VII, half of each group received intramedullary nails only, and in the other half intramedullary nailing was done and a closed transverse diaphyseal fracture was produced. With two different fluorochrome labels, rates of mineral apposition were measured in the left and right tibiae of all animals. The labeling periods differed in each group and were designed to determine when the peak response occurred, how long it lasted, and whether aging during the course of the experiment affected the response. ",20 254,"Soft tissue sarcomas of the head and neck in adults. We reviewed the clinical records and pathologic material of 176 adults with primary soft tissue sarcomas treated at Memorial Sloan-Kettering Cancer Center between 1950 and 1985. Seventy-two patients (41%) had low-grade sarcomas and 104 (59%) had high-grade sarcomas. All but 18 patients underwent some form of excision as initial therapy. Adjuvant radiotherapy and chemotherapy combined with surgical excision showed no significant effect. A significantly increased risk of treatment failure was associated with large tumor size, positive surgical margins, bone involvement, local recurrence, metastatic spread, and high histologic grade. Except for recurrence, the p value by univariate analysis in the log-rank test for comparison of survival according to these clinical and pathologic characteristics was p less than 0.0001. Although the overall survival was 75% at 2 years, 55% at 5 years, and 46% at 10 years, only 20% of the patients with high-grade sarcomas were alive 10 years after treatment. Most patients with rhabdomyosarcoma, high-grade peripheral nerve tumor, and high-grade fibrous histiocytoma and all patients with high-grade angiosarcoma died of disease less than 5 years after diagnosis. New therapeutic strategies are needed to improve the survival of adult patients with high-grade soft tissue sarcomas of the head and neck. ",3 2231,"Effects of newborn screening of cystic fibrosis on reported maternal behaviour. Screening for cystic fibrosis is highly controversial. Concerns have been expressed that newborn screening may cause mothers, who had considered their child to be healthy before diagnosis, to overprotect their child. Some critics of screening also suggest that a period of delay from onset of symptoms to diagnosis may help a mother adjust to the reality of the child's lethal condition. This study compared the strength of overprotective child rearing attitudes of 29 mothers whose children were screened (13 had symptomatic children and 16 asymptomatic children) with the attitudes of 29 mothers whose children were diagnosed after the onset of symptoms. Results indicate that newborn screening had not increased a mother's tendency to overprotect her child with cystic fibrosis and in some cases the tendency had decreased. Further, delay in diagnosis when screening was not conducted usually caused mothers considerable personal distress. ",15 2874,"Hair dryer burns in children. Three children with burn injuries caused by home hair dryers are described. In one patient the injury was believed to be accidental, and in the other two cases the injuries were deliberately caused by a caretaker. The lack of prior experience with hair dryer burns initially led to suspicion of other causes. The characteristics of each case aided in the final determination of accidental vs nonaccidental injury. These cases prompted testing of home hair dryers to determine their heat output. At the highest heat settings, the dryers rapidly generated temperatures in excess of 110 degrees C. After the dryers were turned off, the protective grills maintained sufficient temperatures to cause full-thickness burns for up to 2 minutes. These cases and the results of testing demonstrate that hair dryers must be added to the list of known causes of accidental and nonaccidental burns in children. ",20 28,"Intraocular pressure changes and postural changes of intraocular pressure in experimentally induced Hansen's disease of rhesus, mangabey, and African green monkeys. In our long term evaluation of patients with Hansen's disease we have frequently found reduction of their intraocular pressure. Furthermore, we noted changes in their intraocular pressure on change of posture. To determine if these changes have any significance we measured the intraocular pressures of 24 experimentally infected and 39 control monkeys in both sitting and reclining positions. We found significant reduction of intraocular pressure in 66.7% compared with controls in the sitting position, and a significant increase in intraocular pressure in 79% when checked first in the sitting then in the reclining position. We offer a possible pathophysiological explanation as to why the changes occur. ",0 1908,"Timing and triggers of transient myocardial ischemia. Use of exercise tolerance testing and new techniques of ambulatory electrocardiographic monitoring to more objectively measure myocardial ischemia have enabled clinicians to better recognize the magnitude, timing and variable characteristics of transient ischemic events. These commonly occurring events in patients with coronary artery disease have a diurnal pattern strikingly similar to that reported for catastrophic cardiovascular events such as myocardial infarction, sudden cardiac death and stroke. Whether those factors that contribute to reversible ischemic events are similar to those causing infarction and sudden death has not been resolved. However, the parallel increase in morning activity for these related phenomena suggests that a better understanding of the triggers of reversible myocardial ischemia may help improve understanding of the causes of myocardial infarction and sudden cardiac death. ",13 1850,"Plaque morphology and pathologic changes in arteries from patients dying after coronary balloon angioplasty Morphologic correlates of pathologic success or failure were studied at autopsy in 28 patients with 40 coronary arteries that had been subjected to balloon angioplasty. The presence of the following histologic features was evaluated: plaque concentricity or eccentricity, calcification, fibrous or fibropultaceous plaque, medial disruption, luminal thrombus and inflammation. Angioplasty was considered successful (residual cross-sectional luminal area greater than 25%) on pathologic examination in 14 arteries and unsuccessful in 26 arteries. Eccentric plaques were more likely to be successfully dilated than were concentric lesions (p less than 0.05). Six (50%) of 12 fibropultaceous plaques were successfully dilated compared with only 8 (29%) of 28 fibrous plaques. Moderate to severe calcification did not preclude morphologic success. Medial stretching or dissection, or both, was more often associated with a successful result. Thus, plaque morphology may be an important determinant of pathologic outcome after coronary angioplasty. ",13 578,"Basic studies on a new material for inducing antitumor immune cells. Recently, adoptive immunotherapy for cancer with lymphokine activated killer (LAK) cells has been widely used experimentally. The therapy has several problems, including difficulty in handling, sterilization, and time consumption. To solve these problems, new materials able to induce antitumor immune cells were investigated. Pokeweed mitogen (PWM) and PWM-conjugated materials (CMC-1) could induce strong killer cells by short-term stimulation of human peripheral blood lymphocytes (PBL). The induced killer cells showed a wide killing spectrum in vitro against human tumor cell lines (MKK-1, PRMI4788, NBT-2, ZR-7530, H-1, Hela, KB, HMV-1, PC-10, C-1). Human PBL stimulated for a short time by CMC-1 also showed a tumoricidal effect on tumor bearing (MKN-1, MKN-45) nude mice. These results suggest that CMC-1 may solve the problems with currently used LAK therapy and may provide easily applicable extracorporeal immunotherapy for cancer. ",3 2962,"Case report: severe ethylene glycol intoxication with normal osmolal gap--""a chilling thought"". This is a case of a 23-year-old male presenting with altered sensorium, vomiting, and right flank pain. Despite a normal osmolal gap, he was found to be suffering from ethylene glycol intoxication. This little-described presentation can result in the clinician failing to consider ethylene glycol as a causative agent. ",20 1335,"Ionized calcium, parathormone, and mortality in critically ill surgical patients. A prospective study measured ionized calcium and parathormone sequentially at 48- to 72-hour intervals in 25 surgical intensive care unit patients. Twelve patients (48%) died at mean day 40 and median day 26. Levels of ionized calcium, parathormone, blood urea nitrogen, creatinine, albumin, magnesium, and phosphate for patients who lived were compared with levels for patients who died. The incidence of hypotension, renal failure (creatinine greater than or equal to 3.0), and bacteremia, as well as the amount of red cell, crystalloid, and colloid administration for the two groups was compared. Hypotension, bacteremia, red cells, crystalloid, and colloid were no different. On days 1 and 2 ionized calcium levels were significantly lower and parathormone levels significantly higher in nonsurviving patients; this difference persisted through days 3 and 4. Blood urea nitrogen and creatinine levels increased early in nonsurviving patients but renal failure, which occurred in nine nonsurviving patients, did not develop until mean day 14, median day 18. The phosphate level was slightly higher but still within normal range in nonsurviving patients. By days 5 and 6 ionized calcium and parathormone levels were no different in nonsurviving patients, despite there being no improvement in renal function. Magnesium and albumin levels were no different between groups. Ionized calcium levels are lower and parathormone levels higher early in nonsurviving patients. This difference is not readily explained by associated clinical conditions, including renal dysfunction. Although etiology remains unclear, low ionized calcium and elevated parathormone are early predictors of mortality in critically ill surgical patients. ",11 3055,"Muscle relaxation rates in individuals susceptible to malignant hyperthermia. Muscle relaxation rate following a tetanic stimulus of adductor pollicis muscle was measured prospectively in 26 patients potentially susceptible to malignant hyperthermia (MH) the day before a muscle biopsy was obtained for MH in vitro screening. Eleven subjects were found to be MH susceptible (MHS) and 15 subjects MH-negative (MHN). In all patients, relaxation rate was recorded at three different temperatures of the skin overlying adductor pollicis (30, 34 and 38 degrees C) achieved by a small surface heating unit placed over the thenar eminence. The MHS group exhibited slightly higher relaxation rate at 34 and 38 degrees C compared with the MHN group and this difference was accentuated with increasing temperature, but was not statistically different. The results of the present study suggest that relaxation rates are normal in MHS individuals under physiological conditions and cannot be used diagnostically for MH screening. ",22 3120,"Porcelain and resin veneers clinically evaluated: 2-year results. A clinical comparison of two different types of dental veneers--baked porcelain veneer and heat-and-pressure processed urethane resin veneer--was made after 2 years. Although the esthetic appearance and gingival response were equal for both systems, the resin veneers had a greater tendency to chip and fracture. By the end of 2 years, 20% of the resin veneers had failed, whereas all of the porcelain veneers remained. ",22 627,"Quantitative electromyography in polymyositis: a reappraisal. Manual analysis of motor unit action potentials (MUAPs) was performed in 33 patients with polymyositis of whom 16 were studied in the acute stage and 17 in the chronic stage. Contrary to common description of ""myopathic potentials"" as being of low amplitude, short duration, and polyphasic shape, the quantitated study revealed no difference as to amplitude of short duration MUAPs in patients and normal subjects though short-duration MUAP and short duration polyphasic potentials were 4 and 3 times, respectively, more common in patients than in controls. Although the mean duration of MUAPs usually was significantly shorter in polymyositis than in controls, the average scatter of MUAPs duration was the same in the 2 groups. The average incidence of polyphasic MUAPs was 4 times higher in patients than in controls, as was the incidence of those of long duration. To avoid misinterpretation of EMG findings due to an excess of polyphasic MUAPs, a greater number of individual potentials than usually recommended should be collected allowing a valid estimate of the mean duration of MUAPs of simple configuration. ",4 2532,"Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. Tumor necrosis factor-alpha (TNF) is believed to be an important mediator in many diseases that are associated with the sick euthyroid syndrome. To investigate the effect of TNF on thyroid hormone metabolism, we performed a controlled study in six healthy postabsorptive males, in whom plasma thyroid hormones and TSH were sequentially measured after iv bolus injections of recombinant human TNF (50 micrograms/m2) and isotonic saline. During the 10.5-h study TNF produced the characteristic changes in circulating thyroid hormones and TSH observed in the sick euthyroid syndrome. Compared with the control experiment, TNF induced significant decreases in T3 (-36 +/- 2%; saline, -20 +/- 3%; P less than 0.05) and TSH levels (-68 +/- 3%; saline, -44 +/- 8%; P less than 0.05) and a significant increase in rT3 values (+48 +/- 11%; saline, -12 +/- 7%; P less than 0.05). T4 and free T4 index were not affected by TNF. Free T4 showed a mean transient increase of 18% in five subjects (nonsignificant), which occurred synchronically with a transient 3.5-fold rise in circulating FFA levels. Our results suggest that TNF is involved, either directly or indirectly, in the pathogenesis of the sick euthyroid syndrome. ",18 1961,"Prevalence of symptoms of Raynaud's phenomenon in general practice. OBJECTIVE--To investigate the prevalence of Raynaud's phenomenon in the populations of five general practices. DESIGN--Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices. SETTING--General practices in inner London, Merseyside, and Cheshire. SUBJECTS--1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)). MAIN OUTCOME MEASURES--Response to questionnaire on symptoms of Raynaud's phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire. RESULTS--The prevalence of Raynaud's phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey. CONCLUSION--The prevalence of Raynaud's phenomenon is high compared with the low number of patients who seek treatment for the disease. ",13 1885,"Ultrasonic evaluation of early carotid atherosclerosis. We investigated the prevalence of carotid atherosclerosis, including mild early lesions, and its association with cervical bruits and various risk factors (age, male sex, hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking) in 232 consecutive Japanese patients. High-resolution real-time B-mode ultrasonography was performed to determine the extent of atherosclerosis, and it was quantified by using a scoring system. The prevalence of carotid atherosclerosis was 49%, 59%, and 41% in all 232 patients, the 100 symptomatic patients, and the 132 asymptomatic patients, respectively. Although carotid lesions were detected frequently (87%) in the 30 patients with cervical bruits, bruits were noted in only 30% of the 88 examined patients with carotid atherosclerosis. Independent risk factors for carotid atherosclerosis in these patients were found to be age, male sex, and hyperlipidemia; diabetes mellitus was a possible risk factor for carotid atherosclerosis. Our study did not show a close association between hypertension and carotid atherosclerosis, and this might be caused by the high prevalence of hypertension in our patients. Our findings suggest an increasing prevalence of carotid atherosclerosis in the Japanese, though this should be confirmed in a population-based study. Our study demonstrates the clinical usefulness of high-resolution B-mode ultrasonography for the evaluation of early carotid atherosclerosis. ",13 446,"Lipiodol computerized tomography: how sensitive and specific is the technique in the diagnosis of hepatocellular carcinoma? Computerized tomography (CT) following the intra-arterial injection of Lipiodol (Lipiodol-CT) was performed on 60 patients suspected of having a hepatocellular carcinoma (HCC). Four main patterns of uptake of the Lipiodol within the liver were seen on CT. Of the 14 well circumscribed lesions with dense homogeneous uptake of Lipiodol, 13 were confirmed to be HCCs. Of the 25 lesions with dense patchy uptake of Lipiodol at the periphery and/or in the centre, 19 were confirmed to be HCCs. In 18 patients, in whom only ill defined faint patchy uptake of Lipiodol was present in the liver, or in whom no hepatic uptake was present at all, only one patient was found later to have an HCC. Of the three hypodense lesions in the liver with no Lipiodol uptake, one was found to be necrotic HCC, one a cholangiocarcinoma and one a regenerative nodule. In the diagnosis of HCC, Lipiodol-CT had an overall sensitivity of 97.1%, an accuracy of 88.3% and a specificity of 76.9%. Of the 34 patients with HCC, only 23 were solitary at diagnosis. The size of the HCCs ranged from 0.8 cm to 11 cm in diameter with the median size at 2.2 cm. Eleven of 34 HCCs (32.3%) were resectable. We conclude that, as part of a screening programme for high risk patients. Lipiodol-CT is useful in the early detection of HCCs. The technique also plays an important role in determining whether the tumour should be resected or managed with chemotherapy. By detecting HCCs while still small, the resectability rate can also be improved. ",3 2258,"Treatment of hirsutism with the pure antiandrogen flutamide. The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexamethasone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 to 20 patients but increased significantly during therapy. No clinically significant side effects were observed. ",16 57,"Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children. We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989. Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30. Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990. Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP. Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination. We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age. ",0 3255,"Cytomegalovirus infections in pediatric liver transplantation. From 1986 to 1989, 26 consecutive pediatric liver transplant recipients were followed up at The Hospital for Sick Children, Toronto, Canada. The patients were reviewed to assess the incidence of infection with cytomegalovirus, the severity of disease, and the relationship of recipient and donor serostatus to cytomegalovirus disease. Overall, the incidence of infection was 54% (14/26). Over 90% of patients who were seropositive or whose donors were seropositive developed evidence of cytomegalovirus infection after transplantation. Forty-three percent (6/14) of those with cytomegalovirus infections developed severe, fatal cytomegalovirus disease, despite treatment with immunoglobulins and ganciclovir (Syntex Laboratories Inc, Palo Alto, Calif) or foscarnet sodium (Astra, Pharmaceutical Products Inc, Westborough, Mass). Of all posttransplant deaths, two thirds were associated with severe cytomegalovirus infection. Cytomegalovirus-related deaths occurred in three of four seronegative patients with seropositive donors and three of six seropositive patients with seropositive donors. Therefore, a seropositive donor appeared to be a major risk factor for severe cytomegalovirus disease. ",22 590,"Intertrochanteric corrective osteotomy in slipped capital femoral epiphysis. A long-term follow-up study of 26 patients. The results of intertrochanteric corrective osteotomy in a series of 26 hips with moderate to severe chronic slipped capital femoral epiphysis are reported from follow-up studies in 1976 and 1986. In hips with a slippage of less than 40 degrees (ten hips), arthrosis was present in one hip. In the remaining 16 cases in which slippage exceeded 40 degrees, osteoarthrosis was present in 15, even though correction was adequate. From these observations it can be concluded that intertrochanteric corrective osteotomy does not prevent degeneration in cases with the most severe slip. On the basis of the present observations on treated and untreated cases, the authors advocate treatment by fixation without realignment, accepting the deformity in moderate and severe chronic slips. Rotational osteotomy may be considered in the event of hip joint contracture. ",4 1538,"The use of rectus abdominis myocutaneous flaps following excision of vulvar cancer. Rectus abdominis myocutaneous flaps have been used in 16 women following radical excision of extensive vulvar cancer. In two women the procedure was part of the primary surgery, in 11 for recurrence of vulvar cancer and in three for symptomatic palliation. Fifteen (94%) of the grafts took with primary healing. Thirteen of the 16 patients are alive 6-60 months (median 29 months) after surgery and the three who died benefited from symptomatic palliation. Simultaneous vulvar reconstruction allows good cosmetic rehabilitation and is an important part of the armamentarium for the management of patients with advanced primary or recurrent vulvar carcinoma. This technique offers excellent surgical clearance of massive offensive and painful vulvar tumors. ",12 357,"The impact of the U.S. Preventive Services Task Force guidelines on cancer screening: perspective from the National Cancer Institute. The U.S. Preventive Services Task Force evaluated the medical literature, utilizing strict criteria to judge the merits of experimental trials designed to show benefit in screening for cancer. For individuals at normal risk, the task force was not able to make recommendations for or against screening for colorectal, prostate, skin, oral, or testicular cancers. Only one physical-examination cancer-screening procedure has ever been tested in a randomized trial. During the past 27 years, the National Cancer Institute (NCI) has funded six randomized screening trials. Thus far, only one has shown a decrease in mortality. Recognizing the limitations of such trials, the NCI published ""Working Guidelines for Early Cancer Detection."" Designed for the practicing physician, these guidelines were based upon the best available evidence and on the judgment of representatives of medical professional organizations. ",3 2270,"Diminished incidence of severe rheumatoid arthritis associated with oral contraceptive use. It has been suggested that the negative association between rheumatoid arthritis (RA) and oral contraceptive (OC) use might be limited to the more severe forms of RA. To investigate this further, we studied 121 consecutive female patients with definite RA, 52 female patients with probable RA, and 378 female controls. All patients had RA symptoms of recent onset. After a mean followup period of 6 years, patients with definite RA were classified as having either a severe disease course (n = 76) or a mild disease course (n = 45). The negative association between OC use prior to the onset of RA symptoms and the development of RA was limited to those patients with definite RA who had a severe disease course. We therefore conclude that OC use prior to the onset of RA symptoms is only associated with a reduction in the incidence of severe RA. This may explain the divergent results of previous studies. ",16 845,"Crohn's disease in the city of Derby, 1951-85. An epidemiological survey of Crohn's disease in the city of Derby showed that the incidence of the condition increased from 0.7/10(5) per year between 1951 and 1955 to 6.67/10(5) per year between 1981 and 1985 but seemed to reach a plateau between 1976 and 1985. Large bowel Crohn's disease was more common in patients presenting aged 60-79 years than in those aged 20-39 years. The increase in incidence was not solely due to the detection of milder disease. There was no evidence that the Asian (Indian subcontinent) population of Derby was resistant to the development of Crohn's disease. ",5 3139,"The detubularized right colonic segment as urinary reservoir: evolution of technique for continent diversion. Continent diversion of urine via a cecal-right colonic reservoir has been performed at our university hospital since 1977. Several modifications of surgical technique have been devised to prevent problems of urinary leakage and difficulties in catheterization. The current technique, used during the last 3 years on 14 patients, involves use of a detubularized right colonic segment as a reservoir, ileal mesenteric exclusion, fashioning the intussuscepted ileal nipple valve with staples and anchoring of a fascia strip sling around the nipple base to the anterior rectus sheath. Complication from the reservoir outlet occurred in only 1 patient. ",22 2726,"Search for epitope-specific antibody responses to the human immunodeficiency virus (HIV-1) envelope glycoproteins signifying resistance to disease development. It is essential for the development of strategies for prevention and therapy of human immunodeficiency virus (HIV-1) infections to define host factors playing a dominant role in determining the clinical outcome of infection. Antibodies directed against restricted regions of the HIV-1 glycoproteins gp120 and gp41 are likely to represent important factors involved in host defense against HIV-1. Definition of qualitative and quantitative differences in the spectrum of anti-gp120 and anti-gp41 antibodies between two vastly different groups of HIV-1-infected individuals, long-term asymptomatic carriers, and individuals with acquired immunodeficiency syndrome (AIDS) who died, might reveal the epitope specificity of antibodies contributing to prevention of clinical disease. To accomplish this goal, sera from both groups were assayed for antibodies recognizing synthetic peptides from gp120/gp41 which were shown in earlier experiments to mimic epitopes on the two HIV-1 glycoproteins. None of the sera recognized all of the distinct 27 peptides from gp120 and gp41. The spectrum of antibodies was distinct for each of the sera from both groups of HIV-1-infected individuals. Nevertheless, antibody responses distinguishing the two groups from each other were discerned. In particular, it was possible to predict the unfavorable outcome of disease by comparative measurements of levels of antibodies to a peptide (303-338), corresponding to the entire V3 hypervariable loop of gp120 and/or by providing evidence for declining levels of these antibodies during the course of infection. Antibodies recognizing additional peptides [(219-245), (280-306), (425-452), (658-682), (729-758), (808-845), and (845-862)] were significantly less prevalent in AIDS patients than in asymptomatic carriers. It appears possible that maintenance of high levels of the respective antibodies would contribute to preventing AIDS in HIV-1-infected individuals. Active immunization with antigens containing epitopes defined by the respective peptides and/or administration of the corresponding antibodies may be considered as a modality for therapy of HIV-1 infections. ",19 2586,"The effect of repetitive exercise on airway temperatures To determine if a relationship exists between intra-airway thermal events and the reduction in pulmonary mechanics that occur in asthmatics when they perform repetitive exercise, we recorded intrathoracic airstream temperatures in seven subjects during and after two identical bouts of cycle ergometry performed 30 min apart. From these data, global and regional thermal energy exchanges were calculated. Inspired air conditions, work loads, and minute ventilations were held constant for both trials. Pulmonary mechanics were measured prior to and serially after each challenge. As expected, the second provocation produced a smaller response than did the first. In association with these mechanical changes, the second challenge also produced less airway cooling and slower rewarming in the central airways. Hence, repetitive exercise trials performed over short intervals attenuate the essential thermal gradients necessary to produce obstruction. To the extent that these differences in intra-airway temperature reflect changes in perfusion, our data raise the possibility that the responsivity of the bronchial microcirculation of asthmatics may be altered by repetitive exercise. ",19 530,"Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers. As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration. ",3 44,"Cefuroxime treatment failure of nontypable Haemophilus influenzae meningitis associated with alteration of penicillin-binding proteins. A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4-fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta-lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient. ",0 3299,"Functional and metabolic effects of bupivacaine and lignocaine in the rat heart-lung preparation. We have examined the effects of bupivacaine and lignocaine on myocardial metabolism in the rat isolated heart-lung preparation. Bupivacaine 1, 5 or 25 micrograms ml-1 or lignocaine 4, 20 or 100 micrograms ml-1 was administered 5 min after the start of perfusion. Both bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 reduced heart rate significantly. Bupivacaine 25 micrograms ml-1 was associated with a higher incidence of arrhythmias than the other groups. Three hearts in the bupivacaine 25 micrograms ml-1 group (n = 8) and two hearts in the lignocaine 100 micrograms ml-1 group (n = 8) failed (zero cardiac output) at the end of the experiment. Although there were no significant differences in myocardial lactate and glycogen concentrations between groups, ATP content in the bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 groups was significantly less than that in the control group. The results suggest that myocardial depression and subsequent metabolic deterioration occurred with both the high doses of local anaesthetics; these findings do not account for the apparent increased cardiotoxicity of bupivacaine. ",22 1515,"Experience with a 'physiological' steroid replacement regimen for the establishment of a receptive endometrium in women with premature ovarian failure. Eighteen women with a premature menopause underwent assessment of serial serum oestradiol (E2) and progesterone levels and endometrial histology and function. Patients received continuous transdermal E2, and progesterone either orally or vaginally for 14 days. Physiological levels of E2 were attained. Significantly higher levels of progesterone were achieved with vaginal progesterone (P less than 0.01). Endometrial biopsies obtained during E2 replacement demonstrated normal proliferative features. Expression of an oestrogen related antigen (ER-Ag) was localized in the cytoplasm of the epithelium. After 3 days of progesterone replacement the endometrium showed normal secretory features and expression of ER-Ag in the stroma as well as in the glands. After 7 days of progesterone supplementation, vaginal administration produced a more consistent physiological appearance than oral administration. Thus transdermal E2 combined with vaginal progesterone is a highly satisfactory combination for establishing a physiological endometrium in women with premature ovarian failure. ",12 1148,"Platelet-activating factor. A putative mediator in central nervous system injury? Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a potent lipid autacoid produced by many cell types. Platelet-activating factor is produced by cerebellar granule cells in culture and has been extracted from brain tissue. Multiple platelet-activating factor receptors have been demonstrated in brain tissue. Activation of platelet-activating factor receptors in transformed neuronal cell lines involved increases in intracellular calcium. Platelet-activating factor has potent actions on cerebral vessels and cerebral metabolism when administered in vivo, but may not have direct effects on brain microvessels. Excessive platelet-activating factor production in pathological states of the nervous system such as neurotrauma and stroke has been shown in only a few models (e.g., spinal cord ischemia and reperfusion or focal repercussion brain injury). In multiple studies using highly specific and potent platelet-activating factor antagonists, reversal or prevention of key consequences of brain injury such as hypoperfusion following ischemia, reperfusion and edema, inflammatory cell accumulation, neurologic/motor deficits, and neuronal salvage were demonstrated. This review provides and analyzes evidence in support of the role that platelet-activating factor might have in modulation of brain function and pathophysiological processes in brain ischemia and trauma. ",9 1812,"Short-term effect of hepatic arterial versus portal venous reperfusion on energy levels of liver tissue. The hepatic artery and the portal vein blood vary in flow, oxygenation, and hormonal content. It was uncertain which blood supply has a greater effect on the recuperative process of the hepatocytes in the ischemic liver during the initial reperfusion. The ability of the liver cells to restore its energy phosphates is related to the viability of the liver. This study was designed to determine the differences of the high energy phosphate in the liver predicated upon whether reflow was first provided by either the hepatic artery or the portal vein followed by subsequent reperfusion from both vessels. The recovery of ATP upon 10 min of only hepatic arterial reperfusion after 15 min of total ischemia was much slower compared to the portal venous reperfusion only. It may be undesirable, therefore, to reperfuse the liver with hepatic arterial blood first immediately after warm liver ischemia. ",13 579,"Fine needle aspiration biopsy in the diagnosis and management of fibroadenoma of the breast. Cytological and histological biopsies were obtained on 75 breast lumps clinically diagnosed as fibroadenomas. Of these, 95 per cent of lesions were benign. In 51 (68 per cent) confirmed as fibroadenomas histologically, cytology was benign in 78 per cent, but inadequate for diagnosis in 16 per cent. The remaining 24 lesions included three breast cancers and one lymph node with Hodgkin's disease. In this group cytology was inadequate for diagnosis in 54 per cent, including one breast cancer. No lesion with benign cytology was subsequently shown to be malignant. The study supports the view that clinical diagnosis and cytology are accurate in the diagnosis of benign breast disease of this type. Breast cancer may rarely present with the clinical features of a fibroadenoma and too few lesions have been studied to assess fully the performance of cytological biopsy in detecting these small mobile lesions. A non-excisional policy should therefore include prolonged follow-up and repeat biopsy. ",3 1299,"Myxoid malignant fibrous histiocytoma of the bladder. Although the most common soft tissue sarcoma of adulthood, malignant fibrous histiocytoma (MFH) is an extremely rare tumor of the urinary bladder. Only three well-documented cases have been reported in the world literature. The patient presented in this report represents the first case of the myxoid variant to develop in the urinary bladder. Whereas all previous patients with MFH of the bladder had intermittent hematuria, this patient's chief complaint was bladder outlet obstruction due to extension of the tumor into the prostate. He was managed with radical cystoprostatectomy, postoperative radiation therapy to the tumor bed, and adjuvant chemotherapy using doxorubicin. The patient tolerated the therapy well and was disease-free at the 3-year follow-up visit. The histogenesis, clinical features, pathologic characteristics, and treatment considerations of this rare bladder tumor are discussed in detail. ",11 421,"Primary malignant melanoma of the lower respiratory tract. Report of a case and literature review. The authors report a case of primary bronchial malignant melanoma, occurring in a 34-year-old woman presenting with persistent cough. At bronchoscopic examination, a polypoid mass was found to occlude the left mainstem bronchus. Biopsies showed a malignant epithelioid tumor resembling an atypical carcinoid. Histochemistry, electron microscopic study, and immunohistochemistry confirmed the diagnosis of melanoma. Physical examination and additional clinical history to exclude other possible primary sites were negative. The patient underwent thoracotomy with left pneumonectomy. Nineteen months after resection she was found to have a histologically similar tumor involving her left adrenal gland. Review of the literature shows that melanoma of the lower respiratory tract has been reported only in adults and has a tendency to present as a central polypoid growth that may be responsive to surgical resection. ",3 1064,"Childhood stroke after minor neck trauma: case report. Cerebral infarction after minor trauma to the neck has rarely been reported. A case is presented of a child with trauma to the vertebrobasilar artery resulting in stroke. Computerized tomography scan and angiography results are presented. Despite two subsequent, separate transient episodes of vertigo, the child had good functional recovery with complete restoration of language and cognitive function. After 28 months, residual impairments identified were a mild right-sided ataxia and hemiparesis. ",9 853,"Using periodontal plastic surgery techniques. In the 1980s, mucogingival surgery evolved into periodontal plastic surgery with various techniques designed to produce root coverage in areas of marginal tissue recession, to augment deficient ridges, and to lengthen crowns in cases of excessive gingival display. Periodontal plastic surgery not only enables the dentist to reconstruct but also to regenerate lost tissues. ",6 2857,"Alcohol consumption by college undergraduates: current use and 10-year trends. In a carefully executed study with a high response rate, a random sample of 10% of the undergraduate student body at a rural New England university was surveyed as to the subjects' use of alcohol in 1987. Over 87% of the surveyed students returned questionnaires. The results were compared to similar studies conducted on the campus in 1977 and 1983. ""Daily or almost daily"" use of alcohol was registered by 4.7% of the respondents, which represents a continuing decrease in daily consumption from earlier studies. One-fourth of the sample indicated drinking only one drink or fewer per week, contrary to the common perception on the campus. Nevertheless, 25.5% recorded a hangover, 7.5% recorded vomiting from drinking too much and 4.4% recorded a blackout, all ""in the last week."" Compared to the U.S. population, alcohol consumption appears to be more evenly distributed in the college sample but, still, most of the drinking is done by one-fifth of both groups. ",20 3339,"Development of a small caliber biologic vascular graft: evaluation of its antithrombogenicity and the early healing process. The authors previously showed that a small caliber xenograft using our crosslinking technique was applicable to aortocoronary bypass grafting. In this study of the graft, the antithrombogenicity and healing process was evaluated at an early stage after implantation. Fresh sheep carotid artery (3mm ID) was obtained and cross-linked with polyepoxy compounds, and then used as a small caliber vascular graft. The graft was white and soft. Six cm segments of the graft were implanted into the carotid arteries bilaterally in nine dogs. Sodium heparin was given during the surgery, but no anticoagulant was used postoperatively. Fifteen grafts from eight dogs were removed from 1 hr to 30 days after implantation, and 13 of 15 grafts were found to be patent. Two grafts, one at 3 days, and the other at 14 days, were occluded. The anastomotic area of the occluded grafts felt hard when touched from the outside. In one dog, the grafts were shown angiographically to be patent at 14 days after implantation, and this dog was kept for long-term observation. Macroscopically, no thrombus was observed on any of the patent grafts. Microscopically, the inner surface near the anastomotic lines was covered with endothelial cells, and infiltration of fibroblasts was observed from the outside 7 days after implantation. No foreign body reactions were seen around the graft. After 30 days of implantation, a thin layer of plasma protein at the middle of the graft was observed by scanning electron microscopy (SEM). From these observations, it was concluded that the grafts exhibited satisfactory early antithrombogenicity and healing after implantation. ",22 2541,"Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter. PURPOSE: To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS: A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS: Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION: The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder. ",18 2749,"Chilblains (perniosis). Unfamiliarity of physicians with chilblains (perniosis) gives rise to unnecessary hospital admissions with expensive laboratory and radiologic evaluations and, at times, hazardous therapy. Seven cases of chilblains were seen in San Francisco from November 1986 through January 1987. The patients presented with pruritic, at times painful, purple acral patches or plaques on the fingers, toes, and nose after exposure to a cool or a cold, damp environment. Histologic examination in two cases revealed a perivascular lymphocytic infiltrate with endothelial swelling of the subcutaneous fat and of the upper and lower dermal plexus. ",20 599,"The restorative and surgical technique for the full maxillary subperiosteal implant. The edentulous atrophic maxilla represents one of the most challenging implant restorative opportunities. When prescribed within the appropriate diagnostic range and performed by a highly skilled and experienced practitioner, the full maxillary subperiosteal implant is a predictable solution for the patient with an edentulous atrophic maxilla. ",4 823,"Primary sclerosing cholangitis. Primary sclerosing cholangitis is a rare disease of unknown etiology. Sclerosis of the bile ducts may actually be the final result of multiple factors such as autoimmune, bacterial, congenital, drug, or viral injury. The most commonly associated diseases are ulcerative colitis and chronic pancreatitis. Except in the earliest stages of the disease, liver histologic findings are not specific. Most patients present with jaundice, pain, and pruritus, although an increasing number of asymptomatic patients with inflammatory bowel disease and abnormal liver function are being identified. Cholangiography is key to the diagnosis and is usually pathognomonic except in the unusual case where primary sclerosing cholangitis is confused with cholangiocarcinoma. Many forms of medical therapy have been tried, including antibiotics, azathioprine, cholestyramine, colchicine, cyclosporine, D-penicillamine, steroids, and ursodeoxycholic acid. To date, none of these medications has been proved to alter the course of this disease. Recent reports of ursodeoxycholic acid trials have been encouraging, but long-term results of ongoing randomized trials have yet to be published. In recent years, balloon dilatation of biliary strictures has been accomplished via endoscopic and percutaneous transhepatic approaches. However, in patients with primary sclerosing cholangitis, these nonoperative manipulations must be done repeatedly, may entail multiple general anesthetics, and are difficult to perform. We believe that a direct surgical approach to the biliary tree with long-term transhepatic stenting is indicated in selected patients with severe hilar or extrahepatic stricturing, persistent jaundice or recurrent cholangitis, and no evidence of cirrhosis. Hepatic transplantation should be reserved for patients with primary sclerosing cholangitis who have well-established cirrhosis and have not responded to other therapeutic measures. ",5 1799,"Effects of low perfusate Ca2+ concentration on newborn myocardial function after ischemia. A greater dependence on transsarcolemmal Ca2+ flux and immaturity of Ca2+ sequestration capacity may potentiate Ca2(+)-mediated reperfusion injury in the newborn myocardium. The effect of serum ionized Ca2+ concentration on left ventricular systolic and diastolic function after ischemia was studied in 5-7-day-old piglets undergoing a 90-minute period of cold-blood cardioplegic arrest. In the control group, Ca2+ was maintained at 1.2 mM (Group A [n = 6]). The cardioplegic solution and bypass perfusate were modified to achieve a low Ca2+ concentration, 0.25 mM, in Group B (n = 6). Left ventricular pressure-volume loops were acquired by using high-fidelity pressure-sensor-tipped and volume-conductance catheters. Ventricular function was assessed from the slope of end-systolic (Ees) and end-diastolic (k) pressure-volume relations during transient caval occlusion. Both groups showed a significant reduction in Ees after ischemia (p less than 0.05). Intergroup comparison of Ees after ischemia demonstrated a better recovery of the systolic function in the low Ca2+ group, 64 +/- 7% versus 49 +/- 6% in the normal Ca2+ group (p = 0.05). There was a significant increase in chamber stiffness index in group A (k, 0.48 +/- 0.06 to 0.65 +/- 0.05 ml-1, p less than 0.01) versus no significant change in group B. This study shows 1) the feasibility of acquiring continuous pressure-volume data in neonatal hearts by using a conductance catheter system, and 2) better preservation of systolic function and diastolic compliance in normal newborn myocardium by low Ca2+ concentration in the peri-ischemic period. ",13 2633,"Anaphylaxis following ingestion of a psyllium-containing cereal. Recently, psyllium hydrophilic mucilloid, a bulk-forming laxative, has been added to breakfast cereals for cholesterol-lowering effects. We report a case of a 60-year-old woman with no prior history of psyllium ingestion who developed anaphylactic symptoms after eating a psyllium-containing cereal. Her only previous exposure was dispensing a psyllium-containing laxative as a nurse. Immunoglobulin E-mediated sensitization was documented by skin testing and basophil histamine release. The literature is reviewed regarding allergic reactions to psyllium. Health care workers and pharmaceutical workers handling psyllium may be at increased risk due to sensitization from inhalation. Physicians and consumers should be aware of potential serious reactions from eating psyllium-containing cereals even without prior history of ingestion of psyllium. ",19 2247,"Effects of haem arginate on variegate porphyria. Four patients with variegate porphyria (VP) were treated with repeated haem arginate infusions daily for 4 days and then weekly for 4 weeks. After the initial four daily doses of haem arginate (haem 3 mg/kg), the excretion of faecal protoporphyrin (mean 579 nmol/g dry wt) fell to an almost normal level (mean 123 nmol/g dry wt), and that of coproporphyrin (mean 162 nmol/g dry wt) to the normal level (mean 21 nmol/g dry wt) in all patients. However, during the period of the four weekly infusions of haem the excretion of porphyrins increased almost to the pretreatment level. Phototesting showed no changes in the photoreactivity of the skin, and no improvement in skin lesions was seen during the treatment. Except for one case of thrombophlebitis no side-effects occurred. In a child with homozygous VP, four daily infusions of haem arginate (2 mg/kg) normalized the faecal protoporphyrin content, but had no effect on the increased erythrocyte protoporphyrin concentration. ",16 2073,"Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or beta blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p less than 10(-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration greater than 150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects. ",13 113,"Altered Ca2+ homeostasis and functional correlates in hepatocytes and adipocytes in endotoxemia and sepsis. Decreased cytosolic [Ca2+] and impaired Ca2+ release in response to an IP3 challenge are among perturbations in hepatocyte Ca2+ homeostasis associated with endotoxemia and sepsis. These changes are consistent with the accompanying alterations in appropriate physiologic functions, e.g., activation of glycogen phosphorylase and gluconeogenesis, mediated by [Ca2+]c and defective phosphorylation of relevant enzymes. Attenuation of IP3 binding to the subcellular fractions that are imputed to be targets of IP3 and a decrease in the size of the IP3-sensitive pool of releasable Ca2+ are underlying components of the mechanism of the reduced Ca2+ release upon IP3 stimulation and its metabolic sequelae. ET treatment leads to a significant increase in Ca2+ associated with the cell surface compartment of adipocytes, a reduction in 45Ca2+ uptake by endoplasmic reticulum and higher cytosolic [Ca2+] under basal conditions and upon ACTH stimulation than that observed in cells of control rats. The reduced 45Ca2+ uptake is also manifest in adipocytes of septic rats. Alterations in adipocyte metabolism induced by ET include increased oxidation of glucose to CO2 (an insulin-like effect) and increased lipolysis upon NE and ACTH stimulation. ",0 353,"Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides. A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide-specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes. ",3 842,"Cigarette smoking, gastric acidity and peptic ulceration. What are the relationships? The influence of cigarette smoking on intragastric acidity was assessed in duodenal ulcer patients in symptomatic remission and in healthy volunteers in a retrospective study. Continuous 24-hr pH recordings in 150 nonsmokers and 174 smokers receiving placebo treatment were compared. Daytime intragastric acidity was higher in smokers with a median pH (interquartile range) of 1.56 (1.34-1.80) than in nonsmokers, who had a median pH of 1.70 (1.45-1.97) (P less than 0.001). There was no difference in 24-hr and nighttime median pH between the two groups. The small difference in daytime intragastric acidity in smokers and nonsmokers is unlikely to account for the increased prevalence of peptic ulcer disease in smokers. The analysis of smoking status in duodenal ulcer patients and healthy controls and males and females supports the general trend towards higher daytime acidity in smokers. Again, no differences in pH during the 24-hr or night period were found between the groups. The epidemiological and clinical correlation between smoking and duodenal ulcer disease is not adequately explained by increased intragastric acidity. ",5 1903,"Clinical cardiovascular magnetic resonance imaging. Magnetic resonance imaging (MRI) is a powerful tool providing high-resolution images of the heart and great vessels without the use of ionizing radiation or contrast agents. MRI systems currently in use at many hospitals can be used effectively in the routine, clinical evaluation of many forms of cardiovascular disease, including great vessel disease, ischemic cardiac disease and congenital cardiac disease. Moreover, quantitative and cine MRI techniques are now available, which provide highly accurate measures of chamber size, wall motion and wall thickening. Recent developments in the areas of myocardial tagging, high-speed imaging and MR assessments of flow and perfusion suggest potential for an increasing role of MRI in the clinical evaluation of the cardiovascular system. ",13 506,"Mapping the site of interaction between murine IgE and its high affinity receptor with chimeric Ig. We have investigated the interaction of mouse (m) IgE with its Fc epsilon RI on rat basophilic leukemia cells using a set of chimeric Ig that were constructed by exchanging homologous H chain C domains between human (hu) IgG1 and mIgE. Binding affinities were examined with equilibrium and kinetic measurements, and we found that epsilon/C gamma 3 (mIgE with C epsilon 4 replaced by C gamma 3) was indistinguishable from mIgE. The huIgG1 and the other chimeric Ig, which did not contain both C epsilon 2 and C epsilon 3, did not bind detectably to rat basophilic leukemia cells (Ka less than 10(6) M-1). The ability of these chimeric Ig to stimulate a cellular response (degranulation) in the presence of multivalent Ag was also tested. The epsilon/C gamma 3 was indistinguishable from mIgE in eliciting a high level of degranulation, whereas the other chimeric Ig stimulated no response even when they were preaggregated to enhance their binding avidity. These results demonstrate that C epsilon 4 may be replaced by C gamma 3 without affecting the binding and cell activating properties of mIgE. The lack of binding by the other chimeric Ig indicates that both C epsilon 2 and C epsilon 3 are necessary for the binding interaction. ",3 2038,"Conjugal temporal arteritis. We report the simultaneous occurrence of biopsy-proven temporal arteritis in husband and wife. Serologic and viral studies were negative, including viral culture of the wife's temporal artery. The concurrent incidence of giant cell arteritis in a married couple would suggest a common exogenous exposure. ",13 332,"Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses. To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population. ",3 1655,"Detection and location of myocardial infarction using technetium-99m sestamibi imaging at rest. Technetium-99m (Tc-99m) sestamibi imaging at rest has been used to detect and localize myocardial infarction. The largest study to date is a cooperative study of 146 patients in 17 institutions. There were 24 normal subjects and 122 patients with documented myocardial infarction based on clinical, enzymatic or electrocardiographic criteria. The presence of segmental myocardial perfusion defects was compared to the presence of a Q wave on the electrocardiogram or wall motion abnormality on gated blood pool scans, performed within 48 hours of the Tc-99m sestamibi study. Of the 122 infarct patients, 118 (97%) showed perfusion abnormalities by Tc-99m sestamibi imaging. A perfusion defect was found in 110 (99%) of 111 patients with a Q wave and a wall motion abnormality, 113 (99%) of 114 patients with a wall motion abnormality and 113 (98%) of 115 patients with a Q wave. Of the 24 normal subjects, 22 (92%) had normal Tc-99m sestamibi images. In 75% of 1,986 segments, both a Tc-99m sestamibi defect and a regional wall motion abnormality on gated blood scans were present. In 11% of segments, wall motion was normal but Tc-99m sestamibi imaging was abnormal; in 14% of segments, wall motion was abnormal and Tc-99m sestamibi images were normal. In the 24 control subjects, 99% of the segments were normal. Thirty-eight patients had coronary angiography. A close relation existed between the coronary anatomy and myocardial Tc-99m sestamibi uptake. All 9 territories supplied by an occluded vessel and poor collaterals had grade 0 uptake (scale 0 to 2: 0 = markedly reduced; 2 = normal). ",13 43,"Antimicrobial resistance of Shigella isolates in the USA: the importance of international travelers. A nationwide sample of Shigella isolates was collected and tested for resistance to 12 antimicrobial agents to assess the prevalence and epidemiologic correlates of antimicrobial resistance in Shigella. Of the isolates, 32% were resistant to ampicillin, 7% to trimethoprim-sulfamethoxazole, and 0.4% to nalidixic acid. Fifty (20%) of 252 isolates were associated with foreign travel. The best predictor of clinically important resistance was a history of foreign travel: 20% of isolates from foreign travelers showed trimethoprim-sulfamethoxazole resistance, compared with only 4% of isolates from those without such a history. Quinolone resistance was not identified in travel-related isolates, and quinolones may be more appropriate for initial therapy of travel-related shigellosis than is trimethoprim-sulfamethoxazole. ",0 843,"Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum. The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa. ",5 412,"Decollateralization with silicone rubber sheeting for advanced hepatocellular carcinoma: a preliminary report. A new treatment method, interception of collaterals with a silicone rubber sheet, was applied to three patients with advanced hepatocellular carcinoma in whom arterial chemoembolization was assessed as ineffective because of the developed collateral feeding arteries. This procedure was followed by arterial chemoembolization or intraportal infusion chemotherapy or both. Follow-up celiac angiography confirmed that the long-term decollateralization was achieved by shielding the liver with silicone rubber sheeting. This technique resulted in partial responses without serious complications in all the patients including two who had no responses to chemoembolization before the procedure. The response durations were 5, 21, and 27, months, respectively. One patient died of gastrointestinal bleeding 7 months after the decollateralization. The other two patients are still alive, and the survivals after the procedure are 28 and 30 months, respectively. This therapy is considered promising and may be worth choosing as an adjuvant treatment for advanced hepatic malignancies uncontrolled by arterial chemotherapy or chemoembolization. ",3 2832,"Fatal ethanol intoxication from household products not intended for ingestion. Fatal acute ethanol intoxication is frequently encountered in medicolegal practice. Although the vast majority of acute ethanol toxicity deaths follow the ingestion of conventional alcoholic beverages, ethanol can be obtained from a variety of commercial products, which often contain high levels of ethyl alcohol but are not manufactured or designed for consumption. Such products may be easily purchased in locales where statutory limitations restrict liquor availability on Sundays or during the early morning hours. Several acute ethanol fatalities have been encountered in New Mexico that were directly related to consumption of non-beverage ethanol-containing products, all of them occurring during times when alcoholic beverage sales were restricted. Despite the fact that manufacturers deliberately include compounds in these products that discourage ingestion, this policy apparently does little to deter individuals who are searching for a source of ethanol when no conventional beverages are available. The products that were consumed in these fatalities also contained other compounds which would be toxic at much greater concentrations, but which were inconsequential in their effects in comparison with the direct toxic effect of ethanol. Investigation of the scene and awareness that alcohol-containing products can be fatally abused are essential to detecting these unconventional ethanol sources. ",20 575,"Bilateral familial carotid body paragangliomas. Report of a case with DNA flow cytometric and cytogenetic analyses. A case study of bilateral familial carotid body paragangliomas with DNA flow cytometric and cytogenetic analyses is presented. Analysis of tumor cell nuclear DNA content by flow cytometry revealed aneuploid cell populations in both tumors. Standard cytogenetic analysis (Giemsa-banding technique used) of the right carotid body paraganglioma showed no evidence of numerical or structural abnormalities. We describe parameters currently used to ""predict"" biological behavior in these tumors. ",3 2774,"Deranged vitamin D metabolism but normal bone mineral density in Finnish noncirrhotic male alcoholics. To study the effect of prolonged ethanol consumption on calcium metabolism and on the prevalence of osteoporosis we examined 38 Finnish noncirrhotic male alcoholics (30-55 years of age) with dietary interviews and biochemical measurements and by measuring the bone mineral content of the forearm using single photon absorptiometry (SPA) and the bone mineral density of the spine, humerus and proximal femur using nonquantified computer tomography (CT) and dual-energy x-ray absorptiometry (DEXA). In comparison two groups of healthy controls were studied. The mean daily dietary intake of calcium was 1.3 g in the patients and 1.2 g in the controls. The dietary intake of vitamin D was equal in the study groups, too. The serum levels of calcium, phosphate and parathyroid hormone did not show any difference between the patients and controls but in the alcoholics the urinary excretion of calcium was reduced by 42% (p less than 0.0001) as compared to the controls. The serum levels of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 were reduced in the alcoholics by 40% (p less than 0.0001), 23% (p less than 0.01), and 48% (p less than 0.0001), respectively, as compared to the controls. The alcoholic men had normal levels of serum testosterone and they did not have hypercortisolism. The bone mineral content of the dominant forearm measured by SPA was similar in the study groups as were the bone mineral densities (BMD) of the lumbar and humeral areas measured by CT. The BMD at the lumbar, femoral neck, Ward's triangle and trochanter sites measured by DEXA did not differ, either. ",20 1109,"Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. Autografts of adrenal medulla were implanted into preformed cavities in the caudate nuclei of four rhesus monkeys with hemiparkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Five other hemiparkinsonian monkeys underwent caudate cavitation, but received no tissue implant. All of the animals had marked bradykinesia of the affected arm and stable apomorphine-induced turning before cavitation or implantation. Moderate behavioral recovery was seen in all five monkeys with cavitation and two of the three monkey with long-term adrenal autografts (the fourth adrenal recipient was sacrificed 10 days after grafting). The improvement occurred months after the procedure and was not as early or as complete as that seen after fetal dopaminergic grafts. Surviving adrenal tissue was found only in the animal that showed no behavioral recovery. The other two adrenal autograft recipients (with no surviving adrenal medulla) and all of the animals with cavitation had ingrowth of dopaminergic fibers from the area olfactoria and nucleus accumbens into the caudate, oriented toward the cavity. These findings show that the mechanism of improvement after adrenal medullary implants for parkinsonism is not dopamine secretion by chromaffin cells, but may be related to the sprouted host fibers. The results also indicate that the limited recovery after adrenal implants in parkinsonian patients may be a result of the cavitation, and not necessarily the result of tissue implantation. ",9 2894,"Low bone density is an etiologic factor for stress fractures in athletes. OBJECTIVE: To determine whether low bone density and other risk factors for osteoporosis are associated with stress fractures in athletes. DESIGN: Case-control study. SETTING: Institutional sports injury clinic with primary and secondary care. PARTICIPANTS: Twenty-five athletes (nineteen women) with scintigraphically confirmed stress fractures matched for sex, age, weight, height, and exercise history with 25 control athletes with no history of bone injury. MEASUREMENTS AND MAIN RESULTS: Bone mineral density measured by dual-energy x-ray absorptiometry was significantly lower in athletes with fractures than in control athletes: In the spine, bone mineral density was 1.01 +/- 0.14 g/cm2 in athletes with fractures and 1.11 +/- 0.13 g/cm2 in control athletes (P = 0.02). In the femoral neck, it was 0.84 +/- 0.09 g/cm2 in athletes with fractures and 0.90 +/- 0.11 g/cm2 in control athletes (P = 0.005). It was also significantly lower in the Ward triangle (P = 0.01) and the greater trochanter (P = 0.01). Eight athletes with fractures and no control athletes had less than 90% of predicted age-related spine density (P = 0.01), and three athletes with fractures had bone mineral densities that were 2 SDs or more below this predicted level. More athletes with fractures than control athletes had current menstrual irregularity (amenorrhea or oligomenorrhea) (P less than 0.005). Fewer athletes with fractures were using oral contraceptives (P less than 0.05). Seven-day diet records indicated similar energy and nutrient intakes, except athletes with fractures had lower calcium intakes (697 +/- 242 mg/d compared with 832 +/- 309 mg/d; P = 0.02). Dairy product intake was lower in athletes with fractures since leaving high school (P less than 0.05). The incidence of a family history of osteoporosis was similar in both groups. CONCLUSIONS: In athletes with similar training habits, those with stress fractures are more likely to have lower bone density, lower dietary calcium intake, current menstrual irregularity, and lower oral contraceptive use. ",20 2213,"Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age. ",15 2623,"In vivo immune selection of a Moloney murine leukemia virus-induced tumor results in the loss of viral- but not tumor-associated antigens. A protocol of in vivo immune selection has been used to isolate a variant of the Moloney murine leukemia virus (MuLV)-induced tumor MBL-2. Characterization of the tumor variant indicated that selection resulted in the isolation of a cell which is incapable of producing infectious virus and no longer capable of synthesizing viral proteins. Although the failure to express viral Ag has rendered the variant tumor cells resistant to lysis by CTL specific for MuLV viral Ag, the variant tumor cells retained their susceptibility to lysis by CTL which appear to be directed against an MuLV-induced tumor-associated Ag. The data indicate that the expression of nonviral tumor-associated Ag by MBL-2 is not dependent upon continued viral gene expression. ",19 1068,"The large striatocapsular infarct. A clinical and pathophysiological entity. We examined 29 patients with strictly subcortical large striatocapsular infarctions. Eight of them had aphasia or neglect. All patients underwent transcranial Doppler ultrasonography or selective carotid angiography, magnetic resonance imaging, and single photon emission tomography for assessment of cerebral blood flow, blood volume, and cerebral perfusion reserve. The signs were compatible with cortical territorial infarctions rather than lacunes. On both magnetic resonance imaging and computed tomographic scans, the lesions corresponded to the territories of the medial and lateral group of the lenticulostriate arteries, Heubner's artery, or the anterior choroidal artery. The infarctions were either due to cerebral embolization into the M1 segment of the middle cerebral artery or due to stenosis at the same site, ie, lesions that acutely and simultaneously occluded the orifices of the lenticulostriate or neighboring arteries. Persistent occlusion of the middle cerebral arteries and a decrease of cortical regional cerebral blood flow were only found in patients with aphasia or neglect. All patients without aphasia or neglect showed a rapid recanalization of the middle cerebral artery occlusion or a stenosis of the M1 segment and no cortical regional cerebral blood flow decrease. Large striatocapsular infarctions occur due to occlusive disease of the middle cerebral artery (large-vessel disease) and not due to a disseminated in situ occlusion of the long penetrating arteries (small-vessel disease), as in lacunes. Neuropsychological deficits can be explained by decreased cortical blood flow due to a persistent occlusive lesion of the middle cerebral artery. ",9 1475,"Oocyte retention after follicle luteinization. Indirect evidence supports the existence of the luteinized unruptured follicle syndrome in infertile women. To seek direct evidence of oocyte retention, infertile and normal women were studied in the early and midluteal phase by visual documentation of ovulation stigma, needle aspiration of ovarian follicles, and peritoneal fluid collection for estradiol and progesterone assay. Luteal phase was confirmed by endometrial biopsy (postovulation day 2 to 8). In normal control subjects (n = 16), 25% of test cycles were stigma-negative and no oocytes were recovered. In infertile group (n = 23), 43% of test cycles were stigma-negative. Five oocytes were recovered including one from a stigma-bearing follicle. Peritoneal fluid steroid levels failed to discriminate stigma-positive from stigma-negative cycles in either group. Oocyte retention after luteinization occurs in infertile women. ",12 2082,"Transesophageal echocardiography in critically ill patients. The feasibility, safety and clinical impact of transesophageal echocardiography were evaluated in 51 critically ill intensive care unit patients (28 men and 23 women; mean age 63 years) in whom transthoracic echocardiography was inadequate. At the time of transesophageal echocardiography, 30 patients (59%) were being mechanically ventilated. Transesophageal echocardiography was performed without significant complications in 49 patients (96%), and 2 patients with heart failure had worsening of hemodynamic and respiratory difficulties after insertion of the transesophageal probe. The most frequent indication, in 25 patients (49%), was unexplained hemodynamic instability. Other indications included evaluation of mitral regurgitation severity, prosthetic valvular dysfunction, endocarditis, aortic dissection and potential donor heart. In 30 patients (59%), transesophageal echocardiography identified cardiovascular problems that could not be clearly diagnosed by transthoracic echocardiography. In the remaining patients, transesophageal echocardiography permitted confident exclusion of suspected abnormalities because of its superior imaging qualities. Cardiac surgery was prompted by transesophageal echocardiographic findings in 12 patients (24%) and these findings were confirmed at operation in all. Therefore, transesophageal echocardiography can be safely performed and has a definite role in the diagnosis and expeditious management of critically ill cardiovascular patients. ",13 800,"Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit. Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation. ",5 1411,"5 alpha-reductase deficiency without hypospadias. A boy aged 4 with penoscrotal hypospadias and his brother aged 12 with micropenis had typical changes of homozygous 5 alpha-reductase deficiency. After three injections of chorionic gonadotrophin there was a trivial rise in plasma dihydrotestosterone with a normal increase in plasma testosterone. Urine steroid chromatography showed abnormally high 5 beta: 5 alpha ratios and 5 alpha-reductase activity was appreciably reduced in genital skin fibroblasts. The results indicate that 5 alpha-reductase deficiency is not invariably associated with genital ambiguity. ",11 2985,"Effects of screws and a sleeve on initial fixation in uncemented total knee tibial components. Aseptic loosening of tibial components remains a serious problem in uncemented total knee arthroplasties. Achieving rigid initial fixation of porous-coated components is one of the most important factors in promoting bone ingrowth. The results of a biomechanical study for micromovement of the tibial component under posteroanterior shear and axial compressive loading are presented. Forty anatomic specimen tibiae were stress tested on a servohydraulic mechanical test machine to evaluate the effects of screws and a sleeve on initial fixation of the uncemented total knee tibial component. Twenty specimens were used for posteroanterior shear loading and 20 for anterolateral axial compressive loading. Four cancellous screws were inserted through holes of the tibial tray to pierce the cortex of the proximal tibia. The methylmethacrylate sleeve was applied to the central stem. Rigidity of fixation was significantly improved by the combination of screws and a sleeve. Bone strength was also an important factor affecting the quality of fixation. ",22 2651,"Tartrazine sensitivity. Tartrazine (FD & C Yellow No. 5) is an approved azo dye present in many drugs and food products. During the 1970s, many cases of tartrazine sensitivity were reported. This led to new regulations that required the listing of azo dyes on package inserts of drugs and on packages of food products. Tartrazine sensitivity is most frequently manifested by urticaria and asthma. Although azo dyes have been implicated in accentuating hyperkinetic syndromes, tartrazine is not considered an offender. Vasculitis, purpura and contact dermatitis infrequently occur as manifestations of tartrazine sensitivity. Cross-sensitivity in aspirin-sensitive and NSAID-sensitive patients may also occur. The mechanism of sensitivity is obscure and has been called pseudoallergic. Management consists mainly of avoidance of drugs and food products that contain tartrazine. ",19 1461,"Ovarian pregnancy: a report of twenty cases in one institution. A series of 20 cases of primary ovarian pregnancy that were diagnosed and treated in one institution is reported. The prevalence rate of 1:3600 deliveries seems to be increasing in past years and comprises 3.3% of all extrauterine pregnancies. Clinical presentation, possible pathogenesis, diagnostic steps, preferred management, and future fertility are detailed. Inasmuch as all our 18 fertile patients used an intrauterine contraceptive device before the operation, special emphasis is made on the controversial relationship between use of intrauterine contraceptive devices and ovarian pregnancy. ",12 263,"Surgical treatment of cardiac myxomas: long-term results. Between 1965 and 1988, 22 patients underwent 24 operations for cardiac myxomas. Two patients had the complex myxoma syndrome. Mitral valve replacement was required at initial operation in 2 patients. One patient died perioperatively, and 5 others died subsequently. The 16 surviving patients recently underwent evaluation at a mean duration of 9 years after operation. Ten are asymptomatic and 6 have New York Heart Association class II symptoms. Nine patients continue to be employed. Eleven are in sinus rhythm, 3 have permanent pacemakers, and 2 have chronic atrial arrhythmias. Echocardiography showed atrioventricular valve insufficiency in 3 patients and reduced contractility in 4, but no new tumor recurrences. The long-term prognosis of this relatively large group of patients with cardiac myxomas has been good. Patients without the complex myxoma syndrome had no recurrence, whereas 2 patients did require reoperation for mitral valve replacement. Long-term disability and chronic arrhythmias have been infrequent, and functional status and employability of these patients have been very good. ",3 698,"Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. The relation between sensory perception of rapid balloon distension of the rectum and the motor responses of the rectum and external and internal anal sphincters in 27 normal subjects and 16 patients with faecal incontinence who had impaired rectal sensation but normal sphincter pressures was studied. In both patients and normal subjects, the onset and duration of rectal sensation correlated closely with the external anal sphincter electrical activity (r = 0.8, p less than 0.0001) and with rectal contraction (r = 0.51, p less than 0.001), but not with internal sphincter relaxation. All normal subjects perceived a rectal sensation within one second of rapid inflation of a rectal balloon with volumes of 20 ml or less air. Six patients did not perceive any rectal sensation until 60 ml had been introduced, while in the remaining nine patients the sensation was delayed by at least two seconds. Internal sphincter relaxation occurred before the sensation was perceived in three of 27 normal subjects and 11 of 16 patients (p less than 0.001), and could be associated with anal leakage, which stopped as soon as sensation was perceived. The lowest rectal volumes required to induce anal relaxation, to cause sustained relaxation, or to elicit sensations of a desire to defecate or pain were similar in patients and normal subjects. In conclusion, these results show the close association between rectal sensation and external anal sphincter contraction, and show that faecal incontinence may occur as a result of delayed or absent external anal sphincter contraction when the internal anal sphincter is relaxed. ",5 2900,"The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. II. Late effects on cutaneous and subcutaneous tissues. The late effects of irradiation with single and fractionated doses of X rays (250 kV) and fast neutrons (42 MeVd----Bc), on the cutaneous and subcutaneous tissues of the pig, have been evaluated from measurements of changes in relative field length. These were determined at intervals of 26-104 weeks after irradiation. For fractionated irradiation with X rays the average fractions exponent, N, obtained from a log-log plot of iso-effect dose (ED50) against fraction number was 0.41. This was independent of the period of assessment, with no significant indication of a time factor. However, the exponent N did vary with the level of effect and was in the range 0.33-0.51. It was greatest for a greater than or equal to 10% reduction in relative field length. Assuming the validity of the linear quadratic model of cell survival, the alpha/beta ratio was 1.95 Gy. However, this model fitted the data less well for the least severe levels of damage, and for these the alpha/beta ratios were not significantly different from zero. Irradiation with fast neutrons showed a small effect of fractionation for doses given in greater than or equal to 6 fractions compared with a single dose. There was no significant increase in iso-effect dose when the dose was given in 30 fractions compared with 6 fractions. The relative biological effectiveness for late cutaneous and subcutaneous damage for the energy of fast neutrons used did not vary with the period of assessment, i.e. 26-52 weeks compared with 65-104 weeks, and was not significantly different from that previously obtained for ischaemic dermal necrosis, seen after higher doses, at 12-20 weeks after irradiation. ",20 2341,"Phenotypic characteristics of dissociated mononuclear cells from rheumatoid synovial membrane. The phenotypic characteristics of enzymatically dissociated synovial membrane mononuclear cells from 8 patients (14 samples) with rheumatoid arthritis (RA) were assessed by fluorescence activated flow cytometry and compared to peripheral blood (PB) mononuclear cells from 18 patients with RA and 14 normal controls. There was no significant difference between the percentage of CD4+ and CD8+ lymphocytes in synovial membrane compared to RA and normal PB. Double labelling experiments revealed similar percentages of CD4+ CDw29+ (helper-inducer) and CD4+ CD45R+ (suppressor-inducer) cells in RA and normal PB. In contrast, SM CD4+ CDw29+ cells were present in significantly higher proportions than in RA and normal PB (p less than 0.001). Conversely, synovial membrane CD4+ CD45R+ cells were present in significantly lower proportions than in RA and normal PB (p less than 0.001). A similar pattern of CDw29 and CD45R antigen expression was noted on CD8+ lymphocytes reflecting increased killer-effector (p less than 0.001) and decreased suppressor-effector (p less than 0.001) cells, respectively. Other experiments revealed a significant increase in the percentage of synovial membrane CD20+ cells (B lymphocytes) and HLA-DR+ cells compared to RA PB (p less than 0.02 and p less than 0.001) and normal PB (p less than 0.01 and p less than 0.005), and similar proportions of CD14+ cells (monocytes/macrophages). Our results suggest that RA synovial membrane contains populations of T and B lymphocytes that differ quantitatively and qualitatively from those in PB. These may account for some of the abnormalities in intraarticular humoral and cellular immune responses in patients with RA. ",16 693,"Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis. We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis. ",5 3098,"Retroperitoneal mobilization of the vas deferens in the complex vasovasostomy. Anatomic distances along retroperitoneal, inguinal, and infrainguinal segments of the vas deferens were measured in 14 formalin fixed cadavers and in 15 recently postmortem males. There were no significant differences in segment lengths between the two groups nor between the right and left vasa. Data from the recent postmortem group reveals a mean length of 5.83 +/- .65 cm to be gained from retroperitoneal mobilization of the vas deferens. This information is important to surgical decisions in cases of microsurgical repair of obstructive azoospermia resulting from damage to the inguinal segment of the vas deferens. Data on other vasal segment lengths is beneficial for planning repair in other complex cases of obstructive azoospermia as well. ",22 587,"Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies [published erratum appears in J Clin Invest 1991 Feb;87(2):757] In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma. ",3 2870,"Genucom knee analysis system: reproducibility and database development. The Genucom is a relatively new computerized system that performs a multidimensional analysis of knee laxity. Therefore, the purposes of the present investigation were twofold: 1) to estimate the reproducibility of the testing system in its ability to obtain similar test values on the same test subject within a back-to-back two-test protocol and 2) to develop a database of normal values as a standard against which values of suspected ligament injury can be compared to reliably determine whether, in fact, ligament injury has occurred. In the reproducibility phase of the study, 20 subjects were tested in two trials each of eight tests, yielding 20 separate test values per trial, accounting for each angle of flexion and plane of force tested. Both legs were tested, providing an N of 40. Test-retest correlations of the two trials and dependent t-tests indicated that the Genucom provided generally stable and reproducible results. In the normal value database phase of the study, 218 different subjects were given one trial of the same eight tests. Testing of both legs provided an N greater than 400. Means and standard deviations were calculated for each test. ",20 2891,"Geriatric injury: an analysis of prehospital demographics, mechanisms, and patterns. STUDY OBJECTIVE: To evaluate emergency medical services (EMS) system use, injury mechanisms, and prehospital assessments among elderly victims of trauma. DESIGN: We analyzed all prehospital data for injuries among patients 70 years old or older for whom 911 EMS dispatch was requested in a medium-sized metropolitan area during a 12-month period. RESULTS: A total of 1,154 cases occurred (women, 65.1%), which represented 30.3% of all 911 dispatches involving elderly patients. Injury mechanisms were fall (60.7%), motor vehicle accident (MVA; 21.5%), fight (2.4%), accidental poisoning (2.3%), and choking (2.1%). Persons in their 90s had a lower frequency of MVAs (3.4%) than did younger patients (23.0%) (P less than .005). The most frequent injuries determined by prehospital assessment were head or face (25.1%), upper extremity (17.2%), hip (14.5%), lower extremity (13.8%), back (9.8%), and chest or abdomen (5.0%). The frequency of serious neurologic injuries was less for falls or MVAs than for other mechanisms (P less than .005). Suspected hip (P less than .001) and pelvic (P less than .005) injuries occurred more frequently during falls than during other mechanisms of injury, whereas back injuries occurred most frequently in MVAs (P less than .001). Seventy-one fall victims (10.1%) had suspected medical causes of their fall. Twelve patients (1.0%) were in cardiac arrest. CONCLUSION: We report injury patterns and mechanisms among elderly victims of trauma presenting to an EMS system. A knowledge of these patterns will be useful to emergency physicians and EMS administrators. ",20 164,"Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth. We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL. ",3 925,"Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged. ",7 2631,"Evaluation of the AIDS dementia complex in clinical trials. The AIDS dementia complex (ADC) is one of the most common and important causes of morbidity associated with infection by human immunodeficiency virus type 1 (HIV-1). The evaluation of ADC in clinical trials is significant not only because of the clinical impact of this syndrome, but also because of the value of measuring its cardinal features as an index of drug efficacy and because of its emerging role as a major clinical end point. The objectives of therapy include both prevention of ADC in the presymptomatic patient and alleviation of established disease. At present, the pathogenesis of ADC is incompletely understood in several critical aspects, particularly the processes underlying the clinical manifestations of central nervous system (CNS) HIV-1 infection and, further, how such processes are related to systemic disease. Consequently, it is not yet clear to what extent, or in which patients, it is necessary to achieve ""therapeutic"" drug levels within the CNS. Nevertheless, the assessment of ADC prevention and treatment relies principally on the complementary approach of neurological examination for diagnosis and neuropsychological testing for quantitative serial measurement of treatment effects. Additionally, surrogate markers in cerebrospinal fluid (CSF) may hold promise for objective, rapid assessment of treatment response and dose adjustment. Other measurements, including more routine CSF analysis, neuroimaging, and neurophysiological assessments, are used principally for differential diagnosis rather than for monitoring ADC status. Accumulating experience with available antiviral agents suggests that ADC can be effectively prevented and treated, at least for some period of time, and that assessment of this condition is indeed a valuable approach for measuring antiviral therapy. ",19 3058,"Bleeding complications associated with cardiopulmonary bypass. Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion-transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly. ",22 1810,"Hemodynamic status in critically ill patients with and without acute heart disease. Physicians have been urged to reduce the use of the pulmonary artery catheter. However, there are no guidelines to help the clinician make the decision to use or withhold invasive monitoring in the individual patient. This study was designed to examine the accuracy of physician estimates of cardiac function in a spectrum of patients with hemodynamic instability to determine whether differences in accuracy among subgroups would suggest subgroups of patients who could be managed without invasive measurements. Physician estimates of cardiac index were found to be sufficiently accurate in patients without acute heart disease that initial management without invasive monitoring may be appropriate in selected cases. However, due to the general inaccuracy of physician estimates, efforts to improve the accuracy of clinical judgments of cardiac function and hemodynamic status should be pursued with vigor in patients both with and without acute cardiac dysfunction. ",13 2244,"Neutrophil zinc levels in psoriasis and seborrhoeic dermatitis. The median zinc content of neutrophils was significantly reduced in 16 patients with psoriasis in comparison to both normal controls and six patients with seborrhoeic dermatitis (P less than 0.05). This reduction was unrelated to the extent of skin involvement. Plasma and erythrocyte zinc levels were unchanged. ",16 870,"Parotid gland: plain and gadolinium-enhanced MR imaging. The purpose of this study was to show the typical appearance of lesions of the parotid gland with plain MR imaging and MR imaging enhanced with gadopentetate dimeglumine. Seventeen patients with inflammatory changes and 43 with benign and malignant tumors were studied. The examinations were carried out with plain T1-weighted sequences with a repetition time (TR) of 500 msec and an echo time (TE) of 25 msec (TR/TE = 500/25), T2-weighted sequences (1,600/90), and gadolinium-enhanced T1-weighted sequences in axial, coronal, and sagittal orientations. For identifying normal anatomic structures such as the facial nerve and the main duct, the administration of gadopentetate dimeglumine was helpful. In inflammatory changes, gadolinium-enhanced images showed no diagnostic advantages. Gadopentetate dimeglumine proved helpful in delineating tumorous lesions and in differentiating benign and malignant lesions. However, an exact differentiation of the different histologic types was not possible. Post-operative fibrosis could be differentiated from recurrent tumors after administration of gadolinium. If a question regarding infiltration or definition of the boundaries of a lesion cannot be answered with non-enhanced MR imaging, gadopentetate dimeglumine administration is advised. However, for routine imaging of the parotid gland, its use is not recommended. ",6 3102,"Hepatic injury induced by bile salts: correlation between biochemical and morphological events. Continuous intravenous infusion of taurochenodeoxycholate at a rate of 0.4 mumol.min-1.100 gm-1 for only 30 min in rats caused threefold to tenfold greater release of proteins (alkaline phosphatase, lactate dehydrogenase and albumin) into bile in comparison with animals infused with tauroursodeoxycholate at much higher rates (1.8 mumol.min-1.100 gm-1) for 2 hr. The simultaneous infusion of tauroursodeoxycholate and taurochenodeoxycholate (0.6 and 0.4 mumol.min-1.100 gm-1, respectively) for 2 hr prevented the marked biochemical changes in the bile induced by taurochenodeoxycholate for 15 to 60 min exhibited significantly more necrotic hepatocytes, especially in zone 1, in comparison with animals infused with tauroursodeoxycholate or a combination of taurochenodeoxycholate and tauroursodeoxycholate. A good correlation was observed between biochemical and morphological indices of bile acid-induced hepatocyte injury. These data suggest that (a) primary events induced by the acute infusion of toxic bile salts responsible for cholestasis include zone 1 hepatocellular necrosis and (b) this can be prevented by the simultaneous infusion of tauroursodeoxycholate. ",22 1734,"Sodium-calcium interactions and salt-sensitive hypertension. In humans with essential hypertension, salt-induced increases in blood pressure have been reported to correlate directly with salt-induced increases in intracellular free calcium [( Ca2+]i) in circulating mononuclear cells. These findings are consistent with the hypothesis that salt-induced increases in [Ca2+]i mediate the phenomenon of salt sensitivity. Circumstantial evidence suggests that salt-induced increases in intracellular sodium or in plasma levels of 1,25-dihydroxy vitamin D might mediate salt-induced increases in [Ca2+]i and blood pressure. However, in humans with salt-sensitive hypertension, it remains to be determined: (1) whether salt-induced increases in white blood cell [Ca2+]i reflect corresponding increases in vascular smooth muscle [Ca2+]i; (2) whether salt-induced increases in [Ca2+]i are a cause or consequence of salt-induced increases in blood pressure; and (3) whether salt-induced increases in 1,25-dihydroxy vitamin D or intracellular sodium precede salt-induced increases in [Ca2+]i. ",13 1439,"Gastric mucosal PGE2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects. PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia. ",11 41,"Platelet-activating factor or a platelet-activating factor antagonist decreases tumor necrosis factor-alpha in the plasma of mice treated with endotoxin. When L-platelet-activating factor (PAF) or alprazolam (a PAF antagonist) was administered to lipopolysaccharide (LPS)-treated mice, the level of plasma tumor necrosis factor (TNF alpha) determined by either ELISA or a cytotoxic assay using WEHI cells was significantly lowered. The inactive stereoisomer, D-PAF, was not effective in lowering plasma TNF alpha levels in LPS-treated mice. The decrease in plasma TNF alpha induced by L-PAF or alprazolam was partly reversed by indomethacin. Despite a decrease in plasma TNF alpha, L-PAF or alprazolam caused an increase in the amount of TNF alpha mRNA present in the kidneys and the livers of LPS-treated mice, suggesting that a posttranscriptional event leading to the synthesis or release of TNF alpha was inhibited by these agents. ",0 482,"Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3. B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients. ",3 3157,"Amenorrhea. Amenorrhea, the lack of menstruation, is a gynecologic disorder that may arise from a variety of causes. If a logical and orderly schema is followed, the correct diagnosis and appropriate management plan can be formulated. ",22 0,"Superficial cultures in neonatal sepsis evaluations. Impact on antibiotic decision making. The authors performed a retrospective analysis of neonatal superficial cultures and their effect on antimicrobial decision making during a nine-month period at Nashville General Hospital. They obtained and reviewed charts of infants (n = 66) having paired superficial (skin and/or gastric aspirate) and deep (blood and cerebrospinal fluid) cultures for the evaluation of early-onset sepsis. Superficial cultures were positive for pathogens (any streptococcus or enteric gram-negative) in 15% (10/66) of cases. Antimicrobial decision making was affected in only one of these cases, and in a seemingly inappropriate manner. In summary, there was no evidence or review that superficial cultures used in sepsis evaluation influenced physician antimicrobial decision making; in one case they may have led to unnecessary antibiotic exposure. ",0 1033,"Excitation thresholds for nerves reinnervating the paralyzed canine larynx. Electrical stimulation of paralyzed laryngeal muscles implanted with nerve-muscle pedicles (NMP) has resulted in documented return of motion. No study, however, has yet determined how NMP excitability correlates with that of normal muscle or nerve. In six anesthetized dogs, one hemilarynx was denervated and the paralyzed thyroarytenoid, cricothyroid, and posterior cricoarytenoid muscles were reinnervated via NMPs originating from the ansa hypoglossi nerve. After 4.6 to 5.7 months, an electric stimulator delivering biphasic pulses of variable amplitude and widths was used to test thresholds for contraction in nine stimulatable NMPs, six intact recurrent laryngeal nerves (RLN), and five normal cervical muscles. With one exception (2.1 mA), NMP rheobases varied between 0.0002 and 0.04 mA (mean = 0.020 SD +/- 0.012, n = 6). Two NMPs belonging to animals stimulated for several hours had higher values (0.1 mA). Rheobase varied from 0.01 to 0.09 mA for control RLNs (mean = 0.058 SD +/- 0.025), and from 0.05 to 0.35 mA for muscles (mean = 0.144 SD +/- 0.109). Histologic correspondence with reinnervation was established in implanted muscles by type grouping on ATPase stains. These data suggest that 1) nerve pedicles may offer promise for the eventual construction of implantable low energy consuming laryngeal devices, and 2) the appropriate charge to be injected over time remains to be determined. ",8 2743,"Femoral neck fracture fixation. Comparison of a sliding screw with lag screws. The rigidity of a sliding compression screw and three cannulated lag screws in the treatment of subcapital fractures was compared in five pairs of female cadaver femora. There were no significant differences between the compressive strength, bone density, cortical thickness or Singh index of the bones in each pair. A subcapital fracture was standardised using a perpendicular saw cut across the femoral neck. A uniaxial 'load test system' with force and length measurement facilities was used to mimic cyclical stressing applied in vivo at a frequency of 0.5 Hz from 0 to 3 times body-weight. There was no significant difference between the fixation afforded by the sliding compression screw and three lag screws. Bone quality was the single most important factor in the stability of the bone implant unit. ",20 703,"Towards a true prevalence of peptic ulcer: the Sorreisa gastrointestinal disorder study. This study, designed to overcome methodological problems inherent in earlier prevalence studies of peptic ulcer, was carried out in a municipality in northern Norway. It included the total population of 2027, aged 20-69 years, and comprised a questionnaire and search for previously diagnosed peptic ulcers in the local medical records for all subjects, and additional endoscopy of all subjects with dyspepsia and their matched healthy controls (n = 619). The overall prevalence was 10.5% in men and 9.5% in women, a sex ratio close to one and a higher duodenal:gastric ratio than previously reported from this region. A substantial 1% prevalence of asymptomatic ulcers was also observed. ",5 2013,"Balloon dilatation of the mitral valve by a single bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter. The efficacy of balloon dilatation of the mitral valve by a bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter (single catheter technique) was assessed in 53 patients (mean age 28) with mitral stenosis, most of whom were women. The procedure was unsuccessful in three patients. After balloon dilatation the left atrial pressure decreased from 22 mm Hg to 13 mm Hg and the mitral valve gradient from 12 mm Hg to 4 mm Hg. The mitral valve area increased from 0.7 cm2 to 2.1 cm2. Exercise time on the standard Bruce protocol increased from 3.9 minutes to 7.2 minutes. In 22 (44%) patients mitral regurgitation developed or the grade of regurgitation increased. Left to right shunts with pulmonary to systemic flow ratios greater than 1:5 were detected in four patients. Transient cerebrovascular episodes developed in two patients. One patient died after emergency valve replacement for severe mitral regurgitation. Balloon dilatation of the mitral valve by the single catheter technique with the bifoil or trefoil catheters is an effective treatment for patients with mitral stenosis. Mild mitral regurgitation is a frequent complication of the procedure. ",13 1363,"Polyarteritis nodosa masquerading as a primary testicular neoplasm: a case report and review of the literature. We report a case of polyarteritis nodosa presenting as a mass in the testis mimicking a neoplasm. The diagnosis was confirmed by radical orchiectomy. This is an unusual presentation of this systemic disease. We discuss the physical findings, ultrasonographic features and pathological findings, as well as review the literature for previous similar cases. ",11 960,"Tracheal reconstruction with polytetrafluoroethylene graft in dogs. Use of prosthetic materials for long-segment tracheal reconstruction has been limited owing to infection, graft migration, ingrowth of fibrous tissue, and stenosis. Polytetrafluoroethylene (PTFE) is flexible and porous, and it may resist infection more than previously used materials. We evaluated PTFE for use in long-segment tracheal reconstruction. A 5-cm segment of trachea was resected in 9 dogs and replaced with a 20-mm reinforced PTFE graft using 4-0 Vicryl sutures. In 2 control dogs, one tracheal arch was resected and a primary anastomosis was performed. The animals were followed up with weekly bronchoscopy and endoscopic photography. Euthanasia was performed at 16 weeks or when signs of respiratory distress developed. At postmorten examination, the anastomoses were examined grossly and with light and scanning electron microscopy. In all 9 dogs that underwent tracheal replacement with PTFE, granulation tissue developed at the anastomoses resulting in airway obstruction after 3 to 8 weeks. No epithelial growth occurred over the graft between the anastomoses. The control animals did well. We conclude that granulation tissue formation at the anastomosis and the lack of respiratory epithelial ingrowth across the graft makes PTFE unsuitable for long-segment tracheal reconstruction. ",7 3037,"Laryngeal framework reconstruction with miniplates. Defects of the laryngeal framework after trauma, cancer, and thyroplasty have been reconstructed with mini-reconstruction plates. Six patients had miniplates used to repair the thyroid cartilage defect after type I thyroplasty to prevent lateralization of the Silastic implant; three patients had miniplates used after hemilaryngectomy to bridge the thyroid cartilage remnants, resulting in better deglutition after hemilaryngectomy; and three patients had miniplates used to repair laryngeal fractures. The plates were tolerated well by the patients; there were no major complications. Rigid fixation using miniplates for laryngeal reconstruction has unique advantages over the use of wires. It offers the advantages of rigid and immediate stabilization with the ability to bridge large defects. It can be an alternative to existing techniques of laryngeal reconstruction. ",22 1953,"Prolonged extracorporeal life support of pediatric and adolescent cardiac transplant patients. Options for mechanical support of pediatric patients with severe heart failure who are awaiting transplantation or have undergone transplantation are limited. This report examines 3 patients placed on extracorporeal life support (ECLS) while awaiting transplantation and 3 patients who underwent transplantation and suffered subsequent heart failure due to rejection or postoperative myocardial dysfunction. The overall survival rate was 2 of 6. The 2 surviving patients had a failing transplanted heart. There were no survivors among the patients placed on ECLS as a bridge to transplantation. In each case a contraindication to transplantation developed before a donor heart could be obtained. The mean time of ECLS support was 147.5 hours (range, 70 to 370 hours). The ECLS circuit did not affect cyclosporin levels or antirejection therapy. Extracorporeal life support can be used to support pediatric cardiac transplant patients with biventricular failure due to acute rejection or postoperative dysfunction. Although the results have been discouraging, ECLS may still have a role as a bridge to transplantation. However, complications can develop during ECLS that may preclude transplantation. ",13 3028,"Response of Bitot's spots in preschool children to vitamin A treatment. In a double-masked, placebo-controlled, clinical trial in Indonesia, 88 preschool children between the ages of 36 and 72 months with Bitot's spots were randomly assigned to 200,000 IU of oral vitamin A or placebo and followed up for five weeks. Baseline and follow-up serum vitamin A levels were obtained. Of the 45 children receiving vitamin A, 33 (73.3%) showed complete cure and disappearance of Bitot's spots, six (13.3%) had disappearance of some but not all Bitot's spots, and six (13.3%) were unresponsive to treatment. The nonresponsive children were older, all male, and had higher initial mean serum vitamin A levels, 23.0 micrograms/dl, compared to 15.9 micrograms/dl in the cured group (P = .017). These data suggest that normal vitamin A status may be found in approximately 13% of children with Bitot's spots before vitamin A intervention and that one fourth of those who had Bitot's spots originally will not be cured of all Bitot's spots after intervention. These are important factors to consider when using Bitot's spots in prevalence surveys as a clinical sign of vitamin A deficiency. ",22 1186,"Myelopathy associated with human T cell lymphotropic virus type I (HTLV-I) in natal, South Africa. A clinical and investigative study in 24 patients. Unexplained spastic myelopathy in black (Zulu) patients, similar to that seen in the tropics, has previously been described from Natal, South Africa. Following reports linking the human T cell lymphotropic virus type I (HTLV-I) to spastic myelopathy, we undertook a prospective and retrospective search for HTLV-I antibodies in 36 patients who were labelled as having unexplained myelopathy; 24 (66%) were positive and HTLV-I was isolated from 4 out of the 6 patients whose peripheral blood lymphocytes were cultured. Eighteen (75%) gave a short history (less than 6 months). There was a female preponderance (71%), spinothalamic dysfunction was common (55%) and as many as half were severely disabled (50% wheelchair bound). Routine laboratory studies showed no specific trends apart from hypergammaglobulinaemia and CSF pleocytosis (greater than 5 cells/microliter in 66% of patients). The total CSF protein was raised (greater than 0.4 g/l) in 45% of patients. The IgG index was greater than 0.7 in 15 of 19 patients. Conventional myelography did not show any specific abnormalities. Computer assisted myelography was undertaken in 22 patients; 3 showed arachnoiditis and 2 spinal cord atrophy. Periventricular lucencies were seen in 1 of 10 patients who had computed tomography of the head. Nerve conduction studies demonstrated abnormalities in 46% of the patients indicating that subclinical peripheral nerve dysfunction was common. Visual evoked responses were abnormal in only 1 patient but brainstem auditory evoked response studies showed some abnormality in 42% of the patients. The finding of HTLV-I antibodies in a significant number, and the isolation of HTLV-I from the blood in 6 of our black patients with noncompressive myelopathy, represents a substantial clinical advance. Future studies should define more clearly the role of the virus in this disorder. ",9 817,"Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. By intrasplenic immunization we raised a rat mAb (mAb V1q; IgG2a, kappa) with a potent neutralizing activity against natural mouse TNF (1 microgram/ml mAb V1q/100 U/ml TNF). mAb V1q was used to study the role of endogenous TNF in experimental peritonitis induced by sublethal cecal ligation and puncture. mAb V1q persisted for over 5 days in the serum of mice injected with 100 micrograms of the antibody and, therefore, proved useful for in vivo experiments. As little as 20 micrograms mAb V1q/mouse prevented lethal shock of the animals by 400 micrograms LPS/mouse. In sublethal cecal ligation and puncture i.p. injection of mAb V1q directly and up to 8 h after induction of experimental peritonitis lead to death of the animals within 1 to 3 days. The lethal effect of mAb V1q was compensated by injection of recombinant mouse TNF. Similar mAb V1q effects as in immunocompetent mice were shown in severe combined immune deficiency mice deficient of mature functional B and T cells. Taken together, these data suggest that during the early phase of peritonitis endogenous TNF may stimulate nonlymphoid cells such as granulocytes, macrophages, platelets, and fibroblasts to ingest bacteria and to localize inflammation, respectively. These beneficial effects of TNF may determine survival. Thus, our data may have implications for the therapeutic management of a beginning peritonitis. ",5 2996,"Healing of experimental intestinal anastomoses. Parameters for repair. Anastomotic dehiscence remains a major complication in surgery of the large bowel, and studies on the healing sequence of experimental anastomoses are necessary to define underlying mechanisms and find ways to improve surgical outcome, particularly in high-risk situations. For the quantitative description of anastomotic repair, both mechanical and biochemical parameters are employed, each with their own limitations. Mechanical parameters, either bursting pressure or breaking strength, only reflect growing anastomotic strength as long as disruption occurs within the anastomotic area, which is less than one week after surgery for the bursting pressure and probably up to two weeks for the breaking strength. The biochemical description of anastomotic repair has been limited to behavior of collagen, as represented by its rather unique constituent amino acid hydroxyproline. Conclusions based on collagen concentrations--per unit weight--should be considered with caution since they may change as a consequence of changes in noncollagenous substances. In this respect, collagen content, per unit length, is probably a better parameter to describe anastomotic collagen levels. Few investigations have addressed the quality of collagen (e.g., crosslinking or type). Since, at this time, no distinct correlations have been demonstrated between development of mechanical strength or occurrence of leakage and collagen levels in the healing anastomosis, attention should not be restricted to a description of the quantity of collagen present: the quality of anastomotic collagen should be investigated, perhaps even more so. ",22 1763,"Inflation pressure requirements during coronary angioplasty. To examine the balloon inflation pressures required for successful percutaneous transluminal coronary angioplasty (PTCA), the maximal inflation pressure required for 477 coronary lesions in 200 consecutive patients was determined retrospectively. When graded balloon inflations just sufficient to achieve full expansion were used, the maximal inflation pressure used was less than or equal to 8 atm in 412 stenoses (86%) and was less than or equal to 10 atm in 463 stenoses (97%). Successful PTCA was achieved in 98% of lesions with a 3.5% major procedural complication rate. In a second group of 100 patients studied prospectively, the inflation pressure required to achieve full balloon expansion was less than or equal to 8 atm in 214 of 232 stenoses (92%) and less than or equal to 10 atm in 228 stenoses (98%). Thus, PTCA of coronary stenoses can be achieved with high success rates and low complication rates when graded inflations to pressures just sufficient to achieve full balloon expansion are performed. Most coronary stenoses will respond to pressures less than or equal to 8-10 atm. ",13 1588,"Perioperative myocardial injury in patients undergoing aortic valve replacement. In cases of myocardial hypertrophy myocardial protection may be insufficient. In order to determine the factors responsible for myocardial injury we assessed myocardial injury in 54 patients undergoing isolated aortic valve replacement. In all cases hypothermic cardioplegic arrest was induced. At 13 different times we measured the serum level of creatine-kinase (CK), myocardial bound creatine-kinase (CKmb), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), glutamic oxaloacetic transferase (GOT) and myoglobin. The mean duration of ischemia was 52.6 +/- 16.2 minutes and the mean time of extracorporeal circulation was 85.85 +/- 20.25 minutes. By performance of a multiple regression analysis a significant correlation between ischemia and LDH and alpha-HBDH was found; CK, GOT, LDH and alpha-HBDH correlated with duration of extracorporeal circulation. In none of the patients was a low cardiac output syndrome observed. From our results we conclude that in our study myocardial protection was sufficient and therefore the detrimental effects of extracorporeal circulation were the determining factors of enzyme release. ",13 916,"Community-acquired pneumonia: evidence of functional inactivation of alpha 1 proteinase inhibitor. Quantitative and qualitative elastase inhibitory capacity (EIC) alpha 1 proteinase inhibitor (alpha 1 PI) was measured in pulmonary arterial and systemic arterial blood of patients with community-acquired pneumonia (CAP). Eleven patients with uncomplicated CAP were compared with 16 patients with fulminating pneumonia requiring intensive care management. An appropriate increase in quantitative alpha 1 PI was demonstrated in all patients. A significant functional inactivation of alpha 1 PI was demonstrated in the ICU-treated patients that was not apparent in the uncomplicated CAP patients (p less than .01). This low EIC returned to normal 4 wk after hospital discharge in all survivors. A significant (p less than .02) difference in EIC between the pulmonary arterial and systemic arterial blood was found in the nonsurvivors on admission, which suggests that alpha 1 PI is inactivated in the lungs of patients with fulminating CAP. The present data demonstrate that alpha 1 PI is functionally inactivated in patients with fulminating CAP. This low serum functional alpha 1 PI may result in proteolytic lung damage and an unfavorable outcome. ",7 191,"Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone. The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E2) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function. ",3 3327,"In vivo nonthrombogenicity of heparin immobilized polymer surfaces. The authors developed two different methods to immobilize heparin on polymer surfaces. One method involves in situ heparin immobilization on a segmented polyurethane urea (Biomer) surface via hydrophilic poly(ethylene oxide) (PEO, Mn = 4,000) spacers. The other method uses PEO/poly(dimethylsiloxane) (PDMS) block co-polymer and heparin covalently linked in a block co-polymer system (PEO-PDMS-Hep). These surfaces have demonstrated high heparin bioactivity in vitro and excellent blood compatibility in in vitro-ex vivo experiments. This report evaluates the long-term in vivo blood compatibility of these heparin immobilized surfaces. Vascular grafts (6 mm ID, 7 cm in length) were fabricated with Biomer, and heparin was immobilized in situ with PEO spacers (B-PEO4K) and coated on their luminal surfaces with PEO-PDMS-Hep. Biomer and PEO (Mn = 4,000) grafted Biomer (B-PEO4K) were used as controls. The grafts were implanted in the abdominal aorta of dogs and retrieved at 3 months or when graft occlusion was suspected. Retrieved grafts were evaluated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). TEM measured the thickness of the adsorbed protein layer on the surface and the protein distribution (albumin, fibrinogen, and IgG) visualized by an immunogold method. All heparin immobilized grafts were patent at 3 months, whereas Biomer and B-PEO4K grafts occluded within 1 month. SEM pictures of heparin immobilized surfaces after 3 months demonstrated minimal platelet adhesion and activation without detectable fibrin formation. Heparin immobilized surfaces showed a thin protein layer (300-600 A) even after 3 months, with high concentrations of albumin and IgG and less fibrinogen. ",22 2809,"Spectrum of drinkers and intervention opportunities. Most adults in North America are either light drinkers or abstainers, so alcohol does not cause them problems. However, a small but often highly visible minority--approximately 5% of the adult population--show major symptoms of alcohol dependence. Between these extremes, there is a sizable group of about 20% of the population, particularly young men, who are drinking at risk levels and have encountered some problems related to their alcohol use. Traditionally, physicians' efforts have focused on diagnosing and treating patients with a substantial history of alcohol dependence, and relatively little attention has been given to early intervention with nondependent problem drinkers, such as identifying patients who present in primary care settings with alcohol-related morbidity or an accidental injury. Recent evidence indicates that early intervention by primary care physicians is an effective strategy for reducing alcohol problems among patients. ",20 586,"The Van Nes tibial rotationplasty. A functionally viable reconstructive procedure in children who have a tumor of the distal end of the femur. Twelve patients who had a malignant tumor of the distal end of the femur were treated with a Van Nes tibial rotationplasty. The survival rates were comparable with those for above-the-knee amputees and patients who had an endoprosthetic replacement. The results of functional testing showed that these patients performed as well as those who had endoprosthetic replacement and better than those who had above-the-knee amputation. Rotationplasty is therefore a favorable alternative to amputation or endoprosthetic replacement, either as a primary or as a salvage procedure. ",3 2423,"Reduced membrane fluidity in platelets from diabetic patients. Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups. ",17 1481,"Triplet tubal pregnancy treated by outpatient laparoscopic salpingostomy. To our knowledge, this represents the first case of a laparoscopically treated triplet EP and the first time that a double EP in the same tube was treated conservatively (with preservation of the tube). Multiple EPs may be more common than currently thought, and our report offers an alternative explanation for at least some cases of persistent EP after conservative surgical therapy. Finally, given the substantial cost savings and reduced postoperative recovery time associated with operative laparoscopy, when the patient is stable and the surgeon experienced, the laparoscopic approach should be tried, regardless of the number of EPs or their size. ",12 2024,"""White coat"" versus ""sustained"" borderline hypertension in Tecumseh, Michigan During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had ""white coat"" hypertension (i.e., high clinic but not elevated home readings). The prevalence of ""sustained"" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition. ",13 3082,"Reconstruction of patellar tendon rupture after total knee arthroplasty with an extensor mechanism allograft. Although patellar tendon rupture after total knee arthroplasty (TKA) is a rare complication, the consistently poor outcome of conventional tendon repair has convinced some to abandon such reconstruction in favor of a prospective protocol using an allograft distal extensor mechanism. The graft consists of a quadriceps tendon, a patella with a cemented prosthesis, a patellar tendon, and a tibial tubercle. Since December 1985, 13 knees in 12 patients were reconstructed using this method. Ten knees were followed for six to 51 months; five of these knees were followed for more than 24 months. Knee extension power and improved function were ultimately attained in all cases, although minimal extensor lags were present in three cases. Preoperative motion returned in all but one knee. Healing of the allograft to the host tissue was attained primarily at all of the tibial junctions. Two graft complications occurred, both in the first three months after surgery: one quadriceps junction treated by resuture failed at the one-month mark, and the other graft had to be revised for extensor weakness from rupture of the graft at the patella-patellar tendon junction, which was attributed to surgical damage to the tendon. After completion of healing to the host and rehabilitation of the knee joint, no grafts in the series failed during the course of normal daily activities. One patient fractured the allograft patella in a severe fall. The long-term durability of this construct needs to be studied further. ",22 1273,"The influence of prior therapy on the success of trabeculectomy. The role of early surgery in the management of primary open angle glaucoma is under debate. To determine whether previous medical therapy influences the outcome of subsequent trabeculectomy, we retrospectively reviewed the results of surgery in two groups of patients. The first group underwent primary trabeculectomy, having had an average of 2 weeks of preoperative medical therapy, and this group was compared with a group of patients who had received at least 1 year of topical glaucoma therapy before undergoing trabeculectomy (the multiple-treatment group). The two groups were similar in terms of a number of variables, including race, age, sex, presenting intraocular pressures, and presenting visual fields, and they differed only in the known duration of their disease. The success rate of trabeculectomy was significantly higher in the primary trabeculectomy group as compared with that in the multiple-treatment group (P less than .001). We discuss the possible reasons for this difference and its implications for the future management of primary open angle glaucoma. ",10 656,"Flurbiprofen versus diclofenac for the treatment of osteoarthritis of the knee. Seventy-four patients were enrolled in this double-blind, randomized single-center study to evaluate the therapeutic effectiveness of 50 mg tid regimens of flurbiprofen or diclofenac sodium in patients with osteoarthritis of the knee. By chance, the flurbiprofen patients had a significantly more advanced disease status at baseline than their diclofenac-treated counterparts. However, at subsequent follow-up evaluations, both treatment groups experienced a significant reduction in disease severity regardless of the baseline differences. No serious safety problems were associated with either investigational therapy. The frequency of reported medical events were distributed equally between the flurbiprofen and diclofenac groups. Although the imbalance in disease severity between treatment groups made a rigorous statistical interpretation of the results very difficult, the data from this clinical trial tend to support the equiefficacy of 50 mg tid regimens of flurbiprofen versus diclofenac for treating osteoarthritis of the knee. ",4 1670,"Doppler assessment of left ventricular filling pattern in silent ischemia in patients with Prinzmetal's angina. Spontaneous angina is an ideal condition in which to study left ventricular (LV) dysfunction induced by acute myocardial ischemia. In 6 patients with Prinzmetal's angina, LV diastolic function during 16 episodes of spontaneous angina was studied by simultaneous recordings of electrocardiographic (ECG), echocardiographic and hemodynamic parameters. In particular, pulsed Doppler echocardiography measured peak velocity of early (E) and late (A) transmitral flow and E/A ratio, as indexes of relative early versus late LV filling. During the ischemic attacks, the time sequence of pulsed Doppler echocardiographic and ECG changes showed 3 distinct phases: (1) ""waxing phase: transmitral flow changes with minimal ECG modifications (E/A = 0.85 +/- 0.1); (2) ""steady"" phase: maximal ECG changes (E/A = 0.9 +/- 0.1); and (3) ""waning"" phase: regression of the ECG changes (E/A = 1.26 +/- 0.15). In each phase, E/A ratio showed a significant difference from the baseline value (E/A = 1.17 +/- 0.2) as a result of changes in E, suggesting that myocardial ischemia affects mainly the early phase of diastole. In the waxing phase, LV diastolic dysfunction preceded systolic abnormalities, as documented by a significant reduction of E/A ratio in the absence of alterations in LV ejection fraction, as well as in systemic arterial and pulmonary wedge pressures. Finally, all the recorded parameters were consistent with LV ""contractile rebound"" occurring in the waning phase and affecting both diastole and systole. ",13 2209,"Early amniocentesis: report of 407 cases with neonatal follow-up. Amniocentesis was performed for prenatal diagnosis in 407 pregnancies between the gestational ages of 11-14 weeks. The safety and accuracy of the procedure were compared with data obtained from collaborative studies of amniocentesis performed later in the second trimester. There were no differences observed with respect to accuracy, pseudomosaicism, or maternal-cell contamination related to the timing of the procedure. The fetal loss rate within 4 weeks of the procedure was 2.3%. Fetal losses appeared to be related to maternal complications such as bleeding and leakage of fluid that occurred within a day of the procedure. No major maternal complications were noted. Information regarding neonatal outcome, including pulmonary complications and congenital orthopedic postural deformities, was found to be similar to that in previous reports. ",15 2356,"Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM. The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM. ",17 1323,"Nutritional causes of renal impairment in old age. The occurrence of renal insufficiency tends to increase in late adulthood. This common complication of old age is associated with increased physical dependency, morbidity, and mortality, and a lowered quality of life. In this review, the authors will develop the thesis that dietary practices during early and middle adulthood importantly influence the risk of renal insufficiency in the elderly. ",11 1492,"Recall of alcohol consumption during pregnancy. This is a test-retest reliability study of self-reported alcohol use during pregnancy, in which two groups of women provided two reports about their first trimester drinking over a 3-month interval (Group 1) and over a 5-month interval (Group 2). Women in Group 1 (n = 91) were queried about first trimester alcohol consumption during their fourth month of pregnancy and again during their seventh month, a 3-month recall interval. Group 2 women (n = 88) provided first trimester drinking reports during their fourth month of pregnancy and again at delivery, a 5-month recall interval. The test-retest Pearson correlation coefficient for recall of first trimester average daily volume (ADV) was .61 (p = .000) for Group 1 and .53 (p = .000) for Group 2. When the ADV scores were grouped into five ordinal categories, 51.6% of Group 1 and 56.8% of Group 2 remained in the same category at test and retest. This leads to the conclusion that self-reported alcohol consumption is moderately reliable over a 3-month and a 5-month time period. ",12 1701,"Optimizing heparin utilization in angiographic flush solutions. Various concentrations of heparin in angiographic flush solutions are employed during angiography. In an effort to determine whether differences in outcome are seen when either high or low concentrations of heparin in angiographic flush solutions are utilized, two groups of patients were evaluated. There was no difference in outcome and a small systemic effect from heparin was seen in both groups. Use of a low concentration of heparin is suggested for routine angiography. ",13 1757,"Angioplasty of occluded coronary arteries: use of thin shaft balloon over-the-wire system without pre-dilatation. A retrospective review was done on 13 consecutive patients who underwent PTCA of totally occluded coronary arteries using a recently released thin shaft balloon over-the-wire angioplasty system. Balloon size was determined by the closest fit to the arterial size and used without predilatation techniques. This technique was initially successful in 12 patients with only 2 clinically insignificant episodes of distal embolization and one probable early reclosure. Using thin shaft angioplasty systems, balloon dilatation of totally occluded coronary arteries can be done safely with a single balloon in many cases resulting in simplified procedures and economic benefits. ",13 1719,"Improved cannulation method for extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation has been shown to be useful for patients in reversible cardiogenic shock. Effective arterial cannulation techniques for infants have been developed that are simple to use and require minimal subsequent vascular repair or reconstruction after removal. Groin cannulation in adults frequently requires bidirectional arterial cannulation to ensure adequate distal perfusion as well as frequent complex arterial repairs after discontinuation. We describe a simple arterial cannulation technique using a single right-angle, high-flow arterial cannula. With this technique adequate bidirectional arterial perfusion is maintained with a single arterial cannula while the need for vascular repairs or reconstruction is minimized. ",13 770,"Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance. ",5 3201,"Neuroendocrine features of reactive bile ductules in cholestatic liver disease. Various cholestatic liver diseases are accompanied by a striking increase in the number of bile ductules. This so-called ductular reaction is thought to arise both from ductular metaplasia of hepatocytes and from proliferation of pre-existing bile ductules. Previous studies have shown that these reactive bile ductules differ from their normal counterpart in enzyme and immunohistochemical make-up. Using monoclonal antibodies directed to neuroendocrine markers and immunohistochemistry, we found that reactive bile ductules in cholestatic liver disease display neuroendocrine features. In all cases of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), extrahepatic obstruction, and acute hepatitis A, reactive bile ductules expressed the neural cell adhesion molecule (N-CAM) and reacted with monoclonal antibody A2B5. Both N-CAM and the ganglioside, recognized by A2B5, are restricted to neuroendocrine cells and tissues. In all but four of these cases, the same bile ductules expressed chromogranin-A, present in the matrix of neuroendocrine granules. Furthermore, in three cases of longstanding cholestasis, scattered periportal hepatocytes expressed chromogranin-A but not N-CAM. Other neuroendocrine markers such as neuron-specific enolase, synaptophysin, or myelin-associated glycoprotein were lacking from both bile ductules and hepatocytes. The neuroendocrine phenotype of bile ductules and hepatocytes was confirmed on electronmicroscopy, demonstrating various numbers of dense-cored, neuroendocrine granules near the peripheral cell membrane in bile ductules as well as in cells intermediate between hepatocytes and bile ductular cells. In 10 cases of normal liver tissue without ductular reaction, bile ductules lacked neuroendocrine markers except in two cases in which very weak reactivity for chromogranin-A was observed. These findings illustrate the presence of a new, neuroendocrine cell type that emerges in the liver during cholestasis. Elucidation of the significance of the neuroendocrine substance(s) produced in the dense cored granules of reactive bile ductules awaits their isolation and characterization. We can speculate that this molecule plays an autocrine or paracrine regulatory role in the process of ductular metaplasia of hepatocytes or growth of bile ductules. ",22 2141,"Prognosis of chronic granulomatous disease. The records of 28 patients with chronic granulomatous disease born over a 32 year period were reviewed. The characteristics of the group, and the frequency with which various clinical and laboratory features had been recorded, was assessed. Nine patients were known to have died, in most cases of progressive suppurative infection. Actuarial analysis showed 50% survival through the third decade of life. The long term survival of patients developing symptoms after the end of the first year of life was significantly better than that of patients whose illness started in infancy. Our data confirm that the severity of chronic granulomatous disease is not uniform, and that the prognosis for long term survival is better than that suggested in earlier reports. Early onset may be a poor prognostic sign and invasive aspergillosis is a life threatening complication. In the absence of curative treatment, trials to assess the effectiveness of interferon gamma are necessary and early antenatal diagnosis should be offered to as many affected families as possible. ",14 1247,"From disease to delirium: managing the declining elderly patient. Many geriatric patients have concurrent physical and psychiatric illnesses, but at times it may be difficult to determine which is primary. Delirium, a transient syndrome that presents with psychiatric symptoms, is usually the manifestation of an organic disorder and, if undetected and untreated, can be fatal. Clinicians, therefore, must learn to recognize the syndrome, search diligently for the underlying etiology, and treat accordingly. ",9 2713,"Comparative airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects. Bradykinin, kallidin (lys-bradykinin), and [des-Arg9]bradykinin are oligopeptides that may contribute as mediators in the pathogenesis of asthma by interacting with specific receptors designated B1 and B2. In this study, we have investigated the airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects. Changes in airway caliber were followed as maximum expiratory flow at 30% of the vital capacity (Vp30) and as forced expiratory volume in 1 s (FEV1). Only one of the six normal subjects responded to bradykinin at the maximum cumulative concentration (5.33 mg/ml). Neither kallidin nor [des-Arg9]bradykinin had any measurable bronchoconstrictor effect in the normal subjects whether airway caliber was measured as Vp30 or FEV1. In the 10 subjects with asthma, bradykinin and kallidin, but not [des-Arg9]bradykinin, produced a concentration-related fall in FEV1. The geometric mean provocation concentrations of inhaled agonist reducing FEV1 by 20% of baseline were 0.03, 0.08, and 0.44 mg/ml for bradykinin, kallidin, and histamine, respectively. Bronchoconstriction produced by bradykinin and kallidin was maximal within 3 to 5 min with recovery occurring over 30 to 45 min. Because bradykinin and kallidin are agonists of B2 receptors and [des-Arg9]bradykinin is an agonist for B1 receptors, these in vivo structure activity studies suggest that asthmatic, but not normal, airways are hyperresponsive to kinins when compared to histamine and that this potent bronchoconstrictor action is a specific pharmacologic effect compatible with the stimulation of B2 receptors or a variant of these. ",19 389,"Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator. Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques. ",3 1072,"Effect of flumazenil on midazolam-induced amnesia. We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia. ",9 759,"Left retroperitoneal exposure for distal mesenteric artery repair. Distal disease in the mesenteric arteries has usually been repaired transabdominally since it is believed that only the proximal centimeter of each vessel is accessible through the retroperitoneum. We treated five patients with chronic visceral ischemia and lesions extending beyond the orifice using a retroperitoneal approach. Exposure was obtained with a left flank incision through the tenth interspace. The left crus of the diaphragm was divided in order to control the supraceliac aorta. The mesenteric vessels were identified and dissected until their entrance into the peritoneum. There were no difficulties in exposing the superior mesenteric artery (SMA) as it coursed under the pancreas and over the duodenum for an approximate length of 5 to 10 cm. The uncinate process of the pancreas was not a limiting factor for exposure of the SMA in this region and further distal exposure could be obtained by incising the peritoneum. The trifurcation of the celiac artery and the splenic artery were accessible through this exposure; however, only the first centimeter of the hepatic and gastric branches could be reached. Revascularization was performed with endarterectomy (2 patients) and bypass (3 patients). Bowel viability was assessed at the conclusion of the procedure by incising the peritoneum. There were no complications from this exposure and no patient required reoperation for ischemic bowel. We conclude that the left retroperitoneal approach is not only acceptable for orifice lesions but is also applicable for distal disease. ",5 1987,"The case against childhood cholesterol screening Because some authorities have proposed blood cholesterol screening for children to prevent coronary heart disease, we reviewed published studies to estimate the potential risks and benefits of such screening. Childhood cholesterol levels are a poor predictor of high cholesterol levels in young adulthood and will be an even poorer predictor of coronary heart disease later in life. There is no evidence that blood cholesterol levels can be lowered more easily in children than in adults, and it seems unlikely that cholesterol reduction in childhood will be much more effective at preventing coronary heart disease than cholesterol reduction begun in middle age. Screening and interventions to lower blood cholesterol levels for millions of children would be expensive, could lead to labeling and family conflicts, and may cause malnutrition and increased noncardiovascular mortality. Because the benefits of cholesterol screening are unlikely to exceed these risks, we conclude that children should not be screened for high blood cholesterol levels. ",13 2909,"A profile of alcohol and prescription drug abuse in a high-risk community-based elderly population. Substance abuse among the elderly is relatively common but often remains undetected or ignored by health and social workers. Psychosocial and health factors related to the aging process are the major contributors to alcoholism and other drug abuse. It is estimated that between two and ten percent of individuals over the age of 60 suffer from alcoholism. This article profiles alcohol and prescription drug abuse among the geriatric clientele of Elderly Services of Spokane (ESS), a division of the Spokane (Washington) Community Mental Health Center. In addition to traditional channels, ESS uses a unique gatekeeper network to identify high-risk, community-based elderly. Elderly persons referred by gatekeepers are regarded as ""hidden"" elderly and at highest risk; notably, 37 percent of ESS clients are referred via this mechanism. Case management records of 1668 ESS clients were reviewed for a history of alcoholism, and a total of 161 persons (9.6 percent) were diagnosed with either primary or secondary alcohol abuse. Fifty subjects (about five percent of the average active ESS caseload) were referred for prescription drug abuse. Misused prescription drug classes were sedative-hypnotics, antianxiety agents, and analgesics. Diazepam, codeine, meprobamate, and flurazepam were the top four agents, and 92 percent of the subjects were found to have a duration of prescription drug abuse in excess of five years. A 60 percent correlation between prescription drug abuse and previous or active alcoholism was found. Additional characteristics of the geriatric study population are discussed in detail, including specific psychosocial factors, source of referral, age, gender, living situation, marital status, psychiatric history, and presence of polypharmacy. ",20 2266,"Ionizing radiation-induced pemphigus. Case presentations and literature review. Reports of pemphigus following ionizing radiation exposure are rare. We report two cases and review the literature regarding this association. Characteristics common to these cases include a prodromal persistent nonspecific dermatitic eruption that is often interpreted as radiation dermatitis, and latency of variable duration before the onset of a vesiculobullous eruption that begins at the portal of irradiation. Direct immunofluorescence is positive for intercellular IgG, while indirect immunofluorescence is commonly positive only at low titers; HLA correlations have not been studied. Documentation of clinical course and laboratory confirmation of the diagnosis, including hematoxylin-eosin, direct and indirect immunofluorescence, and HLA determinations (if available), should be recorded to enable further clarification of this entity. ",16 2772,"Application of the Tridimensional Personality Questionnaire to a population of alcoholics and other substance abusers. To assess its construct validity and application, Cloninger's Tridimensional Personality Questionnaire (TPQ) was administered to 267 inpatient substance abusers. One hundred seventy-two of the patients were alcoholic, 47 abused stimulants, and 48 abused other drugs, primarily benzodiazepines, marijuana, or were polysubstance abusers. Of the sample 33.8% were female. Analyses were conducted to (1) determine whether TPQ scores could be used to classify alcoholics as either Cloninger Type I or Type II; (2) examine the intercorrelations of TPQ scales and identify differences in these patterns due to drug of choice; (3) replicate previously obtained gender differences on the TPQ. The results indicate that (1) TPQ scores did not classify the alcoholics into the expected frequencies for Type I and Type II; (2) the scales were not independent and did not give rise to any differences among drug user groups, but (3) did confirm previously reported gender differences. These results indicate that Cloninger's model and the TPQ must be subjected to careful empirical study prior to their widespread acceptance. ",20 1245,"Safety, stability, and effectiveness of immunoadsorption under membrane plasmapheresis treatment for myasthenia gravis. Nine patients (five women and four men, average age 50.4 years) with refractory myasthenia gravis (MG) underwent thymectomy and were then treated with immunoadsorption under membrane plasmaphersis (IAP). Thymic histology showed hyperplasia in nine patients. An immunoadsorption column (ASAHI, Med, Co) was made with tryptophan. A Plasouto 1,000 (ASAHI, Med, Co) was used as the machine. The plasma separator was a first filter (ASAHI, Med, Co), and immunoadsorption columns were used for plasma perfusion. IAP treatment was performed three times weekly for a total of six times, after which IAP was done every 3 weeks. The removal rate of anti-Ach-R titer was 54 +/- 12%; IgG, IgA, and IgM levels improved in nine of nine patients after IAP treatment, and improvement of gait disturbances were seen in two of two. Muscle strength improved in all nine patients, whereas speech disturbances improved in two of three. Eye ptosis improved in nine of nine patients. Subjective improvement was reported by nine of nine patients, and none had severe side effects with IAP. In conclusion, IAP is a safe, stable, effective, and clinically useful treatment. for MG. ",9 261,"Histopathologic spectrum of clinically atypical melanocytic nevi. II. Studies of nonfamilial melanoma [published erratum appears in Arch Dermatol 1990 Dec;126(12):1616] We studied the clinically most atypical pigmented lesion removed from each of 142 patients with newly diagnosed sporadic melanoma. The specimens were categorized as to the type of nevus, ie, junctional or compound, presence of congenital features, and degree of nuclear atypicality--presence of nuclear enlargement, nuclear pleomorphism, hyperchromatism, and prominent nucleoli--of intraepidermal nevomelanocytes. The frequency of nuclear abnormality was graded as 1 (rare cells), 2 (10% to 50% of cells), or 3 (greater than 50% of cells) for each nuclear parameter. Among all lesions, 42 (29.6%) were junctional nevi, 74 (52.1%) were compound nevi, and 14 (9.9%) were dermal nevi. Eighteen percent of the total were either dysplastic nevi (23 cases) or malignant melanoma in situ (three cases). Fourteen nevi (9.9%) had congenital features. There were 12 junctional and 39 compound nevi and one dermal nevus that exhibited nuclear abnormality, but only four junctional nevi compared with 19 compound nevi had sufficient atypia for a designation of dysplastic nevus. Only two nevi with congenital features demonstrated any nuclear abnormality, and these were clearly nondysplastic. Thus, among nevi surgically removed as the clinically most atypical lesion in this study, compound nevi were much more likely to demonstrate nuclear atypia (and dysplasia) than were other nevi, ie, junctional or dermal nevi, or nevi with congenital features. ",3 2905,"Childhood injuries: where we are. In this paper we present the leading causes of fatal childhood injury in the United States. We examine three types of explanations for why injury rates are so high in the United States compared with what they could be and actually are in a number of industrialized European countries. Our conclusions are based on what we learn when we look at specific injury problems and apply that knowledge to the field of childhood-injury prevention as a whole. To decrease the number of fatal injuries to children, we should: 1. Recognize injuries as a major public health problem. Injuries have been perceived not as problems to be solved but as ""accidents"" which are determined by fate, not understandable, and consequently not preventable. In addition, injuries have not been addressed in the multidisciplinary fashion that typifies the successful public health approach to other problems. 2. Address intentional injury as part of the problem. Intentional injury has been treated as a separate field entirely and not addressed scientifically as a public health problem. One consequence of this is that injuries due to firearms have been addressed most frequently as a problem of ""unintentional injury."" As a result, 93% of all firearm injuries, ie, those which are intentional, have not been studied or addressed adequately. This situation is like studying motor vehicle injuries but excluding drunk driving and speeding as contributing factors, or like studying acquired immunodeficiency syndrome but ignoring anal intercourse or intravenous drug use. 3. Develop and support organizations that can plan and coordinate effectively a national approach to injury control. ",20 1403,"Fertility prognosis for infertile men: results of follow-up study of semen analysis in infertile men from two different populations evaluated by the Cox regression model. Using the Cox proportional hazard regression model on one material (group I = 765, 1950 to 1951) we have identified four variables of semen analysis with significant prognostic information about fertility. The four variables were combined into a model for establishing the probability of the individual male to achieve pregnancy as a function of time. This model is tested first on another material (group II = 321, 1977 to 1985). A Goodness-of-fit test indicates excellent agreement between the expectations from the model and the observed number of pregnancies in group II. Second, the two groups are pooled (= 1,086). Then only three variables give significant prognostic information about the time until pregnancy: (1) the man's age at semen analysis (years); (2) the percentage of morphologically normal spermatozoa (ln %); and (3) the degree of motility (good/poor). These three important variables enter into a new and better prognostic model. ",11 1076,"A randomized comparison of manipulation of the fractured nose under local and general anaesthesia. Reduction of simple nasal fractures may be performed under local or general anaesthesia: the latter is by far the most popular method in Britain, though why is hard to define. We have attempted to compare the 2 approaches by means of a randomized, prospective trial. Fifty consecutive, adult patients with radiologically proved fractures of the nasal bones were randomized to a local or general anaesthesia group and underwent manipulation with Asch's and Walsham's forceps between 7 and 15 days post-injury. Analysis of results at 4 h and 8 weeks post-operatively showed no significant benefit conferred by fracture reduction under general anaesthesia as opposed to local anaesthesia with respect to post-operative airway patency or cosmesis. It is suggested that significant benefits can be obtained in terms of patient convenience and cost effectiveness if nasal fractures are reduced under local anaesthesia as an outpatient procedure. ",9 672,"Joint inflammation provoked by a local synovial allergic reaction. Homocytotropic antibody was stimulated in animals by administering protein antigens in a vaccine with B. pertussis adjuvant. The titers of the allergic antibody responses were judged by passive cutaneous anaphylaxis reactions. Sera or globulin fractions containing high titers of antibody activity were injected into the knee joints of experimental animals. After sufficient delay for unfixed proteins to be cleared from the knee joints, animals were challenged intravenously with the corresponding antigen. The resultant local reaction of swelling and warmth (passive synovial anaphylaxis) was judged visually and by scanning procedures. Histological studies showed evidence of mast cell degranulation concurrent with synovial reaction. ",4 2981,"Induction of mixed erythroid-megakaryocyte colonies and bipotential blast cell colonies by recombinant human erythropoietin in serum-free culture. The effects of recombinant human erythropoietin (rEp) on murine hematopoietic progenitors were studied using a serum-free culture. A high concentration of rEp stimulated the formation of mixed erythroid-megakaryocyte colonies (EM colonies) and blast cell colonies, as well as erythroid colonies, erythroid bursts, and megakaryocyte colonies from normal mouse bone marrow cells. Direct effects of rEp on EM colony, megakaryocyte colony, and erythroid burst formation were confirmed by depletion of accessory cells such as T cells, B cells, and macrophages from crude bone marrow cells, and inhibition of the colonies by the addition of rabbit anti-rEp antibody to the culture in a dose-dependent fashion. Replating experiments were performed to confirm the differentiating ability of blast cell colonies grown in the presence of rEp. Most of the blast cell colonies yielded not only secondary erythroid colonies but also megakaryocyte colonies in the presence of 2 IU/mL rEp. Some of the blast cell colonies produced secondary EM colonies in the presence of 16 IU/ml rEp of 2 IU/mL rEp plus interleukin-3, although no granulocyte-macrophage colonies were found in the secondary culture. These results suggest that Ep acts not only as a late-acting factor that is specific for erythroid progenitors, but also as a bipotential EM-stimulating factor for murine hematopoietic cells. ",22 3076,"Treatment with desmopressin acetate in routine coronary artery bypass surgery to improve postoperative hemostasis. Desmopressin acetate (DDAVP) has been shown to decrease blood loss and transfusions in complex cardiac operations with long extracorporeal times. Its use in routine cardiac valve operations has been shown not to be beneficial, but its role in routine coronary artery bypass grafting operations has not been defined. We examined the effect of DDAVP in a prospective study of 60 patients undergoing uncomplicated primary coronary artery bypass grafting operations. Thirty consecutive patients received DDAVP (0.3 micrograms/kg) after cardiopulmonary bypass and were compared with 30 consecutive patients who did not receive DDAVP. No significant differences were seen in 12-hour mediastinal blood loss (465 +/- 207 ml with DDAVP versus 511 +/- 221 ml without DDAVP) or 12-24-hour mediastinal blood loss (236 +/- 127 ml with DDAVP versus 260 +/- 112 ml without DDAVP). Transfusion of blood products were similar for both groups. Platelet aggregometry at intraoperative and postoperative time points using ADP, collagen, and ristocetin was not significantly different from baseline values in either group. In a subgroup of patients with poor initial ristocetin-induced platelet aggregometry, a significant increase (p less than 0.05) in ristocetin-induced platelet aggregometry was seen postoperatively only in those patients who had received DDAVP. A decrease in blood loss and transfusions, however, was not demonstrable. In those patients who had been on aspirin or nonsteroidal anti-inflammatory drugs preoperatively, DDAVP did not improve mediastinal blood loss or transfusion needs. ",22 1678,"Relevance of intrinsic sympathomimetic activity for beta blockers. Intrinsic sympathomimetic activity (ISA) characterizes a group of beta blockers that are able to stimulate beta-adrenergic receptors (agonist effect) and to oppose the stimulating effects of catecholamines (antagonist effect) in a competitive way. Partial agonists are ligands that elicit a submaximal response when bound to beta receptors at maximal occupancy. In the isolated rat atrium, acebutolol produces a maximal stimulatory effect that is only 17 +/- 8% of the maximal effect induced by the full beta agonist isoproterenol. The presence of ISA results in less resting bradycardia and less of a reduction in cardiac output than is observed with beta blockers without ISA. In the long term, partial beta agonists may produce arterial vasodilation and increase arterial compliance, possibly leading to additional beneficial effects in the treatment of hypertension. beta blockers with ISA do not have adverse effects on plasma lipoproteins during long-term treatment; in addition, the presence of ISA could counteract the up-regulation of beta adrenoceptors often observed with beta blockers without ISA. Finally, the presence of ISA has been a conflicting issue for the use of such beta blockers in secondary prevention after myocardial infarction. However, the impressive results of the Acebutolol Prevention of Secondary Infarction trial in high-risk patients after myocardial infarction show that acebutolol, a beta blocker with moderate partial agonist activity, can be effective in decreasing the postinfarction mortality rate. By exhibiting a strikingly different hemodynamic profile from that of beta blockers without ISA, the partial beta agonists form an intriguing pharmacologic class of drugs for which prospective clinical trials should be extensively pursued. ",13 2564,"Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects. Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted. ",19 2131,"Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF. Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics. ",14 2078,"Arterial vasodilator effects of the dihydropyridine calcium antagonist amlodipine alone and in combination with verapamil in systemic hypertension. The arterial vasodilator properties of the dihydropyridine calcium antagonist amlodipine were compared with the effects of vascular muscle cyclic guanosine monophosphate production by sodium nitroprusside and with the effects of a combined infusion of amlodipine and the nondihydropyridine calcium antagonist verapamil in 8 untreated patients with primary hypertension. Arterial vasodilation was assessed by measurement of changes of forearm blood flow by mercury in Silastic strain-gauge plethysmography during brachial artery drug infusions. Forearm blood flow increased during amlodipine infusions (0.4 to 45 micrograms/min/100 ml forearm tissue) from 2.9 +/- 1.7 to a maximum of 23.6 +/- 7.6 ml/min/100 ml (687%), while sodium nitroprusside caused an increase from 3.0 +/- 1.8 to 16.2 +/- 5.4 ml/min/100 ml (449%), attesting to the importance of transmembrane calcium influx for the maintenance of vascular tone. The addition of verapamil 40 micrograms/min/100 ml to an infusion of amlodipine 44.5 micrograms/min/100 ml resulted in a further increase of forearm blood flow, from 23.6 +/- 7.6 to 34.4 +/- 9.8 ml/min/100 ml (p less than 0.05). The precise mechanisms of this finding have yet to be elucidated but may be due to interactions of the effects of the binding of these 2 chemically and pharmacologically different calcium antagonists to distinct binding sites at calcium channels. The clinical relevance of this observation for the treatment of coronary artery disease and systemic hypertension needs further study. ",13 1692,"Oral contraceptives, lipoproteins, and atherosclerosis. A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high-density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives. ",13 743,"Cirrhosis of the liver. A risk factor for development of cholelithiasis in males. An ultrasonographic study about the prevalence of cholelithiasis was performed in 410 cirrhotic patients and in 414 controls matched for age and sex. Gallstone disease was found more often in cirrhotic patients (31.9%) than in controls (20.7%) (P less than 0.001). The female-to-male ratio of gallstones prevalence in cirrhotic patients approached to 1:1. Gallstone disease in cirrhotic patients vs controls was significantly higher (30.2% vs 16.5%) (P less than 0.001) in males only. No difference was found, for gallstone disease prevalence in cirrhosis of different etiology. The prevalence of cholelithiasis increased from Child's A to Child's C with a significant trend (P less than 0.001); this difference was significant in males (12.3% vs 40.5%) (P less than 0.001) but not in females. This study shows that cirrhosis represents a risk factor for the development of cholelithiasis in males. We suggest that high levels of estrogens could play a role in these patients, by an impairment of gallbladder emptying similar to that observed in pregnant women. ",5 2869,"Pulsed carbon dioxide laser ablation of burned skin: in vitro and in vivo analysis. Pulsed lasers produce efficient and precise tissue ablation with limited residual thermal damage. In this study, the efficiency of pulsed CO2 laser ablation of burned and normal swine skin was studied in vitro with a mass loss technique. The heats of ablation for normal and burned skin were 2,706 and 2,416 J/cm3 of tissue ablated, respectively. The mean threshold radiant exposures for ablating normal skin and eschar were 2.6 J/cm2 and 3.0 J/cm2, respectively. Radiant exposures greater than 19 J/cm2 produced a plasma, which decreased the efficiency of laser ablation. Thus the radiant exposures for efficient ablation range from 4 to 19 J/cm2, and within this radiant exposure range 20-40 microns of tissue are ablated per pulse. We also examined, on a gross and histopathologic basis, in vivo burn eschar excision with a pulsed CO2 laser. The laser allowed bloodless excisions of full thickness burns on the backs of male hairless rats. The zone of thermal damage was approximately 85 microns over the subjacent fascia. The pulsed CO2 laser can ablate burn eschar efficiently, precisely, and bloodlessly and may prove valuable for the excision of burned and necrotic tissue. ",20 1994,"Changes in plasma free fatty acids and glycerols during prolonged exercise in trained and hypertensive persons taking propranolol and pindolol. The extent to which lipolysis is attenuated during prolonged submaximal exercise during beta blockade was determined in 12 normotensive endurance-trained and 12 hypertensive sedentary men using nonselective drugs with and without intrinsic sympathomimetic activity (ISA). Initially, subjects performed a graded treadmill test to determine maximal oxygen uptake (VO2max). This was followed by 2-hour walks at 25 and 45% of the subject's VO2max under each of 3 treatments: pindolol (ISA), propranolol (non-ISA) and placebo. The distribution of medication was randomized and double blinded. Blood samples taken at rest and every 30 minutes during the 2-hour walks were analyzed to determine the concentrations of free fatty acids (FFA) and glycerol. On the basis of the respective changes in FFA, glycerols and the respiratory exchange ratio, beta-adrenergic blockade did not attenuate lipolysis in the untrained hypertensive subjects when compared with the placebo administration. However, beta blockade did demonstrate a tendency to attenuate lipolysis in the trained, normotensive subjects when compared with results after placebo administration. This was particularly evident at 30 minutes of exercise, when both glycerol and FFA concentrations were not increased above resting values under both conditions of beta blockade. No differences between pindolol and propranolol were observed. Therefore, a beta-blocking agent with ISA properties appears to have no clear benefit with respect to lipid metabolism during low and moderate intensity exercise. Furthermore, these data demonstrate that beta blockade does not inhibit exercise-induced lipolysis at low and moderate intensities of exercise as formerly believed, and is unlikely to be the cause of fatigue normally observed during work in patient populations taking beta-blocking medication. ",13 2969,"Evaluation and management of patients with inhalation injury. Inhalation injury, present in approximately one third of burned patients treated at burn centers, increases mortality by a maximum of 20% in relation to age and extent of burn. The development of animal models of inhalation injury has made possible the identification of both the airway and vascular responses evoked by smoke inhalation. Inflammatory occlusion of terminal bronchioles and necrosis of the endobronchial mucosa render the airway and pulmonary parenchyma susceptible to infection and the resulting pneumonitis further increases mortality. Early diagnosis, best achieved by endoscopic bronchoscopy and 133xeon ventilation perfusion scan, permits timely application of high-frequency ventilation that appears to reduce the incidence of pneumonia and to decrease mortality. Pharmacologic agents give promise of ameliorating the deleterious changes of the vasculature. The recent advances in understanding inhalation injury have identified the research needed to further improve patient salvage. ",20 643,"Effects of rib elongation on the spine. II. Correction of scoliosis in the rabbit. Three intercostal nerves on the right side of growing rabbits were resected partially. From 1 to 3 months later, moderate left-convex thoracic scoliosis with rotation of vertebrae had developed, and the sagittal curvatures of the spine had diminished. In one group of these animals, a mechanically produced increase of 1 cm in the length of one rib on the side of the convexity resulted in an immediate correction of the scoliotic deformity, an improvement that was still evident 3 weeks after the operation. In two other groups of rabbits, a further resection of three intercostal nerves, this time on the left convex side, 1 and 2 months after the first operation, resulted in regression of scoliosis or halted its progression. These results further support a new concept in which the precipitating factor in the development of scoliosis is ascribed to asymmetric longitudinal growth of the ribs. They also suggest that regulation of the rib length could be a promising approach to the effective correction of progressive scoliosis at an early stage in man. ",4 886,"Lactate levels as predictors of the relationship between oxygen delivery and consumption in ARDS. We reviewed the changes in Do2 and Vo2 in 58 patients with ARDS after interventions which included fluid loading, blood transfusion, and PEEP. After a significant change in Do2, patients with lactic acidosis (lactate level greater than 2.4 mmol/L) exhibited significant corresponding changes in Vo2 (p less than 0.001); however, no change in Vo2 was observed in patients without lactic acidosis (1-beta greater than 0.8). We conclude that a biphasic pattern of oxygen utilization in patients with ARDS emerges when subsets of patients with and without lactic acidosis are compared. Lactic acidosis, a marker of anaerobic metabolism, may be a characteristic of patients with ARDS who exhibit changes in Vo2 that are dependent on changes in Do2. ",7 1365,"Mechanical properties of the urethra in healthy and stress incontinent females: dynamic measurements in the resting urethra. The relationship between pressure and cross-sectional area in the resting urethra during its inflation and deflation was examined in 30 healthy females and in 30 patients with genuine stress incontinence (GSI). Measurements were performed at the bladder neck, in the high-pressure zone and distally in the urethra. The mechanical properties of the urethra were found to vary significantly as a function of time after induction of a cross-sectional area (stress episode) in both groups of women. The pattern of response of the urethra showed significant differences between normals and GSI particularly during dynamic conditions. Our results indicate that mechanical laxity of the urethra at the bladder neck and midurethrally especially at dynamic events (stress episodes) is of pathophysiological importance in GSI. ",11 171,"Doxorubicin for unresectable hepatocellular carcinoma. A prospective study on the addition of verapamil. A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC). All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling. The overall median survival was 57 days. Chemotherapy was terminated in seven patients after one course of treatment. Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated. Side effects related to the chemotherapy were present in all patients studied. Death from fulminating sepsis occurred in three of the 13 patients with leukopenia. Symptomatic myocardial dysfunction developed in one patient. The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications. ",3 2508,"Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia. Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment. ",17 1881,"Factors determining success and energy requirements for cardioversion of atrial fibrillation. Factors thought to affect the success of and energy requirements for cardioversion of atrial fibrillation were studied in 80 (49 male, 31 female) patients aged 21-88 (mean 61.5 years). Transthoracic impedance was measured in advance of the countershock using a 30 kHz low amplitude AC current passed through self-adhesive ECG/defibrillator pads (diameters 8-12 cm) applied to the chest in the antero-posterior (AP) position in 57 patients and the anteroapical (AA) position in 23 patients. Mean transthoracic impedance for all patients was 69.3 +/- 16 (SD) ohms (range 39-131 ohms), but transthoracic impedance was significantly greater in the AA than the AP position (75.4 +/- 13 vs. 66.7 +/- 16 ohms, p = 0.02). Initial energy was 50 J (delivered) and was gradually increased to a maximum of 360 J if required. Cardioversion was successful in 73 of 80 (91.2 per cent), and low energy shocks (less than or equal to 200 J) were successful in 45 of 80 (56.2 per cent) patients. Using single factor analysis, sex, left atrial enlargement, electrode pad positions, aetiology of atrial fibrillation, presence of left ventricular failure, and prior treatment with verapamil or beta-adrenergic blockers were not significant determinants of cardioversion success or success of low energy shocks but prior treatment with digoxin was, both for cardioversion success and success at low energies. In patients with transthoracic impedance less than or equal to 70 ohms, low energy shocks were more often successful (33 or 50, 66 per cent) than in patients with transthoracic impedance greater than 70 ohms (12 of 30, 40 per cent), p = 0.04. Using univariate analysis, cardioversion success with low energy shocks was not only significantly associated with prior treatment with digoxin but also with the duration of atrial fibrillation (24 hours to one month and one month to three years) and for shocks of less than or equal to 100 J, with prior treatment with amiodarone. Multifactorial linear regression analysis selected, in rank order, only duration of atrial fibrillation of 24 hours to less than one month and one month to three years as significant predictors of both cardioversion success irrespective of shock strength, and success of low energy shocks. ",13 995,"Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. To investigate the long-term effect of cigarette smoke on pulmonary structure and function, we exposed groups of guinea pigs to the smoke of 10 cigarettes each day, 5 days per week, for 1, 3, 6, and 12 months. We found that the guinea pigs developed progressive lung destruction (emphysema) and alterations in their pulmonary function tests similar to that seen in humans with cigarette smoke-induced chronic obstructive lung disease. This method of smoke-induced lung destruction should provide a good model for the study of the early changes of emphysema. ",7 3022,"Persistence of arrhythmia exercise response in healthy young men. This study assesses the persistence of arrhythmia at rest or during exercise tests, or both, after a mean follow-up period of 6.7 years in 76 young men (mean age 21.5 years) without evidence of organic heart disease. The exercise test was performed using a near-maximal protocol based on progressively increasing intermittent work loads, each of 5 minutes' duration. The initial work load was 50 W. The electrocardiogram was continuously registered throughout all stages of the examination. Arrhythmia was defined as the occurrence of greater than or equal to 1 supraventricular or 1 ventricular premature beat at any stage of the examination. At the follow-up examination, the rate of persistence of arrhythmia did not differ significantly among the subgroups, irrespective of follow-up interval, type of arrhythmia, or arrhythmia patterns of response to exercise. Two-dimensional echocardiography did not show any structural abnormalities and Doppler examination did not demonstrate significant abnormal flow patterns. Our data show that almost all patients continued to present arrhythmia after the follow-up period, without any evidence of development of organic heart disease. Moreover, the arrhythmia pattern of response to exercise remained constant throughout the years. At this time, arrhythmia without underlying heart disease seems to be of a benign natural course in these young men. ",22 2701,"Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV-mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV-infected cells for the therapy of HIV-mediated pathogenesis. ",19 2556,"Genetic aspects of juvenile chronic arthritis. Immunogenetic studies in the past decade have confirmed the theory of an association between one's immunogenetic background and the manifestation of several forms of juvenile chronic arthritis (JCA), in particular pauciarticular-onset JCA. Considerable work has been done at the serologic level to demonstrate disease association with the major histocompatibility Class II antigens in pauciarticular-onset JCA. The polygenic nature of JCA is best illustrated by the findings in this particularly well-defined clinical subgroup. Evidence is now emerging that analysis of the DNA sequence, the derived protein sequence, and the structure of Class II molecules will yield significant insight into the genetic predisposition to JCA. ",19 383,"Multiple intracranial tumors of different cell types. Multiple intracranial tumors of different cell types are rare. We report nine patients with multiple intracranial tumors, who did not have a history of trauma, irradiation, or phacomatosis. The clinical, radiological, and histopathological findings as well as indications for operations in patients with asymptomatic second tumors are discussed. ",3 2821,"Alcoholism and society. The problems of alcohol abuse are rampant in society and permeate the Emergency Department experience. The cost to society as measured by social, medical, occupational, and legal effects is exceedingly high and probably underestimated. Emergency physicians have the opportunity to intervene in this vicious cycle and must learn their role in the process. ",20 312,"Anionic complex-carbohydrate units of human thyroglobulin. Human thyroglobulin (hTG) contains sulfate in chondroitin 6-sulfate chains and in complex carbohydrates. In this study the sulfate-containing complex carbohydrates were characterized by the number of sulfate and sialic acid residues that they contain. Samples of normal and nodular thyroid tissue were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified from the tissues and the media. Complex carbohydrates were enzymatically removed from hTG. Subsequent analysis on an HPLC anion exchange column at pH 2.2 separated the carbohydrate units according to their number of negative charges. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing peaks were identified by their shift to lower charge after treatment with neuraminidase. Peaks corresponding to sialic acid-free carbohydrate units with one to four sulfates were identified. Also, carbohydrate units with two and three negative charges containing both sulfate and sialic acid were present. In the nodular tissue of one patient there were more sulfated units with higher charge, especially units containing sialic acid. In this patient the proportion of sulfated polyvalent units with sialic acid was 22.4% for normal and 64.6% for nodular tissue. No difference in the composition of the charged units between the tissues and their corresponding media was seen, making it unlikely that the sulfate-containing carbohydrates play a role in hTG release. It is concluded that hTG contains complex carbohydrate units with up to four sulfate groups and units with both sulfate and sialic acid. In some patients, the sulfate-containing anionic carbohydrate units of hTG from normal and nodular thyroid tissue are different. ",3 2756,"Orthotic stabilization of thoracolumbar injuries. A biomechanical analysis of the Jewett hyperextension orthosis. Spinal orthoses have been traditionally used in the management of thoracolumbar injuries treated with or without surgical stabilization. However, the orthotic treatment modality in the management of spinal fractures remains subjective since few objective data are available on the effectiveness of orthoses in stabilizing injured segments. This study used a finite element model of the spine to evaluate the effectiveness of a hyperextension orthosis in controlling the progression of deformities at the injury site under gravitational and flexion loads. Two types of injuries were simulated: a single-level injury at T12-L1 and a two-level injury at T11-T12-L1 segments. An injury of increasing severity was simulated by progressively reducing the bending stiffness of the affected segments relative to the normal values in flexion-extension mode. The interaction of a three-point hyperextension orthosis with the spine was simulated using experimentally measured stiffness properties of the orthosis. The authors' results suggest that in single-level injuries that cause up to 50% loss of segmental stiffness, the orthosis can restore normal resistance to deformity at the injured segments, under gravitational as well as large flexion loads. In loss of stiffness between 50% and 85% of normal, such as severe two-column disruptions, the orthosis can restore resistance to deformity under restricted patient activity level in the brace (low-flexion moment). Beyond 85% loss of segmental stiffness, such as three-column injuries, the orthosis alone appears to be ineffective in preventing progression of deformity. ",20 3193,"""Cloggology"" revisited: endoscopic or surgical decompression of malignant biliary obstruction. In this study, 50 consecutive patients over age 60 with obstructive jaundice secondary to malignant stricture of the distal common bile duct were identified by endoscopic cholangiography. The patients were then randomized to palliative therapy with either endoscopic endoprosthesis or bypass surgery. Prospective indices of survival time, complication rates, hospitalization requirements, and quality of life were followed. All 25 patients randomized to endoprosthesis were treated by this procedure, whereas only 19 of 25 patients randomized to bypass surgery underwent operative biliary-digestive anastomosis. No difference in the above indices were found between the two groups. The authors concluded that palliation of obstructive jaundice due to a malignant bile duct stricture with endoscopically placed biliary stent is as effective as operative bypass. ",22 1913,"Beta-blocker duration of action and implications for therapy. Two studies were conducted to measure the effect of serum half-life on beta-blocker-related heart rate reduction throughout the 24-hour period. In the first study, nadolol, atenolol and pindolol were associated with significant (p less than 0.01) heart rate reduction even at 24 hours after dose. Nadolol, with a plasma half-life of 15.5 hours, had the most pronounced heart rate-lowering effect 24 hours after the daily dose compared to pindolol, which had a half-life of 5.5 hours. In a randomized, double-blind, crossover study, nadolol and atenolol had similar effects 3 to 4 hours after the daily dose. Nadolol, however, produced greater suppression of heart rate and double product (blood pressure x heart rate) than atenolol (compared to placebo) 24 hours after ingestion of the daily dose. On ambulatory electrocardiography 24 hours after medication administration, 80 to 100% of the heart rate-attenuating effect of nadolol was maintained versus only 20 to 45% of atenolol's effect. Statistically significant (p less than 0.05) reductions in heart rate were produced by nadolol, but not by atenolol, between 4 and 5 A.M., 6 and 7 A.M., 8 and 9 A.M. and 9 and 10 A.M. Furthermore, nadolol remained at 52% of peak blood level at 24 hours, whereas atenolol was at 20%. The data from these 2 studies indicate that significant differences in duration of action exist between beta blockers. ",13 3216,"The diagnostic impact of prehospital 12-lead electrocardiography. STUDY HYPOTHESIS: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital diagnostic accuracy is improved compared with single-lead telemetry. POPULATION: One-hundred sixty-six stable adult patients who sought paramedic evaluation for a chief complaint of nontraumatic chest pain. METHODS: One-hundred fifty-one prehospital 12-lead ECGs of diagnostic quality were obtained by paramedics on 166 adult patients presenting with nontraumatic chest pain. Paramedics and base station physicians were blinded to the information on acquired prehospital 12-lead ECGs and treated patients according to current standard of care-clinical diagnosis and single-lead telemetry. Final hospital diagnoses were classified into three groups: acute myocardial infarction (24); suspected angina or ischemia (61); and nonischemic chest pain (66). Paramedics and base station physicians' clinical diagnoses and prehospital and emergency department ECGs were similarly classified and compared. Prehospital and ED 12-lead ECGs were read retrospectively by two cardiologists. RESULTS: Paramedics achieved a high success rate (98.7%) in obtaining diagnostic quality prehospital 12-lead ECGs in 94.6% of eligible prehospital patients. For patients with acute myocardial infarction, prehospital ECG alone had significantly higher specificity than did the paramedic clinical diagnosis (99.2% vs 70.9%; P less than .001), and significantly higher positive predictive value (92.9% vs 32.7%; P less than .001). For patients with angina, combining the paramedic clinical diagnosis and the prehospital ECG significantly improved sensitivity (90.2% vs 62.3%; P less than .001) and increased negative predictive value (88.9% vs 71.3%; P less than .02) compared with paramedic clinical diagnosis alone. There was a high concordance between prehospital and ED ECG diagnosis (99.3% for acute myocardial infarction and 92.8% for angina). Furthermore, ten patients whose prehospital ECGs demonstrated ischemia and who had final hospital diagnoses of angina or acute myocardial infarction were mistriaged by paramedics and/or received no base station physician-directed therapy. CONCLUSION: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital 12-lead ECGs have the potential to significantly increase the diagnostic accuracy in chest pain patients, approach congruity with ED 12-lead ECG diagnoses, and may allow for consideration of altering and improving prehospital and hospital-based management in this patient population. ",22 1677,"Improvement in early diastolic filling dynamics after aortic valve replacement. With use of ultrafast computed tomography, 13 patients undergoing aortic valve replacement for aortic stenosis were prospectively followed to evaluate the relation between left ventricular mass and diastolic function. Studies were done before intervention, and then at 4 and 8 months later. Mass decreased from 161 +/- 11 g/m2 (+/- standard error of the mean) at baseline to 106 +/- 5 g/m2, and then to 97 +/- 7 g/m2 at 4 and 8 months, respectively, in 12 patients who demonstrated significant (greater than 20%) mass regression after operation. One patient failed to show significant changes in mass. Diastolic function, as defined by the peak filling rate of early diastole, improved (p less than 0.02) in the group with mass regression, from 2.11 +/- 0.17 s-1 at baseline to 2.12 +/- 0.23 s-1, and then to 2.62 +/- 0.26 s-1 at 4 and 8 months, respectively. Improvement in the time to peak filling rate was also noted. Heart rates were unchanged, whereas end-diastolic volumes decreased and ejection fractions increased slightly. Postoperative increase in peak filling rate correlated with regression of ventricular mass to within normal range (+/- 2 standard deviations) and attainment of New York Heart Association class I status by 8 months (p less than 0.02). Thus, improvement in diastolic function can be seen after aortic valve surgery and is associated with improved functional class. Diastolic function improves later than the regression in wall mass and may imply a delayed remodeling of the ventricle. ",13 766,"Clinical significance of cholelithiasis in patients with decompensated cirrhosis. There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis, severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1-91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients. ",5 1275,"Serous retinal detachment following glaucoma filtering surgery. We report the occurrence of serous retinal detachment in association with choroidal effusion and hypotony in six eyes that had undergone glaucoma filtering surgery. Hypotony with choroidal effusion was documented in five patients before the onset of serous retinal detachment. While one patient underwent vitrectomy, treatment was conservative in the other patients. Serous retinal detachment and choroidal effusions resolved spontaneously as the intraocular pressure normalized. Although one patient regained preoperative visual acuity, all other patients lost at least one line of Snellen acuity. ",10 2757,"Evaluation of surgical treatment for burst fractures. The authors instituted a prospective, randomized study of patients presenting with acute burst fractures of the thoracolumbar and lumbar spine. Patients were alternately treated by posterior distraction using pedicle instrumentation (AO fixateur interne) or anterior decompression and instrumentation (Kostuik-Harrington device). Forty patients are presented with a mean follow-up of 20 months. Preoperatively, there was significant canal compromise in 39 patients. This measured 44.5% in those patients undergoing posterior surgery and 58% in those patients undergoing anterior surgery. Postoperatively, this was reduced to 16.5% and 4%, respectively. There is a statistically significant difference between these two groups (P less than 0.0001). The mean preoperative kyphotic deformity was 18.7 degrees in those patients treated by anterior surgery and 18.2 degrees in the group treated by posterior surgery. At last follow-up, the mean improvement in kyphotic deformity was 9.3 degrees in the anterior group and 11.3 degrees in the posterior group. There is no statistically significant difference between these two groups. There were two implant failures of the anterior Kostuik-Harrington construct and two implant failures of the AO fixateur interne. Blood loss was significantly higher in the patients undergoing anterior surgery, but there were no complications from thoracotomy and anterior decompression of the dural sac. This study supports the hypothesis that posterior distraction instrumentation can effectively decompress the canal and correct kyphosis in patients sustaining burst-type injuries. Anterior surgery, however, results in a more complete and reliable decompression of the canal. ",20 135,"Increasing incidence of varicella hospitalizations in United States Army and Navy personnel: are today's teenagers more susceptible? Should recruits be vaccinated? Hospital records for 10,687 United States Army and Navy adult varicella (chickenpox) admissions were reviewed. Annual hospital admission rates for varicella increased more than fourfold in the active-duty army during 1980 to 1988 and more than 18-fold among active-duty navy enlisted personnel during 1975 to 1988. Fifty-seven percent of varicella admissions occurred in the most junior military members, aged 17 to 20. More than half of the total varicella admissions occurred in personnel with less than a year of military service. Multivariate analysis of the navy data confirmed increasing time-related trends of risk, suggesting a national temporal trend of increased varicella susceptibility in US teenagers and young adults. Administering a safe and effective varicella vaccine to army and navy recruits could prevent more than 7260 hospital-bed days during the first year of use. ",1 1901,"Noninvasive assessment of cardiac output in children using impedance cardiography. This study evaluated the effect of intracardiac shunting on the accuracy of thoracic bioimpedance-derived cardiac output determinations. Twenty-six patients, ranging in age from 3 months to 17 years, underwent cardiac catheterization during which simultaneous Fick and impedance measurements of cardiac output were obtained. The subjects were divided into three groups: 10 children with no intracardiac shunts, nine children with predominant left-to-right intracardiac shunts, and seven children with predominant right-to-left intracardiac shunts. Positive correlations between impedance and Fick-derived cardiac output determinations were obtained in the non-shunt group (r = 0.84), with lower correlations in the left-to-right shunt group (r = 0.70). In the right-to-left shunt group, the impedance derived cardiac output correlated with Fick pulmonary flow (r = 0.82), but the variability was unacceptably large. Although further study is needed, impedance cardiography appears to have validity as a methodology in pediatric critical care and cardiovascular health research. ",13 340,"A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02). ",3 1936,"Long-term impact of smoking cessation on the incidence of coronary heart disease. Using a simulation model of the US male population, we estimated the long-term impact that future smoking cessation programs would have on the distribution and occurrence of coronary heart disease in males ages 35-84. For interventions that reduce the number of smokers by 25 percent in 1990, the number of men free of coronary heart disease is projected to increase by 416,787 (0.7 percent) in 2015, and the age-standardized absolute incidence to decline by 2.3 percent. Incidence rates and absolute incidences are projected to fall in men under age 65, but absolute incidence would rise in men over age 65, in large part because of the increased number of men who were at risk for coronary heart disease because of a reduction in non-coronary smoking-related mortality. These trends were more marked for greater smoking reductions and were generally unaffected in a variety of analyses using alternative assumptions, which considered smoking as a risk factor in the elderly, a lag-time before benefits from smoking cessation were realized and secular declines in smoking prevalence. Subject to the assumptions of our model, we conclude that smoking reductions will markedly reduce coronary heart disease, especially in younger age groups, and that this benefit will be slightly offset by a small increase in absolute incidence in elderly men. ",13 2217,"Functional residual capacity in anesthetized children: normal values and values in children with cardiac anomalies. To assess the increase in functional residual capacity (FRC) with growth, FRC was measured after induction of anesthesia in two groups of children. One group consisted of 74 children, 0.1-11.2 yr of age, without signs of cardiorespiratory disease (referred to here as ""normal"" children), and the other of 21 children, 0.2-6.9 yr of age, with cardiac malformations. Anesthesia was maintained with halothane in the normal children and with fentanyl, droperidol, and nitrous oxide in the children with cardiac anomalies. All patients were paralyzed, their tracheas intubated, and their lungs mechanically ventilated. FRC was measured with an automated tracer gas washout technique. In 70 patients the measurements were performed in duplicate with a mean coefficient of variation of 2.0%. FRC correlated significantly with height, weight, and age in both groups. Multiple regression analysis for both groups considered together indicated no significant improvement when factors for the sex of the child or for the presence of cardiac anomalies were incorporated into the model. In normal children the simple linear and nonlinear regression equations for FRC (in milliliters) versus height (in centimeters) were: FRC = -529 + 9.48 x height, r = 0.96; and FRC = 0.00175 x height2.66, r = 0.97, respectively. The corresponding equations for FRC (in milliliters) versus weight (in kilograms) were: FRC = -92 + 29.9 x weight, r = 0.93; and FRC = 9.51 x weight1.31, r = 0.95. ",15 1116,"Sensitivity for detecting fibrillation potentials: a comparison between concentric and monopolar needle electrodes. The sensitivity of monopolar and concentric electrodes for detecting fibrillation potentials (FP) has never been formally compared. We studied 35 muscles with FP, sampling 20 sites each with concentric and monopolar needles. The concentric needle identified 0.88 +/- 3.44 (mean +/- standard deviation) more sites with spontaneous activity. Although statistically significant (Wilcoxon signed rank test P less than .03), this difference in sensitivity did not appreciably affect diagnostic interpretation. Subjects described the concentric needles as more painful. Needle insertions in 25 other muscles demonstrated that needle movement generated the majority of FP. We suggest that the increased tissue injury caused by concentric needles may account for both their increased sensitivity and discomfort. ",9 1893,"Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA. The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg. ",13 1697,"Changes in cerebral blood flow velocity after release of intraoperative tourniquets in humans: a transcranial Doppler study. The effect of release of intraoperative thigh tourniquets on velocity of blood flow in the middle cerebral artery was examined in five patients given general anesthesia with controlled ventilation for lower extremity orthopedic procedures using transcranial Doppler sonography. Middle cerebral artery blood flow velocity increased significantly from 52 +/- 6 (SEM) to 82 +/- 24 cm/s (an increase of 58% +/- 13%) within 4 +/- 1 min after tourniquet release and remained significantly elevated for 7 min. A positive linear correlation was found between middle cerebral artery blood flow velocity and PETCO2 on each occasion (0.97 greater than or equal to r greater than or equal to 0.84, 0.001 greater than P greater than 0.0001) after tourniquet deflation. Assuming a linear relationship between flow velocity and flow, these findings suggest that significant increase in cerebral blood flow can occur after intraoperative tourniquet release and that this increase appears to be mostly CO2-dependent. ",13 1789,"Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation. Although triple-drug immunosuppression with a combination of cyclosporine, prednisone, and azathioprine has been shown to improve short-term survival after cardiac transplantation, its long-term effects still are unknown. From December 1983 through December 1988, all patients (N = 139) who underwent orthotopic cardiac transplant at our institution received triple-drug immunosuppressant therapy. Follow-up averaged 32.2 +/- 15.8 months. Twenty-one patients died; 134 survived more than 30 days. Actuarial survival was 92% at 1 year, 85% at 3 years, and 78% at 5 years. Twenty-five episodes of acute graft rejection were diagnosed in 21 of the 139 recipients (0.18 episode per patient). In patients, the incidence of infection was 0.82 episode; 72% of infections were viral, with 10% due to cytomegalovirus. The incidence of coronary artery disease was 10% at 1 year, 25% at 3 years, and 36% at 5 years. Coronary artery disease was responsible for 60% of late deaths. Arterial hypertension developed in 81% of patients, despite relatively well-maintained renal function (serum creatinine, 1.7 +/- 0.3 mg/dl). Skeletal complications occurred in 15.8% and lymphoma in 1.4% of recipients. Complete long-term rehabilitation was achieved in all but two of the surviving patients. These data support the short- and long-term effectiveness of triple-drug therapy. This regimen reduces the incidence of rejection, infection, and lymphoma, as well as the degree of renal failure. However, the incidence of posttransplant coronary artery disease has not been reduced, and graft atherosclerosis represents the major cause of late graft failure and death. ",13 1775,"Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS) Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic. ",13 2511,"HLA antigens and nailfold capillary microscopy studies in patients with insulin dependent and noninsulin dependent diabetes mellitus and limited joint mobility. We investigated the HLA status of patients with diabetes associated with limited joint mobility and microvascular complications. An increased frequency of HLA-B8, DR3 and DR4 in patients with insulin dependent diabetes mellitus (IDDM) compared to controls and patients with noninsulin dependent diabetes mellitus (NIDDM) was confirmed. HLA antigen DQw1 was detected less frequently in patients with IDDM and was negatively associated with limited joint mobility and retinopathy. Limited joint mobility was significantly correlated with disease duration in IDDM, and was associated with neuropathy in both IDDM and NIDDM and with retinopathy in IDDM. No correlation was found between DR3, DR4 and limited joint mobility or diabetic complications. We also investigated the usefulness of nailfold capillary microscopy in a large group of patients with IDDM and NIDDM. Although capillary enlargement and avascular areas were noted in a few patients, nailfold capillary microscopy was not felt to be a useful tool in the evaluation of diabetes. ",17 2127,"Components of delay time in suspected acute myocardial infarction with particular emphasis on patient delay. Two hundred and thirty-four patients admitted to a coronary care unit (CCU) were interviewed a few days after arrival in hospital to determine reasons for patient delay and the various components of total delay time from onset of symptoms to arrival in CCU. Of the three major components of delay, decision time (time from onset of symptoms to decision to go to hospital), and hospital procedure time (time from arrival in hospital to arrival in the CCU), were of the same magnitude, 1 h 15 min and 1 h 30 min (median), whereas the median time for preparation and transportation to hospital was somewhat shorter, being 45 min. Decision time appeared to be similar in patients with confirmed and non-confirmed acute myocardial infarction (AMI) and was not associated with intensity of pain or infarct size. Half of the patients hesitated to go to hospital, which resulted in a prolonged decision delay (3 h). It is concluded that patient indecision to seek medical help is the most important reason for delay in hospital arrival in patients with suspected AMI. ",13 1513,"Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. The effects of clonidine added to lidocaine solution used for epidural anesthesia were assessed in 92 women scheduled for surgery and premedicated with diazepam 10 mg po. Patients received 18 ml 2% lidocaine with clonidine 5 micrograms.ml-1 (group C-5, n = 26), with clonidine 10 micrograms.ml-1 (group C-10, n = 20), with epinephrine 5 micrograms.ml-1 (group E, n = 26), or plain (group P, n = 20). No significant difference in the number of segments of analgesia was found at any observation period among the four groups of patients. The decreases in mean blood pressure (BP) observed 20 min after epidural injection in those given clonidine (5 +/- 8% for C-5, 10 +/- 11% for C-10, mean +/- SD) were similar to those given plain lidocaine (7 +/- 12%) but significantly less than those given epinephrine (18 +/- 12%, P less than 0.01 vs. C-5 or P). The response of BP to ephedrine given for restoring BP during anesthesia was not attenuated in patients who received epidural clonidine. Heart rate (HR) decreased significantly in patients given clonidine 10 micrograms.ml-1 (7 +/- 8%, P less than 0.01), but not in those given clonidine 5 micrograms.ml-1, whereas HR increased significantly in those given lidocaine plain or with epinephrine (10 +/- 8% and 28 +/- 14%, respectively, P less than 0.01). The incidence of sinus bradycardia was similar among the four groups of patients. Significant differences were also observed in sedation score between clonidine groups and groups P or E; sedation appeared approximately 10-20 min after epidural injection in both clonidine groups. ",12 617,"Arthrometric evaluation of knees that have a torn anterior cruciate ligament. We used the KT-1000 arthrometer to test the knees of 107 patients who had an acute tear of the anterior cruciate ligament, 153 patients who had a chronic tear, and 141 control subjects, for a total of 401 individuals. The three testing parameters were the extent of anterior translation at eighty-nine newtons of force and at maximum manual force, and the compliance index. The differences between the involved and the uninvolved knees were calculated. At eighty-nine newtons, all but one of the control subjects had anterior translation of ten millimeters or less, compared with 58 per cent of the patients who had a chronic tear. At maximum manual force, all but two of the control subjects had translation of ten millimeters or less, compared with 20 per cent of the patients who had an acute or a chronic tear. Analysis of variance showed that the clinical diagnosis correlated well with the results for all tests (p less than 0.001). However, when the uninjured knees of patients who had an acute or a chronic tear were compared with the knees of the control subjects, significant differences were noted (p less than 0.001 to 0.006). In the patients who had a chronic tear, there was no relationship between the time from injury to operation and the extent of anterior translation. The arthrometric test at maximum manual force was the strongest discriminant; it differentiated normal from abnormal knees (p less than 0.001) with high sensitivity (92 per cent), high specificity (95 per cent), and high positive predictive accuracy; the cut-off point was eleven millimeters or less. ",4 2316,"The familial occurrence of bullous mastocytosis (diffuse cutaneous mastocytosis). We studied four patients (a mother, her two daughters, and her son) with bullous mastocytosis, or diffuse cutaneous mastocytosis, whose genetic inheritance suggested an autosomal dominant pattern. The clinical characteristics included extensive bullae, numerous urticaria, pruritus, flushing, and pseudolichenified skin over all body surfaces without systemic organ involvement. The histopathologic findings disclosed a pronounced accumulation of mast cells in the dermis. Electron microscopic studies of lesional skin obtained in infancy showed round or spindle-shaped mast cells with numerous fingerlike villous protrusions. The cytoplasmic granules varied in size and shape, and the appearance of degranulation was markedly noted. In the adult, most mast cells had markedly decreased numbers of granules and cytoplasmic villi. Some cells displayed degenerative or necrotic appearances. These findings correlated well with the clinical course of these cases, which improved spontaneously over time. ",16 1451,"The fate of residual fragments after extracorporeal shock wave lithotripsy monotherapy of infection stones. We reviewed 53 patients with infection stones treated by extracorporeal shock wave lithotripsy (ESWL*) monotherapy to determine the long-term rate free of stones and the stone recurrence rate as correlated with the pre-treatment stone burden and the radiological presence of sand or fragments after the procedure. Long-term followup (mean 26.6 months) was available on 33 patients representing 38 kidneys. Although only 3 kidneys were free of stones immediately after ESWL, 20 were without stones at 3 months and 18 (47%) were stone-free at followup. Of 9 kidneys with fragments of more than 5 mm. after the final treatment 7 (78%) had residual fragments at 3 months and experienced stone progression. Of 9 kidneys with sand remaining 6 (66%) and all 3 kidneys that appeared to be free of stones after ESWL were without stones at followup. The 3-month plain film of the kidneys, ureters and bladder was a reliable indicator of eventual outcome. Of 20 kidneys that were free of stones at 3 months 16 remained without stones. Of 18 kidneys with residual stone particles at 3 months 14 showed disease progression, 2 had stable disease and 2 passed residual sand. Only 1 of 17 patients who were free of stones or had stable stone disease had a positive urine culture at followup. Patients with infection stone fragments 3 months after ESWL monotherapy have a high rate of stone progression (78%) and should undergo further treatment. ESWL monotherapy of infection stones requires close patient followup to assure that all residual fragments have passed and urine remains sterile. ",11 791,"Outpatient laparoscopic laser cholecystectomy. Laparoscopic laser cholecystectomy has been performed clinically in the United States since 1988. After refinement of the technique, the procedure was offered on an outpatient basis. Eighty-three patients underwent laparoscopic laser cholecystectomy during the study period. Thirty-seven (45%) had the procedure as an outpatient. Younger patients were more suited for the outpatient procedure and those without previous surgery were more likely to have the procedure done as an outpatient. Weight, operating time, and gallbladder pathology were similar, although patients with acute inflammation of the gallbladder were more likely to require hospitalization. The primary reason for patient admission was patient preference. ",5 2491,"Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The non-obese diabetic mouse is a good spontaneous animal model of the human disease, with IDDM developing in 50-80% of female mice by the age of 6 months. The disease can be transferred by splenic T cells from diabetic donors and is prevented by T-cell depletion. The mechanism(s) by which the beta cell is specifically destroyed is not known, but T cells and macrophages have both been implicated, based on the presence of macrophages in the infiltrated islet and the ability of chronic silica treatment to prevent disease. The monoclonal antibody 5C6 is specific for the myelomonocytic adhesion-promoting type-3 complement receptor (CR3 or CD11b/CD18) and does not bind to T cells. Here we show that blockade of macrophage CR3 in vivo prevents intra-islet infiltration by both macrophages and T cells and inhibits development of IDDM. We conclude that both T cells and macrophages have an essential role in the onset of IDDM. ",17 2997,"Behavioral modification of colonic function. Can constipation be learned? We challenged the two hypotheses: first, that defecation can be suppressed for an extended time, and second, if so, that this has an effect on upper colonic motility. Thus we studied 12 male volunteers with conditions of identical nutrition and patterns of physical activity over a two-week period, where one week with normal defecation and one week with voluntary prolonged suppression of defecation followed each other in randomized order. Frequencies of defecation, stool weights, total and segmental colonic transit times (using radiopaque markers) were compared. Frequency of defecations and stool weights were lower during suppressed defecation [8.9 +/- 0.66 vs 3.7 +/- 0.41 (mean +/- SE) bowel movements per week, P = 0.003, and 1.30 +/- 0.09 vs 0.98 +/- 0.13 kg/week, P = 0.01]. Total transit times were increased from 28.8 +/- 4.4 to 53.1 +/- 4.3 hr, P = 0.004. Segmental transit times were increased in the rectosigmoid (from 8.83 +/- 3.6 to 32.1 +/- 5.6 hr, P = 0.04) and right hemicolon (from 14.5 +/- 0.9 hr to 19.7 +/- 1.5 hr, P = 0.02) by suppression of defecation. We conclude that defecation habits may induce changes in colonic function such as those seen in constipation and that functional anorectal outlet obstruction may, probably by reflex mediation, affect the right colon. ",22 970,"Midfacial hypoplasia associated with long-term intubation for bronchopulmonary dysplasia. Six preterm infants with bronchopulmonary dysplasia were nasotracheally intubated for 68 to 243 days. Gestational age at birth ranged from 24 to 35 weeks. Endotracheal tube size was changed to account for growth and varied from 2.5 to 4.0 mm. These infants developed features of midfacial hypoplasia, namely, depressed nasal bridge, small-tipped nose, long philtrum, underdeveloped malar areas, and carplike mouth. These features have not been associated with long-term intubation in premature infants. We suggest that features of prolonged nasotracheal intubation, such as direct compression by the tube and the method of tube fixation, decreased air flow through the developing nares and sinuses and reduced faciomuscular activity, resulting in the observed midfacial hypoplasia. The degree to which growth corrects these deformations is unknown. ",7 1417,"Cancer of the urinary bladder in blacks and whites. A case-control study. Racial differences in the risk of cancer of the urinary bladder associated with cigarette smoking and alcohol consumption were examined in a study of 1663 cases (1534 whites and 129 blacks) and 4930 controls matched 3:1 by sex, race, and age to the cases. Significant increases in cancer risk associated with cigarette smoking were observed in whites and blacks; however, the dose-response patterns appeared to differ by race. In whites, statistically significant elevations of threefold and higher were observed in the odds ratios at all smoking levels above 20 pack-years, whereas in blacks, the corresponding point estimates did not increase significantly until greater than 60 pack-years of smoking. Although these risk patterns are compatible with the higher incidence of bladder cancer in white men, the sample of blacks was small, and tests of significance were only suggestive of higher risks for whites at specific amounts of smoking (P less than 0.15). Effects of alcohol consumption were inconsistent, and there was no detectable synergism between smoking and drinking. Additional study of race-specific risk factors and tobacco metabolism will be needed to determine the true nature of the apparent racial differences in the risk of urinary bladder cancer associated with cigarette smoking. ",11 3242,"L-tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats. The effects of L-tyrosine (L-TYR) on the anorectic activity of several mixed-acting sympathomimetics were determined during the dark cycle in rats made hyperphagic by food deprivation. L-TYR (200 mg/kg) significantly potentiated the anorectic activity of phenylpropanolamine, (-)-ephedrine and (+)-amphetamine by 48, 50 and 37%, respectively. When the dose of L-TYR was varied (25-400 mg/kg), a significant dose-dependent relationship was noted. The observed potentiation was positively correlated with increases in brain TYR concentrations; blockade of L-TYR uptake into the brain by the coadministration of L-valine prevented this potentiation. Various other L-amino acids, as well as D-TYR, failed to mimic the potentiating action of L-TYR. As determined by alpha-methyl-p-TYR pretreatment, the L-TYR-induced potentiation was dependent upon increased catecholamine synthesis. Although various other mixed-acting sympathomimetic anorexiants were similarly potentiated by L-TYR, the direct-acting beta-2 adrenoceptor anorexiants, salbutamol and methoxyphenamine, were not. These results indicate that L-TYR specifically potentiates the anorectic activity of the studied mixed-acting sympathomimetics and are consistent with the requirement of the central conversion of L-TYR to catecholamines via TYR hydroxylase for this response. The possibility that the effect of mixed-acting sympathomimetics is normally limited by the availability of L-TYR is suggested. ",22 2867,"The effect of gender and subtype on platelet MAO in alcoholism. Decreased platelet MAO activity has been identified in male alcoholics with suggestions that this is primarily true of Type 2 alcoholics as defined by criteria from the Stockholm Adoption Study. Little information has been available regarding platelet MAO activity in female alcoholics. This study evaluated a group of 71 alcoholics receiving inpatient treatment, including 16 female alcoholics, for platelet MAO activity compared to controls. Female alcoholic's platelet MAO was significantly lower than controls and not different from activity levels in male alcoholics. Among male alcoholics, both Type 1 and Type 2 subgroups were lower than controls and Type 2 levels did not differ from Type 1 levels. Thus, we were unable to replicate a gender and subgroup low platelet MAO specificity among alcoholics, but did find significant differences between alcoholics and controls. ",20 1603,"Does intracoronary infusion of Fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty? Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood. ",13 1905,"Positron emission tomography and interventional cardiology. Current noninvasive diagnostic techniques have limited accuracy for detection of coronary artery disease (CAD) in symptomatic and (particularly) asymptomatic patients with silent disease. Furthermore, no standard noninvasive method provides reliable diagnostic information on the location of the coronary arteries involved, the severity of stenosis, the presence of collaterals and myocardial viability. Based on greater than 1,000 cardiac studies at the University of Texas, cardiac positron emission tomography (PET) with either generator-produced rubidium-82, cyclotron-produced N-13 ammonia, or F-18 deoxyglucose is suitable for 4 routine diagnostic purposes: (1) noninvasive diagnosis of CAD in either symptomatic or asymptomatic subjects with a sensitivity of 95 to 98% and specificity of 95 to 100%. This accuracy is now sufficient to schedule diagnostic catheterization and multivessel angioplasty with surgical backup on the basis of the PET scan. At the University of Texas we carry out PET in asymptomatic and symptomatic patients to direct those with mild disease to cholesterol-lowering reversal therapy and those with severe disease to percutaneous transluminal coronary angioplasty (PTCA); (2) assessment of physiologic severity of coronary artery stenosis as compared to automated quantitative coronary arteriographic analysis. Changes in stenosis severity are followed before and after interventions including PTCA, bypass surgery, vasodilator drugs and cholesterol control regimens for reversal of coronary atherosclerosis; (3) imaging myocardial infarction, ischemia, viability, zone at risk and sizing of these pathophysiologic processes. ",13 3248,"Hypothermia. Safe and efficient methods of rewarming the patient. Hypothermia, a relatively common problem in the winter months, can cause significant morbidity. It presents in a variety of situations and affects a wide age range. Diagnosis requires a high index of suspicion, because the symptoms, which are primarily related to the central nervous system, are not distinctive. Appropriate management requires accurate measurement of core body temperature. Treatment is centered on rewarming the patient safely and efficiently while providing other supportive measures. Care should be taken to avoid arrhythmias. Simple precautions greatly reduce the risk of hypothermia. ",22 1081,"Feasibility and safety of vagal stimulation in monkey model. The feasibility, safety, and preliminary effects of chronic vagal stimulation were studied in an aluminagel monkey model. Pilot studies to perfect the equipment, determine stimulation thresholds, and insure the comfort and safety of the animals preceded this study. Four monkeys were equipped with an indwelling, 2-electrode cuff (titanium bands spaced 7 mm apart; silicone encased; 1.5 cm total length) in contact around the right vagus nerve; avoidance of the cardiac branch was confirmed by electrocardiograms. After postsurgical recovery, the intact and awake animals received constant-current stimulation (5 mA; 83 Hz, 143 Hz, or 50-250 Hz randomly; 0.5-ms pulse width) at the onset of every spontaneous seizure for the duration of the seizure or every 3 h for 40 s if stimulation had not occurred in the preceding hour. Stimulation periods of 2-6 weeks, with differing levels of stimulation, were preceded and followed by at least a 2-week baseline period of no stimulation. During the stimulation periods, the seizure rate decreased to zero in two monkeys and the interseizure intervals became invariable in the remaining two monkeys. These effects carried over temporarily into the poststimulation baseline periods. Vagal stimulation had no consistent effects on seizure severity or EEG interictal spikes. Histological studies of six vagus nerves were unable to separate electrode cuff damage from any direct effects stimulation may have had on the nerves. Although it appears that chronic vagal stimulation is feasible and that epileptogenic processes are influenced, the safety and efficacy of the procedure are still in question. ",9 1174,"Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. Schindler disease is a recently recognized infantile neuroaxonal dystrophy resulting from the deficient activity of the lysosomal hydrolase, alpha-N-acetylgalctosaminidase (alpha-GalNAc). The recent isolation and expression of the full-length cDNA encoding alpha-GalNAc facilitated the identification of the molecular lesions in the affected brothers from family D, the first cases described with this autosomal recessive disease. Southern and Northern hybridization analyses of DNA and RNA from the affected homozygotes revealed a grossly normal alpha-GalNAc gene structure and normal transcript sizes and amounts. Therefore, the alpha-GalNAc transcript from an affected homozygote was reverse-transcribed, amplified by the polymerase chain reaction (PCR), and sequenced. A single G to A transition at nucleotide 973 was detected in multiple subclones containing the PCR products. This point mutation resulted in a glutamic acid to lysine substitution in residue 325 (E325K) of the alpha-GalNAc polypeptide. The base substitution was confirmed by dot blot hybridization analyses of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Furthermore, transient expression of an alpha-GalNAc construct containing the E325K mutation resulted in the expression of an immunoreactive polypeptide which had no detectable alpha-GalNAc activity. ",9 2001,"Impact of a public cholesterol screening program. The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease. ",13 1608,"Traumatic rupture of the thoracic aorta presenting as transient paraplegia. A patient involved in a high-speed motor vehicle accident presented paraplegic to the emergency department. He was noted to have an abnormal chest x-ray and, subsequently, underwent aortography which revealed aortic transection. The patient's paraplegia resolved spontaneously prior to definitive aortic repair hours later. Aortic rupture presenting as paraplegia is a rare association, but one an emergency physician should be cognizant of, especially in the case of blunt or decelerating trauma. ",13 1857,"Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris. We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively. ",13 1369,"Hyperfiltration-induced renal injury in normal man: myth or reality. Current knowledge fails to support the notion that adaptive hyperfiltration of the remnant kidney after donor nephrectomy is deleterious. Rather than being maladaptive, hyperfiltration appropriately compensates for the loss of functional renal mass. Accordingly, most kidney donors can be expected to maintain a stable level of renal function without proteinuria or hypertension. Essential to this is proper selection of donors for nephrectomy and exclusion of high risk potential donors, bearing in mind the fact that apparently healthy, asymptomatic relatives of end stage renal disease patients are prone to the same disease processes that inflict the general population and have a higher risk of underlying renal disease. ",11 1389,"Magnetic resonance imaging of cystic, partially differentiated nephroblastoma. The magnetic resonance imaging (MRI) appearance of a cystic, partially differentiated nephroblastoma is described, together with pathologic correlation. The difficulty in reaching a correct preoperative diagnosis even with multimodal imaging techniques is emphasized. MRI is an adjunct to ultrasonography and may be superior to computerized tomography (CT) scan in the evaluation of a child with multiloculated cystic renal mass. ",11 2627,"Frequency of indeterminate western blot tests in healthy adults at low risk for human immunodeficiency virus infection. The NIAID AIDS Vaccine Clinical Trails Network. As part of a phase 1 trial of a candidate AIDS vaccine, blood specimens were collected from 168 healthy adult volunteers at minimal or no risk for becoming infected with human immunodeficiency virus type 1 (HIV-1). These specimens were screened for evidence of HIV-1 infection by enzyme immunoassay (EIA) and the Biotech/Du Pont Western blot (n = 168), culture (n = 122), and polymerase chain reaction assay (n = 20). None of the subjects had a positive test result by any of these assays, but 32% had indeterminate Western blot tests, most of which demonstrated a single band of low intensity. The most common bands were p24 (47%), p55 (34%), and p66 (36%); envelope bands were unusual (gp41, 2%; gp120, 2%). No serum specimen collected after 2-11 months from individuals with indeterminate Western blot results was positive by EIA or Western blot. There was 91% agreement in the test results of the first and second serum samples when the same lot of Western blot kit was used but only 36% agreement when different lots were used. The Biotech/Du Pont Western blot kit thus frequently yields indeterminate test results in the absence of HIV-1 infection, the reproducibility of which is subject to lot-to-lot variability. ",19 282,"Occurrence of beta-hexachlorocyclohexane in breast cancer patients. The residues of polycyclic aromatic hydrocarbon (PAH) and neutral organochlorine compounds in breast fat of 44 breast cancer patients and 33 women free of cancer were determined. No statistically significant differences appeared between the two comparison groups with regard to occurrence of PAH compounds. Of the neutral organochlorine compounds, residues of beta-hexachlorocyclohexane (HCH) were found more frequently in breast cancer patients. After adjusting for age and parity by stepwise logistic regression, beta-HCH remained a significant risk factor of breast cancer. Using a cutoff point for the residue level of beta-HCH in breast adipose tissue of more than 0.1 mg/kg fat, the odds ratio was 10.51 (95% CI, 2.00-55.26). ",3 1249,"Magnetic resonance imaging in the evaluation of vitreoretinal disease in eyes with intraocular silicone oil. Media opacification in eyes filled with silicone oil makes the evaluation of recurrent retinal detachment difficult. Ultrasonography through silicone oil is subject to significant imaging artifacts. We performed magnetic resonance imaging on six patients with unilateral intravitreal silicone oil to determine if the technique would detect detached retina and subretinal oil. All patients had undergone pars plana vitrectomy with silicone oil injection for proliferative vitreoretinopathy; five patients had encircling solid silicone scleral buckles. In five patients the media were clear, and ophthalmoscopic findings were correlated with magnetic resonance findings. Four patients had recurrence of inferior retinal detachment; magnetic resonance imaging demonstrated subretinal oil in three of these patients. One patient had a concentric, shallow, anterior retinal detachment; magnetic resonance scanning demonstrated a globular hyperintensity suggestive of subretinal oil. In the sixth patient, who had an opaque cornea, magnetic resonance imaging suggested that the retina was attached preoperatively; this was confirmed at subsequent surgery. A chemical shift artifact was helpful in defining the contour of retinal detachments and the presence of subretinal oil by outlining the silicone oil within the eye. ",10 1490,"Perinatal outcomes of twin pregnancies at term. A review of a two-year experience in our community disclosed that 57% of twin pregnancies (118/207) deliver at term. Little attention has been focused on perinatal outcomes of twin pregnancies remaining undelivered after 36 completed weeks. Therefore, we reviewed our experience to determine whether our practice should change to maximize perinatal care. Nearly all the study pregnancies (115/117, or 97.5%) delivered by the estimated date of confinement. Fetal malpresentation, failure to progress and the patient's lack of desire for a vaginal birth after cesarean delivery were common reasons for the high cesarean rate (62/117, or 52%). The neonatal outcomes were favorable regardless of the route or interval between deliveries. Discordant fetal growth was found in only eight cases (6.8%). No perinatal deaths occurred, and five-minute Apgar scores less than 7 (2/234, or 0.9%) and rates of anomalies (5/234, or 2.1%) were not different from those in singleton pregnancies delivering during the same period. Using the principles of obstetric practice used in our community, we would expect the perinatal outcomes in term twin gestations to be favorable. ",12 2294,"Speculations on the immunopathogenesis of psoriasis: T-cell violation of a keratinocyte sphere of influence. The thesis is advanced that the differences in antigen processing and presentation described for ""fresh"" and ""cultured"" Langerhans cells in vitro reflect similar differences between intraepidermal and intranodal Langerhans cells in vivo. The functional properties of Langerhans cells are dependent upon the microenvironment in which they reside; thus, intraepidermal Langerhans cells are under the influence of cytokines secreted by keratinocytes, whereas intranodal Langerhans cells come under the influence of lymphokines from T lymphocytes. It is speculated that a genetic lesion in psoriasis robs keratinocytes of their capacity to create an ""appropriate"" epidermal microenvironment. As a consequence, intraepidermal Langerhans cells adopt the functional program of intranodal cells. When ""uninvolved"" psoriatic skin receives a cutaneous challenge with antigen, Langerhans cells, by activating naive T cells in situ, unwittingly engender a microenvironment that is more appropriate to a lymph node. This skin becomes ""involved"" as it gradually acquires features associated with lymph nodes (such as high endothelial venules). And the derangement is further complicated by abnormalities of proliferation and differentiation among keratinocytes and dermal fibroblasts as they respond to the inappropriate T-cell-derived lymphokines, giving rising to the typical, active psoriatic lesion. ",16 1932,"The association between Type A behavior and change in coronary risk factors among young adults. The association of Type A/B behavior pattern and changes in blood pressure, total serum cholesterol, serum triglyceride, body mass, and smoking was estimated in a cohort of 375 young Black and White men and women from a rural county in Central Kentucky between 1978-79 and 1985-88. Type A participants experienced significant increases in systolic (2.90 +/- 1.29 mmHg) and diastolic (3.80 +/- 1.17 mmHg) blood pressure and in cigarette smoking (3.26 +/- 0.89 cigarettes per day) over the eight-year follow-up period, but Type B participants experienced no change. Type A and B individuals showed similar changes in total serum cholesterol, serum triglyceride, or body mass. Differences between behavioral types in blood pressure were present for women but not men, and for Blacks but not for Whites. These findings suggest a possible significance of the Type A pattern for the development of cardiovascular risk of young adults. ",13 1430,"Long-term experience with Swan Neck Missouri catheters. The Swan Neck Missouri catheters are designed to reduce major complications including 1) exit/tunnel infections, by a downward directed exit hole; 2) pericatheter leaks, by placement of the deep cuff in the rectus muscle; 3) catheter tip migration, by caudal direction of the intraperitoneal segment; and 4) outer cuff extrusion, by a permanent bend between the 5 cm or 3 cm spaced cuffs in SN-M2 and SN-M3 catheters, respectively. Between April 1986 and April 1990, 103 swan neck catheters were implanted. Comparison of prospective data from 103 swan neck catheters and retrospective data from 148 standard (Tenckhoff and Toronto Western Hospital) catheters implanted between January 1982 and June 1985 showed reduced complication rates with swan neck catheters. An overall survival of 64% at 36 months for swan neck catheters is significantly better than that of 29% for standard catheters. ",11 882,"Diagnostic value of nonfluoroscopic percutaneous lung needle aspiration in patients with pneumonia. In forty-one patients (mean [+/- SD] age 51 +/- 19 years; range, 11 to 88 years; seven female and 34 male) with clinical signs and symptoms of pneumonia, we performed a nonfluoroscopic percutaneous lung needle (22 gauges) aspiration (PLNA) to investigate the diagnostic yield of this technique. All the patients were receiving antibiotics at the time of the study, and PLNA was performed either because of a lack of response to empiric antibiotic treatment or because of the severity of the pneumonia or the underlying condition of the patient. Eight patients were mechanically ventilated (MV) due to acute respiratory failure. The PLNA was performed at bedside and without fluoroscopic guidance. Twenty-two microorganisms were identified by means of stains and/or cultures of PLNA samples. Sensitivity of PLNA was 43 percent (18/41). We detected three false-positive cultures probably due to contamination from the skin area punctured. In the eight MV patients studied, the sensitivity of PLNA was 37.5 percent, and the microbiologic findings turned out to be crucial for the outcome of the patients. Pneumothorax developed in three patients (7 percent) after PLNA. None of these three patients developed a pleural infection but two of them required thoracostomy drainage. None of the MV patients presented complications. Our results showed that nonfluoroscopic PLNA is a technique with moderately good sensitivity and with a low rate of false-positive cultures (8 percent) to diagnose pulmonary infections in patients with unresponsiveness to empiric antibiotic treatment or with severe pneumonia. Further evaluation of its diagnostic value and complications in MV patients is needed, although our preliminary results suggest that PLNA can be an alternative technique to other methods for diagnosing pulmonary infections in patients receiving artificial ventilatory support. ",7 2949,"Tertiary trauma care in a rural state. Trauma patients in rural areas usually have no access to regional trauma systems or designated trauma centers. Efforts to provide quality trauma care in small hospitals may seriously overextend local capabilities. The urban trauma center retains an important role in trauma care even when the initial care must be provided at the local level. Twenty-five trauma patients were transferred to University Hospital between 1985 and 1988 after definitive care was initiated in community hospitals. During the same time period, a total of 147 trauma patients were transferred to the trauma service. No information was available on the total incidence of trauma. Medical records were reviewed to determine the reasons for transfer. Major reasons included the need for further complex surgery, better critical care support, and inadequate blood banks. Trauma centers serving rural areas provide a valuable resource well beyond the initial 24 hours. ",20 1591,"Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. Transthoracic and transesophageal echocardiography was performed in 23 consecutive adult patients with an atrial septal aneurysm. In three patients with a cerebrovascular event the diagnosis was established by the transesophageal approach only. Interatrial shunting on transthoracic imaging with use of echocardiographic contrast imaging or Doppler color mapping, or both, was detected in 7 (41%) of 17 patients. On performing contrast imaging in combination with color flow mapping during transesophageal echocardiography, positive shunting was demonstrated in 15 (83%) of 18 patients. Echocardiographic identification of multiple fenestrations (n = 4) and thrombus within the aneurysm (n = 2) could be achieved for the first time by transesophageal ultrasound application. Cerebrovascular events occurred in 12 (52%) of 23 patients and were regarded as being definitely thromboembolic in 10 (43%); 8 (67%) of the 12 patients had repeated cerebral events. Except for mitral valve prolapse in one patient, no other potential cardiac source of embolism could be identified despite the use of transesophageal echocardiography. A thickening of the aneurysmal membrane greater than or equal to 5 mm was found in 9 (75%) of 12 patients with versus 3 (27%) of 11 patients without a cerebrovascular event (p less than 0.05); this proved to be the only significant difference between the two patient groups. The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxic embolization through an interatrial communication as demonstrated by the findings in two patients. It is concluded that atrial septal aneurysm is a cardiac abnormality with thromboembolic potential. In patients with this lesion and a history of an embolic event, long-term anticoagulant therapy is indicated. ",13 1648,"Clinical and hemodynamic assessment of the hepatojugular reflux. The hepatojugular reflux (HJR) test was studied to assess the ability to clinically predict response during cardiac catheterization and to determine its significance in patients without heart failure and correlate it to their baseline hemodynamic parameters. Sixty-five patients considered to be free of heart failure undergoing routine cardiac catheterization were enrolled. The HJR test, defined as the venous pressure response to sustained abdominal compression, was performed in a standardized manner at the bedside assessing change in internal jugular venous pressure and during right-sided cardiac catheterization measuring change in right atrial pressure. For comparison a sustained increase greater than or equal to 1 cm was considered positive. In 62 of 65 patients the HJR test stabilized by 15 seconds. The results during examination at the bedside agreed with those at catheterization (K = 0.74, p less than 0.001). The HJR test result correlated best with baseline mean right atrial pressure (r = 0.59) and right ventricular end-diastolic pressure (r = 0.51), and in bivariate regression analysis predicted right atrial (F(1,63) = 32.8, R2 = 0.34, p less than 0.0001) and right ventricular end-diastolic (F(1,63) = 22, R2 = 0.26, p less than 0.0001) pressures. A positive test had high sensitivity and specificity for predicting right atrial pressure greater than 9 mm Hg (1.0, 0.85) and right ventricular end-diastolic pressure greater than 12 mm Hg (0.90, 0.89). It is concluded that 15 seconds is adequate for interpretation, and bedside observation predicts the response during right-sided cardiac catheterization. ",13 2111,"The dynamics of platelet thrombus formation rate, thrombus retention time, and rate of embolization on a control and heparin bonded polyurethane angio-catheter. The dynamics of platelet deposition and embolization from control and heparin bonded polyurethane catheters (CPC and HBPC) was evaluated with In-111 labeled autologous platelets (IN-PLT) and a computerized gamma camera (CGC). Ten non-heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis) 24 hr after injection of 300-420 microCi of In-PLT, and imaged for 3 hr with the computerized gamma camera. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the curves were analyzed for early rate of thrombus formation (upswing), thrombus retention time (full width at half maxima of the RPDC-peak), and rate of embolization (downswing) on both catheters. The four parameters (mean +/- SD) of thrombosis on catheters and integral of the radioactivity time curve for the 3 hr duration of imaging were calculated from normalized counts/sec. The rate of thrombus formation and rate of embolization are higher for the control than HBPC, suggesting that heparin-bonding decreases the early rate of thrombosis and embolization. The thrombus adhesivity and retention time appear shorter for the control catheter, indicating that the control thrombogenic catheter forms multiple thrombi and emboli than HBPC. The integral appears larger for the control catheter than HBPC. In vivo (dynamic) studies, in vitro studies, and critical analyses of the radioactivity time curve were essential for complete evaluation of thrombogenicity of catheters and other cardiovascular prostheses. ",13 319,"Endothelin-like immunoreactivity in human breast cyst fluid. Immunoreactive endothelin has been detected in 21 of 43 samples of breast cyst fluid (21 cases; 3.5 +/- 0.6 pmol/l, mean +/- SEM. Other 22 cases; not detectable, less than 0.5 pmol/l). Fast protein liquid chromatographic analysis of the immunoreactive endothelin of pooled breast cyst fluid showed two immunoreactive peaks; one in the void volume and the other in the position of endothelin-1. It is probable that endothelin-1 is produced by the epithelial cells lining breast cysts, but significance of the presence of endothelin-1 in breast cyst fluid remains to be elucidated. ",3 2119,"Origin and significance of diastolic Doppler flow signals in the left ventricular outflow tract. Diastolic Doppler flow signals (greater than or equal to 0.2 m/s) in the left ventricular outflow tract have not been well characterized, and their origin and significance remain controversial. Fifty-nine patients (55 +/- 16 years of age) with technically good Doppler echocardiographic studies were studied prospectively. There were 14 normal subjects, 21 patients with left ventricular hypertrophy, 10 with dilated cardiomyopathy and 14 with other cardiac disease. The rhythm was sinus in 55 and atrial fibrillation in 4. Two distinct Doppler flow signals were detected in the left ventricular outflow tract during diastole. These were termed E' (early) and A' (active) because they occurred 40 to 100 ms after higher velocity mitral inflow E (passive filling) and A (atrial contraction) signals. Among 59 patients, E' signals were present in 48 (81%) and had a mean velocity of 0.41 +/- 0.23 m/s. In 55 patients with normal sinus rhythm, A' signals were present in 52 (95%) and had a mean velocity of 0.52 +/- 0.24 m/s. No A' signals were present in the four patients with atrial fibrillation. The E' and A' velocities by pulsed wave Doppler ultrasound were low at the left ventricular apex and increased along the basal septum in the left ventricular outflow tract. Prominent A' velocities (greater than or equal to 0.45 m/s) were seen in 62% of patients with left ventricular hypertrophy, 50% of normal subjects and 10% of patients with dilated cardiomyopathy. The A' velocity was higher in patients with left ventricular hypertrophy (0.63 +/- 0.26 m/s) than in those with a normal heart (0.45 +/- 0.16 m/s; p less than 0.05) or dilated cardiomyopathy (0.25 +/- 0.13 m/s; p less than 0.01). The major determinants of diastolic outflow tract velocity were the mitral inflow E and A velocities and left end-diastolic dimension, particularly when combined (r = 0.64, p less than 0.0001 for E'; r = 0.72, p less than 0.0001 for A'). Distinctive E' and A' Doppler outflow tract signals result from mitral inflow and may be detected in most patients with normal heart size. These E' and A' velocities increase from apex to base and are more prominent in patients with a small, normally contracting heart or left ventricular hypertrophy. ",13 190,"The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome. Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins. ",3 1718,"Polytetrafluoroethylene graft for spontaneous coronary dissection: 7-year follow-up. Spontaneous coronary artery dissection remains an exceedingly rare cause of myocardial ischemia. The patients are usually young and female, and the dissection is frequently fatal. The use of polytetrafluoroethylene as an aortocoronary conduit is generally followed by early occlusion. We report a case of spontaneous right coronary dissection in which a polytetrafluoroethylene graft was placed that was observed to remain patent by angiography at least 72 months after operation. ",13 1315,"Radiation therapy for localized prostate cancer. Justification by long-term follow-up. In the series presented here, survival patterns at 15 years after radiotherapy for patients with clinical stage A carcinoma of the prostate did not deviate significantly from those of an age-matched peer group. For patients with clinical stage B disease (nodular disease that did not exceed involvement of one lateral lobe), survival was only 5% less at 15 years than for the age-matched group of California men. This was in spite of the fact that the lymph node status and the true incidence of capsular penetration were unknown. Moreover, the patients were not stratified by histopathologic grade or by either acid phosphatase or prostate-specific antigen values. If one were to restrict the patients to those with intermediate and low Gleason scores, normal acid phosphatase, and low prostate-specific antigen values, it is likely that there would have been no difference between the survival of those with prostatic cancer and their age-matched peers. As one deviates from these conservative selection criteria and includes patients with more advanced stages, the likelihood of achieving 15-year survival diminishes. With radiation treatment, however, patients whose disease, by clinical examination, extends beyond the prostate and who seem too advanced for radical prostatectomy still may have a 20 per cent to 30 per cent chance of 15-year survival. ",11 496,"The epidemiology of cancer among Hispanic women. The experience in Florida. To explore cancer incidence among Hispanic women living in Dade County, Florida, data were analyzed from the statewide cancer registry. For all but three sites, Hispanics had lower rates of the 15 most prevalent cancers than non-Hispanics. However, higher rates of cancer among Hispanics were noted for cancers of the gallbladder, liver, and heart and soft tissue. Subgroups of women had significantly higher rates of cervical cancer and thyroid cancer. Lower rates among Hispanics were observed for cancers of the esophagus, vagina, breast, colon, buccal cavity and pharynx, and malignant melanoma. These data suggest that most cancer sites traditionally higher among US Latino women were not higher among Dade Hispanics, and that sites more common among non-Hispanics have not yet shown an increased incidence among Hispanic women in Dade County. ",3 705,"Duodenal ulcer is associated with low dietary linoleic acid intake. It has been suggested that the falling incidence and virulence of duodenal ulcer is related to increased dietary polyunsaturated essential fatty acid intake. The adipose fatty acid profile, which closely reflects dietary intake, was measured in 35 men with chronic duodenal ulcer and 35 matched control men. The mean percentage of linoleic acid in adipose tissue was significantly lower in the ulcer group (10.0 (0.7) v 12.3 (0.7)%, p less than 0.01) and this difference was found in both smokers and non-smokers. This finding suggests that the diets of duodenal ulcer patients are deficient in linoleic acid and this could be of aetiological importance. ",5 1950,"Electroencephalography laboratory diagnosis of prolonged QT interval. Patients with prolongation of the QT interval are at risk for significant neurological morbidity and mortality secondary to ventricular tachyarrhythmias. These patients frequently undergo electroencephalographic (EEG) examination to evaluate episodes of loss of consciousness, which may be associated with convulsions. Electrocardiogram recording as a part of the EEG is a simple and common practice, but analysis for possible QT prolongation is not routinely performed by electroencephalographers. This is, in part, due to the fact that while calculation of the corrected QT interval is straight forward, a calculator is generally required. A nomogram that is presented simplifies determination of the corrected QT interval, facilitating diagnosis of prolongation of the QT interval in the EEG laboratory. ",13 1008,"Analgesia and removal of nasal packing. We present a prospective controlled trial, comparing methods of analgesia for the relief of discomfort on removing nasal packing, including a general discussion on the considerations for, and methods of, nasal tamponade. On the basis that nasal packing is likely to continue to be used frequently, nitrous oxide (as Entonox) is advocated as a safe and relatively cheap means of pain relief with a statistically significant advantage over papaveretum. ",8 75,"Air contamination in open heart surgery with disposable coveralls, gowns, and drapes. The effect of a polypropylene coverall, replacing shirt and trousers, combined with sterile laminated gowns and drapes compared with an all-cotton system was studied in regard to the dispersion of bacteria and particles in a conventionally ventilated operating theater. The operations carried out were open heart procedures in 30 adult patients. Blood agar sedimentation plates were placed in the operative, anesthesia, and perfusion areas. The mean sedimentation values during 1 hour after the start of operation were as follows in the laminate group: 63 colony-forming units (cfu)/m2 in the operative area; 77 cfu/m2 in the anesthesia area; and 143 cfu/m2 in the perfusion area. The corresponding figures in the cotton group were 350 cfu/m2, 364 cfu/m2, and 437 cfu/m2, respectively (p less than 0.0002). At the beginning of the operation, the mean values noted for colony-forming units in the air at the operative site were 8.0 cfu/m3 in the laminate group and 31 cfu/m3 in the cotton group. One hour later, the values were 10 cfu/m3 and 22 cfu/m3, respectively (p less than 0.0002). At the end of the operation, the number of particles 5 microns or larger in the air at the operative site was 278/m3 in the laminate group and 592/m3 in the cotton group. It is concluded that the use of a polypropylene coverall and laminated gowns and drapes significantly reduces the particle and bacterial contamination of the air and the bacterial sedimentation during cardiac operations. ",0 3306,"Home treatment for acute psychiatric illness OBJECTIVE--To determine the factors influencing the successful outcome of community treatment for severe acute psychiatric illnesses that are traditionally treated in hospital. DESIGN--All patients from a single electoral ward who were either admitted to hospital or treated at home over a two year period (1 October 1987 to 30 September 1989) were included in the study and their case notes audited. The second year of the study is reported. SETTING--Electoral ward of Sparkbrook, Birmingham. SUBJECTS--99 Patients aged 16-65 with severe acute psychiatric illness. RESULTS--65 Patients were managed by home treatment alone; 34 required admission to hospital. The location of treatment was significantly (all p less than 0.05) influenced by social characteristics of the patients (marital state, age (in men), ethnicity, and living alone) and by characteristics of the referral (occurring out of hours; assessment taking place at hospital or police station). DSM-III-R diagnosis was more weakly associated with outcome. Violence during the episode was significantly related to admission, although deliberate self harm was not. CONCLUSIONS--Home treatment is feasible for most patients with acute psychiatric illness. A 24 hour on call assessment service increases the likelihood of success because admission is determined more strongly by social characteristics of the patient and the referral than by illness factors. Admission will still be required for some patients. A locally based mental health resource centre, a 24 hour on call service, an open referral system, and an active follow up policy increase the effectiveness of a home treatment service. ",22 581,"Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. From 1960 to 1987, 1209 patients with colorectal liver metastases were recorded, and followed until 1 January 1990. In 242 cases the diagnosis was based on external imaging, whereas 967 patients had operative confirmation and staging of their liver disease. Three groups of patients were analysed: group 1 involved 921 cases, of whom 902 were deemed non-resectable whereas 19 could not be unequivocally classified. Only 21 patients lived for longer than 3 years, seven survived for 4 years, but there were no 5-year survivors. Group 2 comprised 62 highly selected patients who at laparotomy demonstrated resectable metastatic spread confined to the liver, but this was not treated mainly because of a formerly different therapeutic approach. These patients had a significantly longer median survival time (14.2 versus 6.9 months), but also failed to achieve 5-year survival. The 226 patients forming group 3 underwent hepatic resection with intent to cure. Nine of them had minimal macroscopic disease left, and 34 with all gross tumour removed had positive margins. Survival of patients with these 43 eventually non-radical resections followed an identical course as in group 2 (median survival 13.3 months, maximum 42 months). Of the 183 patients with potentially curative resection ten died after surgery (5.5 per cent). Actuarial 5 and 10-year survival rates in the remaining 173 patients were 40 and 27 per cent with 25 and seven patients alive at respective periods of time. Until 1 January 1990, 64 patients remained free from recurrent disease for up to 24 years. In three patients the tumour status at death was unclear. The other 106 patients developed definite cancer relapse. Nevertheless they demonstrated a prolongation of survival time by a median of 1 year when compared with the 43 non-radically resected patients or the 62 untreated patients with resectable liver-only metastases, and accomplished a maximum survival time of 8 years. Radical excision of colorectal secondaries to the liver therefore offers effective palliation, and in a small number the chance of a cure. ",3 2074,"Prehospital thrombolysis in acute myocardial infarction. The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in-hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left-sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs -2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function. ",13 3246,"A computerized laboratory alerting system. A computerized laboratory alerting system (CLAS) has been developed as part of an ongoing effort to improve the quality of care at LDS Hospital. The system identifies potentially life-threatening conditions on the basis of laboratory findings and then generates appropriate warnings and transmits them to clinicians. Use of the system has led to a significant increase in the proportion of patients in life-threatening situations who have received appropriate care (50.8% before implementation vs. 62.5% afterward, P less than 0.05). Among patients with hypokalemia, falling potassium levels, hyperkalemia, hypokalemia during treatment with digoxin, hyponatremia, falling sodium levels, hypernatremia, hypoglycemia, or hyperglycemia, the average length of time spent in the life-threatening situation has decreased from 30.4 to 15.7 hours (P less than 0.05) and the average length of stay has decreased from 14.6 to 8.8 days (P less than 0.05). There has been little change in the proportion of patients with findings indicating metabolic acidosis who have received appropriate care (32.3 vs. 34.6%). We conclude that CLAS has an important role in patient care at our hospital. ",22 1834,"Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure. ",13 558,"Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in children. High rates of leukaemia in children and young people have been associated with features of community isolation and population growth. Incidence data collected by two specialist registries were used to compare incidence rates at ward level with relevant ward characteristics derived from routine census and Ordnance Survey data for England and Wales. An excess risk of childhood acute lymphoblastic leukaemia (ALL) was found for wards which are farthest from large urban centres. The excess was greatest for wards of higher socioeconomic status and for children aged 1-7 years (the childhood peak), for which a two-fold excess was seen. These findings in general support the hypothesis that childhood leukaemia has an infectious aetiology. ",3 2979,"Evidence against a requisite role for defective virus in the establishment of persistent hepadnavirus infections. The factors involved in the establishment of persistent hepadnavirus infection are poorly understood. Recent findings demonstrate that the sequence of the genome of hepatitis B virus (HBV) is variable in infected individuals and that, in some cases, virus mutants predominate. Our objectives in the present study were to analyze the variability of woodchuck hepatitis virus (WHV) genomes in an infected animal and to determine whether sequence heterogeneity played a critical role in the ability of WHV to induce chronic infection. We cloned and determined the complete nucleotide sequence of three supercoiled genomes from an animal that became infected after inoculation with a standardized WHV serum pool (i.e., the WHV7 virus pool). We found that there were four nucleotide substitutions among the three genome sequences as well as a 73-nucleotide deletion in one of the recombinants. DNA transfection experiments revealed that only one of the three recombinants was capable of independent replication. These data suggest that a significant proportion of replicative templates in woodchucks that are infected with WHV are defective virus genomes. Next, we compared the outcome of acute infection after inoculation with a serum pool containing a uniform population of replication competent virus (i.e., the WHV7R pool) with a serum pool composed of WHV genomes of variable sequence. The WHV7R serum pool originated from a woodchuck that became a chronic carrier after in vivo transfection of the liver with the infectious WHV7 recombinant. Neonatal woodchucks were inoculated with 5 x 10(6) WHV genome equivalents of either the WHV7 pool or the WHV7R pool. All animals in the study became acutely infected with WHV. Of the animals infected with the WHV7 serum pool, 65% became chronic carriers, while 80% of the animals infected with the WHV7R serum pool developed chronic infection. Thus, infection of woodchucks with a serum pool containing defective virus resulted in a rate of chronic WHV infection that was similar to, or even lower than, a rate from a pool containing only wild-type virus. This suggests that the presence of defective virus in the inoculum is not a prerequisite for the establishment of persistent hepadnavirus infections. ",21 1760,"Diagnosis of left atrial thrombi in mitral valve disease by coronary arteriography. Arteriographic findings of neovascularity and fistula formation between coronary arteries and left atrium have occasionally been described in association with left atrial thrombosis in patients with mitral valve disease. The validity of these coronary arteriographic findings in diagnosis of atrial thrombi has been evaluated in 112 patients with mitral valve disease. Comparison was made with surgery. The study furnished these diagnostic values: sensitivity 70%, specificity 85%, positive predictive value 72%. Even if this angiographic finding is complementary in diagnosis of atrial thrombosis, its identification during coronary arteriography in patients with mitral valve disease is useful. Its detection could improve diagnostic prediction of thrombosis, especially in patients without previous embolic events or where echocardiography failed to reveal thrombi. ",13 1255,"Aqueous humour and serum zinc and copper concentrations of patients with glaucoma and cataract. Serum and aqueous humour zinc and copper concentrations of 44 patients with glaucoma and cataract were determined. Serum values were found within normal ranges. The highest mean copper concentration was seen in the glaucoma group. In addition there was a significant negative correlation between the aqueous humour levels of zinc and copper in patients with glaucoma. It was concluded that an increased copper value together with a low zinc value might be of importance in patients with glaucoma. ",10 1386,"Stress incontinence: a new endoscopic approach. We describe our experience in using a new endoscopic technique for suspending the bladder neck and urethra in 16 patients with stress incontinence. The procedure was started by dissecting the retropubic space, first with a sound and then with a Foley catheter before passing an absorbable suture from the abdominal fascia to the bladder neck using an elbowed needle introduced into the bladder through the neck and exteriorized through the urethra. The dissection of the retropubic space helped to form postoperative adherences which fixed the bladder neck and the urethra firmly to the pubic symphysis. The technique is simple, it does not require vaginal surgery, and the incidence of complications is minimal. ",11 1917,"Effects of theophylline, atenolol and their combination on myocardial ischemia in stable angina pectoris. The effects of theophylline (400 mg twice a day), atenolol (50 mg twice a day) and their combination on myocardial ischemia were studied in 9 patients with stable angina pectoris in a randomized, single-blind, triple crossover trial. Placebo was administered to the patients during the run-in and the run-off periods. A treadmill exercise test and 24-hour ambulatory electrocardiographic monitoring were obtained at the end of each treatment period. Compared with placebo, theophylline significantly improved the time to onset of myocardial ischemia (1 mm of ST-segment depression) from 7.8 +/- 3.7 to 9.5 +/- 3.7 minutes (p less than 0.03) and the exercise duration from 9 +/- 3.4 to 10.1 +/- 3.5 minutes (p less than 0.04). During atenolol and during combination treatment, the time to the onset of ischemia and the exercise duration were similar (10.8 +/- 4.2 and 11.2 +/- 3.2 minutes, 11.2 +/- 3.6 and 11.5 +/- 3.2 minutes, respectively) and longer than during theophylline administration (p less than 0.05). Ambulatory electrocardiographic monitoring showed that, during theophylline administration, the heart rate was higher than during placebo throughout the 24 hours (p less than 0.05). During atenolol and during combination treatment the heart rate was similar and in both cases lower than during placebo (p less than 0.05). Compared with placebo, theophylline decreased the total ischemic time from 97 +/- 110 to 70 +/- 103 minutes (p less than 0.05). ",13 3175,"Biliary endoprostheses. Plastic versus metal stents. Plastic biliary endoprostheses relieved malignant obstructive jaundice in 80% to 90% of the patients. The comfort of a completely indwelling endoprosthesis should be offered to all palliatively treated tumor patients, and external-internal catheters should be reserved for the minority of patients who return with reoccluded endoprostheses. These patients have bacterial flora that rapidly contaminates the endoprosthesis and causes encrustations and reocclusions. Thus, a second endoprosthesis also would reocclude quickly. The mechanism of reocclusion of plastic and metal endoprostheses is completely different. In plastic endoprostheses, bacterial contamination causes decomposition of the bile and subsequent encrustation. In metal endoprostheses tumor ingrowths between the struts of the stent cause reocclusion. Tumor ingrowths were observed in only 6.5% of metal prostheses with a narrow woven mesh (Wallstent), whereas prostheses with large distances between the struts (Gianturco stent) had ingrowth rates of 19% to 50%. This fact shows that tumor ingrowths can be reduced by narrowing the spaces between the metallic network, and, therefore, improvements in the design of the metal stents should reduce the occlusion rate to or below that of plastic endoprostheses, which currently have a lower encrustation rate. The major advantages of expandable metal prostheses are the relative ease and the minimal trauma of the implantation procedure. The Wallstent endoprosthesis, in particular, can be inserted through a 7-F introducer sheath and offers the chance of single-step placement. The 30-day mortality rate, therefore, was only 5%. This is significantly lower than the 30-day mortality rate after insertion of plastic prostheses (15% to 24%). Even simple external catheter drainage procedures have a higher reported 30-day mortality rate (27%). Expandable metal endoprostheses would be the most useful device if the occlusion rate could be kept under 10% in large series. Increasing the length of the endoprostheses to 10 cm in the expanded state could also improve the long-term patency rates. ",22 1571,"Traumatic rupture of aorta. Diagnosis by Doppler echocardiography. Traumatic rupture of aorta is a serious complication in accidents, mainly road accidents, with a high mortality unless an immediate diagnosis and surgical correction is made. A case of traumatic rupture of the aorta shown in the acute phase by Doppler-echocardiography is reported. This technique can be of great value in the study of patients with thoracic trauma who do not show clear signs of aortic rupture which require urgent aortography. ",13 2812,"Preventing alcohol problems: survey of Canadian medical schools. In preparation for a national conference on medical education in the prevention of alcohol problems, a survey of conference participants was conducted. Participants were undergraduate and postgraduate representatives from each Canadian medical school and representatives from 11 provincial and territorial alcohol and other drug agencies. There was agreement that physicians and medical schools have important roles in prevention and treatment of alcohol problems, with ""traditional"" medical roles seen as the most important. Current training is variable and was seen as inadequate, with more time devoted to treatment than prevention. To correct this situation, renewed priorities and faculty leadership are needed. Respondents felt that there should be uniform standards for assessing undergraduate students' skills in dealing with alcohol problems. Provincial alcohol and other drug agencies are underused in medical education in the prevention and treatment of alcohol problems. ",20 551,"Segregation analysis of breast cancer from the cancer and steroid hormone study: histologic subtypes The segregation pattern of breast cancer in white families from the Cancer and Steroid Hormone Study was investigated. Families were categorized into four groups based on the histologic type of breast cancer in the probands:ductal cancer, lobular cancer, adenocarcinoma, and medullary cancer. The ductal cancer sample was further split into a premenopausal-proband and a postmenopausal-proband subset. Results for six complex segregation analyses are presented; the findings suggest heterogeneity in the transmission of breast cancer. For all analyses, there was no evidence for a multifactorial component in the mixed model, ie, a major locus plus other transmission, genetic and/or cultural. Interpretation of the medullary cancer, adenocarcinoma, and lobular cancer analyses does not permit discrimination among the major locus models. Segregation of breast cancer in the entire ductal sample was consistent with autosomal recessive transmission. In the ductal subanalyses, a recessive gene was sufficient to explain the breast cancer distribution when the proband had postmenopausal breast cancer. In contrast, when the proband had premenopausal breast cancer, the transmission model was consistent with a dominant major gene, with sporadic cases of disease. ",3 1824,"Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. Recently we replaced the ascending aorta and aortic arch in 8 patients with aneurysm or dissection, using profound hypothermic circulatory arrest with retrograde cerebral perfusion. There were no operative deaths. Open aortic anastomosis facilitated repair of the aortic arch without clamping the arch tributaries, and embolism due to particulate debris from clamping of the arch vessels was eliminated. Retrograde cerebral perfusion during profound hypothermic circulatory arrest is a simplified technique that may protect the brain. This method offers advantages over previously described methods, particularly in obviating dissection of the arch tributaries and the clamping thereof, and in protecting the central nervous system. ",13 205,"Campylobacter pylori interactions with gastric cell tissue culture. Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. jejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells. ",3 913,"Identification of somatostatin receptors in human small cell lung carcinoma. Biopsy specimens obtained from eight patients with lung cancer were tested for content of somatostatin receptors by autoradiography. Somatostatin receptors were detected in two of three patients with small cell lung cancer (SCLC) but in none of five patients with non-small cell lung cancer (NSCLC) including adenocarcinoma (two), squamous cell carcinoma (two), and bronchoalveolar carcinoma (one). In those with SCLC, specific somatostatin receptor binding was evidenced only in tumor foci and not in surrounding stroma or normal lung parenchyma. Further tissue characterization by immunoperoxidase staining with the pancytokeratin monoclonal antibody, mAB-lu-5, revealed labeling to all of the NSCLC but to none of the SCLC specimen. Selective immunoreactivity was detected in both the SCLC and the NSCLC specimen to chromogranin and neuron-specific enolase (NSE) whereas none of the specimen had detectable immunostaining to somatostatin, bombesin, serotonin, adrenocorticotropic hormone, neurofilament, calcitonin, and synaptophysin. The identification of somatostatin receptors in primary human lung cancer may have a bearing on the biology of this disease and perhaps on the clinical application of somatostatin analogues in patients with SCLC. ",7 1921,"Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass grafting. The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium-111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium-111 antimyosin uptake was present in 19 of 23 patients (82%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited ST-segment changes. No good relation was found among indium-111 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG. ",13 3227,"Myotonic dystrophy: quantification of muscle weakness and myotonia and the effect of amitriptyline and exercise. The purpose of this study was to quantify the degree of muscle weakness and myotonia in 12 patients with myotonic dystrophy (MD), and to quantitatively determine the effects of a four- to six-month therapeutic trial of amitriptyline. Patients had exercised with weights for one or more years. Some had shown initial improvement in muscle strength, but had reached a plateau; others had not improved when the study began. Muscle weakness was quantified by comparing the five-second maximum voluntary contraction (MVC) in newtons (N) per kg (body weight) of 12 patients and 20 healthy subjects. Knee extensor, elbow flexor, and first dorsal interosseous (FDI) muscles were compared. Myotonia was quantified by measuring relaxation times (RTs) at the end of the five-second MVC produced by FDI, as the time taken for the MVC to decrease by 50% and 75% (referred to as 1/2 and 3/4RT). The results were as follows: (1) the mean muscle strength of each of the three muscles of the patients was significantly (p less than .001) reduced compared with healthy subjects; and (2) 1/2 and 3/4RT means of the patients (vs healthy subjects) were significantly prolonged (p less than .01). Eight of the patients participated in a therapeutic trial of amitriptyline. Therapeutic effects were quantified by measuring muscle strength, 1/2 and 3/4RT, and percent change in evoked muscle action potential (MAP) from the FDI muscle after a ten-second MVC, to determine change in excitability. Mean muscle strength of FDI improved from .27 to .33N/kg, (p less than .05). ",22 322,"Giant eccrine acrospiroma. Four cases of large eccrine acrospiroma (three benign, one malignant) are reported. The benign tumors involved the lower extremities of two women and one man (73 to 89 years of age). The duration of the lesions ranged from 10 to 20 years. The malignant tumor involved the left side of the chest of a 60-year-old man. Its occurrence in a lesion that had been present for 40 years suggested malignant transformation of a pre-existing benign eccrine acrospiroma. Each tumor showed little to no cellular atypia. Mitotic rates (mitotic figures per 10 high-power fields) varied both between and within lesions. Average mitotic rates did not differentiate the benign from the malignant tumors. The most important distinguishing features of large benign eccrine acrospiromas are the relative circumscription, the lack of cellular atypia, and the absence of stromal, perineurial, and angiolymphatic invasion. ",3 749,"Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary ""pseudolithiasis"" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying. ",5 92,"Lack of association between medication use and the presence or absence of bacteriuria in elderly women. This study was undertaken to determine if there is an association between medication use and the presence or absence of bacteriuria in elderly ambulatory women. Of 198 women who participated in three urine culture surveys (every 6 months) during the 18-month study period, 66 (34.4%) had bacteriuria on at least one survey. Both univariate and multivariate analyses for the demographics, age, place of residence, and medication use (by drug class) revealed that only place of residence had a significant association with the presence or absence of bacteriuria. In this regard, bacteriuric subjects more commonly resided in the nursing home and less commonly lived in the apartment-house complex compared with nonbacteriuric subjects (P less than .05). Therefore, this study demonstrates that in elderly ambulatory women, medication use does not appear to be associated with the presence or absence of bacteriuria. ",0 402,"Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase. The molecular structure of a rat hepatoma 70-kDa insulin/mitogen-stimulated S6 protein kinase, obtained by molecular cloning, is compared to that of a rat homolog of the 85-kDa Xenopus S6 protein kinase alpha; both kinases were cloned from H4 hepatoma cDNA libraries. The 70-kDa S6 kinase (calculated molecular mass of 59,186 Da) exhibits a single catalytic domain that is most closely related in amino acid sequence (56% identity) to the amino-terminal, kinase C-like domain of the rat p85 S6 kinase (calculated molecular mass of 82,695 Da); strong similarity extends through a further 67 residues carboxyl-terminal to the catalytic domain (40% identity), corresponding to a region also conserved among the kinase C family. Outside of this segment of approximately 330 amino acids, the structures of the p70 and p85 S6 kinases diverge substantially. The p70 S6 kinase is known to be activated through serine/threonine phosphorylation by unidentified insulin/mitogen-activated protein kinases. A model for the regulation of p70 S6 protein kinase activity is proposed wherein the low activity of the unphosphorylated enzyme results from the binding of a basic, inhibitory pseudosubstrate site (located carboxyl-terminal to the extended catalytic domain) to an acidic substrate binding region (located amino-terminal to the catalytic domain); substrate binding is thereby prevented. S6 kinase activation requires displacement of this inhibitory segment, which is proposed to occur consequent to its multiple phosphorylation. The putative autoinhibitory segment contains several serine and threonine residues, each followed directly by a proline residue. This motif may prevent autophosphorylation but permit transphosphorylation; two of these serine residues reside in a maturation promoting factor (MPF)/cdc-2 consensus motif. Thus, hormonal regulation of S6 kinase may involve the action of MPF/cdc-2 or protein kinases with related substrate specificity. ",3 169,"Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study. Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered. ",3 1086,"Effects of vagal stimulation on experimentally induced seizures in rats. Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded. ",9 2368,"Leucine metabolism in IDDM. Role of insulin and substrate availability. The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine. All diabetic subjects were studied while in poor metabolic control (fasting glucose 13.3 +/- 1.1 mM; HbA1c 10.8 +/- 0.2%) and again after 2 mo of intensified insulin therapy (fasting glucose 7.2 +/- 0.5 mM; HbA1c 8.0 +/- 0.2%). Insulin-mediated total-body glucose uptake in poorly controlled diabetic subjects (3.6 +/- 0.5 mg.kg-1.min-1) was significantly reduced compared with control subjects (7.5 +/- 0.2 mg.kg-1.min-1; P less than .001) and improved slightly after insulin therapy (4.8 +/- 0.3 mg.kg-1.min-1; P less than .05), although it still remained significantly lower than in control subjects (P less than .01). During the insulin-clamp study performed in subjects with poorly controlled IDDM, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) all decreased (50.1 +/- 2.0 to 26.4 +/- 0.4; 9.2 +/- 0.4 to 6.0 +/- 0.3; 40.9 +/- 2.0 to 20.4 +/- 2.0 mumol.m-2.min-1, respectively) to the same extent as in control subjects. After 2 mo of intensified insulin therapy, the effect of acute hyperinsulinemia on ELF, LO, and NOLD was comparable to that of control subjects, whereas insulin-stimulated glucose metabolism was still impaired. To examine the effect of substrate availability on leucine turnover, well-regulated IDDM and control subjects underwent a repeat insulin-clamp study combined with a balanced amino acid infusion designed to increase circulating plasma amino acid levels approximately twofold. Under these conditions, NOLD was equally enhanced above baseline in both control and IDDM subjects (P less than .01), whereas ELF was inhibited to a greater extent (P less than .01) than during the insulin clamp performed without amino acid infusion (control vs. diabetic subjects, NS). In conclusion, insulin-mediated glucose metabolism is severely impaired in subjects with both poorly controlled and well-controlled IDDM, whereas the effect of acute insulin infusion on leucine turnover is normal, and combined hyperaminoacidemia/hyperinsulinemia stimulated NOLD to a similar extent in both IDDM and control subjects. ",17 1135,"Controlling stability of a complex movement system. Human movement systems have frequently been treated as one-dimensional, single-axis, rigid bodies in order to simplify the gathering, analysis, and interpretation of data. The problem with this approach is that the results of such assumptions often lead to conclusions about the production and control of movement that do not relate to the control demands placed on the central nervous system. In order to truly understand how the central nervous system plans and produces movements to match environmental demands, we must take into account the many variations available within the body. The purpose of this article is to examine two movement systems that have the potential to act in multiple spatial dimensions with variable muscle action patterns when performing a stabilizing task. Methods of analyzing how the systems operate under differing task constraints and results of the experiments will be presented. Hypothetical models that have been proposed to explain how complex movement systems operate will also be discussed. ",9 2040,"The estimation of post-test probability of coronary disease following exercise testing using the sequential application of two Bayesian methods. Recent studies have revealed that Bayesian methods to estimate post-test probability following exercise testing differ in their sensitivity and specificity across the range of post-test probability. To take advantage of the relative strengths of each method, we combined two of these methods into a single method (DUAL BAYES) and compared it with the two original methods in 436 patients who underwent stress testing followed within 2 months by coronary arteriography. All patients had post-test probabilities determined using CADENZA (better sensitivity). Those CADENZA-derived probabilities greater than or equal to 50% were substituted with post-test probabilities determined by Diamond and Forrester's original TABULAR method (better specificity). Mean post-test probabilities were as follows: TABULAR 34, CADENZA 48, DUAL BAYES 37 (actual incidence 38%). Comparison of sensitivity and specificity at every fifth percentile of post-test probability revealed that the sensitivity of DUAL BAYES was better than that of TABULAR and equal to that of CADENZA at thresholds less than or equal to 10 and that the specificity was better than that of CADENZA and equal to that of TABULAR at thresholds greater than or equal to 60. Therefore using both methods as indicated above was better than using either method alone. ",13 1514,"Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population. Familial predisposition and patterns of genetic inheritance of eclampsia and pre-eclampsia were investigated through three or four generations in 94 families from the homogenous island population of Iceland. The families descended from index women delivered in the years 1931-47 and who had either eclampsia (n = 38) or severe pre-eclampsia (n = 69). Inheritance was followed both through sons and daughters. The prevalence of pre-eclampsia and eclampsia in daughters was significantly higher (23%) than that in daughters-in-law (10%). No difference was noted in the prevalence of these diseases by whether the daughter was born of an eclamptic or pre-eclamptic mother or whether she was a first or later born daughter. There was a non-significantly higher occurrence of pre-eclampsia among grand-daughters than in grand-daughters-in-law. No difference was seen by whether grand-daughters descended through sons or daughters. With increasing numbers of affected daughters or grand-daughters the probability rose of finding more affected women in a family. Hypotheses of single recessive and dominant gene inheritance were compared and maximum likelihood estimates for gene frequency obtained. For a single recessive gene model this was 0.31 reflecting a population prevalence of 9.6%, whereas a dominant model with incomplete penetrance gave 0.14 at 48% gene penetrance, corresponding to a population prevalence of 0.9% homozygous expression of severe disease and 11% heterozygous expression of milder disease. Either genetic model could fit the data. ",12 1750,"Use of computed tomographic scanning and aortography in the diagnosis of acute dissection of the thoracic aorta. Before the introduction of computed tomographic (CT) scanning, aortography was the investigation of choice for acute aortic dissection. Between 1978 and 1982, 24 patients were referred to the Brompton Hospital with suspected acute thoracic aortic dissection; all had aortography with diagnosis confirmed at surgery (n = 12) or necropsy (n = 2) or supported by clinical outcome (n = 8). One patient in whom aortography was negative had type B dissection at necropsy and another patient was lost to follow up. CT scanning became available in this unit in 1983 and between 1983 and 1987 was used as the only imaging investigation in 32 patients with suspected acute dissection of the thoracic aorta while in a further 22 patients aortography was used alone. Results were confirmed at surgery (n = 18), necropsy (n = 3), or supported by clinical outcome (n = 31). Two patients were lost to follow up. In an additional 16 patients both aortography and CT scanning were performed with concordant findings in 10. In six in whom the results were discordant, aortography was normal in three in whom subsequent CT scanning showed type B dissection and CT scanning was normal in three patients in whom aortography showed type A dissection. Both CT scanning and aortography are reliable techniques for assessment of suspected acute dissection of the thoracic aorta. Both techniques misdiagnose occasionally and the frequency of misdiagnosis will be minimised by performing both investigations in patients where the level of clinical suspicion is high and the initial investigation negative. CT scanning tends to miss type A dissection and in view of the success of surgery in this condition this failing has the more serious clinical consequences. ",13 2156,"Antigenic recognition by intravenous gamma-globulin of selected bacteria isolated from throats of patients with Kawasaki syndrome. Kawasaki syndrome (KS) or mucocutaneous lymph node syndrome is an acute febrile exanthematous illness of unknown etiology. Therapy with intravenous gamma-globulin (IVGG) results in rapid defervescence, disappearance of signs and symptoms of inflammation and prevention of coronary artery aneurysms. We hypothesized that IVGG might neutralize a bacterial toxin produced by a staphylococcus or streptococcus present in the nasopharynx. We further speculated that this toxin might be detectable in serum or urine of patients. The goal of this work was to identify microbial antigens in different materials taken from patients with a clinical diagnosis of KS. We tested 23 aerobic bacterial isolates from throat cultures from 15 patients with KS, acute serum from 121 patients and 38 acute urine specimens from patients with KS. The patients ranged in age from 1 to 6 years. Specimens were tested in a standard system of counterimmunoelectrophoresis and reacted against IVGG prepared in a 25% solution. Ten of 23 aerobic bacteria (43.5%) isolated from throat cultures demonstrated a precipitation reaction with IVGG. Counterimmunoelectrophoresis testing of IVGG against acute serum and acute urine specimens was uniformly negative. IVGG contains precipitating antibody against a limited number of aerobic throat organisms. It is possible that antigenic products of one of these bacteria may be involved in the pathogenesis of KS. ",14 805,"Geographic variation of inflammatory bowel disease within the United States. One approach to learn about possible environmental risks in inflammatory bowel disease relates to studying its geographic pattern of occurrence. The geographic variation of inflammatory bowel disease within the United States was analyzed using the accumulated 17.5 million hospital discharges of all U.S. Medicare beneficiaries during two consecutive years. To validate the geographic pattern shown by the Medicare data, hospitalization was compared with mortality from inflammatory bowel disease among different states. Mortality and hospitalization statistics both suggested that the occurrence of inflammatory bowel disease was determined by environmental factors that had a marked geographic variation within the United States. Both Crohn's disease and ulcerative colitis appeared to be more frequent in northern parts of the United States than in southern and in urban more than rural parts. These trends were observed for men and women and for blacks and whites alike. Similar geographic patterns of Crohn's disease and ulcerative colitis suggested the influence of one or more identical risk factors for both diseases. ",5 3304,"Nitrous oxide antagonizes CNS stimulation by laudanosine in mice. We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine. ",22 1020,"Lasers for otosclerosis--which one if any and why. Laboratory stapedotomy and stapedectomy revisions were performed in human temporal bones while pyroelectric wave energy analyzers and ultrasensitive thermocouples measured energy absorption at the stapes footplate and in the vestibule. Analysis of these data shows that the visible lasers (argon and KTP-532) possess ideal optical properties and precision for otosclerosis surgery but conversely have less than ideal tissue characteristics. The CO2 laser possesses ideal tissue characteristics. Recent advances in optical engineering and pulsing the energy have increased the precision of this laser to now provide the accuracy required for delicate microsurgery. Two clinical studies analyze the long-term hearing results and complications in patients who had undergone CO2 laser stapedectomy revision (59 patients) and CO2 laser stapedotomy (153 patients). The advantages that these laser techniques provide over conventional surgery methods are discussed. ",8 1374,"Flutamide in hormone-resistant prostatic cancer. Flutamide (250 mg. orally 3 times daily) yielded a subjective response in 5 of 25 fully evaluable patients with hormone-resistant prostatic cancer. Four additional patients had early progression. A 40% or greater decrease in the pre-treatment prostate specific antigen level was observed in 7 of 24 patients and this finding was correlated with improved survival. Toxicity was mainly gastrointestinal and resulted in permanent discontinuation of flutamide in 5 patients. Flutamide or similar antiandrogens may have a role in the management of hormone-resistant prostatic cancer when relief of subjective symptoms should be an important treatment goal together with improvement of survival. However, before the drug should be used routinely in the management of hormone-resistant prostatic cancer phase 3 studies must confirm its effectiveness, especially in comparison to less expensive drugs. ",11 1540,"Ovarian response to exogenous gonadotropins during pregnancy. Multiple ovarian follicles were successfully induced in a patient undergoing superovulation for a gamete intrafallopian transfer (GIFT) procedure despite the presence of an undiagnosed ectopic pregnancy. Midluteal gonadotropin releasing hormone agonist (GnRH-a) treatment should be coupled with mechanical contraception in the previous cycle in patients with patent tubes. ",12 520,"Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Extraadrenal retroperitoneal paragangliomas (RP) are uncommon tumors. Because of their rarity, little is known of their natural history or response to treatment. We reviewed 22 patients with RP who were seen at our center between 1949 and 1990. The distribution of male and female patients was nearly equal, and the mean age was 42. Most patients were admitted with pain or a mass, and eight of 22 tumors were functional. No significant difference was noted in duration of symptoms, size of the tumor, or survival between functional and nonfunctional tumors. Eleven of 22 (50%) RP metastasized and were therefore classified as malignant. Five-year and 10-year disease free survival rates were 19% and 19% for tumors not resected and 75% and 45% for those completely resected. Once metastases occurred, the 5-year survival rate was 36%, but no patient survived beyond 76 months. Predictors of survival included complete resection of the tumor but not size or functional status. Although some patients who received chemotherapy or radiotherapy had clinical responses, a survival benefit could not be shown. RP have a high rate of malignant behavior and should be treated aggressively with operation. Late metastases are not uncommon, and prolonged follow-up is necessary. Once metastases have occurred, some patients may have prolonged survival. ",3 3100,"Sincalide-aided ultrasonography of the common bile duct as a predictor of biliary obstruction determined by ERCP and biliary manometry. Sonographically observed changes in common bile duct caliber following intravenous sincalide injection were correlated with distal common duct pathology as defined by endoscopic retrograde cholangiopancreatography and biliary manometry. Thirty-two patients, 17 with prior cholecystectomies, were studied. In post-cholecystectomy patients, a 1-mm or greater diminution of duct caliber within 5 min represented a normal response. When gallbladder contraction occurred in normal patients with an intact gallbladder, no change or a diminution in duct caliber was observed. When gallbladder contraction was not observed, a normal response was considered to be the same as that in post-cholecystectomy patients with a diminution in duct caliber occurring. By using these criteria two false negatives, both with hypertensive sphincters of Oddi that responded normally to sincalide injection, were encountered. This technique was valuable in defining non-obstructed post-cholecystectomy dilated bile ducts which demonstrated a prompt diminution in caliber following sincalide injection. ",22 1402,"The placebo response of subfertile couples to attending a tertiary referral centre. The objective of this study was to determine whether there was a placebo response to clinic attendance in couples with prolonged (greater than 4 years) subfertility. From 4 to 18 years of subfertility we observed a treatment independent cumulative conception rate of 22%, which was independent of the length of subfertility. Twenty-seven women conceived after 1 to 4 years' subfertility, and 30 conceived after greater than 4 years' subfertility. The fecundity of the latter group was significantly greater than that of women with 1 to 4 years' subfertility, being similar to ""normal"" subjects who had stopped contraception. This study demonstrates that a subgroup of apparently normal women with greater than 4 years' subfertility responded positively to clinic attendance independent of any investigation(s) or therapy. ",11 90,"Pseudomonas aeruginosa compared with Escherichia coli produces less endotoxemia but more cardiovascular dysfunction and mortality in a canine model of septic shock. We investigated the effects of two different Gram-negative bacteria and radiation-induced leukopenia on endotoxemia, cardiovascular abnormalities, and mortality in a canine model of septic shock. Serial hemodynamics were measured in conscious dogs using radionuclide heart scans and thermodilution cardiac output catheters. Plasma endotoxin concentrations were determined with a chromogenic Limulus amebocyte lysate assay. Viable Pseudomonas aeruginosa or Escherichia coli implanted intraperitoneally produced concordant hemodynamic patterns of septic shock (p less than 0.01). Endotoxin concentrations were more than tenfold lower in dogs infected with P aeruginosa compared with E coli (p less than 0.0001). Despite lower endotoxin levels, P aeruginosa-infected dogs had a higher mortality (p less than 0.01), more severe hypotension (p less than 0.05), and greater depression of the left ventricular ejection fraction (p less than 0.05) than dogs with E coli sepsis. A nonlethal E coli challenge combined with leukopenia (induced by a nonlethal dose of radiation) resulted in a mortality of 60 percent (p less than 0.01) without greater cardiovascular dysfunction or higher endotoxin concentrations. These findings suggest that bacterial products other than endotoxin and host-related factors may be important contributors to the toxicity, cardiovascular instability, and mortality of Gram-negative septic shock. Quantitative determinations of plasma endotoxin are unlikely to correlate with the clinical severity of septicemia in heterogeneous patient populations infected with different Gram-negative organisms. ",0 309,"Prospective study of alcohol intake and large bowel cancer. The alcohol intake of a cohort of Japanese men in Hawaii is directly and significantly related to the risk of developing rectal cancer, whether assessed on the basis of amount consumed or as a percent of total calories. Wine and whiskey are directly related to rectal cancer, but beer is the only alcoholic beverage that displays a statistically significant dose-response (P = 0.008). Colon cancer risk also is related directly to alcohol intake, but the association is statistically significant only when measured as a percent of energy intake. This suggests that alcohol might displace cancer inhibitors from the diet. Calcium, vitamin C, and dietary fiber are inversely related to colon cancer risk in this cohort, and each of these micronutrients displays statistically significant negative correlation with alcohol intake. A possible positive association between alcohol and lung cancer was ruled out after adjusting for cigarette smoking. Cancers of the prostate and stomach were unrelated to alcohol intake, but the risk of acquiring cancer at all other sites combined was strongly related to alcohol intake. ",3 2800,"Controlling for the severity of injuries in emergency medicine research. The injury severity score (ISS) and age have been used retrospectively to control for trauma severity. Other control variables such as the revised trauma score (RTS) and the TRISS method (which estimates the probability of survival for each patient) additionally require that values of blood pressure, Glasgow coma scale, and respiratory rate, be recorded in the emergency department. The authors question when the RTS, ISS, the ISS and age, or the probability of survival calculated using the TRISS method should be used to control for severity of injuries in trauma research. Relations between predictor variables and (1) survival to hospital discharge, (2) hospital length of stay for survivors, and (3) length of ICU stay were compared by cause of injury: penetrating, motor vehicle accident, low fall, or other blunt. Data were collected over 12 months for 2,914 consecutive adult patients who died or stayed in five nontrauma and three trauma centers for 48 hours or more. For survival, the false-negative rates of probability of survival calculated using the TRISS method were approximately half that of the ISS and age; no variable adequately explained survival among those with low falls. Combinations of ISS, RTS, and age explained the most variation in lengths of hospital stay among survivors, while ISS explained the most variation in lengths of intensive care unit (ICU) stay. Researchers should consider the ISS with RTS and age to control for severity when lengths of hospital or ICU stay are studied. The TRISS method should be used in studies of survival. In both cases, the RTS which requires data collection in the emergency department must be calculated. ",20 293,"Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17. One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life-threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck. ",3 2071,"Multiple arterial fenestrations, multiple aneurysms, and an arteriovenous malformation in a patient with subarachnoid hemorrhage. We report the case of a 49-year-old, right-handed man with multiple vascular pathologies, including a fenestrated anterior communicating artery and middle cerebral artery, an aneurysm of the anterior communicating artery, multiple aneurysms of the middle cerebral artery, and an arteriovenous malformation. Diagnoses were made through computed tomography, cerebral angiography, magnetic resonance imaging, and intraoperative dissection. The lesions were managed surgically in stages with satisfactory results. Congenital and hemodynamic factors may have combined to manifest in the anomalies present in this unique case. We believe that no similar combination of vascular pathology has been reported previously. ",13 2034,"A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy. ",13 2945,"Early detection of myocardial contusion and its complications in patients with blunt trauma. Myocardial contusion remains an elusive clinical entity, which consumes a disproportionate amount of scarce and expensive critical care resources for the purpose of cardiac monitoring. This study attempts to define a group of patients at high risk who can be identified from the available data present at the time of admission. All patients admitted with the suspicion of a myocardial contusion over a 3-year period were retrospectively studied. The records were examined for history, physical findings, electrocardiographic (ECG) results, creatine kinase levels, Injury Severity Score (ISS), and echocardiographic findings. A diagnosis of a myocardial contusion was made if patients had an ECG consistent with acute injury, increased creatine kinase-MB, or an abnormal echocardiogram consistent with acute injury. Patients were stratified into two groups: Group 1 patients satisfied the criteria for a myocardial contusion and Group 2 patients lacked sufficient evidence to substantiate this diagnosis. The records were then examined for the presence of factors available in the emergency room that might be predictive of a myocardial contusion or its complications. A total of 88 patients were evaluated; 27 of these were found to have a myocardial contusion (Group 1) with 61 patients placed in Group 2 (no myocardial contusion). Group 1 patients had an abnormal admission ECG (p less than 0.05), and an ISS greater than or equal to 10 (p less than 0.05). Multivariate analysis identified two factors predictive of a myocardial contusion: an abnormal ECG and an ISS greater than 10. When these two predictors were absent, the probability of a myocardial contusion was 1%. No predictors of a complication of a myocardial contusion were identified. These data suggest that a combination of easily obtained variables in the emergency department can be used to select a patient population at high risk for myocardial contusion. Prospective evaluation of these variables is necessary. ",20 2126,"Nisoldipine--effects on the renin-angiotensin-aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects. We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short-term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels. ",13 1208,"Motor unit discharge characteristics and short term synchrony in paraplegic humans. Frequency of firing and regularity of discharge of human motor units, and short term synchrony between pairs of motor units, have been assessed in extensor digitorum communis (EDC) and tibialis anterior (TA) muscles in control subjects and in clinically complete paraplegic subjects. The discharge pattern of TA motor units in paraplegia ranged from extremely regular to very irregular for different motor units whereas in the control population, and in EDC of both groups, there was a narrow, but intermediate, range of regularity. There was little difference in the incidence and degree of short term synchrony (STS) in EDC between paraplegic and normal subjects. In contrast, virtually no STS of motor units was observed in the TA muscles of the paraplegic group whereas control subjects exhibited approximately the same amount of STS in their TA and EDC muscles. It is concluded that the extra burden placed on arm muscles in paraplegia does not change the amount of synchronisation between motor units. Furthermore, section of the spinal cord does not increase STS as predicted from lesions of the reticulospinal tract in cats. This may reflect the coincidental removal of supraspinal synchronising inputs of motoneurons or the reorganisation of synaptic inputs in chronic paraplegia. ",9 3000,"Family recovery after vascular surgery. Twenty-one families were observed in a 3-month study to assess family coping with major vascular surgery and recovery. Analysis of family measures data (the Family APGAR, the Family Inventory of Resource for Management, and the Family Crisis Oriented Personal Evaluation Scales) was combined with grounded theory method to assess family responses over time and recovery outcomes. Containment emerged as the major conceptual category of the grounded theory. Containment refers to a constellation of constructed meanings for events and behavioral responses used by families to regulate the impact of the surgical crisis and reduce family disruption. This ""contained"" coping pattern was manifested in families' avoidant behaviors and narrow definitions of the problem: that is, they defined their situation in terms of the surgical repair as cure rather than palliative intervention for a chronic, progressive disease. Situational factors such as the insidious development of the illness and the primary focus of care providers in the hospital on surgical care (allowing families' narrow definitions of their situation to remain unchallenged) also contributed to containment. Containment resulted in poor risk factor management as a major recovery outcome. Isolation and family conflict were evident throughout the recovery period. Concerns generated by continued evidence of morbidity during recovery contributed to a developing awareness of underlying disease, and diminishing containment when this growing awareness was openly shared within the family. Significant findings of the family measures analysis were compared with the grounded theory of the qualitative data. Each corroborated the other in key dimensions. ",22 2199,"Clinical approach to prenatal detection of human structural defects. Tremendous advances in prenatal diagnosis have allowed clinicians to recognize a variety of structural defects in the developing fetus. Guidelines for fetal ultrasonography and an approach to fetal evaluation are outlined. The developmental morphologic approach is emphasized as a way of categorizing congenital anomalies whether they are detected during prenatal or postnatal life. The use of this approach for diagnosing and managing fetal malformation syndromes is illustrated. ",15 2129,"Alcohol consumption and blood pressure: a comparison of native Japanese to American men. We compared the cross-sectional association of alcohol consumption with blood pressure in 810 Japanese men (JM) living in Tokyo and 946 white men (WM) living in New York. Mean systolic (JM and WM, p less than 0.001) and diastolic blood pressure (JM, p less than 0.002; WM, p less than 0.001) were associated with alcohol consumption in both groups. Compared to abstainers, the heaviest drinkers had the highest systolic (JM, p = 0.001; WM, p less than 0.01) and diastolic (JM, p less than 0.002; WM, p less than 0.05) blood pressures. The relation of blood pressure to alcohol intake was J-shaped in the Americans, but linear in the Japanese. Exploratory analyses revealed that the J-shape may have been due to under-reporting of heavy alcohol ingestion by American abstainers. When abstainers were excluded, the relationships were similar in both the American and Japanese. The positive association between blood pressure and alcohol consumption persisted after adjustment for age, cigarette smoking, use of antihypertensive medications, body mass index, heart rate, abdominal skinfold thickness, hematocrit, fasting blood glucose, serum uric acid levels and urinary sodium/potassium ratio. Alcohol use was also related to prevalence of hypertension. These findings confirm the presence of an independent association between alcohol intake and blood pressure in both JM and WM and suggest that, despite differences in the metabolism of alcohol, the relation of alcohol consumption to blood pressure is similar in both nationalities. ",13 779,"Diarrhea. Diarrhea is one manifestation of GI disturbance. Symptoms may be acute if caused by such things as infections, drug reactions, alterations in diet, heavy metal poisoning, or fecal impaction. Chronic diarrhea is a symptom of GI diseases such as irritable bowel syndrome, lactase deficiency, cancer of the colon, inflammatory bowel disease, and malabsorption diseases. Chronic diarrhea may also be associated with GI surgery, radiation therapy, laxative abuse, alcohol abuse, and chemotherapeutic agents. When interventions are required to deal with diarrhea, they may include such things as alteration in tube feeding products and methods of administration, fluid replacement by oral rehydration procedures, a rapid return to feeding, and education aimed at the health information clients need to prevent or control the symptom of diarrhea. ",5 3277,"Mechanical deficit persists during long-term muscle hypertrophy. Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production. ",22 683,"Phospholipids from rat, human, and canine gastric mucosa. Composition and metabolism of molecular classes of phosphatidylcholine. To validate a recent proposal that a phospholipid lining with a high content of dipalmitoylphosphatidylcholine may protect gastric mucosa against luminal acid, it was decided to study composition and metabolism of phospholipids in the gastric mucosa. Phospholipids were analyzed in rat, human, and dog gastric mucosal surface tissue and in a chloroform/methanol-lavage of rat and canine stomach. Phosphatidylcholine and phosphatidylethanolamine were the main components. Saturated fatty acids were almost exclusively esterified at the sn-1 position of the glycerol moiety of phosphatidylcholine, and unsaturated fatty acids mainly at the sn-2 position. The disaturated class of phosphatidylcholine comprised 2%-6% of total phosphatidylcholine. Precursors of phosphatidylcholine, i.e., [32P]orthophosphate and [methyl-14C]choline, were preferentially incorporated into the disaturated molecular class 0.5-6 hours after IV administration. It can be speculated that disaturated phosphatidylcholine, although quantitatively a minor component, is specifically triggered in mucosal renewal processes. ",5 1606,"Dietary preference for sweet foods in patients with dementia Using a telephone survey, patients with probable Alzheimer's disease (n = 31) and vascular dementia (n = 14) were compared with elderly normal controls (n = 43) in preferences for different foods. Patients with Alzheimer's disease had a greater preference than normal controls for relatively high-fat, sweet foods and for high-sugar, low-fat foods, but did not significantly differ in preference for other foods, including those high in complex carbohydrates and protein. Vascular dementia patients showed a similar pattern, not significantly different from that for Alzheimer's patients. Results did not consistently support a hypothesis that increased sweet preference is a nonspecific form of disinhibited behavior related to declining mental status, nor was a hypothesis relating sweet preference to serotonin activity within the brain consistently supported. Results provide preliminary evidence that craving for sweet food may be a significant part of the clinical syndrome of dementia, but further research is needed to delineate the psychological and biological mechanisms accounting for it. ",13 2319,"Dermal mast cell degranulation in systemic sclerosis. Paired biopsy samples from involved and uninvolved skin were obtained from 19 patients with generalized scleroderma (11 with early, progressive disease and 8 with late, improving disease). Skin biopsy samples were double stained for mast cell granules and for mast cell membrane. The number of mast cells was increased in patients with systemic sclerosis (SSc), in both involved and uninvolved skin and in both early and late disease. There was an increase in the number of degranulated mast cells in the involved skin of patients with both early and late disease and in the not-yet-involved skin of patients with early disease; however, there was no increase in the number of degranulated mast cells in areas of previously involved but now normal skin of patients with late disease. Increases in mast cell number and degranulation precede clinically apparent dermal fibrosis in SSc. These observations and the absence of mast cell degranulation in regressing skin suggest a participatory role of the mast cell in the clinical progression of skin changes in SSc. ",16 2054,"Efficacy of ibopamine in the treatment of heart failure. Loss of myocardial contractility, reflexly enhanced vasoconstriction, and neuroendocrine excitation are the pathophysiologic hallmarks of low-output heart failure. Drugs that counter both consequences afford considerable therapeutic potential in retarding and perhaps even in staying the consequences of the syndrome. Ibopamine possesses such potential through its unique ability to stimulate both dopaminergic- and beta-adrenoreceptors in the heart and circulatory system. Stimulation of dopaminergic- receptors and beta 2-adrenoreceptors results in vasodilatation in all regional vascular territories. beta 2-Adrenoreceptor agonist activity also affords mild positive inotropic activity in the heart, whereas stimulation of presynaptic dopaminergic- receptors (DA2) attenuates the increased sympathetic neural outflow. The drug also suppresses the renin-angiotensin-aldosterone system in addition to having a direct natriuretic activity. The pharmacodynamic effects of ibopamine, exerted through its metabolite epinine, are translated into measurable therapeutic benefits in patients with chronic heart failure. The increase in peripheral blood flow induced in all regional vascular territories, including the kidneys, is associated with increased cardiac output and stroke volume and reduction in left ventricular pressure work, wall stress, and myocardial oxygen consumption. Plasma norepinephrine, angiotensin, and aldosterone are also reduced, and renal sodium excretion is enhanced. These hemodynamic and neuroendocrine activities, which are not subject to tolerance during sustained administration of the drug, are accompanied by clinically significant improvement in symptoms, exercise tolerance, and the New York Heart Association classification of disability. More important, no proarrhythmic effects have been observed during sustained treatment, and the minimal side effects observed during long-term treatment enhance the safety profile of the drug. ",13 3064,"Reduction of postoperative morbidity following patient-controlled morphine The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery. ",22 400,"Introduction of nerve growth factor (NGF) receptors into a medulloblastoma cell line results in expression of high- and low-affinity NGF receptors but not NGF-mediated differentiation. Expression of the cloned human nerve growth factor receptor (NGFR) cDNA in cell lines can generate both high- and low-affinity binding sites. Since the inability to respond appropriately to differentiation factors such as NGF may contribute to determining the malignant phenotype of neuroblastomas, we sought to determine whether the same is true of medulloblastomas. To generate a human central nervous system neuronal cell line that would respond to NGF, we infected the medulloblastoma cell line D283 MED with a defective retrovirus carrying the cDNA coding for the human NGFR. The resultant cells (MED-NGFR) expressed abundant low- and high-affinity NGFRs, and NGF treatment induced a rapid transient increase of c-fos mRNA in the NGFR-expressing cells but not in the parent line or in cells infected with virus lacking the cDNA insert. However, the MED-NGFR cells did not internalize the NGFR at high efficiency, nor did they differentiate in response to NGF. Three important conclusions emerge from this study: (i) internalization of NGFRs is not necessary for some early rapid transcriptional effects of NGF; (ii) an unknown factor(s) that cooperates with the cloned NGFR in allowing high-affinity NGF binding is found in a primitive central nervous system cell line; and (iii) NGFRs introduced into and expressed by D283 MED (i.e., MED-NGFR) cells are partially functional but are unable to induce differentiation in these primitive neuron-like tumor cells, implying that high-efficiency receptor-mediated endocytosis of NGF and its receptor may be a necessary step in the cascade of events leading to NGF-mediated differentiation. ",3 2865,"The relationship between ethanol intake and DSM-III-R alcohol dependence. The purpose of this investigation was to quantify the relationship between ethanol consumption and DSM-III-R alcohol dependence using mathematical modeling techniques that allowed for the control of confounding and assessment of interaction. Although sex, education, ethnicity and marital status were not identified as actual confounders in the logistic regression model, the ethanol intake-dependence association was stronger among younger as opposed to older respondents. For 20 year olds, the average log odds for dependence increased .62 for each additional ounce of ethanol consumed daily, while the corresponding increase in risk among 60 year olds was .26. Implications of these results are discussed in terms of age differences in drinking patterns and differential social control of drinking behavior. Separate analyses in which aggregates of the alcohol dependence criteria served as outcome measures helped qualify the interpretation of the overall ethanol intake-dependence relationship. The need to examine components of global classifications of alcohol dependence using better operationalizations is highlighted. ",20 1398,"In vivo human testicular function assessed with P-31 MR spectroscopy. The clinical feasibility of assessing testicular metabolic integrity with phosphorus-31 magnetic resonance (MR) spectroscopy was investigated in six healthy volunteers and 23 patients with azoospermia. MR spectroscopic findings were compared with sperm count and motility in all patients and with findings at testicular biopsy in 23 patients. Significant differences (P less than .05) were found between the P-31 spectra of normal and azoospermic testicles in the following peak area ratios: phosphomonoester (PM)/beta-adenosine triphosphate, PM/phosphodiester, and inorganic phosphate/PM. In the patients with azoospermia, there were significant differences in these same peak area ratios between patients with primary testicular failure and those with chronic tubular obstruction. Although the differences between these two groups were statistically significant, there was a large overlap in numbers, and therefore a study with a larger patient population will be required. P-31 MR spectroscopy is a sensitive tool for assessment of testicular metabolic integrity and differentiation of normal testicles from those with markedly decreased spermatogenesis. ",11 2829,"The Hymenoptera venom study. III: Safety of venom immunotherapy. One thousand four hundred ten (44%) of the 3236 subjects in the Hymenoptera venom study accepted venom immunotherapy (VIT). Time to maintenance averaged 95 days, and the largest number achieved maintenance (147 subjects, 10.4%) at day 56. Ninety-two percent of the treated subjects achieved maintenance, and 84% continued therapy, most subjects (91%) until the study was terminated. One hundred seventy-one subjects (12%) experienced 327 treatment systemic reactions (Srs). The incidence of pruritus and angioedema/urticaria was similar with mild, moderate, or severe SRs. The SR severity did not correlate with the severity of the most recent sting before entry into the Hymenoptera-venom study, the most severe historical sting SR, the most severe SR during venom skin tests, the total dose of venom, the degree of skin test reactivity, or the lowest concentration yielding a positive skin test. Most SRs occurred between 1 and 50 micrograms and at maintenance; honeybee or wasp venoms were most likely to produce SR. This study, the largest of its kind with the use of standardized extracts, demonstrates (1) that there was good compliance, (2) that various historical and diagnostic criteria did not predict SRs to VIT, (3) that SRs to VIT were most likely to occur between 1 and 50 micrograms and at maintenance, (4) that honeybee or wasp venoms were most likely to produce an SR, and (5) that VIT is relatively safe. ",20 2810,"Early identification of alcohol problems. A high proportion of patients seen in clinical practice have an underlying alcohol problem. This is often difficult to detect, but failure to make the diagnosis may result in unnecessary investigations and inappropriate treatment. Furthermore, there is now good evidence of the effectiveness of brief intervention for problem drinking when it is still at an early stage. Several questionnaires and procedures based on clinical examination findings and laboratory tests are available to help in early diagnosis. They can be incorporated into the standard medical assessment and form the basis for screening programs for health risk factors. ",20 2656,"The AIDS-related experiences and practices of primary care physicians in Los Angeles: 1984-89. Telephone interviews of random samples of Los Angeles primary care physicians in 1984, 1986, and 1989 obtained information about their AIDS-related practice experiences, and sexual history taking. Data from mid-1989 reveal almost 74 percent have worked up at least one patient for AIDS or HIV infection in the past six months and 39.5 percent are caring for at least one patient with AIDS or AIDS-related complex. Self-reported use of appropriate sexual history questions has improved substantially over this five-year period. ",19 875,"Detection of a human intracisternal A-type retroviral particle antigenically related to HIV. Sjogren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria. ",6 2189,"Anterior fontanel pressure and visual evoked potentials in neonates and infants undergoing profound hypothermic circulatory arrest. To determine the effects of cardiopulmonary bypass with profound hypothermic circulatory arrest (PHCA) on anterior fontanel pressure (AFP) and visual evoked potentials (VEPs), 21 neonates and infants undergoing cardiopulmonary bypass (CPB) with PHCA for surgical correction of congenital heart defects were studied. Mean (+/- SD) minimum nasopharyngeal, esophageal, and rectal temperatures of 16.4 +/- 2.2, 11.2 +/- 2.7, and 17.7 +/- 1.9 degrees C, respectively, were achieved for a mean duration of PHCA of 51.6 +/- 18.7 min. AFP increased significantly above pre-CPB values for the first 21.7 +/- 8.1 min of rewarming. The duration of this increase in AFP was related logarithmically and directly to the product of the nasopharyngeal temperature (NPT) at the end of PHCA and the duration of PHCA (r2 = 0.82, P less than 0.0001). Nineteen of these patients had simultaneous monitoring of VEPs. The latency of both the N70 and P100 components of the VEPs increased as temperature decreased. The cerebral perfusion pressure was linearly and inversely related to the AFP (r2 = 0.72, P less than 0.01). The VEPs disappeared as a nasopharyngeal temperature (NPT) of 18.9 +/- 2.8 degrees C and reappeared after 21.9 +/- 8.8 min post-PHCA at an NPT of 32.8 +/- 1.4 degrees C. There was no significant difference between duration of increased AFP (20.9 +/- 8.1 min) and the duration of absence of VEPs during the post-PHCA period. The duration of increased AFP correlated linearly and directly with the duration of absence of VEPs (r2 = 0.84, P less than 0.005). These data demonstrate that transient neurophysiologic dysfunction occurs after PHCA. This dysfunction is related to the duration of elevation of the AFP and cannot be explained solely by a temperature effect. ",15 1142,"Influence of amphetamine treatment on somatosensory function of the normal and infarcted rat brain. The consequences of acute amphetamine administration on the metabolic responsiveness of the cerebral cortex to physiologic activation were studied in normal and infarcted rats. Treated rats received a 4 mg/kg intravenous injection of d-amphetamine 1 hour before unilateral vibrissae stimulation and 2-deoxyglucose study. In nontreated normal rats, metabolic activation was restricted to the major relay stations of the vibrissae-barrel circuit. In amphetamine-treated rats, stimulation-induced increased glucose utilization was widespread, including ipsilateral and contralateral cortical regions outside the barrel field circuit. For example, an 84% increase in glucose utilization above control was seen in cortical areas anterior to the barrel field region. Increased glucose utilization induced by stimulation was severely depressed in nontreated rats that had undergone infarction of the left cortical barrel field 2 weeks previously. Vibrissae stimulation failed to increase glucose utilization significantly in cortical areas remote from the infarct. In contrast, bilateral increases in glucose utilization were observed within cortical regions of treated infarcted rats. For example, a 50% increase in glucose utilization was detected in cortical areas bordering the infarct. Thus, in the normal and infarcted rat, amphetamine appears to promote alternate circuit activation--a pharmacologic property that may be advantageous for recovery after injury. ",9 2485,"Management of hypercholesterolemia in a family practice setting. A study was undertaken to assess physician adherence and patient compliance with the National Cholesterol Education Program guidelines for the management of newly detected hypercholesterolemia. The study site was the Department of Family Medicine, Medical University of South Carolina, Charleston, a university-based family medicine residency program. All serum cholesterol levels measured between July 1, 1988, and September 30, 1988, were reviewed. Patients were classified as normal, borderline, or hypercholesterolemic based on serum cholesterol levels and coronary heart disease risk factors. Patients previously recognized to be hypercholesterolemic were excluded. Six months later, medical record reviews were performed for the 192 hypercholesterolemic and 107 borderline hypercholesterolemic patients. Only 39 of the hypercholesterolemic patients (20%) had received appropriate dietary therapy and follow-up. Patient compliance with physician recommendations was excellent. There was minimal unnecessary testing or treatment of borderline hypercholesterolemia. Low rates of appropriate management of hypercholesterolemia may be related to inadequate physician knowledge, low physician-perceived self-efficacy regarding dietary counseling, or time constraints. ",17 22,"Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers. beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. ",0 2837,"Nicotine dependence: a preventable risk factor for other diseases. Nicotine meets all critical criteria for an addictive drug. Furthermore, there is no evidence that there would be widespread compulsive use of tobacco without nicotine. These findings have led to consideration of the cigarette as a contaminated vehicle for an addictive drug (nicotine). Nevertheless, nicotine itself may also be used therapeutically to reduce exposure to carcinogens and other tobacco toxins. Nicotine replacement is a useful adjunct in treating tobacco dependence. For example, nicotine replacement in the form of a polacrilex resin (chewing gum) can alleviate physically based signs and symptoms of tobacco abstinence. The fact that this form of nicotine replacement is not attractive to non-users of tobacco has opened the door to the use of nicotine in a therapeutic modality, permitting hope of eliminating tobacco dependence. ",20 1222,"Onset phase of spinal bupivacaine analgesia assessed quantitatively by laser stimulation. Analgesia was assessed quantitatively at various dermatomes (C7, T8, T10, T12, L1, L3, S1) for the first 30 min after subarachnoid administration of 0.5% bupivacaine 3.5 ml. Stimulation with 10 needles and laser stimulation could evoke pain in dermatomes with adequate analgesia to single needle stimulation. Analgesia was assessed by thresholds (sensory and pain) and by pain-related brain potentials (amplitude and latency) to laser stimulation. Little analgesia was found at T10, but it increased gradually towards caudal segments. The dermatome related to the site of the injection (L3) was not blocked to a greater extent than the surrounding dermatomes. Conduction time (the latency of the evoked brain potential) was increased relatively more from the S1 dermatome compared with L1. ",9 244,"Equal parental origin of chromosome 22 losses in human sporadic meningioma: no evidence for genomic imprinting. Inactivation of tumor suppressor genes can occur either by mutation at the gene locus or by loss of part or all of the chromosome region containing the gene. The latter is most frequently detected by DNA markers as loss of heterozygosity in the tumor tissue. In several reports, the paternal homologue was preferentially retained in embryonal tumors associated with loss of particular chromosomal regions, suggesting genomic imprinting of the corresponding tumor suppressor loci. To explore the generality of these findings and the possible role of genomic imprinting in adult tumors of the nervous system, we have determined the parental origin of chromosome 22 loss in sporadic meningioma. Of nine cases studied, five tumors retained the maternally derived chromosome 22 homologue while four retained the paternally derived chromosome 22. Thus, in contrast to the embryonal tumors, the meningioma locus on chromosome 22 is inactivated by random mutation in sporadic adult meningiomas. ",3 2148,"Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of disease activity in sarcoidosis. We investigated the clinical value of measuring serum concentrations of soluble IL-2R in monitoring sarcoidosis. Serum concentrations of soluble IL-2R were measured in 70 patients with sarcoidosis. The mean value for active untreated sarcoidosis was 1,143 +/- 509 U/ml, while the normal range in 97 healthy control subjects was 80 to 300 U/ml. The mean value for active untreated sarcoidosis was significantly higher than that for dormant disease (353 +/- 183 U/ml) or that for corticosteroid-treated patients (380 +/- 151 U/ml). Serial changes in serum soluble IL-2R level were studied in cases of spontaneous remission or in corticosteroid-treated patients; a good correlation was noted between the changes in serum level of soluble IL-2R and clinical status. A positive correlation was noted between serum concentration of soluble IL-2R and serum ACE activity. These data confirmed that measurement of serum concentration of soluble IL-2R could be used in monitoring the disease activity in sarcoidosis. ",14 908,"Selection factors resulting in improved survival after surgical resection of tumors metastatic to the lungs. From 1973 through 1987, a total of 140 patients underwent 184 operations for removal of metastatic tumors to the lungs. The number of lesions removed ranged form one to 30. Of the patients, 44% had solitary lesions. Overall 3-year survival was 62.6%, and 5-year survival was 48.2%. In all primary tumors except melanoma and breast cancer, 3-year survival was greater than 50% and 5-year survival was greater than 40%. With rare exceptions, the operation of choice for unilateral lesions was ipsilateral thoracotomy, and for bilateral lesions it was median sternotomy. Adequate conservative resection was the rule. There were three pneumonectomies, 25 lobectomies, 71 single wedge resections, 38 multiple unilateral wedge resections, and 47 bilateral wedge resections. There were no postoperative hospital deaths. Cox covariate analysis demonstrated improved survival in patients whose largest lesion was less than 1.5 cm in diameter and with disease-free interval longer than 1 year, but survival was not related to number of lesions or age of patient. An aggressive surgical approach is justified in patients with most primary tumors and a limited number of lung metastases less than 1.5 cm in diameter. Resection of metastases from melanoma and breast cancer should be accomplished after other sites of metastatic disease have been ruled out by the most stringent criteria. ",7 2206,"Child abuse of one of a pair of twins in Japan. A nationwide survey in Japan on child abuse and neglect revealed that 10% of the victims were products of multiple births. None of the victims who were singletons had multiple-birth siblings, and only in a few cases were both twins abused. The findings indicated that one rather than both of a pair of twins was likely to be abused in Japan. Abuse of both twins was likely when there were serious parental or family problems, whereas abuse of one twin was associated with the child's medical problems or non-home care. There was no instance of abuse of a pair of twins when both were handicapped. Comparisons of the abused twin with the non-abused co-twin and examination of the abuser's attitude to the victim suggested that the difference between twins in their development or in their response to parents increased the stress of child-rearing and encouraged favouritism, which resulted in abuse of only one twin. Comparison by parents of children with their siblings may be a common factor in general child abuse because it is a natural thing for parents to do. ",15 331,"Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma. One prominent lesion induced in DNA by ultraviolet (UV) radiation is the cyclobutyl pyrimidine dimer formed between adjacent pyrimidines on the same DNA strand. We investigated whether people who have developed basal cell carcinoma on sun-exposed skin have an altered ability to repair UV-induced pyrimidine dimers in DNA. Twenty-two patients with at least one basal cell carcinoma, aged 31-84 years, and 19 healthy volunteers, aged 25-61 years, took part in the study. Both groups were given one minimal erythema dose (MED) of simulated solar radiation on the lower back. DNA was extracted from the irradiated skin 0 to 6 h later, and the number of UV-induced pyrimidine dimers was determined using a dimer-specific endonuclease. At time 0, the average number of dimers per unit of DNA was similar in the two groups. After 6 h, an average of 22 +/- 4% of the dimers were removed in the group with basal cell carcinoma compared to 33 +/- 4% in the cancer-free group. In the basal cell carcinoma group, only 23% of the patients repaired more than 30% of the dimers after 6 h, compared with 53% of the cancer-free subjects (p less than 0.05). We conclude that patients who develop basal cell carcinoma on sun-exposed skin may have a decreased ability to repair pyrimidine dimers induced in skin exposed to simulated solar radiation. ",3 1093,"Dissociation between pain and autonomic disturbances in cluster headache. The relationship between pain and autonomic disturbances in cluster headache was studied in 54 patients whose attack always recurred on the same side, and in 7 others whose attack had affected either side on different occasions. In one of these seven patients, facial flushing and ocular sympathetic deficit was observed on the original side of headaches. In most patients, the orbital region was warmer on the painful side but in three cases this region was cooler during and between attacks. Lacrimation and rhinorrhoea were more common in severe attacks, and the temperature difference between the orbits increased with increasing severity of pain. These findings support the view that certain autonomic disturbances in cluster headache are provoked by pain. Residual autonomic dysfunction could influence autonomic activity during cluster headache. If so, residual dysfunction on the pain-free side could explain the dissociation between autonomic disturbances and pain observed in a few cases. ",9 1274,"Early intraocular pressure rise after trabeculectomy. Intraocular pressure (IOP) was measured 4 to 6 hours after surgery and on the first postoperative day in 35 eyes of 35 consecutive patients undergoing initial trabeculectomy. In 27 eyes, the anterior chamber was re-formed at the completion of surgery with balanced salt solution, and in eight eyes it was reformed with hyaluronate sodium. A total of six eyes (17%) had an IOP of 40 mm Hg or greater 4 to 6 hours after surgery. Patients who received hyaluronate to maintain the depth of the anterior chamber had a significantly greater chance of experiencing a marked postoperative IOP rise, both at 4 to 6 hours (P = .005) and on the first postoperative day (P = .0038). There was no correlation between the postoperative IOP rise and the patient's age, sex, glaucoma diagnosis, preoperative IOP, use of 5-fluorouracil, or the number of sutures used to close the scleral flap. Hyaluronate may contribute to an early increase in IOP that could result in further visual field loss in eyes with severe glaucomatous damage. We recommend early monitoring of IOP after trabeculectomy and avoiding the routine use of hyaluronate. ",10 788,"Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe-moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance. ",5 189,"Characterization and significance of sulfonylurea receptors. This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel. ",3 2488,"Southern blood club symposium: an update on selected aspects of hemochromatosis. Genetic epidemiology studies have indicated that hereditary hemochromatosis (HH) occurs in caucasians with a frequency of 3 to 13 per thousand. Clinical recognition however occurs far less frequently. The disparity is best resolved by defining HH as homozygosity for the HLA-linked hemochromatosis allele, regardless of the total body iron burden. Variability of clinical expression is explained in part by physiologic iron loss in women but variability in males may be due to environmental factors, gene-gene interactions or polymorphisms in mutated hemochromatosis alleles. Although clinical variability is great, the laboratory phenotype of HH is fairly constant and is marked by elevation of the transferrin saturation. The elevated transferrin saturation occurs early in life, before organ iron loading occurs and can be used as a screening tool to detect HH before organ damage occurs. Cloning and characterizing the HH gene, which is located within 1 centimorgan of the HLA-A locus should resolve some of the issues concerning clinical variability. ",17 1132,"Pain in children. The assessment and management of children's pain is a topic that has received a great deal of attention since the late 1970s. Nurse researchers have played a dominant role in all areas of pediatric pain relief and likely will continue to do so. There are currently a number of pediatric pain assessment instruments developed that are used in selected practice settings, but their use should be extended to document the existence of pediatric pain and its relief. Pharmacologic interventions for pediatric pain relief have been hampered by incorrect beliefs about analgesic risks, prescribing and administrating habits, and a virtual explosion of information in the area of analgesics. Although nurses have traditionally used nonpharmacologic interventions for pain relief, these methods have not been well researched. Continued research efforts in this important area will result in improved diagnosis and management of pediatric pain. ",9 143,"Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala. To estimate the degree to which passive case detection underestimates the true incidence of cutaneous leishmaniasis in Guatemala, we compared data from the passive surveillance system of the Guatemalan Ministry of Health with a cross-sectional population-based survey of cutaneous leishmaniasis in Guatemala. Of the 2,938 persons interviewed, 143 (5%) reported having had cutaneous leishmaniasis at some time in the past, 37 (1.3%) reported the onset of infection in the 12 months before the survey, 31 (1.1%) had active infections, and 16 (0.5%) had parasitologically confirmed infections. Calculated on the basis of these reports and the estimated population of the endemic area, the total number of new cases in the leishmaniasis-endemic area in the 12 months before the survey was approximately 2,574; during the same 12 month period, Ministry of Health data based on passive surveillance listed 64 cases of cutaneous leishmaniasis. In Guatemala, incidence estimates based on passive surveillance may underestimate the occurrence of cutaneous leishmaniasis by as much as a factor of 40. ",2 2845,"Subxiphoid pericardial windows--helpful in selected cases. There is a small group of patients who sustain multiple penetrating injuries who present with haemodynamic changes, making it difficult to clinically exclude or prove the presence of penetrating cardiac injury. It is in this select group of patients that we found subxiphoid pericardial windows to be extremely useful to prove or disprove the existence of a cardiac injury and thereby prevent a delay in diagnosing these injuries. ",20 344,"Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas. ",3 2978,"A borna virus cDNA encoding a protein recognized by antibodies in humans with behavioral diseases. Borna disease virus (BDV) causes a rare neurological disease in horses and sheep. The virus has not been classified because neither an infectious particle nor a specific nucleic acid had been identified. To identify the genome of BDV, a subtractive complementary DNA expression library was constructed with polyadenylate-selected RNA from a BDV-infected MDCK cell line. A clone (B8) was isolated that specifically hybridized to RNA isolated from BDV-infected brain tissue and BDV-infected cell lines. This clone hybridized to four BDV-specific positive strand RNAs (10.5, 3.6, 2.1, and 0.85 kilobases) and one negative strand RNA (10.5 kilobases) in BDV-infected rat brain. Nucleotide sequence analysis of the clone suggested that it represented a full-length messenger RNA which contained several open reading frames. In vitro transcription and translation of the clone resulted in the synthesis of the 14- and 24-kilodalton BDV-specific proteins. The 24-kilodalton protein, when translated in vitro from the clone, was recognized by antibodies in the sera of patients (three of seven) with behavioral disorders. This BDV-specific clone will provide the means to isolate the other BDV-specific nucleic acids and to identify the virus responsible for Borna disease. In addition, the significance of BDV or a BDV-related virus as a human pathogen can now be more directly examined. ",21 2569,"Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB X NZW)F1 X NZB backcross mice were hemi-splenectomized at 10 wk and the number and antigenic specificity of their Ig-secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P less than 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P less than 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti-DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation. ",19 393,"E1a-dependent expression of adenovirus genes in OTF963 embryonal carcinoma cells: role of E1a-induced differentiation. Some undifferentiated F9 embryonal carcinoma cells allow adenovirus genes to be expressed independently of the E1a oncogene normally required for their activation; this has been attributed to a cellular equivalent of E1a in F9 cells. However, transcription of all early genes was low in undifferentiated OTF963 embryonic carcinoma cells during the first 48 hr after infection with adenovirus type 5 (Ad5). Transcription then increased to about the level seen 16 hr after infection of cells induced to differentiate by retinoic acid (RA) (referred to as RA-dF9 cells), but this increase did not occur in cells infected by the E1a deletion mutant dl312. Addition of E1a in trans, or of RA, had no immediate effect on viral transcription in OTF963 cells, but viral transcription increased about 48 hr after these additions. Ad5 induced transcription of several differentiation-specific genes in OTF963 cells with about the same kinetics as their induction by RA. These genes were superinduced in RA-dF9 cells by cAMP or infection by adenovirus. We suggest the small amount of E1a produced early in infection of OTF963 cells activates cellular genes, some of which are differentiation specific and required for efficient transcription of viral genes, so that E1a both induces and is induced by differentiation. The simple hypothesis of a cellular equivalent to E1a does not adequately explain the complex interactions between viral and cellular genes in OTF963 embryonic carcinoma cells. ",3 376,"Paraneoplastic cerebellar degeneration: a clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies. In a review of 32 patients with paraneoplastic cerebellar degeneration (PCD), 16 (all of whom were women) had Purkinje cell cytoplasmic antibodies (PCAb) and 16 (8 women) did not. Most patients (15 of 16 seropositive and 12 of 16 seronegative patients) had active cancer at the time of neurologic diagnosis. Gynecologic or breast cancers were found in 14 of 16 seropositive and in 2 of 8 seronegative female patients; lung cancer was diagnosed in 7 of 16 seronegative patients but in no seropositive patient. In seropositive patients, the onset of the syndrome was more often abrupt and abnormalities of affect, mentation, ocular motility, and cerebrospinal fluid IgG index were more common than in seronegative patients. Additional paraneoplastic neurologic syndromes were present in five seronegative patients but in no seropositive patient. Clinical impairment was equivalent in both groups; approximately 75% of patients were confined to a wheelchair or bed at last follow-up. Four of 16 seropositive patients died (4 to 18 months after onset of PCD), and 7 of 16 seronegative patients died (7 to 120 months after onset of PCD). Thus, PCAb seem to be a marker for a clinical subset of female patients with gynecologic or breast cancer. The high frequency of other autoimmune paraneoplastic syndromes in patients with seronegative PCD suggests that PCD in both seropositive and seronegative patients may have a common pathogenic basis that involves an as yet unidentified antineuronal autoimmune mechanism. ",3 733,"Nonoperative management of small-bowel obstruction with endoscopic long intestinal tube placement. Intestinal obstruction remains a major cause of morbidity and mortality in surgical patients. We reviewed the records of 77 patients with mechanical small-bowel obstruction who were treated with endoscopically and fluoroscopically placed Leonard long intestinal tube decompression. Most patients (59%) had failed a trial of nasogastric tube or Miller-Abbott tube decompression. Overall, 29 per cent of patients were able to resolve their obstruction with Leonard tube decompression alone. Subdivision of patients on the basis of the etiology of their obstruction demonstrated a much higher rate of success for tube decompression in adhesive obstruction (37%) versus malignant obstruction (12%) or inflammatory obstruction (no successes). Patients with radiographic and clinical evidence of complete intestinal obstruction were significantly less likely to respond to long intestinal tube treatment (13%). The long intestinal tube was easily passed in all patients. There were no complications of the intubation procedure in our series, and the incidence of tube-related complications was four per cent. We conclude that an initial period of long intestinal tube decompression allows a significant percentage of patients with mechanical small-bowel obstruction to be treated nonoperatively, particularly if a partial obstruction from postoperative adhesions is present. Patients who have failed a trial of nasogastric tube decompression and are poor operative risks should also be considered for long intestinal tube placement. ",5 2899,"Sensory nerve evoked responses in spinal cord injury. Previous studies have documented the presence of fibrillations, positive waves, and decreased motor evoked response amplitudes in spinal cord injury (SCI) subjects. The purpose of this study was to further evaluate sensory nerve status in this population. Twenty-eight subjects with SCI for at least five months and evidence of spasticity were included. Sural sensory and tibial motor evoked response amplitudes were measured. The mean sural sensory amplitude was 8.0 +/- 5.9 microV (normal = 15.0 +/- 5.3 microV). The mean tibial motor amplitude was 5.1 +/- 4.3 mV (normal = 11.7 +/- 3.8 mV). In six subjects with significantly reduced sural sensory amplitudes, more extensive electrodiagnostic testing was performed. These studies showed diffusely decreased lower extremity sensory and motor evoked response amplitudes and diffuse positive waves and fibrillations in no particular distribution. Thus, subjects with SCI may have sensory as well as motor nerve abnormalities. An intact connection between the second order and primary sensory neuron may be necessary for maintenance of axonal integrity of the primary neuron. ",20 3084,"The effect of continuous epidural analgesia on postoperative pain, rehabilitation, and duration of hospitalization in total knee arthroplasty. Efficacies of three alternate methods of postoperative analgesia were studied in 156 patients who had total knee arthroplasty (TKA). Forty-two of these patients received parenteral meperidine hydrochloride or morphine (Group 1), 58 patients received periodic epidural injections of morphine (Group 2), and 56 patients received continuous epidural infusions of bupivacaine hydrochloride and Duramorph (Group 3). The postoperative course of all patients was documented in terms of the incidence and severity of pain, range of joint motion, duration of hospitalization, and occurrence of complications. Although epidural analgesia increased the cost and duration of the operation, good-to-excellent pain relief was attained in 86% (Group 2) and 88% (Group 3) of cases with epidural analgesia compared with 61% of patients (Group 1) receiving conventional analgesia. Moreover, 67% of patients in Group 1 experienced frequent episodes of moderate-to-severe postoperative pain in contrast to 40% of patients in Group 2 and only 10% of patients in Group 3. As a result of diminished pain, greater joint motion was obtained within the first 72 hours in Groups 2 and 3. They also had shorter hospitalization (9.6 days versus 11.2 days for Group 1 and 10.8 days for Group 2). However, the use of epidural analgesia did not reduce the incidence of complications, including nausea. Continuous infusion of epidural bupivacaine and Duramorph provided good-to-excellent control of postoperative pain after TKA. However, better analgesics are needed to reduce the high incidence of side effects associated with various treatment methods. ",22 5,"Selection of antibiotic coverage in vascular patients undergoing cystoscopy. Bacteremic seeding of prosthetic vascular grafts represents a cause for graft infection; transurethral procedures account for one source of bacteremia. Therefore, a prospective study of 200 patients undergoing cystoscopy was conducted to identify the incidence of bacteruria and factors associated with it, organisms involved and their antibiotic sensitivities. Positive cultures were found in 21%. The incidence was 64% in in-patients and 8% in out-patients. Positive cultures were found in 12% of patients who received antibiotics and 29% who did not. Four percent showed signs of bacteremia. The cultures identified both Gram positive and negative organisms; multiple organisms grew in 22%. Gram negative organisms were more common in in-patients. Candida grew in 8%. The Gram positive organisms were sensitive to ampicillin (92%), sulfatrimethoprim (75%) and cefazolin (60%); Gram negative to aminoglycosides (100%) and cefazolin (92%). In view of the unpredictable and multiple organisms, it is recommended that pre-cystoscopy cultures be performed and specific antibiotic coverage be based on the sensitivities. ",0 1754,"Pulse oximetry: a new non-invasive assessment of peripheral arterial occlusive disease. Peripheral skin perfusion reflects the level of vascularity and viability of a limb and may help in planning the site of amputation or bypass surgery in patients with vascular disease. This study used peripheral pulse oximetry in 20 healthy volunteers and in 20 patients with limb ischaemia. Pulse oximetry saturation levels (Psa,O2) were compared with ankle artery Doppler pressures and transcutaneous oxygen measurements (Ptc,O2). Recordings were taken at two standard sites distally and referenced to finger and forearm to calculate an index. A significant correlation was found between Ptc,O2 and Psa,O2 in patients with ischaemia (r = 0.68, P less than 0.01). A further group of 12 patients with acute limb ischaemia was similarly assessed before and after revascularization. After revascularization mean(s.d.) Ptc,O2 increased from 38(13) to 44(1) mmHg (P greater than 0.05) and mean(s.d.) Psa,O2 increased from 86(3) to 90(4) per cent (P less than 0.01). These data suggest that pulse oximetry is a more sensitive index of peripheral perfusion than Ptc,O2 or ankle artery Doppler pressure and that, because of its accuracy and simplicity, it merits further use. ",13 1442,"Comparison of two methods for the estimation of urea kinetics and introduction of a third simplified method. It has been claimed that computed urea kinetic (UK) modelling in hemodialysed patients, for the estimation of protein intake, leads to an overestimation of protein catabolic rate (PCR). In the present study, three different methods of kinetic modelling for the determination of PCR and Kt/V are compared in 24 patients. The first method was the direct quantification method (DDQ) based on the collection of all urea eliminated from the body. The first computed method (ICMI) was the urea kinetic modelling method as described by Sargent. Dialyzer clearances were measured directly and not estimated by theoretical extrapolation. The second computed method (ICMII) is based on the indirect calculation of urea distribution volume (Vu), according to Watson, and of dialyzer clearances from this Vu and from pre- and post-dialysis urea concentrations. All three methods resulted in PCR's that were not significantly different (DDQ: 1.03 +/- 0.19; ICMI: 1.04 +/- 0.22; ICMII: 1.08 +/- 0.25 mg/Kg BW.24 hrs; p greater than 0.05). When the results were correlated, the following results were obtained: ICMI vs ICMII: r = 0.89, p less than 0.001; ICMI vs DDQ: r = 0.68, p less than 0.01; DDQ vs ICMII: r = 0.78, p less than 0.001. Intermutual comparison of Kt/V values resulted in virtually identical results, especially when comparing ICMI and ICMII, where the regression line equalled the identity line. In conclusion, all methods seem equally reliable in determining mean PCR and Kt/V. Our data, obtained with directly measured dialyzer urea clearances, do not confirm the earlier held opinion that computed modelling results in an overestimation of PCR. ",11 1169,"Temporoparietal cortex in aphasia. Evidence from positron emission tomography. Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas. ",9 1002,"A controlled, double-blind study of the effect of quazolast on nasal challenge with ragweed antigen. Quazolast is a potent mediator release inhibitor as determined by in vitro and in vivo testing. A placebo-controlled, double-blind, two-way crossover study compared the safety and efficacy of Quazolast, 400 mg bid orally, with placebo in 23 subjects with ragweed (RW) allergy, out of season. Subjects were assigned to two 7-day treatments in a random sequence with an 8-day washout. Subjects were challenged on days 1 and 7 of each trial with serial dilutions (10, 100, 1000, 1350, and 2700 PNU/0.135 mL) of RW, using metered pump spray bottles, (two sprays delivered 0.135 mL), preceded by saline control. Efficacy evaluation consisted of nasal flow rates measured by rhinomanometry, sneeze counts, nasal itchiness scores, and weight of nasal secretions during challenges. During Quazolast treatment, subjects had significantly lower (P less than .05) mean percent decreases in nasal flow rate at 1350 and 2700 PNU. Nasal itchiness scores were significantly lower (P less than .05) during Quazolast treatment than at placebo at 1000, 1350, and 2700 PNU. Although sneeze counts were lower during treatment with Quazolast than with placebo, the results did not reach statistical significance. No significant improvement was seen in the weight of nasal secretions. Adverse experiences, clinical laboratory results, and physical examinations were unremarkable, posttreatment. Quazolast was superior to placebo in protecting against nasal congestion and nasal itchiness after ragweed nasal challenge. ",8 2134,"Wiskott-Aldrich syndrome. A case report. This paper presents a report on a child with Wiskott-Aldrich syndrome. The clinical picture and laboratory findings are characteristic of this disease. The prevailing symptoms have included recurrent respiratory and alimentary tract infections, seborrhic dermatitis-type skin lesions, and thrombocytopenia. Humoral and cellular immunological disturbances have been noted, and the pedigree pattern is very characteristic. ",14 921,"Bronchoalveolar lavage in liquid paraffin pneumonitis. We evaluated cells and lipids recovered in the bronchoalveolar lavage fluid from seven patients with liquid paraffin pneumonitis. For each patient, the BALF was whitish with oil droplets on the surface. Alveolar macrophages contained numerous, large vacuoles that did not react with May-Grunwald-Giemsa, Papanicolaou, or periodic acid-Schiff but were stained in black with Sudan B, orange with Sudan III and red with oil Red O. Liquid paraffin was identified on thin layer chromatography of BALF-extracted lipids as a very hydrophobic compound migrating on the solvent front as control liquid paraffin. This abnormal spot was definitely identified as liquid paraffin by infrared spectroscopy and gas liquid chromatography for the first patient. The number and percentage of AMs were largely decreased in the BALF of each patient, whereas the number of neutrophils, eosinophils and lymphocytes was increased. These findings suggest that this cell-mediated inflammatory response plays a role in the development of interstitial fibrosis at late stages of liquid paraffin pneumonitis. ",7 2516,"Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes. Human and bovine glomerular basement membrane (GBM) preparations, representing the extracellular matrix of the renal filtration units, were found to contain type VI collagen. This protein was solubilized by guanidine and guanidine-dithiothreitol extractions and characterized after polyacrylamide gel electrophoretic resolution by immunoblotting with an antiserum directed against the alpha 1(VI) and alpha 2(VI) polypeptide chains and by its insensitivity to collagenase digestion in the nonreduced state. In contrast to GBM, which is the product of three distinct cells, type VI collagen could not be detected in extracts from calf lens capsule, an epithelial cell-derived basement membrane. Quantitation by radioimmunoassay of the type VI collagen content of GBM from 17 diabetic and 15 nondiabetic human subjects indicated a 2.8-fold higher level (P less than 0.001) in the diabetic preparations. Because in the glomerulus type VI collagen is considered on the basis of immunohistochemistry to be localized to the mesangium, we believe that measurement of this protein in GBM preparations can provide a valuable index of mesangial expansion in diabetic and other glomerulopathies. ",18 1080,"Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well-defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalographic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desychronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of less than or equal to 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3-mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function. ",9 1894,"Left ventricular asynchrony: an indicator of regional myocardial dysfunction. There is a marked heterogeneity of myocardial wall thickening within the left ventricle and among different individuals. It is therefore difficult to detect regional myocardial dysfunction from absolute values of systolic wall thickening. We tested whether the extent of left ventricular asynchrony during ischemia and reperfusion can be used to quantify the severity of regional myocardial dysfunction when nonischemic baseline function is not known. In six anesthetized, open-chest dogs regional myocardial wall thickness was measured by means of sonomicrometry under control conditions, at three degrees of ischemic dysfunction (mild, moderate, and severe), and after release of a 15-minute occlusion of the left circumflex coronary artery, when degrees of moderate and mild reperfusion dysfunction similar to the preceding ischemic dysfunction were present. Two indexes of left ventricular asynchrony were calculated: (1) postejection thickening (PET) and (2) the phase difference of the first Fourier harmonic of posterior versus anterior myocardial wall motion (PD). Systolic myocardial wall thickening was decreased from 15.3 +/- 3.1 (standard deviation) % (control value) to 9.7 +/- 1.4% (mild ischemia), 4.2 +/- 1.6% (moderate ischemia), and -3.7 +/- 3.1% (severe ischemia). Conversely PET increased from 0.02 +/- 0.04 mm (control value) to 0.15 +/- 0.22 mm (mild ischemia), 0.19 +/- 0.15 mm (moderate ischemia), and 0.50 +/- 0.26 mm (severe ischemia). PD increased from 9 +/- 28 degrees (control value) to 22 +/- 19 degrees (mild ischemia), 54 +/- 18 degrees (moderate ischemia), and 107 +/- 21 degrees (severe ischemia). After release of the 15-minute left circumflex coronary artery occlusion, PET and PD recovered to 0.34 +/- 0.19 mm and 36 +/- 24 degrees (moderate dysfunction) and 0.25 +/- 0.31 mm and 29 +/- 8 degrees (mild dysfunction), respectively. There were inverse linear relationships between systolic wall thickening and PET (r = -0.86, p less than 0.001) and between systolic wall thickening and PD (r = -0.87, p less than 0.001). Inotropic stimulation by postextrasystolic potentiation increased regional systolic myocardial posterior and anterior wall thickening but did not alter the extent of left ventricular asynchrony. Thus, when normal baseline function is not known, the severity of regional myocardial dysfunction at a given inotropic state can be determined by analysis of left ventricular asynchrony. There was no significant correlation between the extent of PET and PD during ischemia and at early reperfusion and the recovery of contractile function at late reperfusion. Thus PET does not provide a prospective marker for the functional outcome of reperfusion. ",13 1062,"Electroencephalography should not be routine in the evaluation of syncope in adults We reviewed the reports of all electroencephalograms obtained at the Nashville (Tenn) Veterans Administration Hospital from September 1987 to August 1989. Seventy-three patients were referred for evaluation of syncope or near syncope. Of these 73 patients, 10 (13.7%) had abnormal findings. Twenty-six patients were referred for other complaints similar to syncope (ie, blackouts, loss of consciousness, falling out, passing out, and fainting). Of these 26 patients, five (19.2%) had abnormal findings. We reviewed the medical records of the patients with abnormal findings and found that the final diagnosis or treatment of the syncope was affected by electroencephalogram in only one patient. These findings suggest that routine electroencephalography is not of significant value in the evaluation of syncope in adults. ",9 1300,"Evaluation of new rapid office test for microalbuminuria and its comparison to fully quantitative radioimmunoassay. A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 micrograms/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of greater than 0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, used in conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3-1280 micrograms/ml) of urinary albumin levels in the office setting. ",11 1088,"Transient hyperprolactinemia is associated with a midcycle luteinizing hormone surge. This study demonstrates that LH surge cycles in IVF patients were associated with significantly higher serum PRL concentrations than cycles in which a spontaneous LH surge did not occur. Our findings support the hypothesis of concomitant LH and PRL release at the time of the midcycle gonadotropin surge, as well as that of estrogen sensitization of pituitary lactotropes, and suggest a possible mechanism for transient midcycle hyperprolactinemia. ",9 2775,"The detection of alcoholism in hospitalized schizophrenics: a comparison of the MAST and the MAC. The Michigan Alcoholism Screening Test (MAST) and the MacAndrew Alcoholism Scale (MAC) were administered to forty-one schizophrenic inpatients also meeting DSM-III criteria for either alcohol abuse or alcohol dependence and 29 schizophrenic inpatients who did not qualify for an additional substance abuse diagnosis other than marijuana abuse/dependence. The MAC failed to differentiate between the alcoholic and nonalcoholic groups and both groups scored above the recommended cutting score. The MAST significantly differentiated the alcoholic and nonalcoholic schizophrenic patients and was as sensitive to a history of alcohol abuse as to alcohol dependence. Neither the MAST nor MAC was sensitive to recent versus more remote drinking. The overall classificatory accuracy of the MAST was found to be 80% and that of the MAC was 56%. A logistic regression analysis revealed that the use of just four MAST items can yield a group classificatory rate of 83%. It was concluded that the MAST exhibited sufficient sensitivity and specificity to be used as an initial screening instrument for alcoholism in schizophrenic patients. ",20 648,"Arachnoid granulation cerebrospinal fluid otorrhea. A case report and review of the temporal bone (TB) collection in the Department of Otolaryngology at SUNY Health Science Center in Syracuse demonstrated the occurrence of arachnoid granulations (AGs) in the posterior fossa surface of the TB and their role in cerebrospinal fluid (CSF) otorrhea. A large AG responsible for CSF otorrhea in a 64-year-old man was excised with soft tissue repair of the dural defect. Sixteen of 188 TBs (8.5%) in the collection contained 24 AGs ranging in size from 0.07 to 80.65 mm3. Nine AGs (37%) were small (less than 1 mm3) and did not demonstrate enlargement. Twelve (50%) were of intermediate size (2.50 to 9.32 mm3), and three (13%) were large (49.82 to 80.65 mm3). The intermediate and large AGs were associated with bone erosion and a high incidence of communication with a pneumatized mastoid complex (serous otitis media or meningitis). These findings suggest that AGs of sufficient size to produce bone erosion are the primary responsible lesions in adult-onset spontaneous CSF otorrhea. ",4 2879,"The role of spinal flexibility in back pain complaints within industry. A prospective study. Commonly used clinical measurements of spinal flexibility in the sagittal and frontal planes were examined as predictors of future back pain reports within industry. The study sample consisted of 3,020 aircraft manufacturing employees who were examined and tracked for more than 4 years for reports of back pain. Modified Schober, sit-and-reach, and lateral bending measurements were not significantly associated with risk of future back pain reporting, nor were any trends present. There was a statistically significant relationship between decreased flexibility and reports of current or previous back problems. However, the differences in flexibility between subjects with and without a history of back problems were too small to be of practical significance. ",20 525,"Actin architecture of cultured human thyroid cancer cells: predictor of differentiation? The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells. ",3 1625,"Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia. To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01). ",13 1458,"Small cell neuroendocrine carcinoma of Bartholin's gland. A small cell neuroendocrine carcinoma that arose in Bartholin's gland in a 30-year-old woman is reported. The tumor had light, electron microscopic, and immunohistochemical features typical of pulmonary small cell carcinoma and was metastatic to inguinal lymph nodes at presentation. This is the first reported example of this tumor occurring in Bartholin's gland. ",12 2773,"Murine model of ethanol-induced immunosuppression. Alcohol abuse has been associated with an increased susceptibility to infectious diseases and certain tumors. On the basis of these observations, an effect of ethanol on the immune system has been suggested. We have used a mouse model system in which male C57Bl/6 mice were fed either Lieber-DeCarli liquid diet containing ethanol sufficient to supply 37% of the total calories or isocaloric control diet in a pair-feeding design to examine the effect of ethanol on the immune system. The group consuming the ethanol-containing diet maintained relatively stable levels of blood ethanol for the 8 days of feeding. Consumption of ethanol for 8 days resulted in a profound loss of thymus and spleen cells, and the recovery of thymus cellularity was delayed relative to the recovery of spleen cell numbers after ethanol feeding was discontinued. Proliferation of spleen lymphocytes to T-cell stimuli (concanavalin A and alloantigens) was diminished; however, B-cell proliferation to lipopolysaccharide was relatively unchanged in mice fed ethanol-containing diet. Also in ethanol-fed mice a significant decrease in the primary antibody response to sheep red blood cells but not to the T-independent antigen trinitrophenol-ficoll occurred. These data establish the murine model system as a means to define further the effect of ethanol on the immune system and host defense mechanisms. ",20 1039,"Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury. Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection. ",9 2196,"Atrial cardiomyoplasty after Fontan-type procedures. The purpose of right atrial cardiomyoplasty is to increase atrial-pulmonary flow in patients undergoing Fontan-type procedures. We developed two surgical techniques to bypass the right ventricle, followed by right atrial cardiomyoplasty with a stimulated latissimus dorsi muscle flap (LDMF). In 10 goats, the left LDMF was transferred into the chest by removal of the second rib. After sternotomy, the right atrial appendages of five goats (group 1) were connected to the distal main pulmonary artery with polytetrafluoroethylene tubing and the proximal pulmonary trunks were ligated. In the other five goats (group 2), under cardiopulmonary bypass, bioprosthetic valves were implanted into the inferior venae cavae. The tricuspid orifice was closed, and the atriopulmonary connection was performed. The left LDMF was sutured over the right atrium and stimulated using synchronous 30-Hz bursts of impulses delivered by a Medtronic Cardiomyostimulator. Hemodynamic studies were performed in the acute phase. Right atrial, pulmonary arterial, and aortic pressures were assessed. Cardiac output was measured using ultrasonic flow studies. LDMF stimulation restored pulsatile pressure patterns in the pulmonary artery and increased the cardiac output. These observations were more evident in the model with caval valvular implant. This functional ""ventricularization"" of the right atrium could improve long-term results after Fontan-type procedures and extend operative indications. Chronic experimental studies are necessary to evaluate the diastolic and systolic functions of the neo-right ventricle. ",15 2923,"Cyclosporine A for prolonging allograft survival in patients with massive burns. Cyclosporine A (CsA) immunosuppression was used in three patients with massive burns to prolong skin allograft survival. Cyclosporine A kinetic studies in patients with burns revealed markedly accelerated blood clearance and high variability in drug absorption when compared with studies in renal transplantation patients. Doses required to maintain therapeutic levels varied widely. While patients were receiving adequate maintenance therapy with CsA immunosuppression the allograft was tightly adherent without gross or microscopic rejection and was indistinguishable from autograft. Ultimately, patients' wounds were permanently covered with sequential autografts by recropping limited donor sites. There were not unusual septic complications, although prophylaxis for opportunistic infections was used. The disadvantage of allograft use is its early rejection and obligatory replacement until permanent coverage with autograft can be accomplished. Cyclosporine A can prolong allograft survival and allow autograft coverage from limited donor sites in a sequential fashion. This may lead to increased survival in patients with massive burns. ",20 1125,"A case-control study of Alzheimer's disease in Australia. We conducted a case-control study of clinically diagnosed Alzheimer's disease (AD) on 170 cases aged 52 to 96 years, and 170 controls matched for age, sex and, where possible, the general practice of origin. Trained lay interviewers naive to the hypotheses and to the clinical status of the elderly person carried out risk-factor interviews with informants. Significant odds ratios were found for 4 variables: a history of either dementia, probable AD, or Down's syndrome in a 1st-degree relative, and underactivity as a behavioral trait in both the recent and more distant past. Previously reported or suggested associations not confirmed by this study include head injury, starvation, thyroid disease, analgesic abuse, antacid use (aluminum exposure), alcohol abuse, smoking, and being left-handed. ",9 3349,"Analysis of base station morphine orders: assessment of supervising physician consistency. Paramedic contact with a base station should gemerate consistent recommendations reflecting a consensus of base station physician care. In our urban EMS system, paramedics must contact a single base station to provide morphine sulfate (MS) for a patient with chest pain. We performed a retrospective cohort analysis of all prehospital MS requests for chest pain to determine the consistency of the circumstances for which the paramedic team was refused MS. These MS requests represented 123 of the 1,715 (7%) on-line physician consultations during the 6-month study. Only 15 of the 123 (12%) MS requests were refused. Neither the mean patient age, sex distribution, or presenting vital signs correlated with MS refusal. A maximum estimate of transport time to the hospital of less than or equal to 5 minutes was noted for 7 of 15 (47%) medication refusals compared to only 11 of 96 (11%) approvals with documented estimated transport times (P less than or equal to 0.005). A simultaneous request for nitroglycerin (NTG) was noted for 6 of the 15 (40%) medication refusals and 15 of the 108 (14%) approvals (P less than 0.05). We found refusal of MS administration to be uncommon. Supervising physicians tended to refuse MS when the transport time was short and when NTG was requested for concomitant administration. We also noted physician inconsistencies in refusal scenarios. These findings can guide physician consensus development to avoid sending mixed messages to paramedics. ",22 984,"Corticosteroids in primary tuberculosis with bronchial obstruction. The usefulness of prednisolone in combination with the modern potent antituberculous drugs has been studied in 29 children with primary lung tuberculosis and hilar adenopathy causing bronchial obstruction. These children were divided at random in two groups of 15 and 14 patients. Both groups were treated similarly except that one group received prednisolone. Both groups were very similar before the onset of treatment for most variables. Tuberculous infection healed in both groups but the group on steroids improved earlier and had significantly fewer complications, both on radiography and bronchoscopy. Only two of the patients on steroids still had progressive lesions: a very young baby probably because he developed two severe viral infections consecutively, and another infant of 7 months whose treatment was unreliable, as the parents were not very compliant. Some patients initially not treated with prednisolone improved only after it was given. Prednisolone treatment is not recommended when the reliability of the treatment cannot be guaranteed, as the hazard of harm would exceed the expected benefit. ",7 891,"Platelet-derived growth factor in idiopathic pulmonary fibrosis. Fibrosis is a complex process involving an inflammatory reaction, fibroblast proliferation, and abnormal accumulation of interstitial collagens. Mononuclear cells are usually present in lung fibrosis. Activated monocytes and macrophages in culture have been shown to produce several growth factors including platelet-derived growth factor (PDGF). PDGF is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells and a stimulator of collagen synthesis. We have studied the expression of c-sis/PDGF-2 mRNA in lung tissues derived from five patients with idiopathic pulmonary fibrosis (IPF) and from four control individuals without IPF. Northern blot analysis of specimens obtained from four patients with IPF revealed the expression of the c-sis/PDGF-2 protooncogene. A control lung tissue without IPF did not express the c-sis protooncogene. In situ hybridization extended these studies demonstrating the expression of the c-sis mRNA in the five specimens with IPF but not in the four control specimens without IPF. The expression of c-sis mRNA was localized primarily in the epithelial cells. Invading alveolar macrophages also expressed c-sis mRNA. The expression of c-sis mRNA was accompanied by the expression of PDGF-like proteins in lung specimens with IPF but not in control lung specimens. These findings demonstrate the in vivo expression of the c-sis/PDGF-2 protooncogene and the production of PDGF-like proteins in the epithelial cells and macrophages of the fibrotic tissue. This localized and sustained production of PDGF-like mitogen may constitute an important contributing factor in the abnormal fibroblast proliferation and collagen production, events associated with pulmonary fibrosis. ",7 1782,"Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs The purpose of the present study was to examine subendocardial flow and function during graded coronary pressure reduction to determine the effect of tachycardia on the lower autoregulatory pressure limit (critical coronary pressure) in unanesthetized dogs. During atrial pacing at a rate of 200 beats/min, subendocardial flow measured by radioactive microspheres averaged 1.55 +/- 0.34 ml/min/g and remained unchanged as pressure was reduced over the autoregulatory plateau from 84 +/- 10 to 59 +/- 7 mm Hg. Further reductions in coronary pressure to below a critical coronary pressure of approximately 60 mm Hg were associated with concomitant reductions in subendocardial flow and the endocardial-epicardial flow ratio during tachycardia. Although regional function remained constant over the autoregulatory plateau, there was a rightward shift of the coronary pressure-function relation during ischemia in response to a steady-state increase in rate from 100 to 200 beats/min. Reductions in regional wall thickening began when coronary pressures reached 38 +/- 7 mm Hg at a heart rate of 100 beats/min and 61 +/- 6 mm Hg at a heart rate of 200 beats/min (p less than 0.005). Similar critical coronary pressure values were obtained for subendocardial segment shortening. Relations between subendocardial flow and myocardial function measured by both transmural wall thickening and subendocardial segment shortening were linear during pacing at a heart rate of 200 beats/min with relative reductions in wall thickening related to reductions in subendocardial flow on a nearly one-to-one basis. The results of this study demonstrate that there is a shift in the lower limit of subendocardial autoregulation during tachycardia as manifest by the onset of subendocardial ischemia at a higher distal coronary artery pressure. The shift in critical coronary pressure relates to an increase in resting flow requirements due to increased demand and diminished subendocardial vasodilator reserve at any given coronary pressure secondary to a reduction in the time available for diastolic subendocardial perfusion during tachycardia. ",13 1681,"Characteristics of participants at baseline in the Treatment of Mild Hypertension Study (TOMHS). The Treatment of Mild Hypertension Study (TOMHS) is a randomized, double-blind clinical trial currently being conducted to compare the effects of nonpharmacologic therapy alone with those of 1 of 5 active drug regimens combined with nonpharmacologic therapy, for long-term management of patients with mild hypertension. Six classes of drugs were studied: (1) acebutolol (beta blocker), (2) amlodipine (calcium antagonist), (3) chlorthalidone (diuretic), (4) doxazosin (alpha 1 antagonist), (5) enalapril (angiotensin-converting enzyme inhibitor) and (6) placebo. All participants received nutritional-hygienic advice to reduce weight and sodium and alcohol intakes and to increase physical activity. End points include blood pressure change, side effects and quality-of-life indices; incidence of electrocardiographic and echocardiographic abnormalities; and incidence of cardiovascular clinical events, including death, among participants receiving drugs as first-step treatment as well as nonpharmacologic treatment compared with incidence among those participants randomized to nonpharmacologic treatment only as the initial step. ",13 544,"Chondrolipoangioma. A cartilage-containing benign mesenchymoma of soft tissue. The clinical and pathologic features of four cases of benign mesenchymoma in which mature cartilage represented the predominant component are reported. The distinctive histologic feature in all four cases was a lobular proliferation of cartilaginous tissue exhibiting a spectrum of hyaline cartilage, fibrocartilage, myxoid cartilage, and cartilage with ossification and even bone marrow formation, intimately associated with mature adipose tissue and vascular elements. The localization of these tumors was in the proximity of a bone, but not attached to the periosteum or in continuity with a joint. Because these lesions may be mistaken for other cartilaginous neoplasms of soft tissue, recognition of this entity has potentially important diagnostic and therapeutic implications in that mutilating surgery may be avoided. ",3 713,"Fluorescence assays to monitor membrane fusion: potential application in biliary lipid secretion and vesicle interactions. Membrane fusion constitutes an essential, intermediate step in numerous cell biological processes, occurring for example during endocytosis, membrane recycling and exocytosis. Also less desirable events such as the infection of cells by animal viruses are mediated by membrane fusion during which the viral envelope merges with a cellular membrane, causing the expulsion of the viral nucleocapsid into the cytoplasm of the cell as an initial step in virus replication. Much of our current knowledge concerning the mechanism of membrane fusion has been derived from studies using simple artificial membranes, such as liposomes or phospholipid vesicles, as model systems. A most essential feature of these studies has been the development of membrane fusion assays that register in a sensitive and continuous fashion the mixing of membranes or the aqueous volumes initially enclosed by these membranes. Not only do these assays allow one to readily detect and quantify fusion, but they also provide the possibility to relate the kinetics of fusion to the rate by which certain molecular changes in membranes take place. Obviously, this insight is of relevance for understanding the mechanism of membrane fusion. The principles and applications of some representative assays that rely on the use of fluorescence spectroscopy will be discussed. Assays that monitor membrane mixing are commonly based on the detection of changes in resonance energy transfer efficiency or the relief of fluorescence self-quenching of appropriate fluorescent lipid analogs. Contents mixing assays rely on either the formation of a (aqueous-soluble) fluorescent complex or quenching of a fluorophore, encapsulated in one vesicle population, by a suitable quencher, entrapped in a second population. ",5 367,"Validation of intermediate end points in cancer research. Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer. ",3 1838,"Determinants of the ventricular rate during atrial fibrillation. Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation. ",13 639,"Factors influencing the result of posterior spinal fusion in the treatment of adolescent idiopathic scoliosis. Sixty-six consecutive patients with adolescent idiopathic scoliosis treated by posterior spinal fusion using Harrington distraction compression instrumentation were followed for a minimum of 3 years. Initial surgical correction was satisfactory, but during the follow-up period, mean 4.4 years (3-5 years), there was a loss of correction. Several factors (age, sex, the number of vertebrae in the fusions, and the use of cross wires) were important influences on correction. A method of assessing the balance of a posterior spinal fusion is described that is useful when assessing radiographs. ",4 3072,"Internal mammary artery and saphenous vein graft patency. Effects of aspirin. As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD. ",22 185,"A newly established human osteosarcoma cell line with osteoblastic properties. A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice. Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells. The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium. The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium. The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells. Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes. However, the stimulation was not observed with a synthetic human thyrocalcitonin. When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced. The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes. HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production. ",3 2576,"HIV disease: a review for the family physician. Part I. Evaluation and conventional therapy. Family physicians will be challenged with caring for increasing numbers of patients infected with human immunodeficiency virus. After confirming the presence of the infection, the physician must follow a logical sequence of evaluation, counseling and treatment. The current Centers for Disease Control classification and a series of evaluation and treatment protocols form the basis for prescribing zidovudine to delay or mitigate involvement of T lymphocytes and neuronal cells. ",19 1835,"Simultaneous transesophageal atrial pacing and transesophageal two-dimensional echocardiography: a new method of stress echocardiography The diagnostic use of exercise echocardiography has been widely reported. However, transthoracic exercise echocardiography is inadequate in up to 20% of patients because of poor image quality related to exercise. In an attempt to overcome these limitations, a system was developed in which transesophageal echocardiography is combined with simultaneous transesophageal atrial pacing by means of the same probe. In a prospective study, transesophageal echocardiography was performed before, during and immediately after maximal atrial pacing in 50 patients with suspected coronary artery disease. Results of transesophageal stress echocardiography were considered abnormal when new pacing-induced regional wall motion abnormalities were observed. Correlative routine bicycle exercise testing was carried out in 44 patients. Cardiac catheterization was performed in all patients. The success rate in obtaining high quality diagnostic images was 100% by transesophageal echocardiography. All nine patients without angiographic evidence of coronary artery disease had a normal result on the transesophageal stress echocardiogram (100% specificity). Thirty-eight of 41 patients with coronary artery disease (defined as greater than or equal to 50% luminal diameter narrowing of at least one major vessel) had an abnormal result on the transesophageal stress echocardiogram (93% sensitivity). The sensitivity of the technique for one, two or three vessel disease was 85%, 100% and 100%, respectively, compared with 44%, 50% and 83%, respectively, for bicycle exercise testing; the 12 lead electrocardiogram (ECG) during rapid atrial pacing showed a sensitivity of 25%, 64% and 86%, respectively. Thus, rapid atrial pacing combined with simultaneous transesophageal echocardiography is a highly specific and sensitive technique for the detection of coronary artery disease. Ischemia-induced wall motion abnormalities were detected earlier than observed ECG changes. The technique appears to be particularly suited to patients who are unable to perform an active stress test or those with poor quality transthoracic echocardiograms. ",13 3009,"Rhodopsin mutants that bind but fail to activate transducin. Rhodopsin is a member of a family of receptors that contain seven transmembrane helices and are coupled to G proteins. The nature of the interactions between rhodopsin mutants and the G protein, transduction (Gt), was investigated by flash photolysis in order to monitor directly Gt binding and dissociation. Three mutant opsins with alterations in their cytoplasmic loops bound 11-cis-retinal to yield pigments with native rhodopsin absorption spectra, but they failed to stimulate the guanosine triphosphatase activity of Gt. The opsin mutations included reversal of a charged pair conserved in all G protein-coupled receptors at the cytoplasmic border of the third transmembrane helix (mutant CD1), replacement of 13 amino acids in the second cytoplasmic loop (mutant CD2), and deletion of 13 amino acids from the third cytoplasmic loop (mutant EF1). Whereas mutant CD1 failed to bind Gt, mutants CD2 and EF1 showed normal Gt binding but failed to release Gt in the presence of guanosine triphosphate. Therefore, it appears that at least the second and third cytoplasmic loops of rhodopsin are required for activation of bound Gt. ",22 1704,"Coronary artery dissection--a case report. Coronary artery dissection, both spontaneous and catheter-induced, is associated with a significant morbidity and mortality. The authors present a case of a middle-aged woman with spontaneous right coronary artery dissection causing inferior wall myocardial infarction and left coronary artery dissection at the time of coronary arteriography. It is suggested that emergency aortocoronary bypass surgery be performed preceded by insertion of an intra-aortic balloon in acute evolving cases where coronary anatomy is favorable to limit infarction and avert loss of life. ",13 3160,"Early magnetic resonance imaging in acute traumatic internuclear ophthalmoplegia. Adduction deficiency following acute head trauma may result not only from orbital damage but also from internuclear ophthalmoplegia, and in most instances this resolves over weeks to months. To date, noninvasive imaging studies during the acute phase following injury have not been definitive in localizing the pathology. Three cases of adduction deficiency following head trauma that were caused by internuclear ophthalmoplegia are reported. A lesion in the brain stem was found in all three cases by magnetic resonance imaging in the subacute post-traumatic period. These lesions were not visible on routine x-ray computed tomography obtained at the time of injury. ",22 465,"Colorectal tumors: an in vitro study of high-resolution MR imaging. To study the potential utility of magnetic resonance (MR) imaging in staging colorectal tumors, 15 resected colonic segments containing 17 elevated lesions were examined on a 1.5- or 1.9-T superconductive MR system. The whole intestinal wall was apparent as three or five layers on images obtained with a short repetition time (TR) and short echo time (TE) and as six or eight distinct layers, including the intestinal wall proper as well as an adherent mucus layer and an outer layer of pericolonic fat, on the long TR/TE images. In cases of colonic carcinoma, MR images correlated well with the pathologic findings, including the macroscopic growth pattern, depth of mural invasion, and the presence of foci of calcific tumor necrosis and pools of extracellular mucin (colloid). These features suggest that MR imaging may be valuable in the clinical evaluation of colorectal tumors. ",3 3127,"Delayed facial palsy following uncomplicated stapedectomy. We report six cases of partial lower motor neurone facial palsy occurring between four and ten days after uncomplicated stapedectomy. The aetiology is unclear but recovery was rapid and complete in all patients. ",22 988,"Rising mortality from cryptogenic fibrosing alveolitis. OBJECTIVE--To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN--A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES--Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS--The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS--The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology. ",7 1585,"Current results of elective aortic reconstruction for aneurysmal and occlusive disease. Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies. ",13 1269,"Lateral wall advancement in orbital decompression. Treatment of dysthyroid orbitopathy can be enhanced with a modified craniofacial approach using a lateral wall osteotomy, and anterolateral advancement and osteosynthesis in conjunction with medial and inferior wall orbital decompression. The technique of lateral wall advancement is described, and the results are discussed. While the authors advocate orbital decompression for dysthyroid optic neuropathy, advancement of the lateral orbital wall can easily be performed as an adjunct to the two- or three-wall decompression procedure. Advancement appears to increase the overall decompressive effect by providing a potential space where lateral expansion can occur and by enlarging the bony orbital volume. It also appears to lessen lid retraction and facilitates (and in some cases, obviates) the need for further lid retraction surgery. ",10 2785,"Whole-bowel irrigation as treatment for zinc sulfate overdose. A 16-year-old boy ingested approximately 50 zinc sulfate tablets (ZnSO4; 500-mg tablets). After spontaneous emesis, ipecac-induced emesis, and orogastric lavage, an abdominal radiograph performed four hours after ingestion still demonstrated approximately 50 ZnSO4 tablets within the stomach and three pills within the colon. Whole-bowel irrigation was begun with a polyethylene glycol lavage solution (PEG; Golytely) that was administered through a nasogastric tube; within one hour, the patient began producing a rectal effluent that contained pills. The patient remained asymptomatic throughout whole-bowel irrigation. Stool guaiac tests were negative. The serum chloride, however, increased from 105 to 127 mEq/L. Follow-up kidney, ureter, and bladder studies demonstrated the clearance of the zinc tablets from the gastrointestinal tract during the next 24 hours. ",20 2238,"The core polypeptide of cystic fibrosis tracheal mucin contains a tandem repeat structure. Evidence for a common mucin in airway and gastrointestinal tissue. A cystic fibrosis trachea cDNA library was constructed and probed with a synthetic oligonucleotide containing a consensus sequence recently identified in human intestinal mucin. One of the isolated clones, AMN-22, has been characterized extensively. The cDNA sequence of this 884-bp fragment was determined, and revealed a tandem repeat structure rich in threonine and proline residues. The repeating sequence of AMN-22 was similar but not identical to that determined for gut mucin. When examined by Northern analysis, the mRNA hybridizing to AMN-22 is extremely polydisperse in cystic fibrosis (CF) trachea, with apparent message length varying from approximately 2 kb to greater than 10 kb. A similar pattern was observed, with less abundant message, in CF bronchiectatic lung parenchyma. The lung cDNA hybridized to a similarly polydisperse message in ulcerative colitis colon RNA, but did not hybridize to control RNA from U937 lymphoma cells or stomach RNA. Pedigree analysis of restriction digests of genomic DNA revealed a pattern indicating a single polymorphic locus for the mucin gene expressed in the lung and the intestine. Southern analyses of human:mouse somatic cell hybrid cell lines allow a chromosomal localization for the mucin gene to human chromosome II, within the region 11p13-11pTer. Taken together, these data demonstrate that a polymorphic gene encodes a mucin core polypeptide expressed in both lung and intestine. ",15 1326,"Hemodialysis and the elderly patient: potential advantages as to quality of life, urea generation, serum creatinine, and less interdialytic weight gain. A total of 204 patients treated by maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were studied to ascertain how advancing age influences adaptation to uremia therapy. No difference in Karnofsky score was noted among patients over 70 years of age and two groups of patients, 16 to 59, and 60 to 69 years of age, respectively. In a subset of 33 hemodialysis patients studied midweek, it was noted that increasing age is associated with a lower serum creatinine concentration, lower interdialytic weight gain, and a lower urea generation rate. These three findings contribute to a relative ease in treating older uremia patients with hemodialysis or CAPD, as they tend to be stable and compliant relative to younger patients. ",11 1951,"Repair of supravalvar aortic stenosis: cardiovascular morphometric and hemodynamic results. Supravalvar aortic stenosis is associated with normal systolic pressure in the aorta and its branches with the singular exception of the coronary arteries, which are hypertensive. This uncommon lesion has been treated by patch aortoplasty of several types. We examined hemodynamics and morphometrics in 13 patients who underwent operation for supravalvar aortic stenosis from 1979 through 1988. They ranged in age from 2 to 43 years (mean age, 14.5 +/- 3.8 years [+/- standard error of the mean]). There were no operative deaths. Preoperative and postoperative (1 to 5 years) catheterization or echocardiography or a combination of these was done in all but 3 patients (1 died late suddenly without a postmortem examination; 1 was lost to follow-up; and 1 has not yet been restudied). Pressure gradients across the stenosis in patients treated with a single-sinus patch (n = 4) were 65 +/- 18 mm Hg preoperatively and 5 +/- 3 mm Hg postoperatively (p less than 0.05) and in patients with a bisinus patch (n = 6), 83 +/- 15 mm Hg preoperatively and 6 +/- 2 mm Hg postoperatively (p less than 0.05); the two groups were not significantly different. Measurements of the diameters of the coronary arteries, aortic annulus, and descending aorta were made, and calculation of the ratio of the coronary artery and annulus diameters to the descending aortic diameters both preoperatively and postoperatively was possible in 5 patients. The left coronary artery was larger than normal before and after operation. Preoperatively there was a disproportionate increase in left coronary artery and annulus size during systole. Left ventricular wall thickness decreased significantly postoperatively (p less than 0.05). Repair of supravalvar aortic stenosis (localized and diffuse) by both single sinus and bisinus patch repair is safe and hemodynamic results are good. ",13 1017,"Myogenic influences on the electrical auditory brainstem response (EABR) in humans. Two cases demonstrating the effects of myogenic artifact on the electrical auditory brainstem response (EABR) when using a promontory stimulation site are presented. Intensity-response functions were obtained in the unparalyzed condition, then repeated after infusion of a neuromuscular paralyzing agent. In both cases, the myogenic response was observed at lower stimulus intensities than the EABR components. As intensity increased, the myogenic responses grew at extremely rapid rates and made any subsequent identification of auditory responses virtually impossible. To alleviate the adverse influence of myogenic components, general anesthesia and a paralyzing agent must be incorporated into the test protocol when acquiring the EABR using a promontory site of stimulation. ",8 924,"Hydraulic conductivity of canine parietal pleura in vivo. The hydraulic conductivity (Lp) of the parietal pleura was measured in vivo in spontaneously breathing anesthetized dogs in either the supine (n = 8) or the prone (n = 7) position and in an excised portion of the chest wall in which the pleura and its adjacent tissue were intact (n = 3). A capsule was glued to the exposed parietal pleura after the intercostal muscles were removed. The capsule was filled with either autologous plasma or isotonic saline. Transpleural fluid flow (V) was measured at several transpleural hydrostatic pressures (delta P) from the rate of meniscus movement within a graduated pipette connected to the capsule. Delta P was defined as the measured difference between capsule and pleural liquid pressures. The Lp of the parietal pleura was calculated from the slope of the line relating V to delta P by use of linear regression analysis. Lp in vivo averaged 1.36 X 10(-3) +/- 0.45 X 10(-3) (SD) ml.h-1.cmH2O-1.cm-2, regardless of whether the capsule was filled with plasma or saline and irrespective of body position. This value was not significantly different from that measured in the excised chest wall preparation (1.43 X 10(-3) +/- 1.1 X 10(-3) ml.h-1.cmH2O-1.cm-2). The parietal pleura offers little resistance to transpleural protein movement, because there was no observed difference between plasma and saline. We conclude that because the Lp for intact parietal pleura and extrapleural interstitium is approximately 100 times smaller than that previously measured in isolated stripped pleural preparations, removal of parietal pleural results in a damaged preparation. ",7 2200,"Teratogenically induced fetal anomalies. A variety of infectious and physical agents, maternal diseases and altered metabolic states, and drugs and chemicals have been shown to cause postnatal structural or functional disabilities when embryonic or fetal exposure occurs during human pregnancy. These disabilities are potentially preventable through public education and awareness. Health-care providers must be equipped to collect relevant data regarding exposures of concern from their pregnant patients, locate and evaluate pertinent current teratology information resources, and sensitively counsel these women regarding the associated potential teratogenic risks. Comprehensive care of the patient exposed to a human teratogen may also include discussion of prenatal diagnostic procedures and other pregnancy management options. ",15 2830,"Unusual type of foreign body in the maxillary sinus. A broken end of the spear presenting as a foreign body in the nasopharynx and right maxillary sinus in a 19-year-old Papua New Guinean is described. The types of foreign bodies and their mechanisms of introduction into this site are summarized. ",20 2059,"Possible triggering of paroxysmal atrial fibrillation in normal hearts by psychological stressors: a report of two cases. Paroxysmal atrial fibrillation was triggered by psychological stress in two patients, both of whom had normal echocardiograms and coronary angiography. Neither patient was alcoholic or had ingested ethanol in relation to the onset of atrial fibrillation and both were free of metabolic derangements. Possible mechanisms involved in the triggering of atrial fibrillation are discussed. ",13 1112,"Auditory-evoked responses in benign intracranial hypertension syndrome. In this study, auditory brainstem-evoked responses were conducted on 28 patients with otologic symptoms (pulsatile tinnitus, hearing loss, aural fullness) secondary to benign intracranial hypertension syndrome. Abnormalities consisting mainly of prolonged interpeak latencies were detected in one third of these patients. It is speculated that the pathophysiologic mechanisms responsible for these auditory brainstem-evoked abnormalities are stretching-compression of the cochlear nerve and brainstem caused by the intracranial hypertension and/or primary edema of the same structures due to the benign intracranial hypertension syndrome itself. Normalization or improvement was noticed in the majority of the patients after management. Since the number of patients in this study is small, it is felt that the diagnostic and prognostic value of this test needs further evaluation. ",9 472,"Trends in conserving treatment of invasive carcinoma of the breast in females. This population-based study presents trends in the treatment of node-negative invasive carcinoma of the breast in females during the 1980s in the Detroit metropolitan area. It was done to determine whether or not there has been a significant shift toward conservation of the breast from 1980 to 1987. Trend analyses of surgical treatment, tumor size, node status, year of diagnosis, age and race were performed for 13,217 patients drawn from the Metropolitan Detroit Cancer Surveillance System. A significant increase in the use of conserving the breast was observed, with younger women receiving this treatment option more often than older women. Implications for a continuing shift in the biologic findings and treatment of carcinoma of the breast are discussed. ",3 1684,"Acebutolol effects on lipid profile [published erratum appears in Am J Cardiol 1990 Dec 1;66(19):A8] The relation between lipid profile and the incidence of coronary artery disease has been confirmed by the results of epidemiologic and intervention studies. Among antihypertensive agents, beta blockers, particularly those without intrinsic sympathomimetic activity (ISA), are generally reported to have negative effects on lipids, which may increase the risk of coronary artery disease. The ongoing Treatment of Mild Hypertension Study, now in its third year, has evaluated 847 patients to date with regard to lipid profile. Additional end points measured in this multicenter, randomized, controlled, double-blind study include blood pressure reduction and target organ deterioration. During the trial, all patients received nutritional and behavioral counselling to modify their diet, exercise habits and alcohol and sodium consumption to control their hypertension by nonpharmacologic means. In addition, some patients were randomized to receive low doses of 1 of the 5 classes of antihypertensive medication: acebutolol, a beta blocker with ISA (n = 124); amlodipine, a calcium channel blocker (n = 122); chlorthalidone, a diuretic (n = 125); doxazosin, an alpha blocker (n = 128); enalapril, an angiotensin-converting enzyme inhibitor (n = 127) or placebo (n = 221). At 1 year, acebutolol showed a statistically significant (p less than 0.001) decrease in total cholesterol (-12.7 mg/dl) compared with placebo (-5.2 mg/dl) and with chlorthalidone (1.0 mg/dl); a significant (p less than 0.001) decrease in low-density lipoprotein cholesterol (-6.0 mg/dl) compared with placebo (+0.7 mg/dl) and with chlorthalidone (+8.0 mg/dl) and no change in high-density lipoprotein cholesterol (-0.4 mg/dl). ",13 2611,"Computer assisted selection and assessment of antibodies in the diagnosis of lymphomas. With increasing numbers of reagents the problem of selecting appropriate antibodies to solve problems in the diagnosis of lymphoma is becoming more complex. One approach is to use a computer program to optimise the selection process. Such a program was devised, incorporating data from an extensive literature search. When presented with a differential diagnosis it selects the most appropriate antibody panel and when given the results evaluates the relative likelihood of each possible diagnosis. In a retrospective study 81% of the tests used had been non-discriminatory, but using the results of the remaining 19% of the tests, the computer was able to select the ""correct"" diagnosis with a high degree of certainty. The development and use of this system illustrated several problems in the application of computer assisted diagnostic techniques in histopathology. These problems include incomplete data and lack of understanding of the process of histopathological diagnosis. ",19 609,"A clinical epidemiological study in low back pain. Description of two clinical syndromes. In 100 patients with mainly chronic low back pain (LBP) signs and symptoms were evaluated prospectively and without preconceived expectation of particular findings. Two clinical syndromes were distinguished, both characterized by 'typical local tenderness' and associated with specific clinical features; these syndromes, described previously in the literature but receiving scant attention, were named the greater trochanteric pain syndrome (trochanteric bursitis) and the iliac crest pain syndrome (iliolumbar syndrome), and occurred in 35% and 43% of the patients, respectively. The recognition of these syndromes may enable us to study aetiology, prognosis, and therapy of LBP in more homogeneous groups of patients. ",4 986,"Effect of oral omeprazole on intragastric pH and volume in women undergoing elective caesarean section We have studied in obstetric patients the efficacy of omeprazole in increasing intragastric pH to more than 2.5 and reducing volume to less than 25 ml. Omeprazole 40 mg was given orally the night before and again on the morning of surgery to 30 Asian women scheduled to undergo elective Caesarean section. After induction of anaesthesia, a gastric tube was inserted and intragastric contents aspirated. Volume and pH were recorded and measurements were repeated on completion of surgery. The median (range) volume was 2 (1-13) ml before surgery and 4 (0-14) ml at the end of surgery. There was insufficient volume to measure pH in all patients. The median (range) pH was 6.7 (4.6-7.4) before surgery in 20 patients and 6.6 (4.6-7.8) at the end of surgery in 28 patients. No adverse drug reactions were noted in mothers or neonates. Omeprazole 40 mg orally twice before elective Caesarean section appeared to be effective in reducing intragastric volume and acidity to acceptable values. ",7 3090,"Myocardial revascularization for the third time. Clinical characteristics and follow-up. Twenty-five patients presenting for a third revascularization procedure were retrospectively reviewed at Loyola University Medical Center, Maywood, IL. This represents 0.5 percent of the total revascularization cases over a five-year period extending from 1985 through 1989. Perioperative mortality was none, and seven complications occurred in six patients. Internal mammary arteries were used for revascularization in 60 percent of this group. Follow-up reveals that only one patient has died secondary to an arrhythmia. All patients except one are symptomatically improved, and 18 patients remain angina free at a mean follow-up of 22.3 months. It is therefore concluded that patients are clinically improved with a third revascularization, and this procedure should be offered as an effective means of treatment. ",22 2553,"Coordinate secretion of interleukin-1 beta and granulocyte-macrophage colony-stimulating factor by the blast cells of acute myeloblastic leukemia: role of interleukin-1 as an endogenous inducer. Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1), IL-6, granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF alpha). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and GM-CSF, we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First, we observe a striking correlation between the levels of GM-CSF and IL-1 beta released by the cells. Thus, a high production of IL-1 beta is always concordant with a high production of GM-CSF and, conversely, low production of IL-1 beta is concordant with low levels of GM-CSF. Second, neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 alpha and -1 beta suppresses the release of GM-CSF by the cells. Third, neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth, the production of both IL-1 beta and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1, suggesting a positive regulation of autocrine growth factor production. Taken together, our results indicate that GM-CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML blasts, although IL-1 beta appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1 beta and GM-CSF, whereas each antibody alone has little effect on blast proliferation. Taken together, our results are consistent with the view that the production of IL-1 beta by AML blasts supports autocrine growth in culture, through induction of CSFs or other cytokines that stimulate blast proliferation. ",19 2252,"Aging and the skin: recognizing and managing common disorders. Senescent changes in structure and function of the skin and chronic solar radiation damage predispose the skin of the elderly to certain inflammatory and infectious diseases. In this context, the diagnosis and treatment of senile xerosis and pruritus are discussed, as are the common types of dermatitides, infections, and infestations. ",16 1040,"Myasthenia gravis. Myasthenia Gravis is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors. The disease is characterized clinically by variable weakness accentuated by repetitive muscular activity and usually responding to the administration of acetylcholinesterase inhibitors. Myasthenia Gravis is a complex disease and requires understanding of the many facets of its natural history and immunological basis to ensure optimal individual patient management. The long-term goal is control of the immunological imbalance; treatment regimens include thymectomy, corticosteroids, azathioprine, and plasmapheresis. The common use of acetylcholinesterase inhibitors provides symptomatic relief during variable daily muscular activity. Disability due to myasthenia gravis is to a large extent reversible and death is preventable. Early recognition of myasthenia gravis and appropriate treatment are often rewarded by remission that may be permanent. ",9 3002,"Effects of endotracheal suctioning on mixed venous oxygen saturation and heart rate in critically ill adults. The purpose of this multisite study was to determine the effects of endotracheal suctioning on mixed venous oxygen saturation (SvO2) and heart rate in 189 critically ill adults. One-pass, intermittent suction was applied for 10 or fewer seconds, with three prehyperoxygenation and three posthyperoxygenation breaths of 100% oxygen. Subjects at three hospitals (n = 127) underwent suctioning using hyperoxygenation with anesthesia bags and traditional suction catheters (open suction method). Subjects at one hospital (n = 62) underwent suctioning with hyperoxygenation by ventilator and in-line suction catheters (closed suction method). For subjects from all hospital sites combined, the SvO2 decreased from 67% to 64% (p = 0.001), a 4% change from baseline, and returned to baseline within 2 minutes. However, in subjects receiving the open method of suction, SvO2 dropped from 66% to 62% immediately after suctioning and returned to baseline within 4 minutes. In contrast, when the closed suction method was used, SvO2 rose from 67.7% to 67.86% immediately after suctioning, drifting upward to 71% for the next 2 minutes before dropping toward the baseline after 4 minutes. Mean heart rate increased from a baseline of 99 beats/min to 104 beats/min immediately after suctioning (p = 0.001), a 5% change from baseline, and gradually returned to baseline over the next 4 minutes. No significant differences were seen in heart rate between subjects having the open versus closed suction method. In conclusion, the closed suction method showed a higher SvO2 after endotracheal suctioning compared with the open suction method (p = 0.0001). Some form of hyperoxygenation before and after endotracheal suctioning is recommended. ",22 1471,"Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/l (IRP) The diagnostic value of vaginal sonography in combination with a discriminatory serum hCG level of 1000 iu/l (International Reference Preparation) was tested prospectively in 200 pregnant women suspected of having an ectopic pregnancy. An ectopic pregnancy was diagnosed in 68 women (34%), a miscarriage in 56 (28%) and a normal pregnancy in 76 (38%). On admission, an intrauterine sac was seen in 89% of the intrauterine pregnancies, but in none of the ectopic pregnancies. Detection of an adnexal mass separate from the ovaries was diagnostic of ectopic pregnancy with a sensitivity of 93%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 96%. In 19 patients (9%) the initial sonogram was non-diagnostic and the final diagnosis was obtained after a repeated scan within 6 days. Five of these women had an ectopic pregnancy, 12 a miscarriage and two a normal pregnancy. On admission the hCG level exceeded 1000 iu/l in 77% of all patients and in 67% of those with ectopic pregnancies. In patients with an initial level exceeding 100 iu/l, an intrauterine sac was found in all the intrauterine pregnancies but in none of the ectopic pregnancies. The use of this threshold in combination with sonographic detection of an adnexal mass was diagnostic of ectopic pregnancy with a sensitivity of 97%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 98%. ",12 458,"585 nm for the treatment of port-wine stains. Although the flashlamp-pulsed-dye laser has been successfully used for the treatment of port-wine stains (PWS) at 577 nm, a number of adult patients had incomplete clearance of their birthmarks with this treatment modality because of residual vessels lying beyond the 0.75-mm penetration depth of 577-nm irradiation. Fifteen adult patients, of whom nine were previously treated with limited success at 577 nm (group A), and six untreated patients (group B) were included in the study. For the group A patients, treatment with 585 nm produced successful clearance of the birthmark. For the six patients in group B, parallel treatment of different sites of the same lesion coupled with skin biopsies and histologic examination revealed that a change in the wavelength from 577 to 585 nm allowed the laser light to penetrate from the midreticular dermis into the subcutaneous fat. This explained the clearance achieved at 585 nm and not at 577 nm. ",3 2764,"Identification of the driver in two-rider motorcycle accidents. Inguinal contusion-laceration as an indication of the driver. In motorcycle accidents involving two riders, medicolegal identification of the driver is necessary when one or both riders die. It is particularly important in the latter case, because the survivor almost always insists that he or she was not driving. One characteristic injury that distinguishes the driver from the passenger is inguinal contusion-laceration (accompanied internally by pelvic fracture). This injury, caused by collision of the pelvis with the fuel tank, identifies the driver. ",20 1990,"The role of preoperative radionuclide ventriculography in defining outcome after revascularization of the extremity. Revascularization of the extremity was performed upon 110 patients after preoperative radionuclide ventriculography (RNVG). Mean ejection fraction (EF) was 50 +/- 13 per cent. Ventricular wall motion abnormalities were present in 46 per cent. Revascularization included inflow procedures, such as aortofemoral (n = 25) or extraanatomic bypass (axillofemoral or femorofemoral, n = 11); infrainguinal reconstruction, including femoropopliteal or distal bypass (n = 43), and other procedures to improve perfusion of the limb or correct complications after previous vascular reconstruction upon the extremity (n = 31). Perioperative (30 days) mortality rate was 0.9 per cent and 97.0 per cent of the patients were discharged alive from the hospital. Myocardial infarction (MI) occurred in 3.6 per cent, new ventricular arrhythmia in 1.8 per cent and congestive heart failure in 6.4 per cent of the patients during the perioperative period. During follow-up study (607 +/- 363 days), 7.3 per cent required major amputation, ipsilateral to reconstruction, 5.5 per cent required surgical or angiographic revision for hemodynamic failure of the reconstruction prior to thrombosis and 12.7 per cent thrombosed part or all of the reconstruction. Revascularization failure did not appear to be related to the level of cardiac function. Those with normal (greater than 50 per cent) EF had greater over-all survival by life table analysis than those with EF less than or equal to 50 per cent (p = 0.0006, Mantel-Cox test). Ventricular wall motion abnormalities were associated with reduced over-all survival (p = 0.008, Mantel-Cox test). The presence of angina or previous MI, singularly or in combination, did not have an adverse effect on over-all survival, whereas diabetes (p = 0.0058, Mantel-Cox test) and cigarette smoking (p = 0.0137, Breslow test) were associated with significantly diminished over-all survival. Preoperative RNVG can identify subgroups at a survival disadvantage after revascularization of the extremity in a population in which the presence of angina or previous MI does not predict survival. ",13 2,"Effect of blood transfusion on oxygen consumption in pediatric septic shock. Treatment plans for pediatric septic shock advocate increasing oxygen consumption (VO2). Recent studies in septic shock indicate that improving oxygen delivery (DO2) by increasing blood flow will increase VO2. We prospectively examined the effect on VO2 of improving DO2 by increasing oxygen content (CO2) with blood transfusion in eight hemodynamically stable septic shock patients. Transfusion consisted of 8 to 10 ml/kg of packed RBC over 1 to 2 h. Hemodynamic and oxygen transport measurements were obtained before and after blood transfusion. Transfusion significantly (p less than .05) increased Hgb and Hct from 10.2 +/- 0.8 g/dl and 30 +/- 2% to 13.2 +/- 1.4 g/dl and 39 +/- 4%, respectively (mean +/- SD). DO2 significantly (p less than .05) increased after transfusion (599 +/- 65 to 818 +/- 189 ml/min.m2), but VO2 did not change (166 +/- 68 to 176 +/- 74 ml/min.m2; NS). In pediatric septic shock patients, increasing CO2 by blood transfusion may not increase VO2. ",0 10,"Treatment of oral candidosis with itraconazole: a review. Oral candidosis is a common infection in infants, elderly persons, patients receiving immunosuppressive therapy, and patients with acquired immunodeficiency syndrome (AIDS). The orally active antifungal agent itraconazole has been evaluated in a number of different patient populations with oral and oropharyngeal candidosis. Initial studies have shown that itraconazole, 100 or 200 mg/day for 14 days, is more active than placebo in treating oral candidosis. A comparative study between itraconazole capsules (200 mg once daily) and clotrimazole troches (10 mg five times daily) showed equivalent results at the end of therapy but a significantly faster response to itraconazole and a faster relapse rate with clotrimazole. A study in AIDS patients with oropharyngeal candidosis demonstrated that itraconazole, 200 mg/day, and ketoconazole, 400 mg day, for 4 weeks give equivalent clinical cure rates and similar relapse rates. A pilot study with an oral solution of itraconazole has given an impressive 100% clinical and mycological response rate within 1 week of treatment. In conclusion, itraconazole in capsule or in solution form may constitute a major addition to the armamentarium of drugs against oropharyngeal candidosis. ",0 364,"Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17 beta-estradiol. The intracellular steady-state levels of methotrexate were previously shown to be reduced in estrogen receptor (ER)-negative human breast cancer MDA-MB-436 cells and ER-positive human breast cancer MCF7 cells following treatment with pharmacologically relevant concentrations of 17 beta-estradiol (E2). We now report that both E2 and tamoxifen (TMX) significantly decreased the fluidity of MCF7 and MDA-MB-436 cellular membranes. With E2 or TMX at concentrations greater than 1 microM, perturbations in membrane fluidity were accompanied by apparently non-ER-mediated cytotoxicity. Alterations in membrane structure may have contributed to the cytotoxicity of high-dose endocrine therapy and to the ability of E2 to inhibit methotrexate transport and cytotoxicity in some human breast cancer cells. ",3 2851,"Case management in addictions treatment. The need for case management in addictions treatment systems has been recognized for at least 10 years. As more attention is paid to developing this treatment component and as more data are available concerning the implementation of case management in addictions, it is becoming apparent that there is a lack of consensus concerning who should provide case management and how it should be defined. This paper reviews sources of variability of case management services identified in the mental health field and discusses the implications for the development of case management in addictions programs. ",20 2759,"Subxiphoid pericardiotomy versus echocardiography: a prospective evaluation of the diagnosis of occult penetrating cardiac injury. Diagnostic subxiphoid pericardiotomy (SP) is presently advocated for the diagnosis of occult cardiac injuries in patients with stable vital signs with juxta-cardiac-penetrating chest wounds. This approach, however, results in a reported 80% negative pericardial exploration rate. To investigate the reliability of bedside two-dimension echocardiography (2-D echo) in predicting cardiac injury as compared to SP, a prospective study was undertaken of patients with stable vital signs who were admitted with penetrating chest wounds that were located within the space bounded by the manubrium, nipples, and subcostal line. Initial evaluation of the patients with bedside 2-D echo was found to have a 96% accuracy, 97% specificity, and 90% sensitivity in predicting cardiac injury. The only false-negative findings were in a patient who consented to SP 18 hours after bedside 2-D echo was performed. The reliability of bedside 2-D echo compared to SP was not significantly different according to the kappa measure of reliability. These data suggest that bedside 2-D echo is an expeditious and reliable method to diagnose occult cardiac injuries during the initial assessment of a patient with stable vital signs who had penetrating chest trauma. This approach may allow for the selective use of SP on patients with positive bedside 2-D echo and could eliminate unnecessary surgical procedures. ",20 267,"Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study. Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death. ",3 271,"Human basophils express interleukin-4 receptors. Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed. ",3 1671,"Comparison of direct and indirect measures of systemic arterial pressure during weightlifting in coronary artery disease. Based on auscultation measurements after exercise, circuit weight training in cardiac patients has been reported to provoke minimal increases in systolic pressure. Direct (brachial artery catheter) and indirect (sphygmomanometry) measures of blood pressure were compared at rest, during lifting with the legs (approximately the fourth, ninth and fourteenth repetition) and during 2 minutes of recovery after lifting with the arms and legs. Subjects performed 15 repetitions of single-arm curl, single-arm military press and single- and double-leg press exercises at 40 and 60% of the maximum load that could be lifted once on a multistation weightlifting apparatus. Indirect measures of systolic pressure at rest were 13% less than those recorded directly (130 +/- 7 vs 149 +/- 8 torr; p less than 0.01); diastolic pressures were similar using either method. This pattern was maintained during lifting with the legs at both intensities, and after exercise with both the legs and the arms. The mean systolic pressure recorded indirectly immediately after exercise was 63 torr (31%) and 76 torr (34%) less than the average peak intraarterial value recorded during leg and arm exercises, respectively. The highest intraarterial pressures were generated during the final repetitions of the set; immediately after the last repetition, both systolic and diastolic pressures rapidly decreased. It is concluded that indirect estimates of systolic pressure are significantly less than true arterial values at rest, and during and after lifting. Moreover, indirect measurements after lifting do not allow accurate conclusions to be drawn about the arterial pressures generated during lifting because of the rapid decrease in pressure that occurs after exercise. ",13 1948,"Selection of patients with acute myocardial infarction for thrombolytic therapy PURPOSE: To critically review the current recommendations regarding the eligibility of patients with myocardial infarction for thrombolytic therapy. DATA IDENTIFICATION: Relevant studies published from January 1980 to January 1990 were identified through a computerized search of the English-language literature using MEDLINE and by a manual search of the bibliographies of all identified articles. STUDY SELECTION: All randomized, controlled trials of intravenous thrombolysis in acute myocardial infarction and unstable angina were reviewed. Smaller, observational studies and previous review articles were included when relevant to the discussion. DATA EXTRACTION: Key data were extracted from each article, including the proportions of patients eligible for thrombolysis, the reasons for exclusion from thrombolytic therapy, and the clinical outcomes of patients treated and of those excluded from treatment. The validity of certain exclusion criteria was examined using subgroup analysis from the large, randomized mortality trials of intravenous thrombolysis and observations from smaller, nonrandomized studies. RESULTS OF DATA SYNTHESIS: To date, relatively few patients with myocardial infarction have been considered eligible for fibrinolytic therapy. In this group, both early and late mortality have been significantly reduced. Patients excluded from thrombolysis, however, continue to have a high early mortality. The data suggest that the potential benefits of this treatment might be extended to selected high-risk subgroups. In particular, the risk-benefit ratio may favor the inclusion of otherwise healthy elderly patients; certain patients presenting more than 6 hours after the onset of symptoms; and patients with a history of controlled systolic hypertension or brief, nontraumatic cardiopulmonary resuscitation. The data do not support the use of fibrinolytic therapy as primary treatment in patients with unstable angina or suspected myocardial infarction in the absence of confirmatory electrocardiographic changes. CONCLUSIONS: The full potential of thrombolytic therapy to alter the natural history of acute myocardial infarction can only be realized through the continued evaluation of selection criteria and the identification and treatment of the greatest possible number of eligible patients. ",13 2784,"Interaction between whole-bowel irrigation solution and activated charcoal: implications for the treatment of toxic ingestions. STUDY OBJECTIVES: The purpose of this study was to address the issues of safety and efficacy of combining whole-bowel irrigation and activated charcoal administration for the treatment of toxic ingestions. STUDY DESIGN: Two in-vitro studies were performed. In the first, serial ratios of polyethylene glycol (PEG) and activated charcoal (AC) powders were added to water and the solutions were analyzed for PEG concentration and osmolality. In the second, serial ratios of a pharmaceutical bowel irrigation solution and an AC preparation were combined with a constant amount of salicylic acid. Solution osmolalities, PEG, and salicylic acid concentrations were then quantified. RESULTS: Adsorption of PEG powder by AC was demonstrated; however, changes in solution osmolality were negligible. Thus, concurrent administration of these therapies appears safe. However, combining bowel irrigation solution with AC resulted in decreased salicylic acid adsorption. This was especially so with smaller amounts of AC that would pertain more to the smaller doses of AC used for multiple-dose charcoal therapy. CONCLUSION: If these in-vitro data are applicable to overdose patients, the administration of a routine initial charcoal dose to those who will be treated with whole-bowel irrigation would be appropriate. However, it is unlikely that the addition of multiple-dose charcoal therapy to whole-bowel irrigation would provide additional benefit for the patient. ",20 994,"Methacholine responsiveness among working populations. Relationship to smoking and airway caliber. It has been suggested that the development of bronchial hyperresponsiveness (BHR) in some smokers may be an intermediate event in the progression to chronic obstructive pulmonary disease in this group. If this is true, prevalence data on BHR in a general population should show an independent association between BHR and smoking status. To test this, we analyzed BHR to inhaled methacholine in 654 white men without known asthma, in relation to smoking, skin-test reactivity, type of work (office versus industrial), and indicators of baseline airway caliber (FEV1 % predicted and FEV1/FVC). BHR was measured in the traditional way (PC20) and as the slope of FEV1 versus the methacholine concentration (linear scale). A PC20 of less than 16 mg/ml was considered ""responsive"" for analyses of this outcome. We found that although a positive skin test, smoking, and being an industrial worker all appeared to be significant predictors of increased BHR (p less than 0.05), once FEV1 (% predicted) and FEV1/FVC% were taken into account, none of these variables alone remained significantly associated with BHR. The strongest predictors of BHR were prechallenge FEV1 and FEV1/FVC (both p less than 0.01). The combination of smoking, atopy, and work groups, which identified a small subgroup of atopic smokers who were office workers, also remained significantly associated with increased BHR. We also used a regression model that allowed for comparison of predictors for BHR between the most responsive subset of the population (n = 84) and the remainder of the study population. ",7 1418,"Shortening of the hemodialysis procedure and mortality in ""healthy"" dialysis patients. The influence of shortening chronic hemodialysis on mortality was studied by following cumulative survival in ""ideal"" nondiabetic dialysis patients, who had no other diseases besides their renal disease when beginning dialysis. It was hoped that thereby problems of shortening dialysis could be separated from problems inherent in the patient. Otherwise healthy dialysis patients (n = 556) were divided into age groups (less than 50, 51-75, and greater than 75 years) and studied during four periods, 1966-75, 1976-82, 1983-85, and 1986-88. Dialysis time was shortened from 17 to 2.7 hr per treatment during that time, but a Kt/V of 1.3 maintained. Generally, both first- and four-year cumulative survival improved as dialysis was shortened, and four-year cumulative survival was best in all age groups during 1986-88 when dialysis was shortest. During this time, the four-year cumulative survival was no different from that of the age-matched total U.S. population. Shortening of dialysis time and increasing efficiency while keeping at least a 4.0, stable, weekly Kt/V has not been harmful to healthy patients on dialysis, but has led to continued improvement on cumulative survival. ",11 2455,"Continuous glucose for treatment of patients with type 1 glycogen-storage disease: comparison of the effects of dextrose and uncooked cornstarch on biochemical variables. Responses to uncooked cornstarch (UCS), dextrose (Dex), and a 3:1 mixture (UCS:Dex) were determined in seven children with type 1 glycogen-storage disease (GSD-1). UCS maintained blood glucose (BG) and serum insulin concentrations between 3.5 +/- 0.3 and 4.0 +/- 0.4 mmol/L (mean +/- SEM) and 50 +/- 7 and 79 +/- 22 pmol/L, respectively, in six of the seven patients for 4 h. Only four of seven patients completed the 4-h test after UCS:Dex (BG 2.9 +/- 0.3 mmol/L): After Dex, tests had to be stopped in all patients by 150 min after initiation (BG 2.7 +/- 0.4 mmol/L). Two methods of providing dietary glucose overnight, continuous intragastric glucose infusion (COG) and intermittent UCS at 2100 and 0200, were compared by monitoring metabolites and glucoregulatory hormones. The use of UCS in amounts equal to the calculated glucose production rate is an effective method of providing a continuous dietary source of glucose overnight to patients with GSD-1. ",17 649,"The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the ""classification tree"" method were 92% sensitive and 98% specific. The ""traditional format"" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands. ",4 1096,"Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea. An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA. ",9 1801,"The antihypertensive efficacy of hydrochlorothiazide is not prostacyclin dependent. We tested the hypothesis that vascular prostacyclin synthesis is stimulated by hydrochlorothiazide and could account for some of the drug's antihypertensive effect. We studied 13 patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin on hydrochlorothiazide's ability to lower blood pressure, alter body weight, stimulate plasma renin activity, and modulate vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), measured by GC/MS. Administration of hydrochlorothiazide, 50 mg daily for 2 weeks, was associated with a significant decrease in both systolic and diastolic blood pressure in both supine (systolic, 148 +/- 3 to 136 +/- 3 mm Hg; diastolic, 97 +/- 2 to 94 +/- 3 mm Hg) and upright (systolic, 151 +/- 4 to 131 +/- 2 mm Hg; diastolic, 103 +/- 2 to 97 +/- 3 mm Hg) positions. Hydrochlorothiazide administration resulted in a 1 kg weight loss and stimulation of plasma renin activity from 1.7 +/- 0.4 to 5.3 +/- 1.1 ng angiotensin I/ml/hr. However, the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was unchanged after administration of hydrochlorothiazide (86 +/- 13/ng/gm creatinine during placebo, 74 +/- 13 ng/gm during week 1 of hydrochlorothiazide, and 70 +/- 9 ng/gm during week 2 of the drug). Administration of indomethacin, 50 mg twice a day, resulted in greater than 60% inhibition of 2,3-dinor-6-keto-PGF1 alpha excretion but did not affect the antihypertensive response to hydrochlorothiazide. Indomethacin did not oppose the diuretic effect of hydrochlorothiazide as assessed by weight loss but did attenuate the rise in plasma renin activity. Our data demonstrate that the blood pressure-lowering effect of a thiazide diuretic does not require enhanced prostacyclin synthesis and the cyclooxygenase inhibitor indomethacin does not antagonize the antihypertensive efficacy of hydrochlorothiazide. ",13 133,"Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama. Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy. However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection. Recent studies indicate that a high percentage of certain groups of i.v. drug users and blood donors are infected with HTLV-II. Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama. To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians. The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions. A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen-capture and immunoblot assays, as well as mature HTLV particles. The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus. ",1 1198,"Neonatal monosodium glutamate abolishes corticotropin-releasing factor-induced epileptogenic activity in rats. Intracerebroventricular (i.c.v.) injection of rat corticotropin-releasing factor (rCRF) at doses of 5-20 micrograms in rats induces epileptogenic activity characterized by pacemaker-like spikes localized in the hippocampal leads. Such an effect was still present in rats neonatally treated with saline but was absent in those neonatally treated with monosodium glutamate (MSG), a treatment that caused marked changes in the concentration of several brain neurotransmitters and neuropeptides in hypothalamic nuclei where CRF is highly concentrated and is believed to induce endocrinologic and behavioral effects. The present results suggest the rCRF-induced spiking activity is mediated by activation of neuronal pathways sensitive to MSG neurotoxic effect. ",9 553,"Effects of FUdR on primary-cultured colon carcinomas metastatic to the liver. Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo. ",3 1776,"Blood pressure level, trend, and variability in Dunedin children. An 8-year study of a single birth cohort In a birth cohort of children in the Dunedin Multidisciplinary Health and Development Study in New Zealand, resting blood pressures were recorded biennially five times from age 7 to 15 years. Using previously described methods, we examined the level, trend, and variability of blood pressures in those children with at least three readings. The level, trend, and variability of height, weight, and body mass index were compared among six separate groups of children. Two groups were categorized on the basis of high systolic pressure levels, one with low variability and the other with high variability, which was thought to resemble adult labile hypertension. Two additional groups were categorized on the basis of increasing and decreasing blood pressure trends; the fifth group had consistently low blood pressures, and the sixth group consisted of the remaining children. There were significant differences among the groups for the level of all the physical measurements and for the trend of body mass index. No significant differences were found among the groups for gender or socioeconomic status. A parental history of high blood pressure, stroke, or heart attack was significantly more common in the first two groups. ",13 2538,"Antidiabetic agents. Although either insulin or oral hypoglycemics may be used in conjunction with diet and exercise in the management of type II diabetes, drug therapy for type I diabetes involves only insulin. C-peptide levels can be tested to assess whether the patient has remaining pancreatic endocrine function. Patients being started on insulin for the first time should receive a single injection of an intermediate-acting insulin of ""human"" origin at a dose of approximately 0.5 U/kg. Thereafter, fasting, mid-morning, mid-afternoon, bedtime, and possibly early morning blood sugars should be examined periodically to determine if the insulin dose needs to be increased, decreased, split, or if the patient needs to be on a two-insulin regimen. Intensive insulin therapy has become commonplace to control plasma glucose levels in the majority of patients receiving insulin therapy. Proper patient education regarding the insulin regimen, injection techniques, blood glucose monitoring, as well as diet, exercise, and foot care are essential if the patient's diabetes is to be controlled adequately. Guidelines for ""adequate"" glycemic control are outlined in Table 6. Recent evidence suggests that tight control of plasma glucose levels may decrease the macrovascular complications of diabetes. Although there is also evidence to suggest that the onset of microvascular complications might be delayed with strict glycemic control, the data are conflicting. The benefits of strict control must be weighted against the problems of hypoglycemia experienced by many patients who attempt tight control of their blood glucose levels. Biguanide compounds are available in Europe, but the sulfonylureas comprise the only class of oral agents in the United States commercially available for the treatment of type II diabetes. The two generations of these drugs reflect their potency and possible side-effect profiles. Of the first-generation agents, tolbutamide and chlorpropamide are the most widely prescribed. Tolbutamide is the weakest of the sulfonylureas, possibly making it a good drug for initiating oral therapy in the elderly. Chlorpropamide is becoming a less popular agent because of its long duration of action and its increased incidence of side effects. Of the second-generation agents, glyburide offers a better dosing schedule (once daily compared with twice daily for glipizide); however, glyburide may produce a greater incidence of hypoglycemia, particularly in the elderly or in patients with significant renal impairment. There are few good studies comparing these two drugs so that recommending one over the other is difficult. Drug interactions are numerous with the first-generation drugs, but less so with the newer second-generation agents.(ABSTRACT TRUNCATED AT 400 WORDS). ",18 1180,"Metoprolol for aggressive behavior in persons with mental retardation. Persons with mental retardation sometimes exhibit behaviors that are difficult to control. Use of neuroleptic medications may be limited by side effects or ineffectiveness. Beta blockers such as propranolol and metoprolol have been shown to decrease aggressive and impulsive behaviors in some patients with mental retardation. ",9 159,"Activated eosinophils increase vascular permeability and resistance in isolated perfused rat lungs The effects of eosinophils activated with phorbol myristate acetate (PMA) on isolated perfused rat lungs were examined. Eosinophils were obtained from lungs of rats infected with Toxocara canis by bronchoalveolar lavage, incubated with PMA, and administered to an isolated perfused rat lung preparation. Vascular endothelial permeability was assessed by measuring the capillary filtration coefficient (Kf,c) in the perfused lungs. In lungs receiving either no eosinophils (control) or nonactivated eosinophils, there were no changes in pulmonary hemodynamics or Kf,c. However, in lungs receiving 2 x 10(6) eosinophils activated with PMA, there was a transient 4.8-fold increase in pulmonary vascular resistance that peaked at 30 min, primarily due to the constriction of small arteries and veins. After the initial pressor response, Kf,c was increased to 7.5 times control at 130 min and resulted in marked lung edema, increased wet-dry weight ratios, and edema on histologic examination. Pulmonary arterial pressure and Kf,c responses were dose related for eosinophil numbers between 1 x 10(6) and 4 x 10(6) cells. Peak airway pressure (Paw) during constant tidal volume ventilation also increased in lungs receiving activated eosinophils compared to the control and nonactivated eosinophil groups. These findings indicate that activated eosinophils are potent effector cells and can cause pulmonary vasoconstriction, bronchoconstriction, and vascular endothelial injury without widespread plugging of capillaries by aggregated eosinophils. ",2 2732,"Paradoxes in the history of the anterior cruciate ligament. A historic review of anterior cruciate ligament (ACL) investigation reveals two important paradoxes. (1) Ideas and concepts recently proposed were first put forth much earlier. (2) Controversy regarding this ligament continues despite the increased amount of information available. Much of the recent ACL literature, although regarded as newly discovered, has its roots in far older, and apparently forgotten or overlooked, work. Examples include: (1) ACL intactness is best tested at full extension; (2) hemarthrosis and ACL rupture are closely associated; and (3) ACL rupture sometimes masquerades as a minor injury. Additionally, early investigators achieved notable advances in surgical techniques. These contributions disappeared from the literature for two major reasons. First, early investigators observed few patients, with typical practitioners rarely seeing ACL injuries, and consequently, little data existed to support their observations. Second, observations could not be confirmed until the advent of widespread, successful surgery. Undoubtedly, orthopedists now know much more about the ACL, yet many issues remain controversial. Does the ACL perform a vital function? What is the efficacy of operative versus nonoperative treatment? What are the relative merits of direct repair, intraarticular substitutes, and extraarticular nonanatomic procedures? The origins and continued existence of controversy stem from several sources, including the less than rigorous study design and the scarcity of natural history, long-term follow-up studies, and basic science studies. The perception of the ACL as a simple structural unit has also perpetuated this controversy. ",20 1246,"Aids for visual impairment. This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue. ",9 72,"Recombinant capsular antigen (fraction 1) from Yersinia pestis induces a protective antibody response in BALB/c mice. Yersinia pestis produces a glycoprotein capsule, the biosynthesis of which appears to be temperature dependent. The fraction I (F1) component of this capsule is specific to Y. pestis and the detection of F1 antibodies is the basis for several serological tests. We report the cloning of the F1 gene and its expression in Escherichia coli using the phagemid vector lambda ZAPII and a F1-specific monoclonal antibody. The recombinant F1 antigen had a molecular weight of 17 kDa, which proved to be identical to that of the F1 antigen produced by Y. pestis. The recombinant cells produced F1 antigen at 37 degrees C but only minimal amounts at 27 degrees C, suggesting that the genetic features affected by temperature in Y. pestis may be operating in the E. coli clone. It is not known if their similar molecular weights reflect the glycosylated nature of both proteins. F1 antigen purified from the E. coli recombinant induced a protective immune response in BALB/c mice challenged with up to 10(5) virulent Y. pestis. The resistance of immunized mice to plague infection correlated with high titers of F1 antibody. The cloned gene expresses an immunogenically competent F1 antigen suitable for use in plague serodiagnostics and vaccine development. ",0 2120,"Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution. The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo-treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy. ",13 2835,"Screening for psychiatric and substance abuse disorders in clinical practice. Psychiatric disorders, particularly depression and alcohol abuse, represent a large burden of illness to the society. Many individuals with these disorders receive all of their care from health care providers who are not mental health specialists. There is evidence that non-psychiatric physicians frequently do not recognize these disorders in their patients. Screening questionnaires have been introduced to improve detection of these patients. Several studies have found that these screening questionnaires can increase detection rates, but no important impact on patient outcomes has been demonstrated. This review article outlines several reasons why it has been difficult to discern improvement in patient outcomes: inadequate study design, insufficient physician education, interdependence of psychiatric and medical conditions, and vague treatment guidelines. Practical use of the current psychiatric screening questionnaires and key areas for further investigation are considered. ",20 1477,"Subzonal insemination for the alleviation of infertility. Methods were developed to facilitate the use of subzonal insemination to achieve fertilization in vitro. A clinical trial was undertaken in those patients having previously failed to achieve fertilization by in vitro fertilization, and in those presenting with severe oligospermia/oligoasthenospermia. From 85 patients, 585 oocytes were obtained. Of these, 0.3% had been ""activated"" parthenogenetically in vivo, 369 (72%) at metaphase II underwent subzonal insemination, 15% were fertilized, and 0.5% had three pronuclei. Thirty-eight percent of the patients had fertilization with 36% having a replacement. One conceptus was replaced in 19 patients, two conceptus in 8 patients, and three in 4 patients. A twin and two singleton pregnancies were established. ",12 243,"Endoscopic ultrasonography in staging rectal cancer. Endoscopic ultrasonography (EUS) was used to stage rectal cancer by assessing depth of invasion through bowel wall layers and/or involvement of lymph nodes. EUS findings were correlated with histopathologic findings to discern the usefulness of this modality in predicting which patients could be candidates for sphinctersaving procedures and the avoidance of abdominoperineal resection. The Olympus EU-M3 endoscopic ultrasound system was used to assess depth of penetration through rectal wall layers and to identify lymph nodes. Comparison of EUS findings to histopathologic findings was possible in 13 patients. EUS agreed with histopathology in 9 of 13 cases (69.3%) ( p = 0.07, kappa statistic). EUS agreed with histopathology as the presence or absence of lymph nodes in 9 of 13 cases (69.3%) (p = 0.07). However, the presence of lymph nodes could not necessarily predict metastatic involvement of these nodes. In one patient, invasion of vaginal cuff was correctly predicted. In nine cases, computed tomographic analysis (CT) was available for comparison to EUS in detection of penetration beyond the bowel wall. CT agreed with histopathology in 3 of 9 (33%), whereas EUS agreed with histopathology in 7 of 9 (78%). ",3 3315,"A retroviral promoter is sufficient to convert proto-src to a transforming gene that is distinct from the src gene of Rous sarcoma virus. The src genes of four natural isolates of avian sarcoma viruses differ from cellular proto-src in two genetic substitutions: the promoter of the cellular gene is replaced by a retroviral counterpart, and at least six codons from the 3' terminus are replaced by retroviral or heterologous cell-derived elements. Since virus constructs with a complete proto-src coding region failed to transform avian cells but acquired transforming function by point mutations of various codons, it has been proposed that point mutation is sufficient to convert proto-src to a transforming gene. However, promoter substitution is sufficient to convert two other proto-onc genes, proto-ras and proto-myc, to retroviral transforming genes. In view of this, we have reexamined whether promoter substitution, point mutation, or both are necessary to convert proto-src into a retroviral transforming gene. It was found that a recombinant virus (RpSV), in which the src gene of Rous sarcoma virus (RSV) was replaced by the complete coding region of proto-src, transformed quail and chicken embryo cells. The oncogene of RpSV differs from the src gene of RSV in three genetic properties: (i) it is weaker--e.g., transformed cells are flatter; (ii) it is slower--e.g., focus formation takes 9 to 12 days compared to 4 days for RSV; and (iii) its host range is narrower than that of RSV--e.g., only subsets of heterogeneous embryo cells are transformed by RpSV even after weeks or months. Replacement of the proto-src 3' terminus of RpSV by that of src from RSV generates a recombinant virus (RpvSV) that equals RSV in transforming function. It is concluded that a retroviral promoter, naturally substituted via illegitimate recombination with retroviruses, is sufficient to convert at least three proto-onc genes, src, myc, and ras, to retroviral transforming genes. ",22 1195,"Maxillofacial surgery and nasal CPAP. A comparison of treatment for obstructive sleep apnea syndrome Nasal continuous positive airway pressure (CPAP) is the primary therapy for obstructive sleep apnea syndrome (OSAS). Recent reports have indicated, however, that there is a small but significant number of failures related to patient compliance. Primary surgical treatment, which has been uvulopalatopharyngoplasty (UPPP), has declined because of poor results. A reviewed of UPPP failures has shown that while UPPP eliminated palatal obstruction, it failed to eliminate base of tongue obstruction. Maxillofacial surgery has been reported as treatment of OSAS by correcting base of tongue obstruction. Thirty patients with severe OSAS were evaluated to compare nasal CPAP and maxillofacial surgery. The goal was to determine if our surgical protocol was as effective as nasal CPAP. All patients initially underwent baseline diagnostic polysomnography to document OSAS. A nasal CPAP study was performed to determine the appropriate positive end-expiratory pressure. The patients in this study were using nasal CPAP, but they found it unacceptable as long-term treatment and elected surgery. Maxillofacial surgery consisted of maxillary, mandibular, and hyoid advancement. Polysomnography was performed six months following surgery and compared with the night 2 CPAP results. The parameters included in the investigation were the respiratory disturbance index (RDI), lowest SaO2, number of SaO2 falls below 90 percent, total sleep time (TST), REM sleep percent, stage 3-4 sleep percent, and wake after sleep onset. The mean RDI before treatment was 72.0 (SD 25.7). After completing therapy, the RDI from surgery and CPAP was 8.8 (SD 6.0) and 8.6 (SD 4.1), respectively. The mean low SaO2 prior to treatment was 61.0 (SD 13.5), and the CPAP results and postsurgical results were 86.2 (SD 5.5) and 86.1 (SD 4.2), respectively. An analysis of variance was used to examine the results, and there was no statistical difference between nasal CPAP and surgery for all respiratory variables. ",9 368,"Anti-idiotype monoclonal antibody carrying the internal image of ganglioside GM3. Murine anti-idiotype monoclonal antibodies were generated against a human IgM monoclonal antibody (L612) that recognizes ganglioside GM3 on human melanoma. Hybridomas secreting antibodies that bound specifically to L612 were selected by enzyme-linked immunosorbent assay using L612 and three negative control human IgMs, including monoclonal anti-GM2 and anti-GD2 antibodies, as well as purified serum IgM, as antigen sources. GM3-binding inhibition and cell-binding inhibition assays were used to identify seven anti-idiotype monoclonal antibodies that recognized determinants located within the antigen-combining sites of L612. To determine whether these anti-idiotype monoclonal antibodies possessed the internal image of the original antigen, we immunized syngeneic BALB/c mice with one of the anti-idiotype monoclonal antibodies, 4C10, coupled with keyhole limpet hemocyanin. Sera from the immunized mice reacted strongly with an antigen-positive M12 melanoma cell line and with purified GM3. Because L612 detects and kills melanoma tumor cells in vitro and in vivo in the presence of complement without affecting normal tissues, anti-idiotype monoclonal antibodies carrying the internal image of GM3 may be an effective tool for active specific immunotherapy in patients with melanoma. ",3 219,"Bilateral breast cancer. A second primary breast cancer in the opposite breast can be either synchronous or metachronous. The majority are metachronous. A woman who has had breast cancer has a fivefold increase in risk for a second breast cancer. Additional risk factors include multifocal cancer, lobular carcinoma in situ, and an original cancer at an early age with long survival. Lobular carcinoma in situ is predominantly a marker for the subsequent development of a second primary breast cancer. The incidence of synchronous bilateral cancer is approximately 1% to 2% and that of metachronous cancer 5% to 6%. The cancer can be invasive or noninvasive. Mammography has increased the number of synchronous cancers found but not the overall incidence. The incidence of invasive cancer detected by random biopsy of the opposite breast is not high enough to justify routine adoption of this procedure. The remaining breast must be followed for the remainder of the patient's life by physical examination and annual mammography. The treatment of the secondary primary breast cancer should be that appropriate for the stage of the disease. The prognosis for the woman with a second primary breast cancer is quite favorable and is dependent on the stage of both the first and the second cancer. ",3 153,"Ultrasonographical investigations of onchocerciasis in Liberia. The efficiency of ultrasonography (US) for the diagnosis and clinical characterization of onchocerciasis was evaluated. US was performed on 120 probands in Liberia. Ninety-two patients had generalized onchocerciasis, 21 patients suffered from the chronic hyperreactive form of onchocerciasis (sowda), and 7 probands served as controls. Patients were examined by US with linear (7.5 MHz and 5 MHz) and sector (3.5 MHz) scanners. US results were evaluated by examination of extirpated nodules. The US structure of nodules revealed a typical pattern consisting of a homogeneous echogenicity with small echodense particles and a lateral acoustic shadow, and differentiation from lymph nodes, lipoma, or fibroma was achieved. Within the onchocercomata, calcifications or fluid were identified. Regarding the estimation of the worm burden, it is important to note that in 24 patients, additional nodules not previously palpated were found by US. Also, the number of worm centers in palpable conglomerate nodules were determined more exactly by US than by palpation. In 4 of 16 sowda patients, impalpable nodules were found by US. In 13 patients with positive microfilaria counts, no nodules could be detected. The highly characteristic ultrasonographical pattern of onchocercomata may serve as a basis for further US investigations in onchocerciasis. ",2 2299,"The role of the immune system in the pathogenesis of psoriasis. Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed ""UM4D4."". This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen-independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti-UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis. ",16 1642,"Long-term follow-up in patients with incessant ventricular tachycardia. Seventeen patients with coronary artery disease, idiopathic dilated cardiomyopathy or no organic heart disease who presented with incessant ventricular tachycardia (VT) were studied and followed for a mean period of 51 +/- 35 months. In these patients the incessant VT included greater than or equal to 3 episodes of sustained VT at a rate of greater than or equal to 120 beats/min and frequent episodes of nonsustained VT over a 24-hour period. No patient had electrolyte disorder, prolonged QT interval, drug-induced arrhythmia or myocardial infarction less than 2 weeks old. Six patients died within 27 months of follow-up; 4 from sudden death and 2 from acute myocardial infarction. Three of the 11 surviving patients had remission of their VT within 1 week after the diagnosis of incessant VT. In 3 other patients in whom antiarrhythmic drugs were discontinued during follow-up because of adverse effects of the drugs or other medical reasons, 2 were found in remission. In the remaining 5 alive patients, deliberate attempts were made to discontinue the antiarrhythmic drugs; 4 of these patients were found in remission when the drugs were discontinued. Thus, 9 of these patients (53%) with incessant VT had remission over a mean follow-up of 55 +/- 34 months after discontinuation of the antiarrhythmic drugs. The probability of remission in patients surviving incessant VT warrants trials of discontinuation of antiarrhythmic drugs in these patients. ",13 1898,"ACE inhibition improves vagal reactivity in patients with heart failure. The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement. ",13 3207,"Intravenous diclofenac sodium. Does its administration before operation suppress postoperative pain? Intravenous diclofenac sodium was evaluated in a double-blind randomised trial relative to intramuscular diclofenac, intravenous fentanyl, and intramuscular placebo in 160 patients undergoing extraction of impacted lower third molar teeth. The test drug was administered before operation in an attempt to alleviate postoperative pain. A 10-cm visual analogue scale was used to assess pain at 30 minutes and one day after surgery, if the patients stayed overnight. Patients who received intravenous diclofenac had significantly less pain than the other groups 30 minutes after operation. They also had significantly less pain one day after surgery than the placebo or opioid groups, but not less than the intramuscular diclofenac group. Capillary bleeding time, in comparison with placebo, was significantly prolonged after the use of intramuscular diclofenac, and a similar but nonsignificant trend was observed in the intravenous diclofenac group. No problems were encountered with excessive bleeding in any group. ",22 2897,"A new orthosis for central cord syndrome and brachial plexus injuries. Proximal upper extremity weakness may develop secondary to central cord syndrome due to spinal cord injury or brachial plexus injury. Functional deficits, pain, decreased upper extremity arm swing during gait, and shoulder subluxation are common sequelae of these injuries. This report describes a new orthotic design that can be easily fabricated in two to four hours from readily available materials to compensate for these deficits. This orthosis allows for early participation in activities of daily living for patients with greater proximal than distal upper extremity weakness. The orthosis consists of a figure-eight shoulder harness and unilateral or bilateral forearm cuffs of orthoplast connected to the harness by flexible rubber tubing. The length of the tubing is adjustable through clamps connected to the forearm cuff to allow for variable arm positioning. Three patients, aged 14, 64, and 68, two with central cord syndrome and one with injury to the upper portion of the brachial plexus (Erb palsy) are described. Shoulder girdle musculature was less than 2, biceps less than 2, triceps less than 4, and hands less than 5 in all patients. Benefits from use of this orthosis may include improved arm swing and balance during ambulation, reduced shoulder pain and subluxation, and increased independence for tasks such as carrying lightweight objects, lower extremity dressing, bathing, light homemaking, and leisure activities such as gardening. ",20 1586,"Synchronous reconstruction for combined aortoiliac and femoropopliteal occlusive lesions. The role of proximal bypass. Between January 1984 and December 1986, 31 patients underwent synchronous revascularization (SR) because of the serious clinical condition of a lower limb and presence of arteriographically visible lesions. Average follow-up was 30 months. Operative mortality was 10%. Two patient populations were identified: Group I (N = 13): patients who underwent ilio-femoral or aorto-femoral proximal revascularization (PR); Group II (N = 18): patients who had axillo-femoral PR. Group I patients were younger than those in Group II (64 yr versus 72 yr; p less than 0.01). An association of pre-operative risk factors (arterial hypertension; coronary, renal or respiratory insufficiency) was twice as frequent in Group II as in Group I (p less than 0.02). The rate of SR compared to PR alone was 15%. However, there was no statistically significant difference between Groups I and II. Comparison of the actuarial survival curves for patients ahd the patency rates of SR in Groups I and II failed to reveal any statistically significant differences. Axillo-femoral bypass can be used for PR when SR is necessary in high risk patients. ",13 570,"Selective nonoperative management of patients referred with abnormal mammograms. Screening mammography provides a means of detecting clinically occult breast carcinoma, but the question of whether all abnormal mammograms require biopsy remains unanswered. We retrospectively reviewed records of 214 women referred over an 8-year period for abnormal mammograms. They were selectively assigned to biopsy or mammographic follow-up based on specific mammographic criteria. Of 114 women initially observed mammographically, 2 were later found by biopsy to have carcinoma. Initial assignment to mammographic observation delayed the recommendation for biopsy 3 and 12 months, respectively, in these patients, but no effect on outcome was documented. Because they have benign lesions by clinical and mammographic criteria, 102 women (53%) have been spared biopsy; they continue to be monitored closely. We believe these data support the use of a selective approach to biopsy based on specific mammographic criteria. ",3 1654,"Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling. ",13 1811,"A randomized trial comparing direct current therapy and bipolar diathermy in the outpatient treatment of third-degree hemorrhoids. Fifty patients with third-degree hemorrhoids were randomized to receive outpatient treatment with either bipolar diathermy or direct current therapy. Direct current therapy was used to treat 26 patients and bipolar diathermy was used to treat 24 patients. Twenty patients in each group were successfully treated as judged by resolution of symptoms and shrinkage of hemorrhoidal tissue. Both treatments are effective in the outpatient management of large, prolapsing hemorrhoids. Bipolar diathermy is less time consuming and better tolerated. ",13 2118,"Ventricular stroke work loss: validation of a method of quantifying the severity of aortic stenosis and derivation of an orifice formula Because aortic stenosis results in the loss of left ventricular stroke work (due to resistance to flow through the valve and turbulence in the aorta), the percentage of stroke work that is lost may reflect the severity of stenosis. This index can be calculated from pressure data alone. The relation between percent stroke work loss and anatomic aortic valve orifice area (measured by planimetry from videotape) was investigated in a pulsatile flow model. Thirteen valves were studied (nine human aortic valves obtained at necropsy and four bioprosthetic valves) at stroke volumes of 40 to 100 ml, giving 57 data points. Valve area ranged from 0.3 to 2.8 cm2 and mean systolic pressure gradient from 3 to 84 mm Hg. Percent stroke work loss, calculated as mean systolic pressure gradient divided by mean ventricular systolic pressure x 100%, ranged from 7 to 68%. It was closely related to anatomic orifice area with an inverse exponential relation and was not significantly related to flow (r = -0.15). An orifice formula was derived that predicted anatomic orifice area with a 95% confidence interval of +/- 0.5 cm2 (orifice area [cm2] = 4.82 [2.39 x log percent stroke work loss], r = -0.94, SEE = 0.029). These results support the clinical use of percent stroke work loss as an easily obtained index of the severity of aortic stenosis. ",13 2080,"Physiologic peripheral pulmonic stenosis in infancy. We studied 14 premature infants with the clinical diagnosis of peripheral pulmonic stenosis (PPS) and 15 normal full-term neonates by echocardiographic Doppler examinations. The PPS group had an average main pulmonary artery (PA) diameter similar to the control group (0.91 vs 0.96 cm, difference not significant), but had smaller branch PA diameters: right PA = 0.41 vs 0.50 cm, p less than 0.001, and left PA = 0.41 vs 0.49 cm, p less than 0.001. The PPS group also had greater peak velocities in the main PA (76 vs 63 cm/s, p less than 0.05), right PA (193 vs 118 cm/s, p less than 0.001) and left PA (187 vs 123 cm/s, p less than 0.001). Similarly, the ratio of peak velocity in the branch/main PA was greater for the PPS group: right/main PA peak velocity = 2.91 vs 1.92, p less than 0.01, and left/main PA peak velocity = 2.73 vs 1.99, p less than 0.05. The calculated right ventricular output for the PPS group was more than the control group: 437 vs 261 ml/min/kg, p less than 0.001. Hematocrits were not done on the control group, but the PPS group had an average hematocrit which was low (34%). It is concluded that patients with PPS have mild underdevelopment of the PA branches, with consequent increased flow velocity and turbulent flow. This turbulent flow may be contributed to by increased cardiac output and mild anemia. ",13 2758,"Inadequate granulopoiesis after major torso trauma: a hematopoietic regulatory paradox. Late postinjury sepsis is largely the result of defective host defense including failure to maintain an adequate number of functioning phagocytic cells. In this study we used stem cell culture techniques to measure colony-stimulating activity and have quantitated the number of circulating myeloid stem cells to see if defects in granulopoiesis occur after major torso trauma. Forty-two acutely injured patients (13 blunt and 29 penetrating injuries; mean age, 29.7 years) undergoing laparotomy with an abdominal trauma index of 15 to 40 were studied prospectively. Blood samples were obtained on days 1, 5, and 10. Patients were segregated by injury severity: abdominal trauma index less than 25 (n = 25) versus abdominal trauma index greater than or equal to 25 (n = 17). The more severely injured (abdominal trauma index greater than or equal to 25) patients had fewer circulating granulocytes and monocytes. Colony-stimulating activity was below normal control levels in all patients and was decreased further with increased injury severity. The more severely injured patients had a blunted bone marrow response (significantly fewer circulating myeloid stem cells) and suffered more major septic complications (24% vs 8%). In conclusion, major trauma to the torso causes a paradoxic depression in granulopoiesis that worsens with increased injury severity and may contribute to late septic morbidity. This colony-stimulating activity deficiency state is similar to that seen after major burns and may be amenable to future modulation. ",20 2852,"The role of buspirone in the management of alcohol withdrawal: a preliminary investigation. One hundred eighteen patients, 77 men and 23 women ranging in age from 18 to 70 years of age, admitted to an inpatient facility in Central New York were administered buspirone HCl for treatment of the alcohol withdrawal syndrome. Although one patient had an unwitnessed seizure, none of the subjects required discontinuance of buspirone HCl because of symptoms of dizziness, nausea, headache, nervousness, or lightheadedness, typical side effects described by the manufacturer. All but one of the individuals given buspirone HCl for alcohol detoxification completed that phase of treatment within six days in a manner which effectively controlled their withdrawal symptoms. The findings were suggestive of an important role for buspirone HCl in the detoxification of the alcohol-dependent patient using a pharmacologic agent other than traditional medications such as benzodiazepines, phenobarbital, beta blockers, magnesium sulphate, or clonidine. ",20 1498,"Objective tocodynamometry identifies labor onset earlier than subjective maternal perception. The ability of women instructed in self-detection of uterine contractions to identify the abrupt rise in uterine activity known to precede the onset of labor has not been evaluated. This study was designed to assess the temporal relationship between objective uterine activity monitoring, subjective maternal perception of uterine activity above a commonly used threshold value (four or more contractions per hour), and progressive cervical change. Daily tocodynamometry (7-9 AM) was recorded in 79 women with preterm premature rupture of the membranes from admission until the onset of spontaneous labor (5.3 +/- 6.3 days). The subjects were at bed rest, received no tocolytic therapy, and were instructed in the signs of labor and uterine self-palpation. Patients simultaneously provided a subjective assessment of uterine activity (four or more contractions per hour). The majority of uterine activity recordings (78%) revealed fewer than four contractions per hour, and the patients' subjective reports agreed in almost all instances (97.6%). On 91 days, four or more contractions per hour were recorded objectively, but the patients' subjective reports agreed in only 25 instances (27%). On the day of labor onset, significantly more women had an objective assessment (32%) (P less than or equal to .01). Patients subjectively identified labor onset 10.6 +/- 6.7 hours after objective monitoring indicated increased uterine activity, and when subjectively identified, both cervical dilatation (4.9 +/- 2.5 cm) and effacement (85 +/- 30%) were significantly advanced (P less than or equal to .001) compared with the admission examination (1.1 +/- 1.2 cm; 20 +/- 30%). ",12 3210,"Nitrous oxide and epinephrine-induced arrhythmias. We asked whether the sympathomimetic effect of nitrous oxide (N2O) predisposed patients receiving N2O to arrhythmias in response to epinephrine administration. We also asked whether aging contributed to the development of arrhythmias, with or without N2O. One hundred patients having transsphenoidal hypophysectomy were randomly assigned to receive anesthesia including (n = 49) or excluding (n = 51) N2O. All patients were given an injection of epinephrine 1:200,000, with 0.5% lidocaine to produce hemostasis. Using intermittent 12-lead and continuous lead II electrocardiography, we determined the incidence of premature ventricular contraction, isorhythmic atrioventricular (AV) dissociation, and changes in T-wave morphology. Patients given N2O had a significantly higher incidence of isorhythmic AV dissociation (61.2% vs 41.2%). A trend toward a higher incidence of multiple premature ventricular contractions (16.3% vs 7.8%) was not statistically significant. Both anesthetic groups had a high incidence of postoperative changes in T-wave morphology (46.9% in the N2O group vs 50.9% in the group not given N2O). Aging alone did not affect the incidence of ventricular ectopic beats, isorhythmic AV dissociation, or changes in electrocardiographic morphology, but correlated with the development of ventricular ectopy during N2O anesthesia. We conclude that the use of N2O correlated with a higher incidence of isorhythmic AV dissociation in response to injection of epinephrine with lidocaine. ",22 2493,"Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig. Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis. ",17 3311,"Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region A deletion DNA rearrangement is associated with immunoglobulin class switching from IgM to IgG, IgA or IgE This recombination occurs in immunoglobulin switch regions, which are complex, highly repetitive regions of DNA. As switch regions become transcriptionally active just before switch recombination, analysis of the behaviour of these sequences during transcription could elucidate the mechanism of switch recombination. Here, we report that transcription of a supercoiled plasmid containing the murine IgA switch region (S alpha) leads to a loss of superhelical turns. The resulting series of less supercoiled plasmids is stabilized by RNA-DNA hybrids formed by the nascent RNA transcripts, which remain base-paired with their DNA templates. ",22 2695,"Regular inhaled beta-agonist treatment in bronchial asthma 89 subjects with stable asthma took part in a double-blind, placebo-controlled, randomized, crossover study of the effects of regular versus on-demand inhaled bronchodilator therapy. The subjects inhaled fenoterol or placebo by a dry powder delivery system for 24 weeks. Control of asthma was judged by daily morning and evening peak expiratory flow rates, symptom diaries, use of additional inhaled bronchodilator, and requirement for short courses of prednisone. Of 64 subjects who completed the trial, 57 showed a clear difference in degree of control of asthma between the fenoterol and placebo periods: in 17 (30% [95% confidence interval 18.4-43.4%]) asthma was better controlled during regular inhaled bronchodilator treatment, whereas in 40 (70% [56.6-81.6%]) control was better during placebo treatment with bronchodilator for symptom relief only. Mean airway responsiveness to methacholine increased slightly during the fenoterol period. The adverse effect of regular bronchodilator inhalation occurred not only among subjects who used a bronchodilator as sole treatment (2 were better and 10 were worse during regular bronchodilator treatment) but also among those who took inhaled corticosteroids (14 were better and 29 were worse). Thus, regular inhalation of a beta-sympathomimetic agent was associated with deterioration of asthma control in the majority of subjects. The trends to use of regular, higher doses or longer-acting inhaled beta-sympathomimetic treatment may be an important causal factor in the worldwide increase in morbidity from asthma. ",19 574,"Enhanced expression of c-myc and H-ras oncogenes in Letterer-Siwe disease. A sequential study using colorimetric in situ hybridization. Tissues from two patients with disseminated histiocytosis X (Letterer-Siwe disease) in which histiocytosis X cells exhibited histologic and cytologic features of malignancy were evaluated by in situ hybridization with the use of biotinylated nucleic acid probes to c-myc and H-ras oncogenes. Enhanced expression of these oncogenes was observed in mononucleated and multinucleated cells of histiocytosis X in the terminal proliferative phase but not in the early quiescent phase of Letterer-Siwe disease in both patients. Our findings indicate that deregulation of c-myc and H-ras in histiocytosis X are late events that likely confer a selective growth advantage to histiocytosis X cells. ",3 2333,"Extracellular collagenase, proteoglycanase and products of their activity, released in organ culture by intact dermal inflammatory lesions produced by sulfur mustard. Peak (1 and 2 d) and healing (3, 6, and 10 d) inflammatory lesions were produced in rabbits by the topical application of the military vesicant, bis(2-chloroethyl)sulfide, commonly called sulfur mustard (SM). SM produces an acute sterile dermal inflammatory reaction with little or no necrosis, except in the epidermis, which dies during the first day. After an animal was killed, its lesions were excised intact, as full-thickness 1.0-cm2 explants. They were then organ-cultured for 3 d in order to maintain the viability of both local and infiltrating cells. The extracellular fluid in each lesion equilibrated with the culture fluid, which was collected daily and analyzed for collagenase and proteoglycanase activities. These metalloproteinase activities were measured after we had i) destroyed the alpha-macroglobulin inhibitors with KSCN, ii) destroyed the tissue inhibitor of metalloproteinases (TIMP) by reduction and alkylation, and iii) activated the latent proteinase activity with aminophenylmercuric acetate (APMA). Hydroxyproline-containing peptides and glycosaminoglycans (GAG) released into the culture fluids were also measured as indicators of local collagenase and proteoglycanase activity within the inflammatory lesions. In general, the levels of both the metalloproteinases and the products of their activity were higher in second- and third-day culture fluids than in first-day culture fluids, and higher in fluids from SM lesions than in those from normal skin. The activated fibroblast was apparently the major cell type producing the collagenase and proteoglycanase. The hydrolysis of collagen and ground substance occurs pericellularly. An excess of inhibitors exists outside the pericellular region. The daily change in culture fluids apparently decreased such inhibitors, so that by the second and third day of culture we could detect the changes in pericellular enzyme activity that were not detectable on the first day of culture. As the inflammatory lesions healed, the extracellular enzyme products (hydroxyproline and GAG) increased more than the enzymes that produced these products. With healing, a decrease occurs in the extravasation of all serum components, especially the large ones such as the alpha-macroglobulin inhibitors. We propose that during healing, the decrease in these inhibitors allows the metalloproteinases to begin the remodeling process, and that during the peak phase of inflammation, these same inhibitors protect extracellular matrix against hydrolysis by such proteinases. ",16 914,"Peak flow nasal patency indices and self-assessment in septoplasty. The present study evaluates the results of septoplasty monitored by the objective peak flow nasal patency indices and the subjective patient self-assessment scores of nasal obstruction. Mini-Wright peak flow meters were used. The peak flow nasal patency index was defined as the ratio between nasal and oral peak flow rates. Uni and bi-lateral, as well as ex and in-spiratory, indices were calculated. Both peak ex and in-spiratory flow nasal patency indices were significantly increased 1 and 6 months post-operatively, indicating improved nasal patency. The most marked post-operative increase of the nasal patency indices was seen for the preoperatively worst airway and the total airway. A weak significant positive correlation was found between the peak flow nasal patency indices and the patient mean self-assessment scores of the uni and bi-lateral nasal obstruction. The change of the peak flow nasal patency indices measured 6 months post-operatively correlated well with the patient overall assessment of the operative changes of the total nasal patency. The method was found quick and easy to handle in monitoring the effect of functional septoplasty and is recommended as an alternative to rhinomanometry. ",7 734,"The influence of sclerotherapy on gastric mucosal blood flow distribution. Hemodynamic events and structural vascular changes of the gastric mucosa in cirrhotics have caught the attention of investigators in the recent past, but as yet it is not known whether therapeutic interruption of variceal blood flow at gastroesophageal level alters such portal hypertensive mucosal features. The newly developed endoscopic laser-Doppler technique was used to assess whether variceal eradication by means of endoscopic sclerotherapy influences the gastric mucosal congestion in portal hypertension patients. Gastric mucosal blood flow was determined at ten defined sites of the stomach, before the first session of sclerotherapy and after complete variceal eradication had been achieved in 15 patients. A statistically significant decrease (P less than 0.01 to 0.05) in microcirculation was found at the gastric antrum and corpus, an increase at the pylorus (P less than 0.05), but no change in the fundic area. An important question following these findings is: What are the consequences of such aggravation of gastric congestion on the integrity of the gastric mucosa?. ",5 935,"Prediction of postoperative clinical course by autologous tumor-killing activity in lung cancer patients. Fifty patients with primary localized lung cancer were tested at the time of surgery for the ability of their lymphocytes to kill autologous, freshly isolated tumor cells, and the assay was evaluated for prognostic significance. Peripheral blood lymphocytes of 27 patients (54%) demonstrated significant autologous tumor-killing activity in 6-hour 51Cr-release assays. Twenty-three of the 27 patients with autologous tumor-killing activity remained tumor free and survived more than 5 years after curative surgery, while all 23 who were negative for autologous tumor-killing activity relapsed by 18 months after surgery and died within 42 months after surgery. The differences in survival curves for the two groups were highly significant (P less than .00003). Autologous tumor-killing activity was not correlated with natural killer (NK) cell activity against K562 human myeloid leukemia cells or proliferation of lymphocytes stimulated with autologous, freshly isolated tumor cells in mixed culture. There were no differences in total survival between patients with positive results and those with negative results in tests of NK cell activity and autologous mixed lymphocyte-tumor culture reaction. These results indicate that autologous tumor-killing activity is a meaningful prognostic indicator and provide evidence for immunological control of tumor growth and metastasis. According to our preliminary data, it is unlikely that lung cancer patients who remain tumor free after 60 months of follow-up will develop recurrence or die from the disease. We are conducting a study to determine whether induction of autologous tumor-killing activity before surgery, by treatment with biological response modifiers,can improve the clinical outcome in patients who do not naturally have this potential. ",7 1566,"Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium. Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals. ",13 3163,"Pre-discharge immunization among hospitalized Filipino children. Identifying opportunities to vaccinate eligible children is one way to boost rates of immunization especially in countries with low immunization coverage and where convalescence from infectious illness is a contraindication to vaccination. To determine the safety and immunogenicity of diphtheria-tetanus toxoid-pertussis and oral polio immunization, 210 convalescing infants and children and community controls, comparable image and nutritional status, were studied. Using the pertussis agglutination and poliovirus neutralization tests, quantitative serologic responses were compared in the two study groups. No significant differences in the incidence rates of febrile reactions (23% in controls; 28% in convalescents) of local reactions (92% in controls; 87% in convalescents) and of seroconversion (P greater than 0.05) were noted between the two groups. Our investigation suggests that infants and children convalescing from infectious illnesses can be safely and effectively vaccinated. This study further suggests that hospitalization provides an opportunity to vaccinate such children. ",22 2226,"Aortic atresia: survival to adulthood without surgery. Aortic atresia is a rare congenital cardiac defect. It usually leads to death in the neonatal period. A patient with aortic atresia has survived to the age of 24 years without any surgical procedure. In view of the uncertain results of reconstructive surgery this case may have therapeutic implications. ",15 1916,"Exercise test predictors of ambulatory silent ischemia during daily life in stable angina pectoris. The predictive value of several exercise test parameters in identifying stable angina patients at risk of silent myocardial ischemia during daily life were examined. A total of 97 patients with coronary artery disease, stable angina and ambulatory electrocardiographic data were evaluated. Of the 86 patients with a positive exercise test, 39 (group 1) had greater than or equal to 1 episodes of ST-segment depression and 47 (group 2) did not develop ST changes during ambulatory electrocardiographic monitoring. Comparison of the exercise test parameters between the 2 groups revealed early onset of ischemia during exercise tests as the single most significant (p less than 0.0005) predictor of ambulatory silent ischemia. The other exercise test parameters showing significant differences between the 2 groups were the peak exercise heart rate (117 +/- 23 vs 126 +/- 20 beats/min, p less than 0.05) and peak systolic blood pressure (160 +/- 27 vs 176 +/- 27 mm Hg, p less than 0.01), both of which were significantly lower in the group 1 patients. These data were used to derive simple mathematical formulas for calculating the risk of ambulatory silent ischemia. These results demonstrate that stable angina patients at risk of silent ischemia during daily life can be accurately identified by evaluation of selected exercise test parameters. ",13 3206,"Minitracheotomy: complications and follow-up with fibreoptic tracheoscopy. Complications and changes in tracheal mucosa after minitracheotomy were evaluated in 28 patients. Tracheal mucosa was inspected fibreoptically after the insertion of a minitracheotomy cannula, and then at 3-day intervals until the cannula was removed. Thereafter, assessments were made every third day until the mucosa was considered normal. Three significant complications occurred: mediastinal puncture, paratracheal entrance of the cannula and subcutaneous emphysema. Difficulties at insertion of the minitracheotomy cannula were encountered in 15 of 28 patients (54%). Air flow detected through the cannula in one patient, and lack of air flow in another patient, were misleading signs of the position of the cannula. Passing a suction catheter in three patients and a normal end-tidal carbon dioxide tracing in one patient, were also found to be misleading. The correct position and possible complications could be verified only by fibreoptic tracheoscopy. Changes in the tracheal mucosa were independent of the duration of minitracheotomy therapy. ",22 217,"Management of local and regional recurrence after mastectomy or breast-conserving treatment. Locoregional failures after primary treatment for breast cancer include a diverse group of lesions that represent different categories of failures with various prognoses. Although patients with chest wall recurrences and regional nodal failures after traditional radical surgery have a poor prognosis, many patients can still achieve a significant degree of palliation and even long-term survival or cure with carefully orchestrated multimodal treatment. In patients who have breast failures after breast-conservation surgery and radiation, long-term salvage and cure can be achieved for the majority with prompt detection and appropriate treatment, which, like treatment for primary breast cancer, includes a consideration not only of local control but also of the risk of subsequent systemic failure and its need for treatment. ",3 2710,"Disease control priorities in developing countries: health policy responses to epidemiological change. Health systems in developing countries are facing major challenges in the 1990s and beyond because of a growing epidemiological diversity as a consequence of rapid economic development and declining fertility. The infectious and parasitic diseases of childhood must remain a priority at the same time the chronic diseases among adults are emerging as a serious problem. Health policymakers must engage in undertaking an epidemiological and economic analysis of the major disease problems, evaluating the cost-effectiveness of alternative intervention strategies; designing health care delivery systems; and, choosing what governments can do through persuasion, taxation, regulation, and provision of services. The World Bank has commissioned studies of over two dozen diseases in developing countries which have confirmed the priority of child survival interventions and revealed that interventions for many neglected and emerging adult health problems have comparable cost-effectiveness. Most developing countries lack information about most major diseases among adults, reflecting lack of national capacities in epidemiological and economic analyses, health technology assessment, and environmental monitoring and control. There is a critical need for national and international investment in capacity building and essential national health research to build the base for health policies. ",19 1551,"The determination of aortic valve area by the Gorlin formula: what the cardiac sonographer should know. The application of the Gorlin formula in the cardiac catheterization laboratory is the standard of reference for the determination of aortic valve area. The continuity equation now enables the cardiac sonographer to determine aortic valve area noninvasively in the echocardiography laboratory. The comparison of the results obtained by the two methods is inevitable. The cardiac sonographer should have a basic understanding of the theory and pitfalls of the Gorlin formula so that when conflicting results are obtained, the possible reasons why will be clear. ",13 3348,"Demonstration of an area of slow conduction in human atrial flutter. Ten patients with chronic atrial flutter were studied prospectively using electrophysiologic mapping and pacing techniques to assess the mechanism of atrial flutter and the presence of an area of slow conduction in the atria. Electrograms recorded from greater than or equal to 30 right atrial sites for each patient during atrial flutter demonstrated that right atrial free wall activation was craniocaudal and that the interatrial septum activation was caudocranial, consistent with a reentrant circuit involving the right atrium. In six patients, slow conduction occurred during atrial flutter in the inferior right atrium and was spatially associated with fractionated electrographic recordings. In the other four patients, a ""missing"" interval of electrical activity occurred in the inferior right atrium for an average of 40% of the atrial flutter cycle. Transient entrainment criteria were demonstrated in each patient during rapid high right atrial pacing. The mean activation time from the high right atrial pacing site to the coronary sinus (inferior left atrial) recording site was long (228 ms) and consistent with activation through an area of slow conduction. During rapid pacing of atrial flutter from the coronary sinus site, no transient entrainment criteria could be demonstrated. The mean activation time from the coronary sinus pacing site to the high right atrial recording site was relatively short (134 ms) and consistent with orthodromic activation of the high right atrium not through an area of slow conduction. High right atrial pacing during sinus rhythm at rates similar to atrial flutter demonstrated a short activation time to the coronary sinus and low right atrial sites (mean 169 and 88 ms, respectively), indicating activation that did not traverse an area of slow conduction. Coronary sinus pacing during sinus rhythm demonstrated the same phenomena. Low right atrial electrograms recorded during sinus rhythm and during rapid pacing of sinus rhythm were not fractionated, although they were during atrial flutter. Thus, atrial mapping and pacing data were complementary, indicating that human atrial flutter in the patients studied was generated by a reentrant circuit in the right atrium, with an area of slow conduction in the low right atrium present only during atrial flutter. ",22 2159,"Life-threatening, antiglobulin test-negative, acute autoimmune hemolytic anemia due to a non-complement-activating IgG1 kappa cold antibody with Pra specificity. A 21-year-old man with fulminant cold autoantibody hemolytic anemia (CAHA) was hospitalized with hemoglobinemia, hemoglobinuria, hemoglobin concentration of 3.3 gm per dL, a negative direct antiglobulin test (DAT) with polyspecific and anti-C3d reagents, a negative Donath-Landsteiner test, and a cold agglutinin titer of 80. He failed to respond to corticosteroids, multiple plasma exchanges, and cyclophosphamide; he required 54 transfusions in 10 days to maintain a hemoglobin concentration of 6.0 to 10.0 g per dL. He improved dramatically after a splenectomy was performed. The wide-thermal-amplitude cold agglutinin proved to be an IgG1 kappa antibody with Pra specificity. The patient's serum exhibited normal complement activation. When the DAT was carried out at 0 to 4 degrees C, the result was strongly positive for IgG; the indirect antiglobulin test at 0 to 4 degrees C was positive with the patient's serum diluted 1 in 640. Within 6 months, he was in complete remission and receiving no therapy. As compared with eight patients with CAHA that was exclusively IgG-mediated, this patient is remarkable for his requirement for many transfusions and for DATs that were consistently negative for C3d. ",14 2044,"Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity. The purpose of the present study was to characterize the effects of xamoterol in the human myocardium. In the presence of forskolin or milrinone, xamoterol increased isometric force of contraction, contraction velocity, and relaxation velocity in isolated, electrically driven preparations from human myocardium, but had no effect alone. There was no difference in the effect of xamoterol between right atrial myocardium and left ventricular myocardium from nonfailing (NF), moderately failing (NYHA II-III), and severely failing (NYHA IV) human hearts. The positive inotropic and lusitropic effects of isoprenaline were reduced depending on the severity of heart failure in left ventricular myocardium (i.e., NF greater than NYHA II-III greater than NYHA IV). In the presence of norepinephrine, xamoterol produced negative inotropic effects similar to those of the beta-adrenoceptor antagonists pindolol and propranolol. Xamoterol alone had no effects on force of contraction, whereas pindolol and propranolol markedly reduced contractile force. In NYHA class IV, isoprenaline stimulated adenylate cyclase about twofold but xamoterol, like pindolol or propranolol, had no effect. Experiments with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, showed that the positive inotropic and lusitropic effects of xamoterol were mediated by beta 1-adrenoceptors. Consistently, xamoterol had a selectivity of 13.8 at beta 1-adrenoceptors as measured in radioligand binding experiments. It is concluded that xamoterol acts as a beta 1-adrenoceptor antagonist with a selectivity of 13.8 in human ventricular myocardium. The compound has an intrinsic sympathomimetic activity, as it produces beta 1-adrenoceptor-mediated positive inotropic and lusitropic effects in the presence of forskolin. The beneficial effects of xamoterol in patients with heart failure could be due to prevention of the detrimental effects of norepinephrine such as beta 1-adrenoceptor downregulation of an increase of Gi (inhibitory guanine-nucleotide binding protein). ",13 441,"Molecular phenotype of a pediatric small round cell tumor. Molecular probes were used to characterize an unusual small round cell abdominal tumor arising from the fallopian tube of a 15-year-old girl. DNA and RNA extracted from the tumor and adjacent normal tissue was subjected to Southern and Northern blot analysis using a variety of different probes. N-myc oncogene RNA was greatly expressed in the tumor, but was not expressed in normal tissue or amplified in chromosomal DNA. Insulin-like growth factor II RNA was similarly overexpressed in the neoplasm, but not in normal tissue. While histopathologic studies could not distinguish between a neuroectodermal neoplasm and Wilms' tumor, electron microscopy and the pattern of gene expression was most consistent with Wilms' tumor. ",3 531,"Use of the levator scapulae muscle flap in head and neck reconstruction. There are numerous techniques available for reconstruction of defects following composite resection of oral cavity and oropharyngeal tumors. No single technique is applicable in all situations. The levator scapulae muscle flap is well known for its application in carotid protection. Little attention is paid to its usefulness in other aspects of head and neck reconstruction. We have been using the levator scapulae muscle flap for a variety of reconstructive problems. The flap is useful for buttressing intraoral suture lines, closing intraoral defects, and providing soft tissue to fill in dead spaces and bulk out lateral and anterior oral defects. The levator flap was found to be easy to elevate, safe, and reliable with a minimum of wound complications. A review of 18 patients, representative case studies, and a discussion of surgical technique and relevant anatomy and blood supply is presented. ",3 2717,"Monocytoid B-cell lymphoma in a patient with human immunodeficiency virus infection. Demonstration of human immunodeficiency virus sequences in paraffin-embedded lymph node sections by polymerase chain reaction amplification. There is a significantly increased incidence of malignant lymphoma in patients with acquired immunodeficiency syndrome (AIDS). The lymphomas are usually of a high grade and of B-cell phenotype. While the frequent presence of reactive monocytoid B lymphocytes in patients with AIDS-related lymphadenopathy has recently been documented in several studies, to our knowledge, there are no reported cases of monocytoid B-cell lymphoma, the neoplastic counterpart of monocytoid B lymphocytes, in patients with AIDS. We now describe a human immunodeficiency virus (HIV)-positive patient with HIV-related lymphadenopathy in whom monocytoid B-cell lymphoma developed during the course of his disease. The morphologic and immunologic features of the lymphoma were characteristic of monocytoid B-cell lymphoma, and the involved lymph node exhibited a reversed CD4/CD8 ratio. Moreover, using the polymerase chain reaction, we were able to demonstrate HIV genome in DNA extracted from the lymph node tissue. To our knowledge, this is the first report of a case of monocytoid B-cell lymphoma occurring in an HIV-positive patient and in which we were able, by using a sensitive molecular biologic technique, to demonstrate HIV sequence in paraffin-embedded, fixed lymph node sections. ",19 1680,"Secondary prevention of acute myocardial infarction with beta-blocking agents and calcium antagonists. The discovery that beta blockers possess clinically useful hypotensive, antianginal and antiarrhythmic properties has attracted the interest of clinicians, researchers and the pharmaceutical community alike. In addition, minor differences in a variety of ancillary properties have led to speculation that specific classes of drugs might have advantages over other classes. The enthusiasm that greeted reports from the first small trials, which showed that beta blockers reduced the postmyocardial infarction mortality rate, attracted the commercial support necessary to evaluate different beta blockers in this clinical setting. The plethora of beta blockers that subsequently became available for study led to considerable improvement in both the design and implementation of large clinical trials. Despite apparent discrepancies in the results of various trials, meta-analysis indicates that most, if not all, beta blockers reduce postinfarction mortality. However, because meta-analysis cannot recommend a particular drug or specific dose for use in an individual patient, clinical practice must be based on the results of individual trials, not on the conclusions of meta-analysis. The clinical utility of beta blockers in the secondary prevention of myocardial infarction, coupled with experimental evidence that calcium antagonists reduce infarct size, led to a series of large studies designed to establish whether calcium antagonists have any effect on reducing mortality in patients with myocardial infarction. Lessons learned from the beta-blocker trials permitted a more rapid evaluation of the efficacy of calcium antagonists in this setting. It is clear that, unlike beta blockers, calcium antagonists are not effective in the secondary prevention of myocardial infarction. ",13 2093,"In vitro and in vivo evaluation of a right ventricular assist device. A simple right ventricular assist device (RVAD) has been developed. This device will be useful in situations where biventricular failure has been partially treated by placement of a left ventricular assist device, or when right ventricular failure occurs in isolation. This pneumatically actuated, R-wave synchronized, sac type pump contains no valves, and is connected by a graft to the pulmonary artery. The RVAD was tested in a circulation simulator to verify its hemodynamic efficacy and then implanted in six calves for 2-4 weeks to evaluate its biocompatibility. In vitro testing of the RVAD demonstrated that it restored normal hemodynamics in the presence of severe simulated RVF. In six animal implantations, a small amount of thrombus was found in one pump. No anticoagulants were employed. Thrombus was present in the connecting graft in three animals; in two this was clearly related to technical implant errors. No evidence of significant hemolysis was found. This simple RVAD has been found to be hemodynamically effective, is simple to use, and is well tolerated. Refinements in the interconnection graft between the pulmonary artery and the device are necessary. ",13 2476,"L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits. ",17 1108,"Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation. To investigate the effects of focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation (lambda = 1060 nm) on regional cerebral blood flow, cerebral protein synthesis, and blood-brain barrier permeability, the parietal brain surface of 44 rats was irradiated with a focused laser beam at a constant output energy of 30 J. Survival times ranged from 5 minutes to 48 hours. Laser irradiation immediately caused well-defined cortical coagulation necrosis. Within 5 minutes after unilateral irradiation, 14C-iodoantipyrine autoradiographs demonstrated severely reduced blood flow to the irradiation site and perilesional neocortex, but a distinct reactive hyperemia in all other areas of the forebrain. Apart from a persistent ischemic focus in the vicinity of the cortical coagulation necrosis, blood flow alterations in remote areas of the brain subsided within 3 hours after irradiation. Autoradiographic assessment of 3H-tyrosine incorporation into brain proteins revealed rapid onset and prolonged duration of protein synthesis inhibition in perifocal morphologically intact cortical and subcortical structures. Impairment of amino acid incorporation proved to be completely reversible within 48 hours. Immunoautoradiographic visualization of extravasated plasma proteins using 3H-labeled rabbit anti-rat immunoglobulins-showed that, up to 1 hour after irradiation, immunoreactive proteins were confined to the neocortex at the irradiation site. At 4 hours, vasogenic edema was present in the vicinity of the irradiation site and the subcortical white matter, and, at later stages (16 to 36 hours), also extended into the contralateral hemisphere. Although this was followed by a gradual decrease in labeling intensity, resolution of edema was still not complete after 48 hours. Analysis of sequential functional changes in conjunction with morphological alterations indicates that the evolution of morphological damage after laser irradiation does not correlate with the time course and spatial distribution of protein synthesis inhibition or vasogenic edema. Although the central coagulation necrosis represents a direct effect of radiation, the final size of the laser-induced lesion is determined by a delayed colliquation necrosis due to persistent perifocal ischemia. Extent and severity of ischemia in a zone with initial preservation of neuroglial cells can be explained by the optical properties of the Nd:YAG laser; extensive scattering of light within brain parenchyma associated with a high blood-to-brain absorption ratio selectively affects blood vessels outside the irradiation focus. ",9 53,"Changing epidemiology of group A streptococcal infection in the USA. To see whether changes in the epidemiology of group A streptococcal disease in the USA have been accompanied by a corresponding change in serotype distribution, epidemiological and M-typing and T-typing data for 5193 strains sent to the Centers for Disease Control, Atlanta, between 1972 and 1988 were analysed. The proportions of M-types 1, 3, and 18 increased significantly during the study period. These M-types were more likely to be invasive, to cause fatal infection, and to occur in a cluster of infections than were other types. By contrast, the proportions of M-types 4 and 12 decreased; they were less invasive and were less likely to be found in clusters than were other types. These data suggest that changes in the epidemiology of group A streptococcal disease may be related to changes in the distribution of M-types causing infection. ",0 1708,"Successful direct PTCA on LAD after first episode of acute myocardial infarction: does it improve cardiac function? Patients who received direct percutaneous transluminal coronary angioplasty (PTCA) after acute mycardial infarction and maintained potency but with unimproved cardiac function were studied. In 15 patients, the first episode of acute myocardial infarction was caused by a left anterior descending branch lesion; 11 had an ejection fraction of 50% or more in the left ventriculogram in the follow-up period (improved group), and 4 patients had ejection fraction of less than 50% (unimproved group). There was so significant difference between the groups in the mean time between the onset of infarction and revascularization (improved group, 259.3 +/- 76.9 min; unimproved group, 168.0 +/- 101.6 min) or in the sigma Q. which was the sum of the Q wave depth of V2, V3, and V4 at the time of admission (improved group, 12.1 +/- 15.6 mm; unimproved group 29.8 +/- 13.4 mm). The maximum creatine kinase concentration was significantly higher in the unimproved group (improved group 2670 +/- 893 IU/L; unimproved group, 7243 +/- 1928 IU/L, p less than 0.05), and the time taken from the onset to reach its peak was significantly shorter in the unimproved group (improved group, 13.0 +/- 5.1 hr; unimproved group, 6.8 +/- 1.3 hr, p less than 0.05.) These results suggest the probability of sudden deterioration of myocardium, and factors other than microcirculatory thromboembolism should be considered as the cause of unimproved cardiac function after successful direct PTCA. ",13 1118,"Spatial dispersion of magnetic stimulation in peripheral nerves. To assess the longitudinal dispersion of the stimulus induced by the magnetic coil, collision experiments were performed in seven normal ulnar nerves. A supramaximal electrical stimulus S1 was delivered at the wrist, and followed by a supramaximal stimulus S2 in the upper arm, which was either electrical (electrical collision studies), or magnetic (magnetic collision studies). The interstimulus interval was varied by 0.2 msec increments from the time of complete cancellation of the S2 evoked motor response onwards, to include the entire span of recovery of that compound motor action potential. Collision curves were obtained for both magnetic and electrical stimuli by plotting the amplitude of the motor response elicited by S2 as a function of the interstimulus interval. In all seven normal ulnar nerves, comparison of the collision curves showed that the S2 evoked motor response is restored significantly more slowly when magnetic stimulation is used. This finding is best explained by longitudinal dispersion of the stimulus induced by the magnetic coil relative to conventional electrical stimulation, the large fibers being stimulated further away from the coil than the small ones. This interpretation is confirmed by the findings obtained with the same method in two cases of ulnar neuropathy, and by comparison of different intensities of magnetic stimulation. ",9 1726,"Amiloride blocks the onset of ACTH-induced hypertension in the sheep. This study investigated the ability of two diuretics, amiloride and frusemide, to prevent the development of ACTH induced hypertension in conscious sheep. Infusion of amiloride (20 mg/day) or frusemide (50 mg/day) for three days into normotensive sheep did not have any significant effects on blood pressure. Amiloride blocked ACTH-induced hypertension and the sodium retention and hypokalemia which is usually associated with ACTH administration. Frusemide failed to completely block the hypertension and potassium loss, however it blocked the transient initial urinary sodium retention associated with ACTH-induced hypertension. As frusemide failed to completely block the hypertension it is unlikely that the amiloride effect is due primarily to effects on urinary Na excretion. It is possible that amiloride is exerting its antihypertensive effects by blocking sodium channels. ",13 2935,"Effects of lesions in the anterolateral columns and dorsolateral funiculi on self-mutilation behavior in rats. The possible role of the anterolateral columns (ALCs) and dorsolateral funiculi (DLF) in pain mechanisms was examined from the effects of lesions in these tracts (alone or combined) on tests for chronic deafferentation pain (autotomy) in rats. Spinal lesions alone (i.e., without denervation) in either ALC or DLF or combined DLF-ALC did not lead to any form of self-mutilation behavior. Cervical surgery, without spinal lesion, followed by limb denervation (sham) resulted in similar autotomy characteristics to those observed following limb denervation alone (control). Both results were considered as one set of controls. ALC lesions simultaneous with, or 1-2 weeks prior to limb denervation (ipsilaterally or contralaterally) produced significant delay in onset of autotomy and decrease in percentage of rats showing this behavior. DLF lesions followed by limb denervation produced significant acceleration of onset of autotomy and increase in percentage of rats showing this behavior. Combined DLF-ALC lesions with limb denervation produced intermediate effects between those observed following either ALC or DLF lesions alone. These results give further support to the concept that autotomy is related to rostral transmission of nociceptive information and that a spino-bulbo-spinal inhibitory loop involving the DLF and ALC is triggered by chronic deafferentation pain. ",20 1874,"The health belief model: predicting compliance and dropout in cardiac rehabilitation. We investigated the health belief model and the health locus of control constructs as predictors of group membership (compliers or dropouts) with cardiac rehabilitation and whether they added predictive utility to routinely assessed patient demographics and health behaviors. Questionnaires were completed on entry into the study by 120 patients with coronary artery disease, and by the end of the 6 month program there were 58 compliers and 62 dropouts. Discriminant function analyses were carried out to determine prediction of group membership. The health belief model predicted group membership 64.6% of the time, explaining 5.2% of the variance. Demographics, health behaviors, and health belief model factors accounted for 21.1% of the variance between compliers and total dropouts with group membership correctly predicted 74.4% of the time; avoidable and unavoidable dropout was correctly predicted 84.2% of the time with 56.9% of the variance explained. Health locus of control did not distinguish between compliers and dropouts. The addition of the health belief model provided additional information about compliance with cardiac rehabilitation beyond that explained by demographic and health behavior variables alone, particularly when predicting avoidable/unavoidable dropout. ",13 1361,"Long-term urinary continence and renal function in neonates with posterior urethral valves. Posterior urethral valves are known to be associated with considerable morbidity and mortality especially in the neonate. Recently the role of bladder dysfunction in the pathophysiology of renal function impairment and urinary incontinence after valve ablation has been questioned. From 1976 to 1986 we treated 50 male newborns with posterior urethral valves at our institution. Initial treatment in all cases consisted of bladder drainage by a urethral catheter, and correction of existing fluid and electrolyte abnormalities. Subsequent treatment was dictated by the degree of upper tract abnormalities and it included valve ablation alone in 24 patients, vesicostomy and later valve ablation in 8, valve ablation and later upper tract reconstruction in 14 and cutaneous ureterostomy in 4. Followup ranges from 2 to 12 years (mean 6.8). Long-term renal functional impairment was related to the serum creatinine at age 1 year. If the serum creatinine was below 1.0 mg.% all patients (31) had normal values at long-term followup and if it was greater than 1.0 mg.% (19) then only 7 patients had normal values at followup. Urinary continence was assessed in 42 patients and it was normal in 34 (81%). The etiology of incontinence in the remaining 8 patients was bladder dysfunction in 6 and sphincter incompetence in 2. Those patients with urinary incontinence also had a high incidence of upper tract abnormalities (6 of 8, 75%) compared to continent valve patients (10 of 34, 29%). ",11 1185,"Rapid eye movement sleep deprivation as a probe in elderly subjects. The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM ""pressure"" with a ""ceiling effect"" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD. ",9 97,"Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. 72 adults with erythema migrans (early Lyme borreliosis) were enrolled in a randomised prospective trial comparing amoxycillin 500 mg plus probenecid 500 mg three times a day with doxycycline 100 mg twice a day for 21 days. These antibiotic regimens were chosen because of the known in-vitro sensitivity of Borrelia burgdorferi, the antibiotic tissue penetration, the pharmacokinetics of the drugs, and because the organism can disseminate early in the course of infection. 72 patients were evaluable (35 in the doxycycline group and 37 in the amoxycillin/probenecid group). The two regimens were equally effective for treatment of erythema migrans. Mild fatigue or arthralgia were the only post-treatment complaints, which resolved within 6 months. None of the patients needed further antibiotic treatment for Lyme borreliosis. ",0 1651,"Functional status after coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Two cohorts of consecutive patients of comparable age with similar preprocedure cardiac function who underwent either coronary artery bypass grafting (CABG; n = 106) or percutaneous transluminal coronary angioplasty (PTCA; n = 64) were entered into a prospective comparison study examining functional status and return to work during the first year of recovery. Patients were evaluated using standardized functional status instruments for activities of daily living, work performance, social activity, mental health and quality of social interaction at 1, 6 and 12 months after the procedure. Within the CABG group, statistically significant improvements of functional status on every subscale were noted over the 1-year follow-up. Patients undergoing PTCA demonstrated significant improvement in all dimensions except for the quality of interaction at 1 year as compared with baseline. When the 2 groups were compared, the PTCA group demonstrated greater participation than the CABG group in routine daily physical and social activities at 1 and 6 months, but this apparent advantage disappeared by 1 year. Measures of psychological functioning were better after CABG than after PTCA. A reduction in the number of those with employment occurred in both the CABG and PTCA groups, independent of physical functional status measures, which improved in both groups after the procedures. For those with employment, the CABG group reported the greatest improvement in work performance. ",13 232,"Effective ultraviolet irradiation of platelet concentrates in teflon bags. Several plastic materials used in blood storage were evaluated for their ability to transmit ultraviolet B (UVB) light. A plastic bag manufactured from sheets of transparent Teflon efficiently (78-86%) transmitted UVB light and was employed in subsequent functional studies of lymphocytes and platelets exposed to UVB light while contained in these bags. In vitro experiments showed a UVB dose-dependent abrogation of lymphocyte responder and stimulator functions, with concurrent preservation of platelet aggregation responses. In a phase I pilot study, UVB-treated platelet concentrates were administered to four bone marrow transplant recipients. Adverse effects attributable to the transfusions were not observed, and patients showed clinically effective transfusion responses. No patient developed lymphocytotoxic HLA or platelet antibodies. These studies suggest that platelets can be effectively irradiated with UVB light in a closed system. However, numerous variables, including container material, volume and composition of contents, steady exposure versus agitation, and exact UV wavelength, must be considered. ",3 2540,"Iodine and selenium deficiency associated with cretinism in northern Zaire. Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa. ",18 2861,"The situational riskiness of alcoholic beverages. Using face-to-face interview data on a sample of young adults, this study investigates the perceived risk of alcohol consumption in drinking and driving, interactions with police and the probability of intoxication. Results show that beer is perceived as less risky than liquor in two risk situations, with men and drinkers in particular ranking beer as a lower risk beverage. When intoxication is considered, drinkers rank their preferred beverage as less risky than their alternative. Finally, an analysis of the relative riskiness of beer in comparison to liquor reveals that beer is perceived as less risky than liquor. This consensus does not vary significantly by sex or most other respondent characteristics. ",20 2505,"Increased hepatic mitochondrial capacity in rats with hydroxy-cobalamin[c-lactam]-induced methylmalonic aciduria. Treatment of rats with the vitamin B12 analogue hydroxy-cobalamin[c-lactam] (HCCL) impairs methylmalonyl-CoA mutase function and leads to methylmalonic aciduria due to intracellular accumulation of propionyl and methylmalonyl-CoA. Since accumulation of these acyl-CoAs disrupts normal cellular regulation, the present investigation characterized metabolism in hepatocytes and liver mitochondria from rats treated subcutaneously with HCCL or saline (control) by osmotic minipump. Consistent with decreased methylmalonyl-CoA mutase activity, 14CO2 production from 1-14C-propionate (1 mM) was decreased by 76% and 82% after 2-3 wk and 5-6 wk of HCCL treatment, respectively. In contrast, after 5-6 wk of HCCL treatment, 14CO2 production from 1-14C-pyruvate (10 mM) and 1-14C-palmitate (0.8 mM) were increased by 45% and 49%, respectively. In isolated liver mitochondria, state 3 oxidation rates were unchanged or decreased, and activities of the mitochondrial enzymes, citrate synthetase, succinate dehydrogenase, carnitine palmitoyltransferase, and glutamate dehydrogenase (expressed per milligram mitochondrial protein) were unaffected by HCCL treatment. In contrast, activities of the same enzymes were significantly increased in both liver homogenate (expressed per gram liver) and isolated hepatocytes (expressed per 10(6) cells) from HCCL-treated rats. The mitochondrial protein per gram liver, calculated on the basis of the recovery of the mitochondrial enzymes, increased by 39% in 5-6 wk HCCL-treated rats. Activities of lactate dehydrogenase, catalase, cyanide-insensitive palmitoyl-CoA oxidation, and arylsulfatase A in liver were not affected by HCCL treatment. Hepatic levels of mitochondrial mRNAs were elevated up to 10-fold in HCCL-treated animals as assessed by Northern blot analysis. Thus, HCCL treatment is associated with enhanced mitochondrial oxidative capacity and an increased mitochondrial protein content per gram liver. Increased mitochondrial oxidative capacity may be a compensatory mechanism in response to the metabolic insult induced by HCCL administration. ",17 1853,"Diagnostic value of a new myocardial perfusion agent, teboroxime (SO 30,217), utilizing a rapid planar imaging protocol: preliminary results [corrected and republished with original paging, article originally printed in J Am Coll Cardiol 1990 Oct;16(4):855-61] Technetium-99m-labeled agents have advantages over thallium-201 in terms of photon statistics, cost and clinical availability. They have been suggested as an alternative to thallium for myocardial perfusion imaging. Teboroxime is a new boronic acid adduct of technetium dioxime (BATO) compound that demonstrates favorable characteristics in preliminary studies. With use of a novel (seated) patient positioning technique and a rapid dynamic acquisition protocol, 30 patients underwent planar imaging with teboroxoime while at rest and after maximal treadmill exercise. Postexercise scans were completed in an average time (mean +/- SD) of 4.4 +/- 1.6 min, with 4.8 +/- 1.5 min for the views at rest. These results were compared with coronary arteriography or thallium scintigraphy after treadmill exercise, or both. Diagnostic agreement (abnormal versus normal) was present in 28 of the 30 patients (p less than 0.001). Regarding physiologic assessment as compared with thallium scintigraphy, the finding of infarction and ischemia was concordant in 89% and 86% of patients, respectively. This report describes the initial use of teboroxime with a rapid dynamic planar imaging technique, resulting in a high correlation with exercise thallium scintigraphy. Delayed postexercise images obtained 5 to 10 min after exercise demonstrated rapid disappearance of exercise-induced defects noted on the initial (0 to 5 min) postexercise views. The rapid differential washout with teboroxime has not been previously described and the possible clinical significance is discussed. ",13 1902,"A hematologist's view of contrast media, clotting in angiography syringes and thrombosis during coronary angiography. While ionic contrast media (CM) are stronger anticoagulants and antiplatelet agents, both nonionic and ionic CM retard clotting, fibrinopeptide A generation and platelet aggregation (at least by Born-O'Brien aggregometry). Thus, nonionic CM do not cause clots and thrombi. Rather, the driving force for clot or thrombus formation, when it occurs, is blood contact with and activation by the foreign surface of a syringe or catheter itself. A marked enhancement of clotting by glass syringes in comparison to plastic ones supports this view. Blood in any syringe or catheter, therefore, will clot more slowly in the presence of nonionic or ionic CM, the inhibitory effects of the latter being more profound. With respect to models of thrombosis at sites of vascular injury or stenosis, the antithrombotic effects of CM may either be transient owing to the dynamic nature of blood flow (local endothelial cell denudation model), or as in the case of ionic CM, actually to enhance local platelet aggregation (stenosis model). In these situations, preservation of the antithrombotic functions of endothelium with nonionic CM may be quite critical. ",13 1476,"Endocervical chlamydial deoxyribonucleic acid in infertile women. The presence of chlamydial deoxyribonucleic acid (DNA) was evaluated by DNA hybridization in endocervical cells of infertile and normal fertile women. Chlamydial DNA was detected in 49 of 186 (26.3%) infertile patients, which is significantly more common than in fertile control individuals (12.5%, or 8 of 64 individuals). Among infertile patients, 49.3% (33 of 67) of those with tubal factors as cause of infertility and 13.4% (16 of 119) of those with nontubal factors were found to contain chlamydial DNA in their endocervical cells. The results show that chlamydial DNA could be found significantly more frequently in endocervical cells of infertile patients with tubal factor than those without tubal factors or in normal controls. ",12 239,"Thyroid carcinoma with mixed tall-cell and columnar-cell features. Tall-cell and columnar-cell carcinomas have been regarded as aggressive variants of papillary thyroid carcinoma. In the present case report the authors describe a composite tumor where these forms of differentiation coexisted, with transitional changes occurring within single follicular structures. This finding indicates that the two variants are closely related. In local recurrences, one or the other feature appeared in separate lesions. Lung metastases developed, and the patient died 5 1/2 years after diagnosis and primary treatment. ",3 1982,"Pathogenesis of hyperadrenergic orthostatic hypotension. Evidence of disordered venous innervation exclusively in the lower limbs. The pathogenesis of hyperadrenergic orthostatic hypotension was studied in eight patients. Correction of the abnormal orthostatic changes by an inflated pressure suit (MAST) confirmed previous evidence of excessive gravitational pooling of blood in the leg veins. Intravenous L-norepinephrine infusion raised diastolic blood pressure in the same relationship to the infusion-induced increments in plasma norepinephrine concentrations as in normal subjects, indicating normal arteriolar responses. Contractile responses of the veins to infused L-norepinephrine were measured with a linear variable differential transformer (LVDT). The venous responses of hand veins in the patients fell within the 95% confidence limits of the responses of normal hand veins, as did the responses of foot veins in the seven normal subjects. However, foot veins of the patients with hyperadrenergic orthostatic hypotension, and both hand and foot veins of patients with ""diffuse"" autonomic failure, were supersensitive to norepinephrine, as reflected by a steeper slope of the regression of log (norepinephrine infusion rate) on percentage reduction in venous distensibility, and a significantly lower ED50 (i.e., norepinephrine infusion rate that induced 50% reduction in venous distensibility). The findings suggest anatomical or functional postganglionic denervation of lower limb veins causing excessive gravitational blood pooling with consequent orthostatic hypotension in these patients. ",13 2426,"Effects of exercise on insulin-induced hypoglycemia. The purpose of this study was to determine the effect of exercise on the rate of onset of hypoglycemia induced by infusion of excess insulin (0.8 mU.min-1.100 g-1). Rats were either fasted overnight (FS) or fed ad libitum (FD). FS rats were killed after 5, 10, or 15 min of infusion at rest or after running on the treadmill at 21 m/min and 15% grade. FD rats were killed after 10, 20, or 40 min of infusion at rest or after exercise. Rats were also killed 15 min postexercise for FS and 60 or 120 min postexercise for FD with continued insulin infusion. The progressive decline in blood glucose was not altered by exercise in the FS rats. FD rats showed a significant difference due to exercise only after 40 min (rest 4.2 +/- 0.3 mM, exercise 3.2 +/- 0.2 mM). A significant postexercise repletion of glycogen was observed in red vastus and soleus muscles of FD rats despite the decreasing blood glucose values. These data indicate that exercise accelerates the rate of development of hypoglycemia in FD rats. In the FS rats, where the rate of decline in blood glucose was greater, exercise had no effect on the time course of development of hypoglycemia. ",17 997,"Recessive oncogenes in lung cancer. The observation that carcinogen exposure is strongly associated with the probability of developing pulmonary neoplasms has suggested for many years that acquired somatic mutations play a key role in the genesis of these environmentally induced cancers. With the advent of new techniques in cytogenetics and in the molecular analysis of DNA extracted from lung tumors, it has now become possible to test this hypothesis and to search for candidate genes that may be targeted by the chronic exposure of these environmental insults. Early work in this field, studying lung tumors of different histologic types, appears to implicate several distinct chromosomal loci (at chromosomes 3p, 13q, 17p, and others), suggesting that sequential genetic events occur during the initiation and progression pathways to pulmonary tumorigenesis. Identifying the candidate gene products and understanding the chronology and stringency of mutational events at these loci will be an essential goal to understanding the cellular basis of lung tumors and for developing strategies for the next generation of diagnostic and therapeutic studies. ",7 748,"Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma. ",5 12,"Itraconazole treatment of phaeohyphomycosis. Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents. ",0 112,"Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis. Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality. Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible. The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established. This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis. ",0 543,"Cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The authors studied data of combination assays of tumor markers, because simultaneous elevation of different types of tumor markers in the serum was puzzling. They interpreted such phenomena regarding cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The tissue expression of the antigens was compared with preoperative serum levels. Several different factors were found to cause the simultaneous elevation of two or three of these markers in the serum. Furthermore, even when the levels of some of the tumor markers were raised in the serum, the ovarian tumor did not always produce the marker by itself. This study indicates that immunohistochemical identification of a marker in tumor tissue is prerequisite to the use of that marker in the serum to monitor disease status. ",3 2289,"Mechanisms involved in allergic contact dermatitis. Allergic contact dermatitis is a common inflammatory skin disease caused by agents such as plants, chemical compounds, and topical medications. Histologic features typically include edema within the epidermis and dermis and a lymphohistiocytic infiltrate with an admixture of basophils. Langerhans cells and keratinocytes play pivotal roles in allergic contact dermatitis reactions. Langerhans cells synthesize and express class II molecules that allow the presentation of exogenous antigens to T lymphocytes. Additionally, keratinocytes and Langerhans cells produce interleukin-1, which is thought to be a second signal that activates T cells. Mast cells and basophils also may play a proinflammatory role. Treatment primarily consists of removal of the offending agent. At times, systemic corticosteroids may be required, especially in the acute phase. In more chronic cases, topical corticosteroids may be beneficial. Antihistamines may be useful because of their soporific effects, but their usefulness is limited. ",16 274,"New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia. A new and rare type of Bcr/Abl junction between exon C3 of the 3' portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph1-positive chronic myelogenous leukemia patients in chronic phase. This is the fourth type of Bcr/Abl junction so far identified in Ph1-positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region (bcr) of the Bcr gene. The new hybrid mRNA is 540 base pairs (bp) longer than that expressed by the K562 cell line and could codify for a Bcr/Abl protein carrying 180 additional aminoacids with respect to the larger P210 protein so far identified. The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr/Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia. ",3 1113,"The efficacy of brainstem auditory evoked potentials in acoustic tumor surgery. As the identification of patients with small acoustic neuromas and salvageable hearing increases, intraoperative auditory nerve monitoring has been used increasingly in an attempt to improve the hearing preservation rate. Far-field recordings obtained by brainstem auditory evoked potentials (BAEP), at times enhanced by electrocochleography, have become a standard method of intraoperative auditory nerve assessment. To evaluate the usefulness of this monitoring technique, the hearing preservation results of a series of unmonitored acoustic tumor removals were compared to a series of patients monitored via the standard brainstem auditory evoked potentials. With comparable average tumor sizes, 4 of 7 unmonitored patients had hearing preserved at preoperative levels compared to 4 of 9 monitored patients. Neither preoperative BAEP assessments nor absolute tumor size were predictive of hearing preservation. This report brings into question the effectiveness of far-field intraoperative BAEP monitoring during acoustic tumor resection and suggests that direct auditory nerve monitoring may be more appropriate. ",9 881,"Cytomegalovirus pneumonia in allogeneic bone marrow transplantation. An immunopathologic process? Recent literature suggests that CMV pneumonia is an immunopathologic process. This case report summarizes the clinical course of a patient which supports this hypothesis. The patient is the recipient of an allogeneic BMT who recovered from an episode of CMV pneumonia that occurred about two months after the transplant. Despite recovery from the viral infection, follow-up BALs revealed persistent lymphocytosis in an apparent asymptomatic patient. He subsequently developed BOOP about four months after the initial CMV infection. These observations suggest that the viral infection may have resulted in the activation of the host's cell-mediated response and provides evidence to support the hypothesis that CMV pneumonia is an immune-mediated process. ",7 677,"The freckle sign--an endoscopic feature of the cecum. Mucosal spots, or ""freckles,"" surrounding the appendiceal orifice are an endoscopic feature of the cecum. These are clusters of 1 to 2 mm round or oval slightly raised spots, each with a pale center and an erythematous border. They correlate microscopically with subepithelial and submucosal lymphoid follicles. The freckling pattern, identified in about one third of colonoscopies, was seen best with the videoendoscope and was identified more commonly in patients with systemic illness. Recognition of mucosal freckling around the appendiceal orifice helps identify the cecum and may be useful in the evaluation of cecal and appendiceal pathology. ",5 2802,"The spectrum of emergency care of agricultural trauma in central Wisconsin. Agriculture is among the most dangerous occupations in the United States. When injuries do occur, the emergency department (ED) is the primary source of care. Over a 2-year period, the emergency medicine section of the Marshfield Clinic/St Joseph's Hospital, cared for 913 victims of agricultural trauma. Although 11% were initially admitted and 4% were later treated, the remainder received their care solely in the ED. Unlike most occupational injuries, people of any age may be involved in agricultural injuries; 27% in this series were less than 18 years of age and 5% were 65 years or older. Just over half of all injuries were from mechanical devices, including tractor and farm machinery. The remainder were from animals, falls, or exposure. Although several different types of injuries occurred, the most common diagnoses were soft tissue injuries and fractures and the most common procedure was diagnostic radiography followed by wound and fracture care. An ED in a rural setting should be prepared to deal with agricultural trauma. ",20 1872,"Simulated left ventricular aneurysm and aneurysm repair in swine. Patch reconstruction of left ventricular aneurysm may be superior to linear closure, but this hypothesis has not been tested experimentally. Accordingly, six anesthetized domestic pigs were instrumented to measure regional left ventricular wall thickening, stroke volume, systolic left ventricular pressure, and myocardial oxygen consumption. With total bypass and cardioplegia, a 6 by 8 cm Dacron patch was inserted into the anteroapical left ventricle. Simulations were as follows: left ventricular aneurysm, patch open; patch reconstruction, 50% patch plication; standard repair, ventriculotomy edges approximated. Global function, from stroke work (stroke volume x integral of left ventricular pressure)-left ventricular end-diastolic pressure curves, was depressed in all three simulations compared with control. A tendency for stroke work to be greater for standard repair than for left ventricular aneurysm and patch reconstruction at higher preloads was not statistically significant. Mechanical efficiency, from stroke work/myocardial oxygen consumption (joules per milliliter oxygen per beat), was 2.43 +/- 0.52 (mean +/- standard error of the mean) (control), 2.22 +/- 0.94 (standard repair), 1.27 +/- 0.39 (patch reconstruction), and 1.09 +/- 0.37 (left ventricular aneurysm) (no significant differences). Regional work was calculated as regional left ventricular wall thickening x integral of left ventricular pressure. The slope of the regional work-end-diastolic wall thickness relation decreased in the posterior wall 14.0 +/- 2.9 (control) versus 8.4 +/- 2.0 (left ventricular aneurysm), 6.9 +/- 1.4 (patch reconstruction), and 7.4 +/- 1.4 (standard repair) (p less than 0.05). In the anterior wall, contractility did not change significantly (7.4 +/- 1.2, control; 7.8 +/- 2.7, left ventricular aneurysm; 5.0 +/- 0.4, patch reconstruction; and 5.3 +/- 0.4, standard repair). Decreased end-diastolic wall thinning anteriorly suggested tethering. These results in the normal left ventricle suggest that patch ventriculoplasty is of no greater benefit than linear repair. Either repair may impede function of adjacent myocardium through restriction of regional diastolic lengthening. ",13 1971,"Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, -0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning). ",13 103,"A resurgence of acute rheumatic fever in a mid-South children's hospital. A resurgence of acute rheumatic fever (ARF) has been reported in many areas of the United States in recent years. We retrospectively reviewed the medical records of inpatients with a new diagnosis of ARF from 1982 through 1988 at a children's hospital that serves a six-state referral area in the mid-South. Thirty patients were identified, 21 of whom were seen in 1987 (13) and 1988 (8). The rate of new cases of ARF per 1000 hospital discharges (0.7) was significantly greater for 1987 and 1988 than it was (0.15) from 1982 through 1986. Patients with recently diagnosed ARF were predominantly from nonurban areas, and polyarthritis was the most common recent major manifestation. Reasons for the resurgence of ARF in the US, including the mid-South, are unclear, but our experience serves to support recently published guidelines for the diagnosis and management of streptococcal pharyngitis in light of this resurgence of ARF. ",0 2798,"Alcohol use and depressive symptoms among Mexican Americans and non-Hispanic Whites. Alcohol use is associated with depressive symptoms in several studies. Using data from a community survey, this study examined whether this relationship (a) can be accounted for by ethnic or sociodemographic differences among persons who engage in various levels of alcohol use; and (b) differs for Mexican Americans (N = 1244) and non-Hispanic Whites (N = 1149). Using large quantities of alcohol, and, among men, daily drinking, were associated with depressed mood. These associations were similar for Mexican Americans and non-Hispanic Whites, and associations of quantity and frequency with depression were independent of each other. Among women, the cultural and demographic characteristics of high-quantity drinkers and abstainers (both of whom tended to be Mexican Americans) accounted for the association of alcohol use with depression. Among men, there was some suggestion that unemployment and unmarried status mediated the association of alcohol quantity with depression. People who drank greater quantities of alcohol per occasion reported more somatic depressive symptoms, and more frequent male drinkers reported more of most types of depressive symptoms. ",20 168,"Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR. ",3 1669,"Circadian rhythm of heart rate variability after acute myocardial infarction and its influence on the prognostic value of heart rate variability. This study examined heart rate (HR) variability in patients surviving acute myocardial infarction (AMI) to find the optimum time and duration of recording of the ambulatory electrocardiogram for the prediction of the risk of sudden cardiac death, or serious arrhythmic events, or both. Twenty patients (group I) who initially survived an AMI but later experienced serious events (death or symptomatic sustained ventricular tachycardia) during a 6-month follow-up were compared with 20 patients (group II) who remained free of complications for greater than 6 months after discharge. Groups I and II were matched with regard to age, gender, infarct site, ejection fraction, and beta-blocker treatment. HR variability was assessed in the 24-hour electrocardiograms recorded during the first 2 weeks after an AMI and in various portions of the complete 24-hour recording, with both the beginning and the length of the analyzed portion varied by 20 minutes (a total of 5,113 possibilities). The maximum reduction of HR variability in group I patients was systematically found when assessing HR variability in recordings starting approximately at 6 A.M. and lasting for approximately 8 hours. In the low-risk patient, the diurnal rhythm of HR variability is more marked than in the high-risk patient and the long-term components of HR variability due to the diurnal variation must be included in the measurement of HR variability when using it as a long-term predictor of risk from arrhythmic events after an AMI. ",13 2889,"Scapular dislocation (locked scapula). We report the case of a 19-year-old woman who presented to the emergency department with pain and inability to move her right shoulder after falling backwards and striking it on a cart. Radiographs of the shoulder revealed a dislocated scapula. Closed reduction in the ED was successful. This rare case of scapular dislocation serves to emphasize that a heightened awareness for this injury is necessary if it is to be recognized and treated appropriately. Its treatment and prognosis are reviewed. ",20 2790,"Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation [published erratum appears in Arch Gen Psychiatry 1991 Jan;48(1):51] We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients (daily use, greater than 1 year). Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents, there were notable residual symptoms of anxiety and depression present at intake (Hamilton Rating Scale for Anxiety score, 17.0; Hamilton Rating Scale for Depression score, 14.0). Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo (n = 47), or continued benzodiazepine use (n = 10). Clinical assessments were performed daily, including benzodiazepine plasma levels. Depending on the outcome criteria used, anywhere from 58% to 100% of patients were judged to have experienced a withdrawal reaction, with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines. Relapse onto benzodiazepines occurred in 27% of patients who were receiving long half-life benzodiazepines and in 57% of patients who were receiving short half-life benzodiazepines. Baseline predictors of relapse were nonpanic diagnoses, a higher benzodiazepine dose, and a higher Eysenck neuroticism score. A short half-life and higher daily doses were associated with greater withdrawal severity, as were personality traits, such as dependency and neuroticism, less education and higher baseline levels of anxious and depressive symptoms. Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation. These results provide a detailed picture of the symptoms, time course, and multidimensional determinants of the benzodiazepine withdrawal syndrome. ",20 1554,"Ischaemic left ventricular failure: evidence of sustained benefit after 18 months' treatment with xamoterol. The long term effects of treatment with xamoterol in 14 patients aged 44-73 with mild to moderate heart failure as a result of ischaemic heart disease are reported. After 18 months' treatment with xamoterol, patients were assessed in a randomised double blind crossover comparison of xamoterol (200 mg twice a day) and placebo, each given for one month. Compared with placebo, xamoterol significantly increased exercise duration and work done on a bicycle ergometer and reduced the maximum exercise heart rate. Assessment of symptoms and activities at 12 months by visual analogue and Likert scales showed a trend towards the relief of symptoms of breathlessness and tiredness and an improvement in activity. There was an improvement in the clinical signs of heart failure and no haemodynamic deterioration over a 12 month period as assessed by ejection fraction. The improvement in exercise tolerance, symptoms, and activities was sustained for 18 months without side effects or development of tolerance. ",13 675,"Prospective trial comparing a combination pH probe-nasogastric tube with aspirated gastric pH in intensive care unit patients. Upper GI bleeding related to stress ulcer syndrome is estimated to affect as much as 15% of patients in an ICU. Since the occurrence of bleeding after ICU admission may be associated with increased morbidity and mortality, many efforts have been directed at defining optimal therapy for stress ulcer prophylaxis. Titration of intragastric pH with antacids or iv doses of H2-receptor antagonists may prevent stress ulcer bleeding in high-risk ICU patients. We evaluated a recently developed pH probe incorporated into an NG tube and compared it with aspiration of gastric contents using pH paper as a means to monitor pH in 22 surgical ICU patients. Regression analysis comparing the intragastric probe pH values with the aspirated pH values showed a good correlation between the two methods (r = .71). This new technique for intragastric pH measurement appears technically simple and clinically applicable for use on patients at risk for stress ulcer bleeding. It may be more accurate than pH paper in patients receiving antacids. ",5 3132,"Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. Among 91 patients with unruptured intracranial arteriovenous malformations (AVM's), 16 patients had 26 unruptured intracranial saccular aneurysms. An actuarial analysis showed the risk of intracranial hemorrhage among patients with coexisting aneurysm and AVM to be 7% per year at 5 years following diagnosis compared to 1.7% for patients with AVM alone. The difference in length of survival free of hemorrhage was significant (log-rank, p less than 0.0007). Several angiographic and clinical parameters were investigated to better understand the relationship of these lesions. The aneurysms occurred in similar percentages in patients with small, medium, and large AVM's. Twenty-five aneurysms were on arteries feeding the malformation system, almost equally distributed proximally and distally. Eleven aneurysms were atypical in location, and all arose from primary or secondary branch feeders to the malformation; 24 were on enlarged feeding arteries. Eleven (16%) of the 67 patients with high-flow AVM's had associated aneurysms, compared with five (21%) of the 24 patients with low-flow AVM's. Four (16%) of 25 low-shunt malformations and 12 (18%) of 65 high-shunt malformations had associated aneurysms. All five aneurysms associated with low-shunt malformations were on a direct arterial feeder of the malformation. These data suggest that the intracranial AVM's predispose to aneurysm formation within AVM feeding systems and that the mechanism is not simply based upon the high blood flow or high arteriovenous shunt in these systems. ",22 2278,"Treatment of molluscum contagiosum using a lidocaine/prilocaine cream (EMLA) for analgesia. Eighty-three 4- to 12-year-old children, scheduled for curettage of at least five molluscum contagiosum lesions, participated in a double-blind study. The children were randomly allocated to receive lidocaine/prilocaine (EMLA) cream (n = 58) or placebo cream (n = 25), applied 15, 30, or 60 minutes before treatment. The pain was assessed by the children and the physician as none, slight, moderate, or severe. In addition, the children rated the pain on a visual analog scale. EMLA cream effectively prevented the pain after all three application times (p less than 0.01). No significant difference in pain was observed among the 15-, 30-, and 60-minute EMLA-treated groups, but the proportion of children reporting no pain on the verbal scale increased from 36% in the 15-minute group to 61% in the 60-minute group. In the placebo group, only one of 24 children (4%) reported no pain. Transient local redness was the only skin reaction noted. In conclusion, an application time of EMLA cream of less than 60 minutes is satisfactory for the curettage of molluscum contagiosum in children. ",16 2408,"Monomeric insulins and their experimental and clinical implications. Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS). ",17 1864,"Doppler color-flow images from a stenosed arterial model: interpretation of flow patterns. The capability of the recently introduced Doppler color-flow mapping devices to accurately detect flow patterns in the region of an arterial stenosis was evaluated by use of an in vitro flow model. Pulsatile flow simulating that in a low-resistance vessel was induced through a straight acrylic tube, which alternatively contained axisymmetric stenoses of 0%, 20%, 40%, 60%, and 80% diameter reduction. Doppler color-flow mapper images were taken in realtime along the tube midplane from 0 to 8 diameters downstream of each stenosis. Comparison of the Doppler color-flow mapping results with similarly recorded flow visualization (hydrogen bubble) images showed a close correspondence of key features of the flow, including detection of a high-velocity, centerline jet and near-wall separated flow zones. Distinctive flow patterns exist with each stenotic case, and these should be of considerable value in diagnosing clinical disease conditions. ",13 3134,"Spontaneous regression of giant arteriovenous fistulae during the perinatal period. Case report. A unique case of spontaneous regression of giant arteriovenous fistulae during infancy is described in this report. A female infant, the product of normal labor and delivery, demonstrated severe ventriculomegaly and an intracranial hemorrhage at birth. Cerebral angiography at 5 days of age revealed several large fistulae fed by the anterior and middle cerebral arteries draining into the deep venous system through a dilated internal cerebral vein and ectatic vein of Galen. Two days following the angiogram, a second intracranial hemorrhage occurred. Active hydrocephalus developed over the next 6 months and was treated with ventriculoperitoneal shunting. When the child was 8 months of age, angiography failed to demonstrate the fistulae. It was postulated that pressure effects from the intracranial hematoma and long-standing intracranial hypertension as well as stenosis in the anomalous venous outflow resulted in vascular stasis, venous thrombosis, and selective arterial occlusion. Hydrocephalus was a result of the compression of the intraventricular foramina by dilated embryonic vessels. This anomaly, predominantly involving the anterior circulation, may be homologous to the vein of Galen aneurysm in the posterior circulation. ",22 1220,"Survey of adolescents with severe intellectual handicap. A diagnostic survey was undertaken of children aged 11 to 19 years in Tameside with severe learning difficulties (intelligence quotient less than or equal to 50). Eighty-two children were identified and their medical records reviewed. A specific diagnosis for the retardation was documented in 25 (30%) of the children, 18 of whom had Down's syndrome. A probable aetiology or a disorder of unknown aetiology had been identified in a further 21 (26%) children. To confirm the existing diagnosis, identify new diagnoses, and offer genetic counselling, the parents of 63 children were offered detailed reassessment of their child. Fifty three children were reviewed, and a specific disorder identified in 25 out of 31 previously undiagnosed children. The most frequent diagnoses made were fragile X syndrome and Rett's syndrome. On completion of the survey, 61 of the 82 children (74%) had a specific diagnosis or probable aetiology identified, 12 (15%) had associated disorders such as cerebral palsy, and in only nine of the 82 children (11%) were there no clues at all to the cause of their retardation. ",9 982,"Late pulmonary sequelae of bronchopulmonary dysplasia BACKGROUND. Bronchopulmonary dysplasia is a chronic lung disease that often develops after mechanical ventilation in prematurely born infants with respiratory failure. It has become the most common form of chronic lung disease in infants in the United States. The long-term outcome for infants with bronchopulmonary dysplasia has not been determined. METHODS. We studied the pulmonary function of 26 adolescents and young adults, born between 1964 and 1973, who had bronchopulmonary dysplasia in infancy. We compared the results with those in two control groups: 26 age-matched adolescents and young adults of similar birth weight and gestational age who had not undergone mechanical ventilation, and 53 age-matched normal subjects. RESULTS. Sixty-eight percent of the subjects with bronchopulmonary dysplasia in infancy (17 of the 25 tested) had airway obstruction, including decreases in forced expiratory volume in one second, forced expiratory flow between 25 and 75 percent of vital capacity, and maximal expiratory flow velocity at 50 percent of vital capacity, as compared with both control groups (P less than 0.0001 for all comparisons). Twenty-four percent of the subjects with bronchopulmonary dysplasia in infancy had fixed airway obstruction, and 52 percent had reactive airway disease, as indicated by their responses to the administration of methacholine or a bronchodilator. Hyperinflation (an increased ratio of residual volume to total lung capacity) was more frequent in the subjects with a history of bronchopulmonary dysplasia than in either the matched cohort (P less than 0.0006) or the normal controls (P less than 0.0004). Six of the subjects who had bronchopulmonary dysplasia in infancy had severe pulmonary dysfunction or current symptoms of respiratory difficulty. CONCLUSIONS. Most adolescents and young adults who had bronchopulmonary dysplasia in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation. The clinical consequences of this dysfunction are not known. ",7 1534,"Measurement of activity of urea resistant neutrophil alkaline phosphatase as an antenatal screening test for Down's syndrome. OBJECTIVE--To investigate the value of measuring maternal urea resistant neutrophil alkaline phosphatase activity as an antenatal screening test for Down's syndrome. DESIGN--Case-control study of blood samples collected at nine to 27 weeks of pregnancy. SETTING--Antenatal clinics in London and Oxford. PATIENTS--72 Women whose fetuses had been diagnosed by amniocentesis or chorionic villus sampling as having Down's syndrome and 156 women whose fetuses did not have the syndrome. Only singleton pregnancies were studied. MAIN OUTCOME MEASURE--Activity of urea resistant neutrophil alkaline phosphatase measured cytochemically. RESULTS--The median enzyme activity in the index patients was 1.65 times the expected median for the controls at the same duration of pregnancy (p less than 0.0001; 95% confidence interval 1.56 to 1.74). A cut off value that identified the 5% of control patients with the highest activities yielded a rate of detection of Down's syndrome of 79% (95% confidence interval 70 to 89%). CONCLUSION--Activity of urea resistant neutrophil alkaline phosphatase is an effective maternal blood marker for Down's syndrome. Its use in antenatal screening could lead to a substantial improvement in the detection of this disorder. Before introducing the test into routine medical practice it will have to be automated so that it can be used on a large scale and is less subjective. ",12 3267,"Cardiac arrhythmias in critically ill patients: epidemiologic study The general prevalence of cardiac arrhythmias in 2,820 consecutive patients was 78%, ranging from 44% in multiple trauma patients to 90% in primary cardiovascular patients. Patients without recorded arrhythmias (22%, n = 621) were used as control subjects. No clinical group was free from cardiac arrhythmias. Atrial tachyarrhythmias had the highest prevalence in the population as a whole (28%) and in all clinical groups except multiple trauma. Atrial fibrillation was the most common atrial arrhythmia (52%); ventricular arrhythmias followed. Patients with atrial tachyarrhythmias, nodal rhythm ventricular bradyarrhythmias, and ventricular rapid rhythms had significantly (p less than .01) increased mortality rates (40%, 44%, 77%, and 51%, respectively) when compared with patients without arrhythmias (35%). The relative risk of dying (RRD) of these clinical groups was increased by 1.16, 1.27, 2.20, and 1.47, respectively. Patients with cardiorespiratory precipitating disease and any arrhythmia except atrial bradyarrhythmia had a mortality rate between 32% and 74%, significantly (p less than .05) different from that of patients within the same clinical groups without arrhythmias. The RRD was increased by 1.67 to 3.40. Septic patients with atrial tachyarrhythmia or nodal rhythm and neurologic patients with nodal or ventricular arrhythmias also had significantly (p less than .01 and .05, respectively) increased mortality and were at higher RRD (1.53 to 2.81). Our data suggest that severe illness may be present in some clinical groups of critically ill patients with cardiac arrhythmias. ",22 1574,"Ventilatory and diffusion abnormalities in potential heart transplant recipients. Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes. ",13 1320,"Treatment of primary nocturnal enuresis by oral androgen mesterolone. A clinical and cystometric study. A double-blind clinical study of 30 boys, six to ten years of age, with primary nocturnal enuresis was undertaken to assess the role of androgens in treating enuresis. The oral synthetic androgen mesterolone was selected because of its minimal potential toxic effects. Twenty boys were treated with mesterolone and 10 received placebo. Fourteen boys (70%) became dry during treatment (20 mg daily for 14 days), and 5 (25%) remained dry for a follow-up period of four months. Increased cystometric bladder capacity and disappearance of uninhibited detrusor contractions were noticed in a significant number of cases after treatment. No side effects were recorded. Mesterolone has probably modulated the autonomic innervation of the vesical musculature with correction of the defective neural mechanism which is believed to be implicated in the pathogenesis of nocturnal enuresis. ",11 901,"Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children. Inhaled albuterol (A) (salbutamol) alone and albuterol plus ipratropium bromide (IB) were administered to 12 asthmatic children. Following administration of A alone or in combination with IB, there was a significant increase in FEV1 and FEF. Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120, 180, and 240 minutes for FEF. The additive effect was present both in the large and small airways. The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction. ",7 3059,"Intraoperative air testing of colorectal anastomoses: a prospective, randomized trial. A total of 145 consecutive patients receiving a colorectal anastomosis were randomized to 'test' or 'no test' once the anastomosis had been completed. Anastomotic testing was performed with the pelvis filled with saline and the rectum distended by sigmoidoscopic insufflation of air. Any leaks demonstrated were oversewn. A water-soluble contrast enema was performed on the tenth postoperative day. Seventy-four patients were randomized to 'test' and 71 to 'no test' but one patient was withdrawn from each group leaving a total of 143 for analysis. The two groups were well matched for age, sex, diagnosis and operative details. Eighteen (25 per cent) air leaks were detected and repaired in the 'test' group. After operation there were three (4 per cent) clinical leaks in the 'test' group and ten (14 per cent) in the 'no test' group (Fisher's exact test, P = 0.043). There were eight (11 per cent) radiological leaks in the 'test' group and 20 (29 per cent) in the 'no test' group (P = 0.006). Intraoperative air testing and repair of colorectal anastomoses significantly reduces the risk of postoperative clinical and radiological leaks. ",22 3352,"Biliary and gut function following shock. The aim of this study was to characterize the alterations in gallbladder and intestinal function after hemorrhagic shock and blood reperfusion in opossums. Animals were subjected to a shock of 30 mm Hg of arterial blood pressure for 60 minutes and resuscitated with blood reinfusion. Gallbladder epithelial ion transport, gallbladder motility in vitro and in vivo, gastrointestinal motility, and flora of the stomach and small bowel were studied 2 and 24 hours after shock. Changes at 2 hours included decreased gallbladder contractility in vitro and decreased emptying in vivo, loss of coordination with intestinal motor activity, decrease in frequency of intestinal electrical slow waves, and reduced duration of the intestinal migrating motor complex cycle. By 24 hours, gallbladder epithelial permeability was increased and in vitro contractility remained reduced but the in vivo functions showed partial recovery. Gastrointestinal flora was not affected by these changes. These data demonstrate that hemorrhagic shock and reperfusion affect digestive motility. The early timing of the alterations observed and the partial recovery 24 hours post shock suggest an ischemia-hypoxia mechanism of injury. ",22 1593,"Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group. ",13 199,"Benign lymphangioendothelioma. We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name ""benign lymphangioendothelioma."" The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults. The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces. Hemorrhage, iron deposition, and inflammation were not part of the lesion. Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative. This histologic pattern and the special studies suggested a lymphatic lesion. Surgical excision, performed in six patients, was not followed by recurrence. ",3 2441,"Removal of an inorganic acid load in subjects with ketoacidosis of chronic fasting. When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 +/- 6 vs. 176 +/- 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 +/- 0.6 vs. 15 +/- 0.5 mmol/liter) and ketoacid anions (3.3 +/- 0.2 vs. 5.5 +/- 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include ""potential bicarbonate"" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 +/- 2 vs. 120 +/- 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 +/- 0.1 vs. 77 +/- 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium. ",17 176,"Expression of Ki-1 antigen (CD30) in mesenchymal tumors. Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors. However, expression of this antigen has also been detected in embryonal carcinomas, in nonembryonal carcinomas, in malignant melanomas, and even in some myeloid cell lines and macrophages at late stages of differentiation. In this study, using monoclonal antibody Ki-1, expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors. The authors found CD30 expressed in two of four leiomyomas, seven of 11 leiomysarcomas, one of six rhabdomyosarcomas, two of two aggressive fibromatoses, one of three fibrosarcomas, two of four synovial sarcomas, one giant cell tumors of tendon sheaths, all five malignant fibrous histiocytomas, all three osteosarcomas, one of three Ewing's sarcomas, in a tumor cell subpopulation of two of ten malignant schwannomas, and in the Schwann cell compartment of one of two ganglioneuromas tested. Furthermore, CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas. However, all five lipomas, all seven liposarcomas, all three neuroblastomas, both ganglioneuroblastomas, both chondrosarcomas, and tumors of disputed origin tested were consistently CD30 negative. These findings indicate that, outside the lymphatic system, CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin. The authors conclude that CD30 antigen, although having limited utility in the differential diagnosis of tumors of questionable histogenesis, may eventually define relevant subgroups within the main tumor categories. ",3 548,"Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease. The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat. ",3 1860,"Management of asymptomatic chronic aortic regurgitation with left ventricular dysfunction: a decision analysis STUDY OBJECTIVE: To determine the optimal strategy for the timing of aortic valve replacement in patients with chronic, severe aortic regurgitation with left ventricular dysfunction. DESIGN: Decision analysis comparing early surgery (timed at the onset of left ventricular dysfunction) with delayed surgery (timed at the onset of symptoms) using data from the literature and expert opinion for variables in a representative case scenario (40-year-old man with bicuspid aortic valve disease). SETTING: Tertiary care center doing valve replacement surgery. MEASUREMENTS AND MAIN RESULTS: The early-surgery approach was preferred based on quality-adjusted life years. Sensitivity analysis showed that the result was not affected by the following variables within their derived ranges: rate of symptom development after onset of left ventricular dysfunction for the delayed-surgery approach, perioperative mortality for both approaches, and occurrence of major nonfatal stroke or congestive heart failure for both approaches. Although the decision was sensitive to the yearly postoperative mortality rates, the delayed-surgery operative mortality rate had to be almost as low as the early-surgery rate to change the preference to the delayed-surgery approach. The preference could also change if survival were much more important to the patient in the first five years than after five years or if the patient disliked living on anticoagulants enough to value a year on anticoagulants as worth only 80% of a year not on anticoagulants. CONCLUSION: This decision analysis provides quantitative support for the impression that patients similar to the case scenario do better with surgery timed at the onset of ventricular dysfunction than with surgery delayed until symptoms develop. It thus supports the practice of following these patients noninvasively in order to time surgery. ",13 1189,"Volume conduction of the parietal N20 potential to the prerolandic frontal area. Somatosensory evoked potentials were recorded from the frontal and parietal areas in patients with various lesions in the central nervous system on stimulation of the median nerve. Five representative cases who showed a selective loss of the positive potential from the frontal area are reported. In each case, the parietal N20 potential was relatively well preserved, and the midposition between the frontal and central areas (FC area) showed a negative potential following P14. The peak of this negative potential was synchronous with that of the parietal N20 potential. This negativity on the FC area is considered to be a volume conducted potential from the parietal N20 to the prerolandic frontal area. Such an anterior volume conduction of the parietal N20 would not be explained by the concept of a tangentially oriented dipole generated in the posterior bank of the central sulcus. Instead, for the generator of the parietal N20 potential, a radically oriented dipole generated mainly in the parietal area is postulated. ",9 1456,"A serial section study of visually normal pelvic peritoneum in patients with endometriosis. Defined criteria were used to select small samples of visually normal study peritoneum for serial section light microscopy in 45 patients with biopsy-proven endometriosis and 10 patients without endometriosis. A glandular element compatible with possible endometriosis was found in only 1 patient. Visually normal peritoneum does not harbor a high prevalence of invisible microscopic endometriosis. ",12 2999,"Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat. The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic-isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic-isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess. ",22 2005,"Transesophageal echocardiography in the diagnosis of left atrial appendage aneurysm. Intrapericardial left atrial appendage aneurysm is rare. We describe the transthoracic and transesophageal echocardiographic findings in a 42-year-old man with atrial arrhythmia and an abnormal left atrial appendage on chest roentgenogram. Presence of an intrapericardial left atrial appendage aneurysm was confirmed at surgery. ",13 1755,"Recent changes in the treatment of aortoiliac occlusive disease by the Oxford Regional Vascular Service. Over the four years from 1 January 1985 to 31 December 1988, 192 patients were treated for aortoiliac occlusive disease by the Oxford Regional Vascular Service. The number of patients treated by percutaneous transluminal angioplasty increased from two in the first year of the study to 34 in the third year of the study. This increase was accompanied by a decrease in the proportion of patients treated by aortobifemoral bypass but the proportion of patients treated by extra-anatomic bypass remained constant at around 30 per cent. Twice as many patients were treated in the fourth year as in the first year of the study so that the number of surgical operations increased despite many patients being treated exclusively by percutaneous transluminal angioplasty. The number of patients requiring mandatory treatment for limb salvage increased by 109 per cent and optional treatment for intermittent claudication by 85 per cent. The introduction of percutaneous transluminal angioplasty in Oxford has coincided with an increase in the number of patients presenting with symptomatic aortoiliac occlusive disease and has allowed twice as many people to be treated while the number of aortobifemoral bypass operations has remained unchanged. It is concluded that the introduction of percutaneous transluminal angioplasty has not only generated its own workload but has also led to an increased demand for surgical reconstruction for aortoiliac occlusive disease. ",13 76,"Antimicrobial prophylaxis for open heart operations. Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram-negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting. ",0 2424,"Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta-cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus. ",17 2434,"Brain glucose metabolism in noninsulin-dependent diabetes mellitus: a study in Pima Indians using positron emission tomography during hyperinsulinemia with euglycemic glucose clamp. To determine whether insulin or noninsulin-dependent diabetes mellitus affects brain glucose metabolism, brain glucose utilization was studied in the basal state and during hyperinsulinemic euglycemic glucose clamps in nondiabetic and diabetic Pima Indians by positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (18FDG). Glucose utilization in 75 brain areas was determined by analysis of single scans and by least squares estimation of the rate parameters for the FDG model; these data were compared to results in normal caucasian volunteers. No effect of ethnicity or diabetic status on brain glucose utilization was observed. During the hyperinsulinemic clamps (mean insulin, 11,708 +/- 3,026 pmol/L), clearance of 18FDG from blood was accelerated, and accumulation of brain radioactivity was reduced. However, glucose utilization by the brain was identical to results during sham glucose clamps (mean insulin, 204 +/- 56 pmol/L) performed in the same patients. During the studies with hyperinsulinemia, k4 (representing loss of tissue radioactivity) was increased in most brain areas (mean increase, 0.0031 +/- 0.0018 min-1; P less than 0.02). The possible mechanisms for this effect are multiple, and the physiological significance, if any, is unknown. Further studies of the effects of insulin on brain glucose metabolism are needed. ",17 2767,"Path of bullet and injuries determined by radiography. Radiography is commonly used to find bullet pathways in forensic pathology. In the case presented here, a man had sustained multiple gunshot wounds and one bullet could not be traced. A radiograph was used to find the bullet and showed an interesting bullet pathway. By observing the bullet pathway on a radiograph, sometimes we can surmise the victim's body posture at the time of an incident. ",20 2109,"LVAS pump performance following initiation of left ventricular assistance. Prevention of disturbed flow (e.g., flow stasis) and consequent thrombosis in heart pumps is based upon design characteristics determined during laboratory bench tests. These tests employ optimal filling and emptying characteristics, such as the full-fill to complete empty mode in the Novacor left ventricular assist system. Filling characteristics of the Novacor LVAS were examined during the first 48 hours after implantation in 14 patients. Fill volume of the pump was reduced in pathologic states, such as cardiac tamponade, and following the initiation of right ventricular mechanical circulatory support. In addition, multiple regression analysis revealed that right ventricular function measured by the amount of inotropic support required, the right ventricular ejection fraction, and the total pulmonary resistance, significantly predicted left ventricular assist pump fill volume during the first 48 hours of support. Flow visualization simulating these clinical conditions of incomplete filling suggest inadequate valve washing, particularly around the inlet valve and its conduit, which may predispose to thrombus formation. ",13 1829,"Primary varicose veins: topographic and hemodynamic correlations. This study was conducted to correlate the clinical presentations of uncomplicated primary varicose veins with the topographic and anatomic source of reflux (escape points). One-hundred sixty-three patients with primary varicose veins (144 females, 19 males; 96 unilateral, 67 bilateral) in 230 involved limbs were examined. The origin and extent of venous reflux was traced with Doppler ultrasound. Three distinct groups were recognized. Group I. Typical saphenous varicosities with junctional escapes occurred in 164 (71.3%). Sapheno-femoral junction (SFJ) incompetence in 147, and sapheno-popliteal junction (SPJ) incompetence in 17 limbs. Group II. Atypical saphenous varicosities with non-junctional escapes occurred in 51 (22.17%) limbs. In 5 limbs, no escape was detected. Twenty-two limbs had escapes localized in the main perforators: mid-thigh perforator 17, upper calf 2, distal ankle in 3. Twenty-four limbs had their escapes in the auxiliary perforators: abdomino-pelvic 17, and circumflex iliac/external epigastric, 7 limbs. Group III. Non saphenous (lateral venous system) varicosities occurred in 15 (6.52%) limbs. Based on physical examination alone, 55 limbs would possibly have undergone unnecessary ankle to groin stripping and 83 limbs an unnecessary SFJ ligation. Doppler US is an essential diagnostic tool that can accurately map the origin and extent of the venous reflux. The obtained hemodynamic information will permit more selective, multimodal therapy and avoid the indiscriminate, often unnecessary stripping of the entire saphenous system in all cases of primary varicose veins. ",13 2467,"Treatment of severe reactive hypoglycemia with a somatostatin analogue (SMS 201-995). Reactive (or postprandial) hypoglycemia can sometimes represent a severe disorder refractory to conventional therapeutic measures. We present in this first individual trial, to our knowledge, that the administration of a somatostatin analogue (SMS 201-995) may alleviate the severity of complaints and does not appear to be diabetogenic. The effects of the somatostatin analogue were documented in a 5-hour oral glucose tolerance test, where not only the glucose-induced and C-peptide rise was clearly attenuated, but also the blood glucose concentration did not fall low enough to induce hypoglycemic symptoms. ",17 689,"Mechanical lithotripsy of common duct stones. Over the past 8 years we have utilized various types of mechanical lithotriptors to crush common bile duct stones. The procedure was performed in 93 patients with an overall success rate of 94%. However, because many accessories were in a developmental stage, entrapment of stones was not always possible on the first attempt, and the procedure was repeated in some patients a second or third time. During the interim, while awaiting another attempt at lithotripsy, cholangitis was prevented by leaving a prosthesis in place. A variety of lithotriptor models from different manufacturers have proven effective. We recommend that endoscopists use these devices to rid the bile duct of retained stones. ",5 1848,"Single photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia: correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography The feasibility, safety and diagnostic accuracy of single photon emission computed tomography (SPECT) with thallium-201 imaging during adenosine-induced coronary hyperemia were evaluated in 53 patients with and 7 without coronary artery disease proved by coronary angiography. Adenosine was infused intravenously at a dose of 0.14 mg/kg body weight per min for 6 min and thallium was injected at 3 min. Adenosine caused an increase in heart rate (68 +/- 12 at baseline versus 87 +/- 18 beats/min at peak effect, p less than 0.0001) but no change in blood pressure. The sensitivity and specificity were 92% (95% confidence intervals 81% to 98%) and 100% (95% confidence intervals 59% to 100%), respectively; 20 (61%) of 33 patients with multivessel coronary artery disease were also correctly identified. In 30 patients, the predictive accuracy of adenosine thallium imaging was slightly higher than that of exercise SPECT thallium imaging (90% versus 80%, p = NS) (95% confidence intervals 72% to 97% and 61% to 92%, respectively). In 25 patients, two-dimensional echocardiography during adenosine infusion disclosed a new wall motion abnormality in 2 (10%) of 20 patients with coronary artery disease; 80% of these patients had reversible thallium defects (p less than 0.001). Side effects were mild and transient; aminophylline was used in only three patients. Thus, adenosine SPECT thallium imaging provides a high degree of accuracy in the diagnosis of coronary artery disease. The results are comparable with those of exercise SPECT thallium imaging. Most reversible defects in the adenosine study are not associated with any transient wall motion abnormality. ",13 1849,"Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: importance of atrial fibrillatory cycle length. The effects of intravenous procainamide (n = 30) or propafenone (n = 25) were evaluated in 55 patients with acute atrial fibrillation and the Wolff-Parkinson-White syndrome. All patients received either procainamide (12 to 15 mg/kg body weight) or propafenone (1 to 2 mg/kg) during sustained (greater than 10 min) atrial fibrillation or after termination of nonsustained atrial fibrillation. Termination of atrial fibrillation was attributed to a drug if it occurred less than or equal to 15 min after infusion. Measurements included mean cycle length of fibrillatory electrograms (mean AA interval) as measured at the high right atrium and shortest RR interval between pre-excited cycles during atrial fibrillation. Atrial fibrillation terminated more frequently after procainamide administration (65%) than after propafenone (46%), although this difference was not significant. Procainamide prolonged the shortest pre-excited RR interval (228 +/- 41 to 339 +/- 23 ms, p = 0.0001) as did propafenone (215 +/- 40 to 415 +/- 198 ms, p = 0.0001) and the magnitude of increase was greater for propafenone (p = 0.048). Patients with sustained atrial fibrillation had shorter mean AA intervals than did their counterparts with nonsustained atrial fibrillation (123 +/- 25 versus 186 +/- 35 ms, p = 0.0001). Termination of sustained atrial fibrillation by either drug was accompanied by prolongation of the mean AA interval but not necessarily by the shortest pre-excited RR interval. Termination of atrial fibrillation was heralded by a 68% increase in the mean AA interval after procainamide administration compared with a 30% increase when the arrhythmia persisted. For propafenone the increases were 90% and 68%, respectively. ",13 51,"Nasal carriage of Staphylococcus aureus: correlation with hormonal status in women. In view of recent observations on hormone-microorganism interactions, a study of Staphylococcus aureus nasal carriage in relation to sex-hormone status was undertaken. Prospectively in 479 women attending a colpocytologic clinic, hormonal status was assessed by determining the karyopyknotic index (KI) on smears stained by the Papanicolaou method. Rates of S. aureus nasal carriage were 29.3% in premenopausal women and 21.9% in postmenopausal women (P not significant). Carriage rates were significantly higher (P = .026, chi 2 7.32) for women with high KIs (40.7%) than for those with intermediate and low KIs (27.03% and 25.1%, respectively). S. aureus nasal carriage also correlated independently and significantly with previous antibiotic use and the presence of insulin-treated diabetes mellitus. This preliminary observation confirms an association between levels of sex hormones as reflected by the KI and S. aureus nasal carriage rates. ",0 3309,"Hypothalamic glucocorticoid implants prevent fetal ovine adrenocorticotropin secretion in response to stress. We evaluated the role of the hypothalamic paraventricular nucleus (PVN) in control of ACTH secretion in fetal sheep. Dexamethasone (DEX, 700 micrograms) (n = 6) or cholesterol (CHOL, 700 micrograms) (n = 5) implants were placed bilaterally 2 mm lateral to PVN of fetal sheep at 108 to 111 days of gestation (dga). After 5 days recovery, fetuses were challenged with: 1) hypotension (50% drop of blood pressure), 2) hypoxemia (fall of greater than 5 mm Hg in fetal PaO2), and 3) corticotropin-releasing hormone (CRH) (10 micrograms iv, single injection to fetus). Hypotension and hypoxemia were repeated after 125 dga. Compared with CHOL, DEX fetuses had lower average concentrations of ACTH in plasma after hypotension [23 +/- 0.5 vs. 149 +/- 83.8 and 31 +/- 13.1 vs. 101 +/- 31.3 pg ml-1 at less than 125 and more than 125 dga, respectively (mean +/- SEM, P less than 0.05)] and during hypoxemia [11 +/- 1.6 vs. 292 +/- 152.8 and 33 +/- 9.4 vs. 304 +/- 91.3 pg ml-1 at less than 125 and more than 125 dga, respectively (P less than 0.05)]. DEX and CHOL responses to CRH at 122 to 127 dga (10 micrograms iv) were not different (38 +/- 23.9 vs. 92 +/- 26.7 pg ml-1, respectively). Immunocytochemistry demonstrated that CRH was decreased in PVN and eliminated from median eminence in DEX, but not in CHOL fetuses. Arginine vasopressin (AVP) immunostaining of PVN of DEX and CHOL fetuses was similar; however, unlike CHOL, DEX fetuses showed no AVP immunostaining of the external zone of median eminence. These results show that, in fetal sheep, high concentrations of glucocorticoid near the fetal PVN prevent increases in plasma ACTH secretion seen in controls in response to hypotension and hypoxemia, and exert at least part of their effect at the level of the CRH- and AVP-producing neurons located in the PVN. ",22 1378,"A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD. Intraperitoneal fluid volume (IPV) changes versus time were followed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using a simple volume recovery method. In each patient dialysates containing 1.36 and 3.86 percent glucose as an osmotic agent were investigated. The patients' IPV versus time data were fitted to a function determined by four ""arbitrary"" coefficients, from which both the initial ultrafiltration (UF) rate immediately following intraperitoneal (i.p.) fluid instillation and the ""final"" peritoneal-to-blood fluid absorption rate could be assessed. The peritoneal osmotic conductance to glucose, that is, the peritoneal ultrafiltration coefficient (Kf), times the peritoneal osmotic reflection coefficient to glucose (sigma g), Kf sigma g, was determined using two related approaches. Kf sigma g is a major determinant of the transperitoneal volume exchange, and it was calculated to be 3.54 +/- 0.85 (+/- SE) and 3.81 +/- 0.52 microliters/min/mm Hg, respectively, depending on the assumption employed. Kf sigma g was further analysed according to a three-pore model of membrane permeability to determine the possible range of Kf and sigma g compatible with a peritoneal small solute sieving coefficient (phi) ranging from 0.3 to 0.61. According to these calculations both Kf and sigma g ranged from 0.043 to 0.081 (ml/min/mm Hg and dimensionless, respectively). The maximal peritoneal lymph flow (L) realistic according to this analysis, and compatible with a measured total peritoneal-to-blood fluid absorption rate of 1.25 +/- 0.14 ml/min, was 0.75 ml/min, the most plausible values, however, falling between 0.3 to 0.5 ml/min. ",11 356,"Colorectal cancer: have we identified an effective screening strategy? Three currently used screening methods are aimed at detecting colorectal cancer when it is asymptomatic and curable, and at detecting polyps so that they can be removed before they can progress to cancer. Digital rectal examinations are relatively cheap and easy but can detect only a small fraction of large-bowel cancers. Sigmoidoscopy is more sensitive, but its low acceptability to patients has been only partially mitigated by the introduction of the 35-cm flexible instrument. Fecal occult blood testing has limited sensitivity because blood from cancers and polyps is neither continuously shed nor uniformly distributed in feces; specificity and positive predictive value are also low because of other sources of blood in the stool. Prudent judgment suggests that all of these screening tests may prevent death from colorectal cancer in some patients. However, none has been proven effective in general use by well-controlled studies. Case-control studies can provide timely and valuable new evidence in this regard; the authors' investigations in progress are described. The current lack of strong evidence in support of these screening tests should not be interpreted as evidence against their use. ",3 16,"Intraamniotic infection in the very early phase of the second trimester. A total of 157 consecutive patients were studied in an effort to examine prospectively the incidence of asymptomatic intraamniotic infection in the early phase of the second trimester. All patients were referred for amniotic fluid karyotyping. In addition, the amniotic fluids were examined for Gram stain and were directly cultured on blood agar and MacConkey agar as well as in thioglycollate broth. We found positive amniotic fluid cultures in eight cases (5.09%); however, results of Gram stain examinations were negative in all amniotic fluid samples. The data indicate that there is no correlation between white blood cells in the amniotic fluid and positive amniotic fluid culture results. Only one pregnancy with positive amniotic fluid culture resulted in a septic abortion. Therefore we can suggest that intraamniotic infection can exist early in pregnancy, even with intact membranes, and in most cases without any clinical symptoms. ",0 136,"A routine tool for detection and assessment of epidemics of influenza-like syndromes in France. A regression model for the nonepidemic level of influenza-like syndrome has been estimated from the 55,200 cases collected between October 1984 and August 1988 using the French Communicable Diseases Computer Network. The start of a major epidemic in 1988-89 was detected early. The size of the epidemic, for the entire country, was estimated at approximately 4.3 million cases. The excess cost of sick-leave, among those of working age, was estimated at $86 million. ",1 2481,"Changes in phosphoinositide turnover, Ca2+ mobilization, and protein phosphorylation in platelets from NIDDM patients. Enhanced platelet functions have been demonstrated in patients with non-insulin-dependent diabetes mellitus (NIDDM). This study evaluated abnormalities in platelet signal transduction in diabetic patients, including turnover of phosphoinositides, mobilization of intracellular Ca2+, and phosphorylation of 20,000- and 47,000-Mr proteins (P20 and P47). Washed platelets were obtained from 6 patients with NIDDM whose platelet aggregation rates were abnormally elevated (DM-A group), 11 NIDDM patients with normal platelet aggregation rates (DM-B group), and 8 age-matched healthy control subjects. The mass and specific radioactivity of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), and phosphatidic acid (PA) in 32P-labeled platelets were not different among the three groups. Hydrolysis of PIP2, PIP, and PI; accumulation of PA; and phosphorylation of P20 in platelets stimulated by 0.05 U/ml thrombin were significantly increased in the DM-A group compared with the control or DM-B group. There was no difference in P47 phosphorylation among the three groups. On the contrary, P20 and P47 phosphorylation induced by 50 nM of 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, was significantly decreased in the DM-A group. Additionally, the intracellular free Ca2+ concentration [( Ca2+]i) was measured with the fluorescent Ca2+ indicator fura 2. Although the basal [Ca2+]i value was similar in the three groups, the rise in [Ca2+]i induced by 0.05 U/ml thrombin in the presence and the absence of extracellular Ca2+ was significantly higher in the DM-A group than the other groups. ",17 2197,"Partial anomalous pulmonary venous return. Anomalous pulmonary venous return from the left lung is an extremely rare condition that is reported sporadically and in general in case reports. From 1964 through 1988, we identified 13 patients with this condition, all of whom underwent surgical correction. This represents the single largest reported institutional experience with this anomaly. The patients ranged in age from 15 months to 40 years. Seven were asymptomatic, and six had symptoms ranging from recurrent pulmonary infection to moderate congestive heart failure. Six had anomalous venous return from the entire left lung, and seven had anomalous return from the upper lobe only. Eight of the patients had associated cardiovascular anomalies. Four of the patients underwent surgical correction via a sternotomy approach with cardiopulmonary bypass to allow correction of coexisting intracardiac anomalies. The remaining patients underwent surgical repair through a left thoracotomy. The technique included high ligation and division of a persistent left superior vena cava with anastomosis to the left atrium at the site of partial excision of the atrial appendage. There were no deaths and only one complication in our series. ",15 1399,"Intrauterine spermatic cord torsion in the newborn: sonographic and pathologic correlation. In five newborn patients with spermatic cord torsion, sonography demonstrated an enlarged and globular testis, hydrocele, and skin thickening. In four of these patients the testicular parenchyma was heterogeneous. Peripheral hypoechoic areas were seen in two of the four patients; the other two had a central hypoechoic region and a peripheral echogenic rim. The testis in the fifth patient was diffusely hyperechoic. Duplex Doppler sonography performed in two patients failed to demonstrate any signal in the spermatic cord in either the abnormal or contralateral hemiscrotum. Scintigraphic findings were positive for testicular torsion in two patients and equivocal in three patients. Surgery was performed 2-12 days after sonography and established the diagnosis of spermatic cord torsion. Pathologic examination demonstrated hemorrhagic infarction of the entire testis as well as scattered calcifications. The authors conclude that a solid globular testicular mass seen during the neonatal period is suggestive of intrauterine spermatic cord torsion. ",11 664,"Effects of 2% lignocaine on somatosensory evoked potentials recorded in the extradural space. We have studied the effects of extradural administration of 2% lignocaine at the L3-4 interspace on somatosensory evoked potentials recorded in the cervical extradural space before corrective surgery for idiopathic adolescent scoliosis. Eight patients in whom the equivalent volume of 0.9% sodium chloride solution was administered into the lumbar extradural space acted as a control group. Lignocaine 2% resulted in a decrease in overall amplitude, but its main effect was a significant decrease in the amplitude of the second and third peaks, suggesting an action on the dorsal columns of the spinal cord. A significant increase in latency was found in both the lignocaine and sodium chloride groups. We conclude that the use of extradural 2% lignocaine in patients undergoing scoliosis surgery may interfere with the intraoperative monitoring of somatosensory evoked potentials. ",4 1100,"Decline in the prevalence of childhood deafness in the Jewish population of Jerusalem: ethnic and genetic aspects. A longitudinal study was performed on 147 Jewish children with bilaterally sensorineural hearing loss of moderately severe to profound degree, born in Jerusalem during the eighteen years 1968-85. The prevalence rate of these children declined during the years 1977-85, and at the same time the rate of consanguinity of their parents decreased; this decline was more evident in the genetic group among children with non-Ashkenazi ethnic origin. No such decline was found among the Ashkenazi children and no consanguinity among parents of these children was recorded. Our study supports the assumption that restriction of consanguineous matings may affect the prevalence of genetic deafness in children in a well-defined population. We have tried to remain unbiased and concede certain shortcomings in our present study. ",9 3287,"Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast [published erratum appears in Proc Natl Acad Sci U S A 1991 Mar 1;88(5):2035] DNA sequencing was used to characterize 208 mutations induced in the SUP4-o tRNA gene of the yeast Saccharomyces cerevisiae by UVB (285-320 nm) radiation. The results were compared to those for an analysis of 211 SUP4-o mutations induced by 254-nm UVC light. In each case, greater than 90% of the mutations were single base-pair changes but G.C----A.T transitions predominated and accounted for more of the mutations induced by UVB than UVC. Double substitutions, single base-pair deletions, and more complex events were also recovered. However, UVB induced 3-fold more tandem substitutions than UVC and nontandem double events were detected only after irradiation with UVC. Virtually all induced substitutions occurred at sites where the pyrimidine of the base pair was part of a dipyrimidine sequence. Although the site specificities were consistent with roles for cyclobutane dimers and pyrimidine-pyrimidone(6-4) lesions in mutation induction, preliminary photoreactivation data implicated cyclobutane dimers as the major form of premutational DNA damage for both agents. Intriguingly, there was a preference for both UVB- and UVC-induced mutations to occur at sites where the dipyrimidine was on the transcribed strand. ",22 1238,"NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats. Systemically administered N-methyl-D-aspartate (NMDA) antagonists, MK-801 ((+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) and CPP (3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate), potentiate the ability of L-dopa (L-3,4-dihydroxyphenylalanine) to reverse akinesia and to alleviate muscular rigidity in monoamine-depleted rats. On the basis of these findings, it is proposed that NMDA antagonists may be beneficial as adjunctive treatment in the therapy of Parkinson's disease. CPP locally injected into the subthalamic nucleus, entopeduncular nucleus--the rat homologue of the internal pallidal segment--or substantia nigra pars reticulata of monoamine-depleted rats stimulates locomotor activity and alleviates rigidity, whereas local microinjection of CPP into the neostriatum is ineffective. These results make it unlikely that the neostriatum is the site of the antiparkinsonian action of NMDA antagonists in monoamine-depleted rats, whereas the subthalamic nucleus, internal pallidal segment, and substantia nigra pars reticulata appear to be important for the effects of NMDA antagonists. ",9 2184,"Characteristics of cholinergic neuroeffector transmission of ganglionic and aganglionic colon in Hirschsprung's disease. Differences in the release and content of acetylcholine and the alpha 2 adrenoceptor mediated interaction between noradrenergic and cholinergic neurons were investigated by neurochemical and pharmacological methods in aganglionic and ganglionic segments of isolated human colon taken from children suffering from Hirschsprung's disease. Both at rest and during transmural stimulation the release of acetylcholine was significantly higher in the spastic (aganglionic) segment than in the proximal dilated bowel. Significant differences were found in the tissue concentration of acetylcholine between ganglionic and aganglionic specimens. The pattern of response to transmural stimulation was also different in the spastic and dilated bowel. Transmural stimulation induced relaxation and contraction in ganglionic specimens but only contractions in aganglionic specimens. The sensitivity of the smooth muscle in the aganglionic portion to exogenous acetylcholine and to field stimulation was found to be higher than in the ganglionic portion. While noradrenaline added to the organ bath reduced the stimulation-evoked release of acetylcholine from spastic segments, via an alpha 2 adrenoceptor mediated process, yohimbine did not enhance the release. It is suggested that in Hirschsprung's disease the increased acetylcholine release, the enhanced sensitivity of smooth muscle cells to acetylcholine, and the lack of alpha 2 adrenoceptor mediated noradrenergic modulation of acetylcholine release from cholinergic interneurons might be responsible for the spasm of aganglionic segments. ",15 2947,"Open versus closed diagnostic peritoneal lavage in the evaluation of abdominal trauma. Two hundred forty-two patients underwent diagnostic peritoneal lavage (DPL) over a 12-month period. One hundred sixteen patients (48%) were randomized to an open lavage technique and 126 (52%) to a percutaneous (closed) guide wire procedure. The closed procedure required an average of 16 minutes to complete with one operator, whereas the open method required two operators and an average time of 26 minutes (p less than 0.001). Technical complications occurred in 31 patients undergoing closed lavage (25%) and 4 patients undergoing open lavage (3%) (p less than 0.01). Fifty-eight percent of the closed lavage complications were related to fluid return and 42% to guide wire placement. All the open lavage complications were caused by inadequate fluid return. These data do not support the initial use of percutaneous lavage. The open technique is favored and certainly used when the closed method fails or when direct visualization of the peritoneal cavity is indicated. Physicians involved in the management of abdominal trauma must be familiar with both methods of DPL. ",20 2328,"Identification and isolation of a phospholipase A2 activating protein in human rheumatoid arthritis synovial fluid: induction of eicosanoid synthesis and an inflammatory response in joints injected in vivo. Eicosanoids are important mediators of the destructive arthropathy observed in rheumatoid arthritis. The rate-limiting step in the eicosanoid synthesis pathway is the availability of free arachidonic acid. The phospholipase enzymes release arachidonic acid from membrane phospholipids and thus play an important role in the regulation of eicosanoid production. We have previously demonstrated enhanced phospholipase A2 and C enzyme activities in cells from patients with rheumatoid arthritis and have also described a phospholipase A2 activating protein (PLAP) in mammalian cell lines. In an attempt to determine the biochemical basis of enhanced phospholipase A2 activity found in patients with inflammatory joint disease, we examined synovial fluid from patients with rheumatoid arthritis for PLAP. To determine whether PLAP was specific for rheumatoid disease, we assayed specimens from patients with other arthropathies. Histologic examination of rheumatoid joint tissue, with the use of immunohistochemical techniques, demonstrated high concentration of PLAP in monocytes, macrophages, chondrocytes, vascular smooth muscle, and endothelial cells. Human PLAP could be biochemically isolated from synovial fluid from patients with rheumatoid arthritis and was found to be similar to PLAP previously isolated from murine and bovine sources. To determine whether PLAP could directly mediate any aspect of inflammatory disease, purified PLAP was injected into rabbit knee joints. This resulted in an acute inflammatory arthritis with synovial cell proliferation and synovial fluid leukocytosis. Purified PLAP also induced eicosanoid formation both in vivo and in vitro. With enzyme-linked immunosorbent assays, we found more PLAP in synovial fluid specimens from patients with rheumatoid arthritis compared with samples from patients with other inflammatory arthropathies as well as osteoarthritis, a noninflammatory arthropathy. These data suggest that PLAP may be responsible, at least in part, for some aspects of the destructive inflammatory arthropathy that is observed in patients with rheumatoid arthritis. ",16 377,"1990 Ogura memorial lecture: moral dilemmas in head and neck cancer. Neither morality nor dilemma can be defined meaningfully in the concept of the practical management of head and neck cancer. Although both have important implications, particularly with regard to ethnic and social factors, they play a relatively minor role in determining management policy. With little knowledge of the intrinsic causes of cancer and with a treatment strategy limited to radiotherapy and surgery, our desire for cure must be tempered by concern to avoid any increase in patient privations. My philosophy, based upon the care of more than 3500 patients over almost 30 years, reflects some of the difficulties of applying the concept ""do nothing that may cause harm,"" while offering each patient the opportunity for long-term cure. ",3 2615,"Basophil histamine release by platelet-activating factor in aspirin-sensitive subjects with asthma. Histamine release induced by platelet-activating factor (PAF) from leukocytes of aspirin-sensitive subjects with asthma was higher than that from normal control subjects, despite the similarity of anti-IgE-induced histamine release. Moreover, basophils of some aspirin-sensitive subjects with asthma released histamine by PAF stimulation in the absence of cytochalasin B that affects histamine release and is required in PAF-induced histamine release from leukocytes of atopic subjects with asthma and normal control subjects. In addition to temperature dependency and inhibition by ethylenediaminetetraacetic acid reported previously, PAF-induced histamine release was enhanced by cytochalasin B and indomethacin and inhibited by dexamethasone. These features are common with IgE-mediated histamine release and suggest the existence of the common pathway to PAF-induced histamine release and IgE-mediated histamine release. The results in the present study indicate the pathophysiologic significance of PAF-induced histamine release and that activation of basophils by PAF may be relevant to the pathogenesis in some aspirin-sensitive subjects with asthma. ",19 2075,"Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease. Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery diseaes. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 +/- 34.7 vs 33 +/- 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p less than 0.0001). Estimated defect size in the stress Tl-201 images (52 +/- 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 +/- 39.9 g; p less than 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT. ",13 2369,"Polymorphisms of HepG2/erythrocyte glucose-transporter gene. Linkage relationships and implications for genetic analysis of NIDDM. To assess the contribution of the HepG2/erythrocyte glucose-transporter (HepG2 GT) gene to the inherited susceptibility to non-insulin-dependent diabetes mellitus (NIDDM), cDNA and genomic probes were used to search for restriction-endonuclease polymorphisms at this locus. Analysis of DNA from 16 unrelated Black American individuals with 19 enzymes and as many as six different probes, defined four polymorphisms over a 45-kilobase region. Nucleotide diversity (pi = 0.006) was low relative to that at other loci, with an average of 1 in 1700 base pairs different between two chromosomes at this locus. The observed combined heterozygosity for these four sites was 0.69, which indicates that the markers at this locus could be useful for linkage analysis in families. Linkage-disequilibrium values between the four polymorphisms were evaluated by pairwise analysis and extended haplotypes. Calculating pairwise associations by the disequilibrium statistic delta or by another measure of disequilibrium, D' (the maximum likelihood of disequilibrium, which is less dependent on frequency), significant linkage disequilibrium could not be demonstrated. However, the frequencies of the observed extended haplotypes were shown to differ (chi 2 = 9.1, df = 2, P less than 0.025) from predicted frequencies if the sites were in linkage equilibrium in Blacks. The frequencies of these four polymorphisms were determined in Black nondiabetic (n = 44) and NIDDM (n = 63) subjects. Neither the allelic nor genotypic frequencies of the polymorphisms differed between the two groups. ",17 2625,"AZT demonstrates anti-HIV-1 activity in persistently infected cell lines: implications for combination chemotherapy and immunotherapy. A sensitive and quantitative focal immunoassay has been used to measure the effects of three different therapeutic agents on tissue culture cells infected with human immunodeficiency virus (HIV). The effects of the drugs were studied on both acutely and persistently infected CD4+ cell lines. The three agents, azidothymidine (AZT), interferon-alpha (IFN-alpha), and an anti-HIV envelope antibody coupled to ricin A chain, were tested alone and in combination. AZT was found to have its greatest effect during early stages of the infection, but also had an action on persistently infected T cell lines. The effect of AZT on persistently infected cells was seen within 24 h, increased with extended exposure to the drug, and persisted after its removal. IFN-alpha had variable effects on acutely infected cells but suppressed chronic infection. Combinations of the therapeutic agents were studied. Using a model that allowed for treatment during both acute and persistent stages of infection, the most effective combination in suppressing HIV infection was the continual use of both AZT and IFN-alpha at the highest tolerable doses. Knowledge of the efficacy of AZT on persistently infected cells will allow for the most effective design of clinical protocols. ",19 1181,"The deja vu experience: remembrance of things past? The deja vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical features, and etiology of the phenomenon of deja vu. They also review the different hypotheses on the psychopathogenesis of the deja vu experience and introduce an explanation based on the hologram as a mnestic model. ",9 2921,"Morphine pharmacokinetics during anesthesia and surgery in patients with burns. The plasma clearance, plasma half-life, and apparent volume of distribution of morphine during anesthesia and surgery were determined in seven patients with burns and compared with seven age-matched control subjects. The burn group had a significantly lower clearance, longer terminal half-life, and smaller volume of distribution than the control group. The clearance was 12 +/- 2 ml/min/kg, the half-life was 123 +/- 24 minutes, and the volume of distribution was 2.2 +/- 0.4 L/kg for the subjects with burns compared with 25 +/- 3 ml/min/kg, 89 +/- 18 minutes, and 3.2 +/- 0.8 L/kg for the control subjects (p less than 0.001, less than 0.02, and less than 0.02, respectively). These data contrast with the theory that patients with burns have a tolerance to narcotics and suggest the need for further study of the pharmacologic effects of burn injury and surgery. ",20 651,"Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study. We conducted a 6-month open-label trial in which 10 patients with active psoriatic arthritis received 2 micrograms of oral 1,25-dihydroxyvitamin D3 daily. Statistically significant improvement was noted in the tender joint count and physician global impression. Of these 10 patients, 4 had substantial (greater than or equal to 50%) improvement, and 3 had moderate (greater than or equal to 25%) improvement in the tender joint count. Two patients were unable to receive therapeutic doses because of hypercalciuria. High-dose vitamin D may be a useful therapeutic agent for psoriatic arthritis. ",4 814,"Gastroesophageal reflux disease: an update on management. Gastroesophageal reflux is commonplace; all humans experience it. For many patients, gastroesophageal reflux disease (GERD) is a manageable condition. For others, GERD can progress to severe symptoms, inflammation, and disruption of the mucosal lining. Effective therapy calls for a clear understanding of the pathogenesis of GERD. The final common denominator to GERD is a lower esophageal sphincter mechanism that relaxes or is incompetent and allows gastroesophageal reflux to occur. Key factors associated with GERD are (a) gastric content, (b) potency of refluxate, (c) esophageal clearance, (d) tissue resistance, and (e) disruption of the anatomic hiatus. GERD is generally a chronic condition characterized by recurrent symptoms. Treatment goals for the GERD patient need to be defined: is therapy directed toward eliminating the symptoms or is therapy designed to eliminate gastroesophageal reflux? Unfortunately, effective therapy for GERD usually does not affect the mechanism(s) underlying the problem. The broad goals of therapy in GERD are to decrease gastroesophageal reflux and neutralize it, to enhance esophageal clearance, and to protect esophageal mucosa. The therapeutic modalities related to each of these situations are numerous and overlap, but treatment strategies for managing the GERD patient can be used in clinical ""stages"" or as the clinical situation dictates. H2-receptor antagonist therapy has become the ""keystone"" in management of GERD. Unfortunately, not all GERD patients respond to conventional H2-receptor antagonist dosage treatment; high-dose H2-receptor antagonist therapy recently has been demonstrated to be more effective in a greater number of GERD patients with severe esophagitis. ",5 2687,"Rapid oral desensitization to isoniazid and rifampin. A 45-year-old black woman, sputum positive for acid-fast bacilli, developed hypersensitivity to both isoniazid and rifampin. She was admitted to the hospital and desensitized to both medications using modified penicillin protocols. Skin testing was negative to both drugs. Desensitization to isoniazid was complicated by a drug fever that was controlled by prednisone. The patient was able to maintain once-a-day dosing without incident even with steroid taper. To our knowledge, this is the first reported case of dual isoniazid and rifampin hypersensitivity with rapid oral desensitization. ",19 233,"Squamous cell carcinoma antigen (TA-4) in penile carcinoma. TA-4 antigen, originally isolated from women with squamous cell carcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites, including esophagus, lungs, and head and neck. In this study, we compared the serum levels of TA-4 in normal volunteers, patients with resected penile squamous cell carcinoma, and patients with metastatic penile squamous cell carcinoma. TA-4 values were elevated in 5 of 11 patients (45%) who had metastatic disease. In 2, TA-4 was normal the first time metastasis was clinically detected but rose as the disease progressed. Moreover, in 3 patients in whom serial determinations were made, serum TA-4 values correlated well with disease progression and response to treatment. We conclude that TA-4 values are elevated in some patients with metastatic squamous cell carcinoma of the penis and may become a useful marker for monitoring response to therapy. ",3 1157,"Improving outcomes of analgesic treatment: is education enough? Frequent undertreatment of analgesic-responsive acute pain and chronic cancer pain persists, despite intensive efforts to provide clinicians with information about analgesics. A set of background factors must be addressed in interventions to improve pain treatment: Traditional patterns of clinician and patient interaction on the ward, quality assurance, and drug regulatory practices do not support prompt recognition and treatment of pain. Possible interventions to modify these patterns of daily practice include monitoring and displaying patient pain ratings routinely, making available educational tools to assist optimal drug ordering, encouraging patients to communicate about unrelieved pain, reviewing quality assurance of pain treatment regimens, increasing behavioral research into analgesic prescribing, and selectively modifying narcotics regulatory practices. ",9 884,"Neutrophilia in bronchoalveolar lavage fluid of diffuse panbronchiolitis. The clinical and pathologic features of diffuse panbronchiolitis (DPB) have been well reported to date, although its pathogenesis remains unknown. In the present study, we performed bronchoalveolar lavage (BAL) on three patients with biopsy specimen-proven DPB and eight patients with highly probable DPB (six women and five men; one smoker and ten nonsmokers), nine patients with chronic bronchitis (all men, five smokers and four nonsmokers), and nine normal control subjects (six women and three men, all nonsmokers) to clarify the cell populations in the lower respiratory tract. Neutrophils comprised 55.3 +/- 24.4 percent of recovered cells by BAL in DPB patients but only 6.6 +/- 6.4 percent in chronic bronchitis patients, and 1.8 +/- 1.5 percent in normal control subjects (p less than 0.001, all comparisons). The DPB patients also exhibited a decreased percentage of alveolar macrophages (34.9 +/- 23.5 percent) compared with chronic bronchitis patients and normal control subjects (p less than 0.001, all comparisons). The percentage of lymphocytes of the recovered lavage cells in DPB patients did not differ from that in chronic bronchitis patients and normal control subjects. These results indicate that neutrophils play an important role in the pathogenesis of DPB. They also suggest that neutrophilia of BAL-recovered fluid is a common finding in diseases associated with bronchiolar inflammation despite some clinical and pathophysiologic differences. ",7 1216,"Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible. ",9 469,"Retroviral recombination and reverse transcription. Recombination occurs at a high rate in retroviral replication, and its observation requires a virion containing two different RNA molecules (heterodimeric particles). Analysis of retroviral recombinants formed after a single round of replication revealed that (i) the nonselected markers changed more frequently than expected from the rate of recombination of selected markers; (ii) the transfer of the initially synthesized minus strand strong stop DNA was either intramolecular or intermolecular; (iii) the transfer of the first synthesized plus strand strong stop DNA was always intramolecular; and (iv) there was a strong correlation between the type of transfer of the minus strand strong stop DNA and the number of template switches observed. These data suggest that retroviral recombination is ordered and occurs during the synthesis of both minus and plus strand DNA. ",3 1952,"Clinical performance of St. Jude and Medtronic-Hall prostheses: a randomized comparative study. Newer and improved models of mechanical prostheses are regularly added to surgeons' armamentarium. This study was designed to compare the clinical performance of two of the most used current models of mechanical prostheses. From August 1983 through July 1985, 182 white patients were prospectively randomized to implantation of the St. Jude Medical (95 patients) or Medtronic-Hall (87 patients) prostheses. There were 84 mitral, 85 aortic, and 13 double (mitral and aortic) valve replacements. There were no differences between the two groups with regard to sex distribution, age, functional class, emergency operation, and site of implantation. Early mortality was 3.2% for patients with the St. Jude valve and 5.7% for those with the Medtronic-Hall (p = NS). The survivors were followed for 3 to 5 years (mean, 4.2 +/- 0.6 years; cumulative follow-up, 559 patient-years). Late mortality was 7.1%/patient-year for the St. Jude group and 3.2%/patient-year for the Medtronic-Hall group (p less than 0.05). However, the valve-related mortality was equal (1.4%/patient-year) for both groups. Noncardiac causes accounted for most of the difference between the St. Jude and Medtronic-Hall groups (2.5%/patient-year and 0.4%/patient-year, respectively). There were no cases of thrombotic obstruction, whereas serious systemic thromboembolism occurred at the rate of 1.8%/patient-year (5 episodes) for the St. Jude group and 2.5%/patient-year (7 episodes) for the Medtronic-Hall group (p = not significant); there were another nine episodes of systemic embolism that left no sequelae. Three patients (St. Jude, 2; Medtronic-Hall, 1), all of whom had aortic valve replacement, required reoperation (0.5%/patient-year) because of prosthetic endocarditis, with two deaths. ",13 285,"The physical state of human papillomavirus 16 DNA in cervical carcinoma and cervical intraepithelial neoplasia. Cervical carcinomas and cervical intraepithelial neoplasias (CIN) were analyzed for the presence of human papillomavirus (HPV) DNA using Southern blot hybridization. Of the five HPV types examined (HPV types 6, 11, 16, 18, and 33), HPV 16 DNA was detected most frequently. In most HPV 16-positive carcinomas examined, HPV 16 DNA was present in an integrated state in cellular DNA with or without the coexistence of episomal species. In one case, however, only episomal species were detected. Among seven cases of HPV 16-positive CIN, four contained HPV 16 DNA only in the episomal state and the rest contained HPV 16 DNA only in the integrated state, but the coexistence of both states was not found. These results suggest that the integration of HPV 16 DNA is not necessary for cells to become malignant, although it is frequently associated with malignant cells. ",3 2834,"An elliptical incised wound of the breast misinterpreted as a bite injury. Bite injuries upon homicide victims are most often initially identified by the forensic pathologist during the course of the autopsy examination. Following such recognition, the injury or photographs of the traumatized site are then referred to a forensic odontologist for his or her examination, further characterization, and subsequent comparison with any suspect's dentition. However, if the pathologist misidentifies an injury caused by another mechanism as a human bite, this mistake can potentially be perpetuated by the dental consultant, since relatively few dentists regularly examine traumatic injuries other than those arising from bites. To illustrate such an event, a case is presented involving an incised wound of the breast, which was originally identified as an avulsive bite wound. Detailed examination by two odontologic consultants confirmed the wound as having been caused by human teeth, and further, they related the ""bite injury"" to a specific individual. The bite injury interpretation represented the only scientific evidence implicating the suspect at a subsequent trial for capital murder. Later examination of the tissues and photographs by a forensic pathologist and another dental consultant revealed that the injury was not due to human dentition, but rather resulted from a sharp-edged instrument. These consultants conducted a unique experiment to reduplicate the injury and prove its causation. This information was presented to the jury during the suspect's trial and resulted in his acquittal on all charges. ",20 3095,"Evaluation of antral mast cells in nonulcer dyspepsia. Two hundred twenty-five patients with the symptoms of nonulcer dyspepsia underwent clinical and endoscopic evaluation including histologic assessment of endoscopic biopsies. Mast cells were counted after special staining with low pH Alcian blue. Of 225 patients, 31 (13%) were found to have 11 or greater mast cells per high-power field. Endoscopic and routine histologic findings were similar between the subset of 31 patients with 11 or more mast cells and the entire group of 225. The 31 patients with increased antral mast cells had failed treatment with standard drug used for peptic ulcer disease. H1-antagonists improved symptoms in the majority of patients (79%) in whom we had adequate follow-up. Patients with increased mast cells on antral biopsy appear to be subset of patients with nonulcer dyspepsia amenable specific treatment with H1-antagonists. ",22 2425,"High frequency of aspartic acid at position 57 of HLA-DQ beta-chain in Japanese IDDM patients and nondiabetic subjects. The HLA-DQ beta-chain (DQB1) genes of 72 Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 85 control subjects were studied with polymerase chain-reaction (PCR) amplification and allele-specific oligonucleotide hybridization. DQW4 (DQBBlank) and DQw9 (DQB3.3) were increased in IDDM patients compared with the control subjects, and DQB1.2, DQB1.9, and DQw7 (DQB3.1) were decreased. Thirty-five (48.6%) IDDM patients had both alleles carrying an aspartic acid at position 57 of the DQ beta-chain (Asp 57), 35 (48.6%) were Asp 57/non-Asp 57 heterozygous, and 2 (2.8%) had non-Asp 57 alleles only. Of 85 control subjects, the respective values for these three genotypes were 49 (57.6%), 29 (34.1%), and 7 (8.2%), respectively. The high frequency of Asp 57 alleles in both IDDM and control subjects contrasts with data for Whites. Therefore, the Asp 57 hypothesis that the presence of an aspartic acid at position 57 of DQ beta-chain provides protection against developing IDDM is not tenable for Japanese IDDM patients. The DRB1 gene, particularly position 57 of the DR beta-chain, may contribute to IDDM susceptibility in Japanese. ",17 1896,"Angiography, angioscopy, and ultrasound imaging before and after percutaneous balloon angioplasty. We report two patients undergoing peripheral percutaneous transluminal angioplasty in whom angiography, angioscopy, and ultrasound imaging were performed before and after balloon angioplasty. The first case with smooth atheroma diagnosed by angiography was found to have unrecognized partially occlusive thrombus by angioscopy. After angioplasty, an intimal tear was identified by angioscopy and ultrasound but it was not seen by angiography. The intravascular ultrasound image showed the tear to extend to the adventitia. In the second case, an apparently smooth intimal surface as imaged by angiography was found by angioscopy and ultrasound to have extensive damage, including subintimal hemorrhage, intimal flaps, and arterial dissection at the angioplasty site. These data suggest that the type of information derived from the three imaging techniques is quite different, and that each may have a specific role in intravascular diagnosis. ",13 1342,"The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin: a two-year prospective trial. Of 52 patients with mesangial IgA nephropathy, 25 were allocated to treatment with cyclophosphamide (6 months), and dipyridamole and warfarin (2 years) and 27 to no treatment in a randomized prospective 2-year study. At entry, the treated and untreated groups of patients did not differ in mean serum creatinines, urinary protein excretions, quantitative urinary erythrocyte counts or blood pressure readings. At the end of the trial mean (+/- SEM) serum creatinine values had gone from 0.12 +/- 0.01 to 0.13 +/- 0.01 mmol/l (p less than 0.05) in untreated patients and from 0.10 +/- 0.01 to 0.12 +/- 0.01 mmol/l (p less than 0.05) in treated patients. Mean (+/- SEM) log values of urinary erythrocyte (rbc) counts had not changed significantly from 5.47 +/- 0.09 to 5.21 +/- 0.14 log rbc/ml in untreated patients, from 5.45 +/- 0.11 to 5.49 +/- 0.19 log rbc/ml in treated patients. However, in treated patients, mean (+/- SEM) urinary protein excretions decreased from 1.67 +/- 0.35 to 1.15 +/- 0.31 g/24 h (p less than 0.01) whereas in untreated patients urinary protein was unchanged between initial values of 1.76 +/- 0.34 and follow-up at 1.89 +/- 0.45 g/24 h. No significant changes in blood pressure occurred in either group. This study supports the observation that treatment of IgA nephropathy with cyclophosphamide, dipyridamole and warfarin is associated with a reduction of urinary protein excretion but a significant effect on preservation of renal function, at least as determined by serum creatinine values, could not be confirmed over this two-year study. ",11 3274,"Control of total peripheral resistance during hyperthermia in rats. To elucidate the effect of blood volume on the circulatory adjustment to heat stress, we studied alpha-chloralose-anesthetized rats at three levels of blood volume: normovolemia (NBV), hypervolemia (HBV; +32% plasma volume by isotonic albumin solution infusion), and hypovolemia (LBV; -16% plasma volume by furosemide administration). Body surface heating was performed with an infrared lamp to raise arterial blood temperature (Tb) at the rate of approximately 0.1 degree C/min. Before heating, central venous pressure (CVP) was significantly higher in HBV (0.41 +/- 0.25 mmHg) and lower in LBV (-1.44 +/- 0.22 mmHg) than in NBV (-0.41 +/- 0.10 mmHg). The Tb at which CVP started to decrease was approximately 40 degrees C in HBV, approximately 41 degrees C in NBV, and approximately 42 degrees C in LBV, and it decreased by 1.53 +/- 0.14, 1.92 +/- 0.24, and 0.62 +/- 0.14 mmHg from 37 to 43 degrees C of Tb in HBV, NBV, and LBV, respectively. Stroke volume was closely correlated with CVP, and this relationship was not affected by Tb. Heart rate responses to the raised Tb were similar among the three groups. Mean arterial pressure (MAP) was not affected by blood volume modification or CVP and was maintained at preheating (Tb 37 degrees C) level until Tb rose to 40 degrees C. Above this Tb, MAP increased until Tb reached 43 degrees C (+30-40 mmHg) for all three groups. Total peripheral resistance (TPR) was inversely correlated with CVP, and the slope of the linear relationship between TPR and CVP in LBV was three- to fourfold steeper than in NBV or HBV. ",22 2146,"Deficiency of glycosyl-phosphatidylinositol-linked membrane glycoproteins of leukocytes in paroxysmal nocturnal hemoglobinuria, description of a new diagnostic cytofluorometric assay. Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that affects not only red cells, but other blood cells as well. The common defect is supposed to be an acquired deficiency of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins, which may be present already at the hematopoietic stem cell level. Recently, a panel of monoclonal antibodies (MoAbs) has become available directed against various GPI-linked membrane proteins. This makes it possible to study various cell lineages for the deficiency of such proteins in PNH in more detail. Using cytofluorography, we could show that the granulocytes of 20 different PNH patients miss not only GPI-linked FcRIII (CD16 antigen), but also three other GPI-linked proteins, ie, CD24 antigen, CD67 antigen and a granulocyte-specific 50 to 80 Kd antigen. The affected granulocytes were not only neutrophils but also eosinophils, as was found in a more detailed analysis of three patients. Moreover, in all 10 PNH patients tested, the monocytes were found to be deficient for the GPI-linked CD14 antigen, and we found with CD24 and CD55 (DAF) antibodies that lymphocytes may be involved as well. However, abnormal B and T lymphocytes were detected only in a subset of patients (2 of 10 tested). The uniform deficiency of GPI-linked proteins of granulocytes allows the introduction of a new diagnostic cytofluorometric assay for PNH with MoAbs against GPI-linked granulocytic antigens. This test was positive in all PNH patients studied and not in a group of 40 control patients or 50 normal donors, with the exception of three of 16 aplastic anemia (AA) patients. In the three AA patients, subpopulations (10% to 20%) of PNH granulocytes could be detected, whereas these patients had a negative acidified serum (Ham) test. This indicates that the new test is more sensitive than the Ham test and allows the early diagnosis of PNH in AA. An advantage of the neutrophil assay is that, in contrast to the Ham test, it is not influenced by recent red-cell transfusions. Moreover, it is possible to quantify the number of affected cells by single cell analysis. ",14 1683,"Documentation of the effective length of action of antihypertensive treatment. The technique of automated ambulatory blood pressure (BP) monitoring offers an innovative means for measuring BP throughout the 24-hour period. Recently available compact monitoring instruments have been shown to be accurate and to provide reproducible measurements of the circadian BP pattern. The monitoring procedure is advantageous in that it minimizes or avoids placebo effects during therapeutic trials. Moreover, its power makes it possible to draw statistically valid conclusions regarding efficacy in fewer patients than would be required if conventional methods were used. This procedure also enhances the diagnosis of hypertension by identifying patients with ""office"" or ""white coat"" hypertension, and thereby facilitates assessment of treatment effects in those patients who are truly hypertensive. Automated monitoring measures BP at critical times of the day, including the preawakening and early morning hours, and it enables peak and trough antihypertensive drug effects to be carefully quantified. Since patient compliance appears to be enhanced with once- or twice-daily dosing, antihypertensive agents with long durations of action (24 hours) are of considerable interest. This report reviews some recent studies in which the monitoring technique has been used to measure the efficacy and duration of action of differing antihypertensive drugs. ",13 948,"Effects of famotidine and cimetidine on plasma levels of epidurally administered lignocaine. The effects of two H2-receptor antagonists, famotidine and cimetidine, on the plasma levels of epidurally administered lignocaine were studied. Group A (n = 20) received famotidine 20 mg orally the night before surgery and 20 mg intramuscularly 60 minutes before induction of anaesthesia. Group B (n = 15) received cimetidine 200 mg orally the night before the surgery and 400 mg orally 60 minutes before the anaesthetic induction. Group C (n = 20) received neither famotidine nor cimetidine and served as controls. Twelve millilitres of 2.0% lignocaine with adrenaline 1:200,000 was injected into the epidural space in all patients, after the establishment of general anaesthesia with nitrous oxide, oxygen, and enflurane (0.3-0.5%). The patients who received cimetidine showed significantly higher plasma concentrations of lignocaine compared with either group A or group C at all investigation times (p less than 0.01). The mean peak plasma concentrations were 2.4 (SEM 0.1), 3.2 (SEM 0.2) and 2.3 (SEM 0.1) micrograms/ml in group A, B, and C, respectively. This study suggests that famotidine is preferable to cimetidine for control of gastric acidity before the use of lignocaine as the epidural anaesthetic. ",7 122,"Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children. Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics. Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%-100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%-85%) in 2 years, separated by a decade. The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were greater than or equal to 40% of the isolates. Subgroups A1 and A2 predominated, while B2, 3, and 4 occurred almost equally. A greater clinical severity for Group A strains was suggested by children with group A infections requiring intensive care significantly more often (15.4 vs. 8.3%, P = .008). Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs. 5.5%, P less than .01). Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and A1 in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated. ",1 2497,"Effect of beta cell distribution on the performance of a bioartificial pancreas. The insulin response of available prototype hollow fiber bioartificial pancreas devices remains unacceptably slow. Although previous experimental and theoretical investigations provide insight into the factors governing the performance of these devices, there are currently no results on the effects of beta cell distribution on insulin response. The authors have developed a detailed theoretical model for insulin response in a hollow fiber bioartificial pancreas. Model predictions have been shown to be in good agreement with literature data on the insulin release from an in vitro hollow fiber device. In this study, model simulations were used to evaluate the effects of axial and radial variations in beta cell density on the insulin response. For a device with no convective recirculation (i.e., a diffusion controlled device), the radical distribution of cells in the matrix and shell plays a critical role in determining device response, but the insulin response is essentially independent of the axial beta cell distribution. In contrast, for a device with substantial recirculation, there is a very strong dependence on the axial beta cell distribution, with a weaker dependence upon the radial distribution. These results clearly demonstrate the potential importance of beta cell distribution in the analysis of in vivo and in vitro experimental data, and in the design of effective clinical devices. ",17 910,"Foam cuffed tracheal tubes: clinical and laboratory assessment. The efficiency of a foam cuffed tracheal tube has been studied in protecting the pulmonary tree from aspiration of oropharyngeal and gastric contents. Following instillation of methylene blue dye above the cuff, subsequent fibreoptic bronchoscopy revealed no instance of dye staining of the tracheal mucosa. A ""bench"" study was undertaken subsequently to estimate the likely pressure that the cuff would exert on the tracheal mucosa as a result of elastic recoil properties of the foam. The results suggested that, under normal clinical conditions, the pressure is not likely to exceed a value at which impairment of the mucosal blood supply would occur. ",7 91,"Reduction of contamination at total hip replacement by special working clothes. We assessed wound, air and operative field contamination at 50 total hip operations, performed in a zonal ventilation system. Theatre staff wore either a specially designed polypropylene non-woven coverall or conventional cotton shirt and trousers. The surgeons wore partially impermeable operating gowns. The polypropylene coverall was associated with significantly lower air and wound counts. The coverall was warmer than cotton but judged to be acceptable. The combined use of zonal ventilation and the coverall achieved ultra-clean air conditions. ",0 907,"Results in 104 patients undergoing bronchoplastic procedures for bronchial lesions. Bronchoplastic procedures were used in 104 patients with various bronchial disorders. Ten had benign lesions and 94, malignant tumors. The principal operative procedures were sleeve lobectomy and sleeve pneumonectomy for bronchogenic carcinoma, but 11 limited bronchial resections were performed in patients with benign lesions, minute bronchogenic carcinomas, and low-grade malignant tumors. Of the 94 patients with malignant tumors, 79 underwent a bronchoplastic procedure without carinal resection (sleeve lobectomy in 75 and limited bronchial resection in 4), and there was one operative death (1.3%). The overall 5-year survival rate for the patients with bronchogenic carcinoma in this group was 45% and that for patients undergoing curative resection, 57% (survival of patients in stages I, II, and IIIA was 79%, 55%, and 30%, respectively). A bronchoplastic procedure with carinal resection was performed in 15 patients. Twelve in this group underwent sleeve pneumonectomy. There were two operative deaths, and 1 patient has survived for longer than 4 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and are still alive. We believe that bronchoplasty is a safe and valuable procedure and that limited bronchial resection appears to be the procedure of choice for localized bronchial lesions. ",7 3343,"Magnetic resonance imaging in idiopathic retroperitoneal fibrosis: measurement of T1 relaxation time. Magnetic resonance imaging at 0.08 Tesla was performed in nine patients with proven idiopathic retroperitoneal fibrosis. A total of 11 scans was performed. Three patients were scanned before diagnosis; one of these also had two follow-up scans. A further six patients were scanned a variable time after diagnosis and treatment. On each scan, a periaortic soft-tissue mass was readily identified, the distribution corresponding to that seen on computed tomography. There was no difference in the mean T1 relaxation time of the mass between patients scanned before diagnosis and those scanned after treatment. However, the patient followed with serial scans showed a progressive reduction in the T1 value of the mass with time. Comparison with results obtained in patients with lymphoma suggests that the T1 values in retroperitoneal fibrosis are lower than in lymphoma, particularly non-Hodgkin's lymphoma. ",22 1922,"Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction. Low-level exercise thallium testing is useful in identifying the high-risk patient after acute myocardial infarction (AMI). To determine whether this use also applies to patients after thrombolytic treatment of AMI, 64 patients who underwent early thrombolytic therapy for AMI and 107 patients without acute intervention were evaluated. The ability of both the electrocardiogram and thallium tests to predict future events was compared in both groups. After a mean follow-up of 374 days, there were 25 and 32% of cardiac events in the 2 groups, respectively, with versus without acute intervention. These included death, another AMI, coronary artery bypass grafting or angioplasty with 75% of the events occurring in the 3 months after the first infarction. The only significant predictors of outcome were left ventricular cavity dilatation in the intervention group and ST-segment depression and increased lung uptake in the nonintervention group. The sensitivity of exercise thallium was 55% in the intervention group and 81% in the nonintervention group (p less than 0.05). Therefore, in patients having thrombolytic therapy for AMI, nearly half the events after discharge are not predicted by predischarge low-level exercise thallium testing. The relatively weak correlation of outcome with unmasking ischemia in the laboratory before discharge may be due to an unstable coronary lesion or rapid progression of disease after the test. Tests considered useful for prognostication after AMI may not necessarily have a similar value if there has been an acute intervention, such as thrombolytic therapy. ",13 2149,"Cardiac abnormalities in children with sickle cell anemia. The cardiac status of 64 children (ages 0.2 to 18 yr) with sickle cell anemia documented by hemoglobin electrophoresis was evaluated by echocardiography. Left atrial, left ventricular and aortic root dimensions were significantly increased in over 60 percent of these children at all ages compared to values for 99 normal black (non-SCA) control subjects. Left ventricular wall thickness was increased in only 20 percent of older children with sickle cell anemia. Estimated LV mass/m2 and left ventricular cardiac index were increased compared to control subjects (p less than 0.001). Left heart abnormalities expressed as a single composite function, derived from multivariate regression analysis, correlated well with severity of anemia expressed as grams of hemoglobin (r = -0.52, p = less than 0.001) and with percentage of hemoglobin S (r = 0.51, p less than 0.001), but not to the same extent with age. Echocardiographically assessed left ventricular function at rest was comparable to that of control subjects. These data suggest that the major cardiac abnormalities in children are related to the volume overload effects of chronic anemia, and that in this age group, there is no evidence for a distinct ""sickle cell cardiomyopathy"" or cardiac dysfunction. ",14 2107,"A blood-liquid interface for prolonged extracorporeal oxygenation with excellent antithrombogenicity. The authors verified the excellent antithrombogenicity of a blood-liquid interface (BLI) and introduced an oxygenator based on the principle of gas exchange across direct BLI. In a newly developed oxygenator, three layers of liquid flowed horizontally, contacting one another: O2 saturated silicone oil on the top, O2 saturated fluorcarbon at the bottom, and blood in the middle. Gas exchange was carried out across both direct BLIs. This system provided excellent antithrombogenicity as well as good gas exchange. The results indicate that this method will become a promising modality for prolonged extracorporeal oxygenation. ",13 2806,"Stress in surgeons. A sample of 1000 members of the Association of Surgeons of Great Britain and Ireland was circulated with a postal questionnaire relating to their occupational stressors, their type A coronary-prone behaviour and their mental health. Six hundred and seventy-two (67 per cent) useable forms were returned anonymously. The major individual stressors were: (1) the interference of the job with personal life, (2) general administration, and (3) the number of patients in clinics. Type A behaviour was similar to that of other professional groups. Surgeons showed mean scores significantly higher than the general population on two subscales of the mental health index (free-floating anxiety and hysterical anxiety). The findings for the few female surgeons (2 per cent) were similar to those in men but they did not exhibit raised free-floating anxiety levels. ",20 1549,"Two-dimensional echocardiographic features of double outlet left ventricle. In a cyanotic newborn infant, the diagnosis of double outlet left ventricle was made from the two-dimensional echocardiographic examination. The diagnosis was later confirmed at cardiac catheterization and surgery. The parasternal and subcostal views were especially useful for identification of the origin of both great arteries from the morphologic left ventricle. A review of the medical literature since 1967 revealed 77 cases of double outlet left ventricle, most of which were diagnosed only at surgery or postmortem examination. The anatomic features demonstrated with two-dimensional echocardiography in this case are representative of the findings cited most often in the cases reported in the medical literature. ",13 968,"Pulmonary masses: contrast enhancement. Radiographic studies to discriminate benign from malignant pulmonary masses have previously focused on the morphologic and, more recently, the computed tomographic (CT) attenuation characteristics of the lung mass. Experience with the use of an intravenously administered iodinated contrast medium in examining the enhancement properties of lung masses was reviewed. Distinctive differences in the vascularity, pathophysiologic features, and pharmacodynamics of malignant versus benign pulmonary masses were identified. Forty-five patients with peripheral pulmonary masses were examined. Enhancement was evaluated by means of optical density values measured on trispiral tomograms of the lung masses before and after bolus injection of contrast medium. Results suggest that contrast enhancement of pulmonary masses can be measured on sectional images and that this may become a feasible diagnostic method in the detection of lung cancer. CT offers a simplified technique that is now being explored by the authors. ",7 443,"Photodynamic therapy in the treatment of squamous cell carcinoma of the head and neck. Photodynamic therapy is an experimental modality for tumor treatment based on the combined action of the tumor-localizing agent, ie, hematoporphyrin derivative, and red light. From 1985 through 1989, 26 patients were treated using hematoporphyrin-derived drugs and 630-nm light delivered by a tunable dye laser. All patients had biopsy-proved squamous cell carcinoma of the head and neck, and they had either failed the traditional treatment modalities or refused conventional therapies. Histological complete responses were achieved in 20 (77%) of 26 patients and partial responses in 5 (19%) of 26 patients for periods up to 48 months. Only minimal toxic reaction was noted in the group. As a guide to treatment planning for a patient group with large tumors, we used an optical dosimetry model based on tissue optics. The rate of complete responses to this treatment was 8 (73%) of 11. Our data indicate that photodynamic therapy is capable of inducing significant clinical and histological responses in the majority of those treated, and in some patients a prolonged response is produced. In certain select head and neck malignancies, photodynamic therapy has an important role as a treatment modality. ",3 806,"Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. Leukocyte adhesion molecules are important in cell-cell interactions of the immune system. Lymphocyte function-associated antigen 1 (cluster designation 11a) mediates interactions between T cells and mononuclear phagocytes through its ligand, the intercellular adhesion molecule 1 (CD54), whereas complement receptors 3 (CD 11b) and 4 (CD11c) are involved in complement-mediated phagocytosis. Expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls. In normal colon, few mononuclear phagocytes expressed lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1 at high densities. The major adhesion molecule was CD11c. Thus, the largest population of normal colonic mononuclear phagocytes was represented by quiescent, resident macrophages with likely phagocytic function. In inflammatory bowel disease, mononuclear phagocytes showed only a slight increase in CD11a expression and no significant change in expression of CD11b and CD11c. By contrast, the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6.9% +/- 3.9% in controls to 69.2% +/- 12.8% in ulcerative colitis (P less than 0.001) and to 45.7% +/- 22.8% in Crohn's disease (P less than 0.01), showing a close relationship with histological activity. The increased expression of intercellular adhesion molecule 1 in inflammatory bowel disease indicates a state of immunological activation induced by local release of inflammatory cytokines. Such induction of intercellular adhesion molecule 1 on mononuclear phagocytes may be important in the maintenance of chronic inflammation by facilitating interactions with T cells and T-cell antigen recognition. ",5 2043,"Double-peaking circadian variation in the occurrence of sustained supraventricular tachyarrhythmias. We studied 251 patients less than or equal to 65 years of age admitted for treatment of symptomatic supraventricular tachyarrhythmia to assess whether these arrhythmias begin evenly throughout the day or manifest circadian variation in occurrence. The arrhythmias included 152 episodes of atrial fibrillation, 50 episodes of supraventricular reentry tachycardia, 30 episodes of atrial flutter, and 19 cases of ectopic atrial tachycardia. A total of 209 patients could tell the exact time their symptoms had started. In 38 of them (18%), the arrhythmia had begun between midnight and 6:00 AM, in 63 (30%) between 6:01 AM and noon, in 46 (22%) between noon and 6:00 PM, and in 62 (30%) between 6:01 PM and midnight. This distribution differed significantly from uniform occurrence (chi square 8.7, p less than 0.05). Fifty patients were using beta-adrenoceptor blocking agents when the arrhythmia occurred. Compared with the other 159 patients, they had no morning surge of arrhythmias (20% versus 33.3% of episodes between 6:01 AM and noon), but instead a much higher incidence at night (34% versus 13.2% of episodes between midnight and 6:00 AM) (chi square 14.4, p less than 0.005). We conclude that the frequency of onset of sustained supraventricular tachyarrhythmias varies with the time of day, showing nearly equal peaks in the morning and in the evening and a trough at night. The modifying effect of beta-adrenoceptor blockage suggests that many morning arrhythmias are of adrenergic origin while other, probably vagal arrhythmogenic mechanisms, prevail at night. ",13 2283,"Prevention of occupational contact dermatitis. Contact dermatitis is the most frequent type of occupational skin disease. Although prevention of contact dermatitis in the workplace should ideally be accomplished through total elimination of cutaneous exposure to hazardous substances, this is often not feasible. Therefore eight basic elements of a multidimensional approach to prevention have been identified. These elements include recognition of potential cutaneous irritants and allergens, engineering controls or chemical substitution to prevent skin exposure, personal protection with appropriate clothing or barrier creams, personal and environmental hygiene, regulation of potential allergens and irritants within the workplace, educational efforts to promote awareness of potential allergens and irritants, motivational techniques to promote safe work conditions and practices, and preemployment and periodic health screening. A comprehensive prevention program based on this multidimensional approach requires the cooperative efforts of employees, employers, engineers, chemists, industrial hygienists, safety and supervisory personnel, union representatives, governmental agencies, and occupational health practitioners. ",16 272,"Developmental regulation of granulocytic cell binding to hemonectin. Hemonectin (HN), a component of the bone marrow (BM) extracellular matrix which promotes adhesion of cells in the granulocytic lineage, was purified to near homogeneity and tested for its ability to mediate attachment of normal and leukemic cells of granulocytic lineage. Purified HN immobilized on plastic substrates promoted serum-free attachment of normal granulocyte/macrophage progenitor cells (CFC-GM), using an in situ attachment assay in which cell attachment is inhibited by specific polyclonal antisera. When unfractionated BM cells were allowed to attach to purified HN and stained in situ, HN preferentially bound cells at earlier stages of granulocytic differentiation. These observations were confirmed using cells of the HL-60 progranulocytic cell line which mirrored this differentiation-stage specific binding to HN. HN promoted attachment of 60% of uninduced HL-60 cells which were arrested at the progranulocyte stage, whereas only 15% of uninduced HL-60 cells attached to uncoated plastic and 4% to attached plastic coated with equal microgram quantities of bovine serum albumin (BSA). When HL-60 cells were induced to differentiate along the granulocytic pathway by incubation with dimethylsulfoxide (DMSO), attachment to hemonectin was reduced. Thus, both primary BM granulocytic cells and a granulocytic cell line show preferential attachment of those cells at earlier stages of differentiation. This developmentally regulated binding suggests a mechanism for release of maturing BM into the peripheral circulation. ",3 2642,"Transforming growth factor beta and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection. This study examines the contribution of transforming growth factor beta (TGF beta), one of the most potent endogenous immunosuppressive factors, to the development of immunodeficiency in human immunodeficiency virus (HIV) infection. Increased titers of TGF beta were found in supernatants of peripheral blood mononuclear cells (PBMCs) from HIV-infected donors as compared to uninfected controls (P less than 0.001). This correlated closely with defective responses of CD4+ lymphocytes to the recall antigens tuberculin purified protein derivative or tetanus toxoid. The addition of TGF beta-neutralizing antibody to PBMCs partially restored these defective T-cell responses. Furthermore, purified TGF beta or HIV+ PBMC culture supernatants preferentially inhibited proliferation of CD4+ lymphocytes as compared to CD8+ cells. The increased expression of the TGF beta protein was associated with increased TGF beta mRNA as determined by a polymerase chain reaction assay. This increase in TGF beta protein and mRNA was due to a selective upregulation of the TGF beta 1 isoform. These results indicate that overexpression of TGF beta 1 occurs in HIV-infected individuals and that this cytokine can contribute to impaired immune functions and to depletion of CD4+ T lymphocytes. ",19 94,"Mycobacterium leprae-specific T cells from a tuberculoid leprosy patient suppress HLA-DR3-restricted T cell responses to an immunodominant epitope on 65-kDa hsp of mycobacteria. The polar tuberculoid type (TT) of leprosy, characterized by high T cell reactivity to Mycobacterium leprae, is associated with HLA-DR3. Surprisingly, DR3-restricted low T cell responsiveness to M. leprae was found in HLA-DR3-positive TT leprosy patients. This low responsiveness was specifically induced by M. leprae but not by M. tuberculosis and was seen only in patients and not in healthy controls. We studied this patient-specific, M. leprae-induced, DR3-restricted low T cell responsiveness in depth in one representative HLA-DR3-positive TT leprosy patient by using T cell clones. From this patient two types of T cell clones were obtained: one type was cross-reactive with M. tuberculosis and recognized an immunodominant epitope (amino acids 3 to 13) on the 65-kDa heat shock protein (hsp) the other type was M. leprae specific and reacted to a protein other than the 65-kDa one. To examine whether these M. leprae-specific T cell clones were responsible for the DR3-restricted low responsiveness to M. leprae, we tested them for the ability to suppress the proliferation of the DR3-restricted, 65-kDa, hsp-reactive clones. The DR3-restricted, M. leprae-specific T cells completely suppressed the proliferative responses of DR3-restricted, cross-reactive T cell clones to the 65-kDa hsp from the same patient as well as from other individuals. Also, DR3-restricted responses to an irrelevant Ag were suppressed by the M. leprae-specific T cell clones. However, no suppression of non-DR3-restricted T cell responses was seen. Although the mechanism must still be elucidated, this M. leprae-induced, DR3-restricted immunosuppression may at least partly explain the observed DR3-associated low T cell responsiveness in TT leprosy patients. ",0 3169,"Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. The ras gene product (p21) is a GTP-binding protein and has been thought to transduce signals regulating proliferation or differentiation of cells. Like other GTP-binding proteins, p21.GTP is an active conformation, which can transduce the signals downstream, whereas p21.GDP is an inactive one. Recently, we have shown that p21.GTP levels increased in cells treated with fetal bovine serum or platelet-derived growth factor to initiate DNA synthesis. In this paper, we report that epidermal growth factor can also increase the amounts of p21.GTP in the cells. Effects of epidermal growth factor and platelet-derived growth factor are not additive. In contrast, mutant [Val12]p21, which has transforming activity, responded neither to platelet-derived growth factor nor to epidermal growth factor. We also found that the ratio of p21.GTP to p21.GDP increased 3- to 4-fold in transformants carrying activated erbB-2/neu or v-src oncogenes. These results strongly suggest an important role of p21 in transduction of signals for both normal proliferation and malignant transformation through growth factor receptors with tyrosine kinase activity or related oncogene products. ",22 3165,"Neurologic assessment. Neurologic nursing assessment requires the knowledge of anatomic and physiologic principles as well as the mastery of complex assessment skills. The nurse who is often the first and most consistent health team member interacting with clients may provide the key to the early recognition, prevention, and treatment of neurologic problems. The nurse, as the dynamic member of the health team, may then be the first line of defense in initiating cost-effective and perhaps life-saving measures in neurologically impaired clients. ",22 361,"Expression of the MDR1 gene in human gastric and colorectal carcinomas. We measured expression of the MDR1 gene (also known as the PGY1 gene) in the human gastrointestinal tract. MDR1 messenger RNA (mRNA) levels were elevated in 13 of 15 colorectal carcinoma specimens and in six of 13 gastric carcinoma specimens. Well-differentiated colorectal carcinomas contained significantly higher concentrations of MDR1 mRNA than moderately differentiated colorectal carcinomas. Similarly, moderately differentiated gastric carcinomas contained higher concentrations of MDR1 mRNA than poorly differentiated gastric carcinomas. MDR1 gene expression in normal colorectal and gastric tissues adjacent to carcinomas was similar to that in the carcinomas. MDR1 gene expression in xenografts of colorectal and gastric carcinomas in nude mice was also investigated. Elevated expression of the MDR1 gene was seen in only four of 18 xenografts of colorectal carcinoma and was not seen in any xenografts of gastric carcinoma. P-glycoprotein was distributed over the luminal surface of the colorectal carcinoma. These results imply that the higher levels of MDR1 mRNA found in well-differentiated carcinomas derived from colorectal tissues are the results of increased expression of the MDR1 gene in the luminal surface cells. The level of expression of the MDR1 gene in colorectal and gastric carcinomas appears to correlate with the degree of differentiation and also appears to be affected by transplantation into nude mice. ",3 480,"The association of selected cancers with service in the US military in Vietnam. II. Soft-tissue and other sarcomas. The Selected Cancers Cooperative Study Group As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of soft-tissue and other sarcomas between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible. Controls were selected by random-digit dialing. Analyses of 342 men with pathologically confirmed sarcoma and 1776 controls showed that Vietnam veterans had a relative risk of 1.0 for sarcoma in comparison with men who did not serve in Vietnam (95% confidence interval, 0.6 to 1.6). Restriction of the analysis to the 254 men with soft-tissue sarcoma yielded a relative risk of 0.9 (95% confidence interval, 0.5 to 1.6). Several attributes of military service in Vietnam (eg, branch, duration of service, military region, and other characteristics that may have been associated with the use of Agent Orange) were examined, and none was associated with an increased risk for the development of sarcoma. Furthermore, no morphologic type of sarcoma was overrepresented among Vietnam veterans. Results were unchanged if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. This study, which had 97% power to detect a relative risk of 2.0 for all sarcomas, provides no evidence that the risk for the development of soft-tissue or other sarcomas is increased among veterans 15 to 25 years following service in Vietnam. ",3 1379,"Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity. During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients. ",11 2177,"Negative screening for sickle cell diseases with a monoclonal immunoassay on newborn blood eluted from filter paper. The most common method of blood sample collection for neonatal screening programs for inherited diseases-blood spots on filter paper--is poorly suited for screening of sickle cell diseases by conventional assays because of the denaturing effects of this medium on hemoglobins that affect their electrophoretic identifications. The monoclonal antibody beta 6-1 specifically recognizes the hemoglobin A beta-chain residue 6 (glutamic acid), that is, the normal counterpart of hemoglobins S and C, and this recognition is unaffected by changes in hemoglobins induced by filter paper storage. The beta 6-1 immunoassay analysis of 67 prescreened samples extracted from filter paper permitted unambiguous group identification, by virtue of nonreactivity, of the pathologic sickle cell disease phenotypes SS (sickle cell anemia) and SC (sickle cell-hemoglobin C disease), along with the homozygous hemoglobin C phenotype (hemoglobin CC disease). Other phenotypes identified by beta 6-1 nonreactivity would include S-beta degrees thalassemia, C-beta degrees thalassemia, and beta degrees thalassemia (Cooley's anemia). As systems for collecting newborn blood specimens on filter paper and their transmittal to centralized laboratories are already established in many states, this assay for sickle cell and hemoglobin C diseases could rapidly be combined with other mass screening programs for inborn errors of metabolism. ",14 851,"Reviewing nonsurgical periodontal therapy. Selection of the appropriate case and clinical competency in treatment modalities results in success in nonsurgical periodontal therapy. The patient with early periodontitis with significant local factors in the form of professionally accessible plaque and calculus is the most receptive to nonsurgical periodontal treatment. The clinician must make decisions centering around the important question, ""Can the patient, or moreover, can the therapist delivering the debridement, gain access to the microbial subgingival plaque on a frequent basis below the host defense threshold of the respective patient?"" If the answer is ""yes,"" nonsurgical periodontal therapy will be rewarding. If the answer is ""no,"" other modalities such as periodontal surgery must be instituted. ",6 1048,"Etiologic importance of the intimal flap of the external carotid artery in the development of postcarotid endarterectomy stroke. A technically unsatisfactory end point (transition from the removed diseased plaque to normal distal intima) leading to an intimal flap of the external carotid artery has been identified as a source of perioperative stroke. The mechanism involves thrombus formation with retrograde propagation of the thrombus and subsequent embolization of the internal carotid artery. This report describes three cases illustrating this mechanism and methods of identification and correction. This mechanism of postoperative stroke adds further justification for the routine use of intraoperative surveillance studies to document the technical result of endarterectomy involving the internal and external carotid arteries. When an unsatisfactory end point is identified in the external carotid artery, it should be corrected with the same sense of concern as a similar finding in the internal carotid artery. ",9 2181,"Treatment with 13-cis-retinoic acid in transfusion-dependent patients with myelodysplastic syndrome and decreased toxicity with addition of alpha-tocopherol. PURPOSE: The purpose of this study was to determine the response and tolerance to long-term treatment using 13-cis-retinoic acid (13-CRA) in transfusion-dependent patients with the myelodysplastic syndrome (MDS) and to determine the effects of therapy on the natural history of the disease. PATIENTS AND METHODS: Sixty-six consecutive patients with transfusion-dependent MDS seen in a medical school hospital and outpatient clinic from 1981 to 1988 were studied. The first 21 patients were treated with 13-CRA alone and the next 45 patients with 13-CRA plus alpha-tocopherol (AT). We compared responses to and toxicities of therapy, rates of transformation, and survival from onset of therapy in 20 evaluable patients treated with 13-CRA alone and 43 patients treated with 13-CRA plus AT. RESULTS: Four patients responded (20%) at 4 to 8 months to 13-CRA alone, but this response was associated with considerable toxicity and resulted in cessation of therapy. Among the responders, only one continued therapy and is currently in remission, whereas three discontinued therapy because of toxicity and have had a relapse and died. In the 13-CRA plus AT group, we observed one prolonged complete remission and 10 partial remissions (26%), with a decrease in skin and constitutional toxicities by the addition of AT, which enabled the continuation of 13-CRA indefinitely. Although the response rates were similar in both groups, fewer patients (28% versus 60%) experienced progression to acute leukemia in the 13-CRA plus AT group than in the group receiving 13-CRA alone, who terminated treatment (p = 0.018). A twofold increase in median survival of the RA/RARS and RAEB/CMML patient groups was observed with 13-CRA plus AT but was not significant (p greater than 0.5). CONCLUSION: This study shows a 20% to 26% response rate to 13-CRA and suggests that 13-CRA, if given continuously, decreases the rate of progression or transformation to acute leukemia in patients with MDS. The addition of AT ameliorates the toxicity of 13-CRA and allows for long-term treatment with 13-CRA. Since the standard treatment for MDS is currently unsatisfactory, these findings indicate that longer treatment with a non-marrow-suppressive agent such as 13-CRA is important, and further trials to determine the role of 13-CRA plus AT in combination with new recombinant growth factors in the therapy for transfusion-dependent MDS should offer a new approach to a disease common in the elderly population. ",14 1431,"Phenotypic characterization of monocytes and macrophages from CAPD patients. The purpose of this study was to phenotypically characterize and compare peripheral blood monocytes from CAPD patients with peritoneal macrophages isolated from their peritoneal dialysis effluents. Monocytes/macrophages were labeled with fluorescent ligands or monoclonal antibodies specific for 1) receptors for C5a, formyl-met-leu-phe (fMLP); Fc region of IgG; C3b (CR1); and C3bi (CR3), 2) Class II histocompatibility antigens HLA-DR and HLA-DQ; and 3) monocyte/macrophage surface antigen CD14. The cells were analyzed using flow cytometry. Results indicated that there were no differences between monocytes and peritoneal macrophages in their receptor expression for fMLP, CR1, or CR3. However, paired t-testing indicated that peritoneal macrophages had significantly increased expression of Fc and C5a receptors, as well as enhanced antigen expression of HLA-DR, HLA-DQ, and CD14. These results suggest that peritoneal macrophages from CAPD patients are activated with increased expression of receptors and antigens important in host defense. ",11 116,"Infection of mice with lactate dehydrogenase-elevating virus destroys the subpopulation of Kupffer cells involved in receptor-mediated endocytosis of lactate dehydrogenase and other enzymes. In previous experiments in rats, we have shown that the rapid plasma clearance of a number of clinically important enzymes is due to receptor-mediated endocytosis by Kupffer cells and other resident macrophages. Others have shown that infection of mice with lactate dehydrogenase-elevating virus, a virus that proliferates in macrophages, leads to reduced plasma elimination of these enzymes. This paper integrates these two sets of experiments. Plasma elimination of intravenously injected, radioactively labeled lactate dehydrogenase M4 and mitochondrial malate dehydrogenase in mice was shown to be caused in part by uptake in liver, spleen and bone. Uptake of lactate dehydrogenase M4 by these tissues was, to a large extent, saturable and the two dehydrogenases competitively inhibited each other's clearance. These results suggest that, also in mice, these enzymes are partly cleared from plasma by endocytosis by way of a common receptor on cells (probably macrophages) from liver, spleen and bone marrow. Morphometrical data showed that normal mouse liver contains 23 x 10(6) Kupffer cells/cm3. This number was reduced to about 30% of that of controls 24 hr after infection of mice with lactate dehydrogenase-elevating virus but returned to normal within the next 9 days. The saturable component of uptake of lactate dehydrogenase M4 by liver, spleen and bone had disappeared 24 hr after infection with the virus, and did not return after the Kupffer cell population had recovered. Our findings suggest that lactate dehydrogenase M4 is, to a large extent, removed from the circulation by way of a receptor on a subpopulation of macrophages that is permissive for replication of lactate dehydrogenase-elevating virus. ",1 727,"Prospective randomized comparison of Brown-McHardy and microvasive balloon dilators in treatment of achalasia. We report the results of a randomized prospective study comparing a standard bougie rubber balloon dilator [Brown-McHardy (BMH)] and a newer polyethylene dilator passed over a guide wire [Microvasive Rigiflex (MVR)]. Twenty achalasia patients (15M, 5F, mean age 45.4 yr) considered candidates for either dilator were randomized. Symptom assessment, body weight, and upright radionuclide solid esophageal emptying study were measured before and 6 months after pneumatic dilatation. All dilatations were performed by one of three experienced gastroenterologists under fluoroscopic guidance. Overall success occurred with 10/10 BMH and 7/10 MVR. One patient not improved with MVR had myotomy; the other two were successfully treated by BMH. No complications occurred with either dilator. ",5 1587,"Primary repair for complete atrioventricular canal: recommendation for early primary repair. Forty patients with complete atrioventricular canal (CAVC) underwent primary repair at Fukuoka Children's Hospital in Fukuoka, Japan, between August 1, 1981 and July 31, 1989. The age at repair ranged from 2 months to 6 years (mean 19 months); weight ranged from 2.3 to 22 kg. The surgical mortality was 2.5%. Justification for early primary repair was examined. Eleven patients underwent repair before 6 months of age (Group 1), 12 patients, between 7 and 11 months of age (Group 2), and 17 patients, after 12 months of age (Group 3). Degenerative changes in the atrioventricular valve increased significantly as age at repair increased (p less than 0.05 Group 1 versus Group 3). The incidence of residual mitral regurgitation tended to increase in the order of Group 1, 2 and 3, though the degree ranged from trivial to mild. Study of the left atrium/aorta ratio by echocardiography revealed that stable values of around 1.1 in Groups 1 and 2 and around 1.3 in Group 3 continued during the follow-up period of 3 years. Assessment of the diameter of the repaired mitral valve in the mean interval of 26 months in groups 1 and 2 revealed normal growth of the mitral valve annulus. The angle between the repaired mitral valve and ventricular septum, which can be affected by the growth of the ventricular septum, converged to normal range in the mean interval of 26 months. Postoperative pulmonary vascular resistance in Groups 2 and 3 was higher at 4.4 +/- 2.3 and 6.3 +/- 2.2, respectively, than in Group 1 at 3.3 +/- 2.2 (p less than 0.01 versus Group 3). ",13 536,"A standard dose of radiation for ""microscopic disease"" is not appropriate. Elective irradiation of sites of potential occult tumor spread is often part of a patient's radiation therapy program. The required radiation dose (D) depends on the probability that occult disease exists (P(occ)), the number of sites at risk (A), the number of tumor clonogens present (Ni), their radiation sensitivity, and the desired control rate. An exponential model of cell survival is used to quantify the importance of these factors. Control Probability = [1 - Pocc x (1 - e-Ni x (SF2)D/2)]A; SF2 = surviving fraction after 2 Gy. Implications for clinical radiation therapy include: 1. Since the number of clonogens in an occult site may vary from 10 degrees to 10(8), Ni is the major determinant of the required dose. The intrinsic radiation sensitivity of the clonogens (SF2) is also extremely important in determining the dose. Other factors are less influential since they vary less. 2. The variability of Ni (8 logs) is larger than the variation in cell number seen with gross disease (1 cm3 versus 1000 cm3, 3 logs). When Ni approximately 10(8), the required dose approaches that needed for small volume gross disease (10(9) cells, 1 cm3). 3. The dose prescribed to elective sites should reflect the risk of occult disease based on the primary tumor site, stage, and grade. 4. Regions where clinicoradiologic evaluation is difficult (e.g., pelvis and obese neck) require higher doses because macroscopic tumor deposits may exist. 5. Relatively low doses (10 to 30 Gy) are often thought to be inadequate for microscopic tumor. However, similar doses have been reported to sterilize microscopic tumor in ovarian, rectal, bladder, breast, and head and neck carcinomas. Relatively low doses should not be discounted since they may be useful in select cases when normal tissue tolerances and/or previous irradiation treatment limit the radiation dose. ",3 2822,"The other alcohols. Methanol, ethylene glycol, and isopropanol. The alcoholic patient, in an attempt to maintain an altered mental status, may ingest ethanol substitutes containing methanol, ethylene glycol, or isopropanol. The subsequent clinical presentation in the Emergency Department is highly variable and depends on the ethanol substitute ingested, the time since ingestion, and concomitant ethanol abuse. This article describes the clinical features of intoxication by the ethanol substitutes. Early diagnosis and therapeutic intervention may prevent irreversible sequelae. The rationale for treatment interventions is discussed. ",20 1895,"Detection and quantitation of ischemic left ventricular dysfunction using a new video intensity technique for regional wall motion evaluation. Eighty patients with ischemic heart disease and 17 normal subjects were evaluated for left ventricular regional wall motion by means of a new method. The wall motion analysis is based on video intensity. This technique uses a temporally sliding analysis to evaluate the cardiac cycle in 100 msec intervals. Presence of coronary artery disease was defined as more than 50% measured diameter stenosis. Wall motion abnormalities in regions perfused by stenotic vessels were most common in early diastole (76%). Sensitivity of this method at rest in patients with coronary artery disease was 79.7% (p less than 0.0001) and overall accuracy was 84.2% (p less than 0.0001). Abnormalities in both systole and diastole were more common in regions perfused by severe lesions (greater than 75%) than in those perfused by moderately stenotic (less than 75%) vessels (p less than 0.05). A comparison of the new method with phase and amplitude analysis was performed in 15 patients and with two-frame analysis in 40 patients. This new method yielded a higher sensitivity than either of the other two methods. ",13 2892,"Porta hepatis disruption from blunt trauma. Extrahepatic porta hepatis injuries from blunt abdominal trauma are exceedingly rare; all recently reported cases involve disruption of the common bile duct at its intrapancreatic portion. We herein report a patient with lacerations of the proper hepatic artery and bile duct occurring from deceleration/torsion of the porta hepatis after high speed vehicular collision. ",20 1858,"Cardiac transplantation in female Emery-Dreifuss muscular dystrophy. A young woman with humeroperoneal muscular dystrophy and contractures received a heart transplant for a severe dilated cardiomyopathy. Cardiac histopathology consisted of myocyte hypertrophy, interstitial fibrosis, and nuclear hyperchromaticity without mitochondrial abnormalities. Myopathy and heart disease were not clinically evident in her family, although three relatives had unexplained shortened Achilles tendons without weakness. Tendon contractures may be a partial expression of this myopathic disorder, suggesting an autosomal dominant inheritance with variable penetrance. A muscular dystrophy clinically similar to that of the Emery-Dreifuss (EDMD) type can thus occur in women. Rather than the cardiac arrhythmias typical of EDMD, a dilated cardiomyopathy may occur and present with severe congestive heart failure. This is the first report of cardiac transplantation in such a case. ",13 3144,"Features of ""near-death experience"" in relation to whether or not patients were near death The medical records of 58 patients, most of whom believed they were near death during an illness or after an injury and all of whom later remembered unusual experiences occurring at the time, were examined. 28 patients were judged to have been so close to death that they would have died without medical intervention; the other 30 patients were not in danger of dying although most of them thought they were. Patients of both groups reported closely similar experiences but patients who really were close to death were more likely than those who were not to report an enhanced perception of light and enhanced cognitive powers. The claim of enhancement of cognitive functions despite the likelihood that brain function had probably become disturbed and possibly diminished, deserves further investigation. ",22 1339,"Prostatic carcinoma: histological and immunohistological factors affecting prognosis. Neuro-endocrine or paracrine cells of the human prostate and urethra have been identified by various methods, predominantly silver stains and immunocytochemistry. The incidence of neuro-endocrine differentiation in prostatic carcinoma has varied considerably from 10 to 100%, but has not been studied previously as an independent factor affecting prognosis. Nucleolar organiser regions (NORs) are loops of ribosomal RNA occurring in the nucleoli of cells which ultimately process RNA genes. NORs have been demonstrated by silver (Ag) staining techniques and have been studied in numerous malignant tumours. A pilot study from this laboratory has shown a distinct and significant difference in AgNOR staining between prostatic carcinoma and benign prostatic epithelial hyperplasia. A retrospective study was performed with at least 6 years' follow-up. This confirmed the presence of neuro-endocrine cells in more than half of the patients under investigation. A significant correlation between survival and the absence of neuro-endocrine cells was demonstrated. AgNOR staining was shown to be of no prognostic value. ",11 541,"Immunohistochemical demonstration of the placental form of glutathione S-transferase, a detoxifying enzyme in human gliomas. Expression of the human placental form of glutathion S-transferase (GST-pi) in human gliomas was investigated by immunohistochemical methods, and the result was compared with that of normal human glial cells. The gliomas in this study were composed of five benign astrocytomas (Grade 2), ten anaplastic astrocytomas (Grade 3), and 16 glioblastomas (Grade 4). Normal human glial cells showed only a weak immunostaining response for GST-pi in the cytoplasm or some nuclear membranes. All of benign astrocytomas had diffusely weak GST-pi immunostaining, resembling that of normal glial cells. With increasing grade, gliomas showed a strongly positive reaction for GST-pi. The positive reactions were remarkable especially in the gemistocytes and giant cells in the high-grade gliomas. These results suggest that cells of gliomas have some detoxifying function and the expression of this detoxifying enzyme, GST-pi, is related to the degree of malignancy of the gliomas. ",3 2934,"Effects of acute and chronic ethanol administration and its withdrawal on the level and binding of somatostatin in rat brain. 1. Acute ethanol administration resulted in an increase in the total number of specific somatostatin receptors in rat frontoparietal cortex and hippocampus, and a decrease in the level of somatostatin-like immunoreactivity in the hippocampus but not in the frontoparietal cortex. 2. Chronic administration of ethanol caused a decrease in the number of somatostatin receptors in the frontoparietal cortex but not in the hippocampus, although the level of somatostatin-like immunoreactivity was unchanged in both brain areas. 3. A week after suppressing ethanol the value for specific binding of tracer to somatostatin receptors in the frontoparietal cortex was not significantly different from that of the control rats, although the actual number of receptors was slightly lower. 4. These results suggest a possible role for somatostatin in the nervous system during alcoholism and the post-withdrawal reaction. ",20 78,"Does survival depend on the amount of autotransplanted splenic tissue? Susceptibility to Streptococcus pneumoniae infection was studied in 11 groups of rats allocated to sham operation, splenectomy, or splenic autotransplantation of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the removed spleen. Three months later, all rats were exposed intravenously to type 1 Streptococcus pneumoniae (median lethal dose, LD50, for control group). Survivors were killed 13 days after the bacterial challenge. Autopsy showed that more splenic tissue was recovered in rats that received less than 50% splenic tissue compared with those that received 50% or more. More survivors were found among sham-operated rats (47.5%; 95% confidence intervals, 32 to 68) and rats that had 40% splenic tissue implanted (35%; confidence interval, 20 to 54) or those that were found to have regenerated 40% splenic tissue. We conclude that 40% of the spleen should be autotransplanted to protect the rat optimally against infection after splenectomy. ",0 3214,"Hypoxemia in the postanesthesia care unit: an observer study To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes. ",22 2489,"Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: roles of growth hormone-releasing factor and somatostatin. GH secretion is markedly blunted in obesity; however, the mechanism(s) mediating this response remains to be elucidated. In the present study we examined the involvement of the two hypothalamic GH-regulatory hormones, GH-releasing factor (GRF) and somatostatin (SRIF), using the genetically obese male Zucker rat. Spontaneous GH, insulin, and glucose secretory profiles obtained from free moving, chronically cannulated rats revealed a marked suppression in amplitude and duration of GH pulses in obese Zucker rats compared to their lean littermates (mean 6-h plasma GH level, 3.9 +/- 0.4 vs. 21.5 +/- 3.8 ng/ml; P less than 0.001). Obese rats also exhibited significant hyperinsulinemia in the presence of normoglycemia. The plasma GH response to an iv bolus of 1 microgram rat GRF-(1-29)NH2, administered during peak and trough periods of the GH rhythm, was significantly attenuated in obese rats at peak (137.4 +/- 26.1 vs. 266.9 +/- 40.7 ng/ml; P less than 0.02), although not at trough, times. Passive immunization of obese rats with a specific antiserum to SRIF failed to restore the amplitude of GH pulses to normal values; the mean 6-h plasma GH level of obese rats given SRIF antiserum was not significantly different from that of obese rats administered normal sheep serum. Both pituitary wet weight and pituitary GH content and concentration were reduced in the obese group. Measurement of hypothalamic GRF immunoreactivity revealed a significant (P less than 0.05) reduction in the mediobasal hypothalamic GRF content in obese rats (503.2 +/- 60.1 pg/fragment) compared to that in lean controls (678.1 +/- 50.2 pg/fragment), although no significant difference was observed in hypothalamic SRIF concentration. Peripheral SRIF immunoreactive levels were significantly (P less than 0.01) elevated in both the pancreas and stomach of obese rats. These results demonstrate that the genetically obese Zucker rat exhibits 1) marked impairment in both spontaneous and GRF-induced GH release, which cannot be reversed by SRIF immunoneutralization, 2) significant reduction in pituitary GH concentration, 3) depressed hypothalamic GRF content, and 4) elevated gastric and pancreatic, but not hypothalamic, SRIF levels. The findings suggest that the defect in pituitary GH secretion observed in the genetically obese Zucker rat is due, at least partially, to insufficient stimulation by hypothalamic GRF, and that SRIF does not play a significant role. ",17 1454,"Treatment of tubal pregnancy by local injection of methotrexate after adrenaline injection into the mesosalpinx: a report of 25 patients. Twenty-five patients with a tubal pregnancy were treated by an injection of methotrexate (MTX) into the tubal swelling after vasoconstriction of the mesosalpinx with adrenaline. Twenty-four of the 25 patients had an uneventful clinical course. In one case, the tube ruptured despite falling serum human chorionic gonadotropin (hCG) concentrations. In 17 of 24 patients, the dose of 100 mg that was locally injected was sufficient. Seven patients were given additional systemic injections. In 3 of the 4 patients with high initial serum hCG levels (greater than 10.000 mIU/mL), the clinical course was uneventful. The side effects of MTX and adrenaline were minimal. Whether this way of treatment guarantees better chances of fertility in the future is unknown. Therefore a prospective, case-controlled study comparing the fertility rates in different ways of treatment is needed. ",12 2007,"Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study Data from 10,359 men and women aged 40-59 years from 22 districts in the Scottish Heart Health Study were used to describe the prevalence rates of coronary heart disease in Scotland in 1984-1986 and their relation to the geographical variation in mortality in these districts. Prevalence was measured by previous history, Rose chest pain questionnaire, and the Minnesota code of a 12 lead resting electrocardiogram. The prevalence of coronary heart disease in Scotland was high compared with studies from other countries that used the same standardised methods. A history of angina was more common in men (5.5%) than in women (3.9%), though in response to the Rose questionnaire 8.5% of women and 6.3% of men reported chest pain. A history of myocardial infarction was three times more common in men than women, as was a Q/QS pattern on the electrocardiogram. There were significant correlations between the different measures of coronary prevalence. District measures of angina correlated well with mortality from coronary heart disease, and these correlations tended to be stronger in women than in men. There was no significant correlation between mortality from coronary heart disease and measures of myocardial infarction. The study provides data on the prevalence of coronary heart disease in men and women that are valuable for the planning of cardiological services. ",13 484,"Predictive value of tumor estrogen and progesterone receptor levels in postmenopausal women with advanced breast cancer treated with toremifene. The predictive value of estrogen receptor (ER) concentrations was evaluated in a group of 113 postmenopausal patients with estrogen-receptor-positive (ER greater than 7 fmol/mg protein) advanced breast cancer. In 103 patients, tumors were also sampled for progesterone receptor (PgR) determination. All patients were treated with toremifene, a novel antiestrogen, 60 mg daily. The median ER in 51 responders was 78 fmol/mg protein, and in 62 nonresponders, 51 fmol/mg protein; the median PgR levels were 40 and 37 fmol/mg protein, respectively. The response rate in patients with ER less than 50 fmol/mg protein was 38%, and 51% in the group with ER greater than 50 fmol/mg protein (not significant [NS]). The response rate in patients with PgR less than 10 fmol/mg protein was 42%, and in patients with greater than 10 fmol/mg protein, 44%. The duration of response in patients with ER greater than 50 fmol/mg protein was significantly longer than with lower ER levels (P = 0.002). PgR was not associated with the duration of response. In Cox's multiple regression analysis, ER was an independent prognostic factor (P = 0.005) for response duration. Thus, the ER concentration of tumor tissue predicts the duration of response but not the response rate to toremifene in patients with advanced breast cancer. The PgR status does not predict the response rate or the duration of response. ",3 1183,"The UCLA-University of Utah epidemiologic survey of autism: the etiologic role of rare diseases. Twelve rare diseases known to cause CNS pathology were found in 26 (11%) of 233 autistic probands identified during a recent epidemiologic survey of Utah. These 26 probands had significantly lower mean IQs than the remaining patients (43 versus 60) but similar sex distribution and prevalence of abnormal EEGs and seizures. The rarity and diversity of these 12 diseases make it highly unlikely that they randomly occurred with autism. Their presence in this epidemiologic survey is the most compelling evidence to date to support the hypothesis that different diseases producing different types of CNS pathology can play an etiologic role in autism. ",9 2030,"The surprising kidney-fluid mechanism for pressure control--its infinite gain! In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966. ",13 2255,"Condylomata acuminata in children: frequent association with human papillomaviruses responsible for cutaneous warts. To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation. ",16 1980,"Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats. To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium. ",13 3046,"Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Transfusion Practices Committee of the American Association of Blood Banks. We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection. ",22 2014,"Interleukin-2-induced lung permeability is mediated by leukotriene B4. Interleukin (IL)-2 therapy leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of the chemoattractant, immunomodulator, and permeability-promoting agent leukotriene (LT) B4 in this setting. Sheep with chronic lung lymph fistulae were given IL-2, 10(5) U/kg as an IV bolus (n = 6). Within 2 hours this led to a significant increase in LTB4 levels in both plasma and lung lymph. The mean pulmonary artery pressure (MPAP) rose while the pulmonary artery wedge pressure was unchanged. Arterial oxygen tension (PaO2) fell. Lung lymph flow (QL) was tripled (P less than 0.05) at 3 hours, coinciding with an increase in the lymph/plasma (L/P) protein ratio (P less than 0.05) resulting in an increase in the lymph protein clearance (P less than 0.05), data documenting increased microvascular permeability to protein. Mild leukopenia and thrombocytopenia (P less than 0.05) occurred. Body temperature rose and shaking chills were common. Pretreatment with the lipoxygenase inhibitor diethylcarbamazine (DEC; n = 6) reduced baseline plasma LTB4 levels and prevented the IL-2-induced increases in LTB4 in plasma and lung lymph (P less than 0.05). In contrast to IL-2 treatment alone, DEC blunted the increase in MPAP and prevented the rises in QL (P less than 0.05), L/P protein ratio (P less than 0.05), and lymph protein clearance (P less than 0.05). DEC also prevented the IL-2-induced leukopenia, the fall in platelet count, and the rise in body temperature (P less than 0.05, respectively). Infusion of IL-2 excipient control (n = 5) did not affect plasma or lymph LTB4 levels but there were mild increases in MPAP (P less than 0.05). The QL also rose but this occurred while the L/P protein ratio fell (P less than 0.05). Body temperature rose moderately. The PaO2, leukocyte, and platelet counts were unaffected. These data indicate that IL-2 administration leads to pulmonary dysfunction manifest by pulmonary hypertension and increased vascular permeability, events associated with LTB4 synthesis and prevented by DEC. Leukotriene B4 appears therefore to mediate the IL-2-induced lung injury. ",13 2652,"Racial, social, and environmental risks for childhood asthma. Unlike a number of childhood problems, it is not clear that there are racial or socioeconomic disparities in the prevalence of childhood asthma. We analyzed data from the Child Health Supplement to the 1981 National health Interview Survey, a population-based survey with information concerning 15,416 children, to address the following questions: are there racial or socioeconomic differences in rates of childhood asthma; if yes, what is the contribution of social and environmental characteristics to the observed differences? In this sample, black children were more likely to have asthma than were white children (4.4% vs. 2.5%). Racial disparities in prevalence emerged early and at all childhood ages were due to higher black rates of onset between the ages of 1 and 3 years. Poverty status, maternal cigarette smoking, large family size, smaller size of home, low birth weight, and maternal age younger than 20 years at the child's birth were all associated with increased rates of childhood asthma. When available social and environmental characteristics were controlled for using multivariate analyses, the increased risk for asthma among black and poor children was reduced to statistical insignificance. We conclude that black and poor children in the United States do have higher rates of asthma, that social and environmental factors exert substantial influences on rates of asthma, and that much of the racial and economic disparity in prevalence can be accounted for by a variety of social and environmental characteristics. ",19 218,"Reconstruction after mastectomy. Advances in materials and techniques, especially those involving transposition of muscle and skin flaps, have made breast reconstruction possible for most women who undergo mastectomy for breast cancer. The availability of this option can alleviate the breast and chest wall deformity that results from virtually all local treatment of breast cancer. It is essential that the reconstruction surgeon be part of the breast cancer management team from the beginning of treatment planning and that this surgeon work closely with the general surgeon, medical oncologist, and radiation therapist as well as the adjunctive treatment team members. The patient's clinical status and the type of local treatment will be significant determinants of the reconstructive options. For women with stage I breast cancer, these decisions may be based largely on the oncologist's local and adjunctive therapy procedures and the woman's desire to proceed or delay. For women with systemic disease, all members of the breast management team may need to agree on the advisability and timing of reconstruction. Central to all of the numerous decisions described in this paper regarding the timing, type, and extent of breast reconstruction is the primary goal of the entire team: the best possible management of the breast cancer itself. The promise of attractive, symmetric, and natural appearing breasts, complete with a symmetric nipple-areolar complex, has eased somewhat the diminishment of self-esteem and the threat to femininity that can accompany the loss of a breast. By lowering fear, the widely recognized availability of breast reconstruction may encourage more women to monitor their breasts and seek diagnosis of changes and may influence selection of the type of local treatment if cancer is detected. Because of the psychological and cultural significance of the breast, the reconstructive surgeon must be particularly sensitive to the psychological and aesthetic expectations of the patient. Even in those patients with metastases and limited life expectancy, breast reconstruction can enhance the quality of life. ",3 2337,"Molecular identification of major and minor bullous pemphigoid antigens. The skin antigens defined by basement membrane zone antibodies in 38 patients with bullous pemphigoid were analyzed by Western immunoblot. Thirty-four patients (89%) had antibodies to a major bullous pemphigoid antigen with a molecular weight of approximately 230 kD. Twelve patients (32%) had antibodies to a minor bullous pemphigoid antigen with a molecular weight of approximately 160 kD; this included four patients who did not have antibodies to the 230 kD antigen. Depending on the epidermal extract used, a variable number of patients (up to 75%) also had antibodies to minor bullous pemphigoid antigens with molecular weights of approximately 180 and 200 kD. The results of this study confirm that bullous pemphigoid antigens are heterogeneous at the molecular level. Approximately 10% of patients have antibodies directed solely to a minor bullous pemphigoid antigen. ",16 872,"Histologic study of eustachian tube cartilage with and without congenital anomalies: a preliminary study. We investigated histopathologically the development of the eustachian tube (ET) cartilage at a cellular level in individuals with and without congenital anomalies. Fourteen specimens were obtained from 14 individuals ranging in age from 24 weeks' gestation to 3 years who had cleft palate or trisomy 21 (Down) syndrome; the 49 specimens in the nonanomaly (control) group were from 49 individuals ranging from 26 weeks' gestation to 85 years of age. All temporal bone specimens included the ET and its accessory structures, and all were processed and stained with hematoxylin and eosin for histologic study in a routine manner. The number of cartilage cells in the midcartilaginous portion of the ET was determined by light microscopy. In all groups, cartilage cell density of the ET decreased with increasing age. However, cell density tended to be higher at all ages for individuals with cleft palate and microtia versus controls, and tended to be lower at all ages for individuals with Down syndrome. ",6 1258,"Pupillary responses in amblyopia. Relative afferent pupillary defects (RAPD) were detected in 32.3% of patients with amblyopia by a modification of the swinging flashlight test and the synoptophore. After consideration of various clinical investigations the significant factors identified in patients showing a RAPD were: anisometropia, early age of onset where strabismus was present, level of visual acuity following treatment, longer period of occlusion therapy. These points bear similarities to the results of pattern electroretinograms (PERG) in amblyopes, and the possibility of the causative defect being at ganglion cell level is discussed. The effect of occlusion treatment cannot be predicted from the presence or absence of a RAPD. ",10 308,"Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990. The effect of a synthetic analogue of CCK (Thr4,Nle7CCK-9) on growth of SW-1990 human pancreatic cancer was examined in two experimental models. Nude mice bearing SW-1990 pancreatic cancer xenografts were injected with CCK (5, 15, or 25 micrograms/kg) or vehicle twice daily for 20 days. Animals were then sacrificed and tumor volume, weight, protein, and deoxyribonucleic acid (DNA) content were evaluated. SW-1990 cells were grown in vitro and the effects of CCK, secretin, vasoactive intestinal peptide (VIP), and proglumide (a CCK-receptor antagonist) on cell number and DNA synthesis were determined. The highest dose of CCK, 25 micrograms/kg, significantly increased tumor weight, protein content, and DNA content (P less than 0.005). In vitro, CCK caused significant increases in cell counts of up to 47% at six days and 66% at 12 days compared to control. Graded concentrations of CCK had a biphasic effect on DNA synthesis with significant increases of up to 65% (P less than 0.005). CCK-induced cell proliferation was inhibited by proglumide. Secretin slightly increased cancer cell growth, although not as potently as CCK, VIP or secretin in combination with CCK did not show potentiation. These results indicate that growth of some human pancreatic cancers may be influenced by gastrointestinal peptides, of which CCK is the most potent. ",3 209,"Carcinoma of the male breast: a review of 41 cases. We reviewed the cases of 41 consecutive men treated for breast carcinoma from 1950 through 1987 at Vanderbilt University Affiliated Hospitals to examine controversies in and methods of therapy for this disease. Twenty-two patients (52%) had stage I or II lesions potentially curable by operative therapy. The overall 5-year survival rates were 100% for stage I, 65% for stage II, 56% for stage III, and 0% for stage IV. Radical mastectomy offered no advantage over modified radical mastectomy in terms of survival or rate of recurrence. Diagnosis at an early clinical stage and no finding of disease in axillary lymph nodes were important factors in survival in this series of patients. All tumors evaluated for hormone receptors were positive. Although experience was limited, encouraging results were obtained with the use of tamoxifen citrate in adjuvant as well as palliative roles. With the exception of a predominance of centrally located lesions and a uniquely high frequency of positive hormone receptor status, carcinoma of the male breast appears biologically similar to the disease in women, and treatment should be guided by similar principles. ",3 1899,"Are ioxaglate and iopamidol equally safe and well tolerated in cardiac angiography? A randomized, double-blind clinical study. A randomized, double-blind, parallel-group study was performed in 50 patients undergoing left ventriculography and coronary arteriography to evaluate ECG changes and the effects on left ventricular function of a low-osmolar ionic contrast agent, ioxaglate, as compared with a low-osmolar nonionic contrast medium, iopamidol. Twenty-five patients received ioxaglate (group 1) and 25 patients received iopamidol (group 2). All patients underwent 48 hours of continuous ECG recording beginning 24 hours before the cardiac catheterization. Left ventricular systolic and end-diastolic pressure, peak positive dp/dt, and dp/dt/P ratio were measured immediately before and after left ventriculography and 3 minutes later. Left ventricular systolic pressure did not change after injection of either contrast medium. Left ventricular end-diastolic pressure increased by 30% in group 1 (p less than 0.01) and by 22% in group 2 (p less than 0.01) immediately after left ventriculography. A further increase by 45% in group 1 (p less than 0.01) and by 24% in group 2 (p less than 0.01) was observed 3 minutes later. No differences were observed between values obtained in the two groups. Peak positive dp/dt did not change immediately after injection of either contrast medium but decreased by 5% (not significant) in group 1 and by 7% (p less than 0.02) in group 2 three minutes after left ventriculography. There were no significant differences between the two groups. Analysis of continuous 48-hour ECGs showed that both ioxaglate and iopamidol induced a slight increase (by 8% and 7%, respectively; p less than 0.05) in heart rate during injection with early and complete recovery. ",13 977,"Altered function of pulmonary surfactant in fatty acid lung injury. To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids. ",7 839,"Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis. Oxygen free radical activity and inhibition were examined in experimental pancreatitis. Twenty-five rats were randomized to five groups: controls received intravenous saline, to simulate pancreatitis one group received intravenous caerulein (5 micrograms kg-1 h-1), and three groups received sodium taurocholate via the pancreatic duct (0.2 ml, 5 per cent), either alone, following allopurinol or immediately before superoxide dismutase. Chemiluminescence (a phenomenon based on the emission of light during chemical reactions and which is dependent on oxygen free radical activity) was used as an index of oxygen free radical activity and was measured in tissue samples at 5-min intervals following induction of pancreatitis. The control mean(s.e.m.) serum amylase level 1 h after induction of pancreatitis was 635(13) units. It was significantly elevated in caerulein-induced pancreatitis, 1833(118) units (P less than 0.05) and exceeded 3000 units in all taurocholate-infused animals. Mean(s.e.m.) chemiluminescence ranged from 44 (8) mV 100 mg-1 at time zero to 404(113) mV 100 mg-1 at 1 h in controls. In caerulein-induced pancreatitis mean(s.e.m.) chemiluminescence peaked at 20 min (1399(239) mV 100 mg-1, P less than 0.02) and in taurocholate-induced pancreatitis at 15 min (2316(95) mV 100 mg-1, P less than 0.004). Superoxide dismutase significantly reduced chemiluminescence and hyperamylasaemia in taurocholate groups. Increasing oxygen free radical activity paralleled evolving pancreatitis. Superoxide dismutase may have a therapeutic role in pancreatitis. ",5 786,"Combined radiologic and retrograde endoscopic and biliary interventions. Methods of treating complex biliary duct problems by a team composed of an endoscopist and interventional radiologist are described. These procedures are of two types: Those in which all manipulations are performed through the endoscope and those in which an antegrade transhepatic and a retrograde endoscopic approach are combined. ",5 1358,"Patient acceptance of and satisfaction with an external negative pressure device for impotence. Patient acceptance of and satisfaction with an external negative pressure device as a treatment for impotence were retrospectively analyzed among 100 men. The over-all satisfaction rate was 68%. Reasons for dissatisfaction with and discontinuing the use of the device included premature loss of penile tumescence and rigidity, pain or discomfort either during application of suction or during intercourse and inconvenience. Negative pressure therapy is an effective treatment for impotence of various etiologies and should be among treatment options offered to the impotent patient. ",11 84,"Impetigo. Current etiology and comparison of penicillin, erythromycin, and cephalexin therapies. We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection. ",0 3151,"An operative complication in a patient with a true posterior communicating artery aneurysm: case report and review of the literature. Intraoperative oculomotor nerve injury in a patient with a true posterior communicating artery aneurysm is reported in detail. A comparison of internal carotid artery aneurysms at the posterior communicating artery junction with true posterior communicating artery aneurysms deserves special attention, because the vascular relationships of the aneurysm are more complex. A clip along the internal carotid artery does not occlude blood flow to the aneurysm, and the aneurysmal neck and the distal posterior communicating artery are closer to the oculomotor nerve. This is the 27th reported case of a true posterior communicating artery aneurysm. The incidence of true posterior communicating artery aneurysms ranges from 0.1 to 2.8% of all aneurysm patients. Such aneurysms constitute 4.6 and 11% of so-called posterior communicating aneurysms in two series. Difficulty associated with a preoperative diagnosis has been documented in at least 4 cases. An awareness of this rare aneurysm is stressed in order to avoid operative complications. ",22 2026,"Role of endothelium in the response to endothelin in hypertension. The relation between endothelin and acetylcholine (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin-induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10(-5) M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 x 10(-6) M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension. ",13 2931,"Monoscleral fixation for posterior chamber intraocular lenses in cases of posterior capsule rupture. A method for monoscleral fixation of posterior chamber intraocular lenses in posterior capsule rupture is described. Five lenses fixated with this technique are reviewed. ",20 2653,"Immune complexes in pediatric human immunodeficiency virus infection. Circulating immune complexes (CIC) were analyzed in a cohort of 30 children infected with the human immunodeficiency virus. Elevated CIC were detected by the C1q assay in 70% (21/30) of all patients and by the Raji cell assay in 93% (28/30) of all patients. While only less than one third of patients with elevated CIC had free serum antibodies to Epstein-Barr virus, 80% (16/20) of them had detectable antibodies to Epstein-Barr virus associated with CIC. Enriched CIC in human immunodeficiency virus-infected children contained low levels of complement. These findings document that, as an expression of the humoral immunodeficiency, CIC in human immunodeficiency virus-infected children are deficient in complement and can thus be underestimated if complement-precipitating methods are used for their detection. ",19 987,"What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust. OBJECTIVE--To investigate the role of occupational and domestic exposure to dust in the aetiology of cryptogenic fibrosing alveolitis. DESIGN--Matched case-control study. SUBJECTS--40 Patients with cryptogenic fibrosing alveolitis and 106 community controls matched for age and sex who responded to a questionnaire. MAIN OUTCOME MEASURE--Responses to self administered questionnaire asking about lifetime exposure to dust, animals, and smoke at home and at work. RESULTS--The patients with cryptogenic fibrosing alveolitis were more likely to report occupational exposure to metal dust (matched odds ratio 10.97 (95% confidence interval 2.30 to 52.4), p less than 0.001) or wood dust (2.94 (0.87 to 9.90), p = 0.08), to have worked with cattle (10.89 (1.24 to 96.0), p = 0.01), and to have lived in a house heated by a wood fire (12.55 (1.04 to 114), p = 0.009). A history of smoking and social class based on occupation were not significantly related to disease state. CONCLUSION--Environmental exposure to dust may be an important factor in the aetiology of cryptogenic fibrosing alveolitis. ",7 362,"Race, nutritional status, and survival from breast cancer. The effects of nutritional status on differences in the survival of black and white women with breast cancer were studied in a cohort of 1,960 Georgia women diagnosed during 1975-1979. After data were adjusted for stage of disease, socioeconomic status, and other prognostic factors, poorer survival rates were shown in black women. Within each stage classification, lower levels of serum albumin and hemoglobin and higher relative body weight were more common among blacks and were independently associated with poorer survival. Among women with stage 3 disease, adjustment for these variables substantially reduced the excess mortality rate among blacks, suggesting that racial differences in survival may be partly explained by differences in nutritional status or extent of disease within stage. ",3 818,"Pathogenesis of gallstones. The many developments in nonoperative methods for the treatment of gallstone disease underscore the importance of understanding the pathogenesis of these stones. Elucidation of the factors responsible for nucleation of crystals and the mechanism by which it occurs would appear to be the challenge if we are to define the cascade of events that results in gallstone formation. ",5 1580,"A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats. Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003). ",13 1509,"A reappraisal of the need for autologous blood donation in the obstetric patient. There has been recent interest in autologous blood donation in obstetric patients, but little attention has been paid to whether such programs are needed or whether the patients that will require transfusion can be accurately predicted. At the University of California San Diego Medical Center from July 1 to Dec. 31, 1988, there were 2265 deliveries; 13 women (0.57%) received blood transfusions. Traditionally accepted risk factors were identified in 251 patients, with only four (1.6%) requiring transfusion. Among the 150 patients delivered by repeat cesarean section, only one (0.7%) required blood. one of 27 (3.7%) multiple gestations, two of eight (25%) patients with placenta previa, and none of the 66 grandmultiparous women had transfusions. These data suggest that autologous blood donation may not be beneficial or cost effective when the low frequency of blood transfusions in this high-risk obstetric population and the difficulty in accurately predicting those likely to require transfusions are considered. ",12 737,"Acalculus lymphoeosinophilic cholecystitis associated with interleukin-2 and lymphokine-activated killer cell therapy. A case of unusual cholecystitis that developed on completion of interleukin-2 and lymphokine-activated killer cell therapy is described. A 62-year-old man was treated with interleukin-2 and lymphokine-activated killer cells for disseminated renal cell carcinoma. During the course of the immunotherapy, his serum alkaline phosphatase level increased, as did the peripheral eosinophil count (0.31). Subsequently, clinical and radiologic evidence of acute cholecystitis was noted. The removed gallbladder showed acalculus cholecystitis with extensive diffuse infiltrates of numerous eosinophils and T lymphocytes, but sparse polymorphonuclear leukocytes. The authors name this unusual cholecystitis acalculus lymphoeosinophilic cholecystitis and believe it to be associated with interleukin-2 and lymphokine-activated killer cell therapy. The pathogenic relationship is discussed. ",5 785,"Ablation of the cystic duct and the gallbladder. Experimental basis and initial clinical observations. Bipolar radiofrequency electrocoagulation of the cystic duct by catheter can be performed safely and reproducibly using fluoroscopic control and induces endoluminal scar formation. The scar within the cystic duct forms a reliable barrier between the gallbladder and the biliary system and avoids recanalization of the cystic duct at a later date. Sclerotherapy of the isolated gallbladder with 95% ethanol and 3% STS can be performed without toxic or otherwise adverse effects and is suitable to ablate the porcine gallbladder. Initial clinical trials with this new technique on a small number of patients are promising and have demonstrated that the protocol can be applied safely to humans. The electrocoagulation technique by catheter appears suitable to ablate the human cystic duct. Follow-up evaluation of our first patients is under way and must determine whether our regimen is appropriate to ablate the human gallbladder on a long-term basis. Further development of this new approach may eventually enable definitive nonoperative treatment of cholecystolithiasis in selected patients. ",5 1463,"Effects of intravascular fetal blood transfusion on fetal intracardiac Doppler velocity waveforms. In 12 fetuses from pregnancies with red blood cell isoimmunization Doppler velocity waveforms were recorded at the level of atrioventricular valves immediately before and at 15-minute intervals for 2 hours after the intravascular transfusion. The left and right cardiac outputs, the ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of both ventricles as well as the heart rate were calculated. Before transfusion, the left and right cardiac outputs were significantly higher than reference ranges for gestation that were constructed from the cross-sectional study of 187 normal pregnancies. After transfusion there was a significant temporary fall in right and left outputs associated with increased ratios between the peak velocities during early passive ventricular filling and active atrial filling. Within 2 hours after transfusion both parameters returned toward the normal range. In addition, no significant changes were found for fetal heart rate values before and after transfusion. The fall of cardiac output was significantly related to the amount of expansion of the feto-placental volume. ",12 1037,"Gross motor patterns in children with cerebral palsy and spastic diplegia. Rolling, sitting, and crawling patterns were motoscopically analyzed in 72 children with cerebral palsy and spastic diplegia; the relation between these patterns and the severity of the locomotive disability was studied. In rolling, trunk rotation and elbow support were difficult for the most severely diplegic children. When sitting, most patients had a between-heel sitting pattern in which the thighs were adducted and the knees were flexed. When crawling, the reciprocal thigh movements were insufficient and accompanied by lateral bending of the trunk in many patients. In the more impaired patients, the thighs supported the weight in flexion and did not move reciprocally. Creeping on the elbows without reciprocal leg movements was demonstrated in the most severely affected children after 2 years of age. ",9 459,"Reasons why mastectomy patients do not have breast reconstruction. Breast reconstruction after mastectomy is valuable, yet only a small percentage of eligible patients ever have reconstruction. Little has been done to determine why so few patients proceed with reconstructive surgery. A homogeneous population of mastectomy patients, some of whom underwent breast reconstruction while others did not, were surveyed regarding their attitudes about breast reconstruction. A total of 245 women were surveyed. One-hundred and fifty-eight (64 percent) responded, 71 of whom had been reconstructed while 87 had not. Comparison of the responses of the two groups suggests factors that play a role in determining whether the mastectomy patient will accept or decline the option of breast reconstruction. Considerations that made it less likely that a woman would pursue reconstruction included advanced age at the time of mastectomy, concern about complications from further surgery, uncertainty about outcome, and fear about the effect of reconstruction on future problems with breast cancer. Marital status, receiving chemotherapy, or knowing a patient who had a bad result from reconstruction did not affect the decision. An awareness and understanding of these factors may be helpful to physicians in counseling patients and in increasing the number of women who enjoy the benefits of breast reconstruction. ",3 3142,"What getting sick means. The concepts of health, disease and death have intrigued man since the beginning of time and are continually evolving. In the nonwestern societies the models which have been proposed for the etiology of disease have a dichotomous view of disease causation which is derived from either natural or supernatural forces. In the Western societies these concepts are well defined. The numerous advances in the fields of genetics and molecular biology have added a new dimension to the understanding of the various factors involved in the pathogenesis of disease processes. These advances have allowed a greater understanding of numerous disease processes including the inborn errors of metabolism, endocrine disorders and human neoplasia. Several recent advances in the areas of molecular biology and physiology allowing this increased understanding of human disease are presented. ",22 764,"Limitations in the evaluation of therapy in inflammatory bowel disease: suggestions for future research. The current treatment of inflammatory bowel disease (IBD), though improved over earlier therapies, remains variable rather than consistent and supportive rather than curative. The similar management of ulcerative colitis (UC) and Crohn's disease (CD), which are thought to be differing though related disorders, suggests that therapy is nonspecific. The variation in therapeutic practices results from the fact that the etiologies of the diseases are obscure, from limited knowledge of the biological and pharmacological actions of drugs commonly prescribed (sulfasalazine, 5-ASA compounds, steroids, 6-MP and azathioprine), from an inadequate understanding of genetic differences influencing drug metabolism, from insufficient awareness of the factors influencing drug efficiency (concurrent use of antimotility drugs, cigarette smoking, food combinations), from the variability of the patient groups studied (extent and severity of disease), and from incomplete documentation of the clinical status of patients at the time of therapeutic trial. Future advances in treatment will depend on gaining new information about the nature of IBD and of drug pharmacology and bioavailability, derived from collaborative studies by clinicians, clinical investigators, and basic scientists. Important areas for IBD research include the biology of intestinal epithelium, the nature of the IBD inflammatory reaction and of gut mucosal immune regulation (via the application of new biotechnologies) and more representative experimental animal models. Decisive multicenter therapeutic studies require agreement on definitions of ulcerative colitis and Crohn's disease, accurate characterization of patient groups, acceptable objective criteria of IBD severity and activity, and reliable indicators of therapeutic response. ",5 3190,"Growth, thermogenesis, and hyperphagia. Resting metabolic rate is demonstrated to be a function of fat-free mass and a growth variable related to food-energy-input imbalance rate. By use of obligatory energy expenditure terms, the two-reservoir energy model applied to hyperphagia shows that growth of the fat-free mass is rapid whereas that of the fat store is slow and that the growth of both is bounded. Most of the excess energy at the onset of hyperphagia initially goes into the fat store, but this decreases with time until the greater fraction is diverted to the fat-free mass. The two-reservoir model predicts that weight gain per unit of excess energy is not constant but decreases monotonically until ultimately reaching an asymptotic value. Departure of theory and experiment in the long term suggests that facultative considerations become increasingly important. ",22 2689,"Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects. Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects. ",19 844,"Paf-acether synthesis by Helicobacter pylori. Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa. ",5 158,"Visceral leishmaniasis in a Scottish child. A Scottish girl acquired visceral leishmaniasis (kala-azar) while on holiday in Majorca. She presented with the infection, six months later, in Scotland. Because of inexperience with the disease and a degree of scepticism unnecessary investigations were carried out resulting in a delay in treatment. ",2 3149,"Isometric features of orthostatic tremor: an electromyographic analysis. A patient is described with ""orthostatic"" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor. ",22 1712,"Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. OBJECTIVE: To determine the discriminant accuracy of exercise thallium-201 myocardial perfusion scintigraphy for the diagnosis and prognosis of patients with known or suspected coronary artery disease. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database. STUDY SELECTION: The key medical subject headings used were coronary disease, myocardial infarction, radionuclide imaging, and thallium. A total of 122 retrieved studies were considered relevant and were reviewed in depth. DATA EXTRACTION: Only studies reporting both the sensitivity and specificity of thallium scintigraphy were analyzed. RESULTS: Discriminant accuracy for diagnosis and prognosis was summarized in terms of pooled sensitivity and specificity. CONCLUSIONS: Exercise thallium scintigraphy is useful in the noninvasive diagnosis of coronary artery disease, especially in patients with abnormal resting electrocardiograms, restricted exercise tolerance, and intermediate probability of having disease at the time of testing as well as of defining the prognosis of patients with known or suspected coronary artery disease, especially in those with previous myocardial infarction. Because of various shortcomings in the published record, however, the marginal discriminant accuracy and cost effectiveness of thallium scintigraphy compared with conventional clinical assessment and exercise electrocardiography remain controversial. ",13 1543,"Gamete intrafallopian transfer (GIFT) in women with bicornuate uteri. Fourteen women with bicornuate uteri underwent a total of 30 gamete intrafallopian transfer procedures. All patients responded adequately to ovarian stimulation. Eight women conceived, two of them twice. Five women delivered at term and three had a premature delivery. There was one spontaneous abortion and an ectopic pregnancy. No neonatal deaths occurred in this series. No increase in the incidence of spontaneous abortion was noted but there appeared to be an increase in the incidence of premature labor. These findings suggest that the prospects of conception for infertile women with bicornuate uteri treated with gamete intrafallopian transfer are similar to those of the rest of the infertile population treated at our center. ",12 1617,"Response of spinal cord blood flow and motor and sensory evoked potentials to aortic ligation. To produce spinal cord ischemia in the lamb, ligation of the thoracic aorta was performed for 15, 30, and 45 minutes in three animals each. Spinal cord blood flow and motor and sensory evoked potentials were measured before, during, and after aortic ligation. Ischemia with a blood flow of zero during ligation was encountered in the thoracic and lumbar cords, followed by hyperemia upon release of the ligature. Both somatosensory and motor evoked potentials were obliterated during aortic ligation and gradually recovered following resumption of flow. Motor and sensory evoked potentials behaved similarly to high aortic ligation. ",13 2057,"Progress in cardioprotection: the role of calcium antagonists. Calcium antagonists are now widely used for the treatment of clinical hypertension and angina pectoris. They are efficacious for the treatment of vasospastic, fixed atherosclerotic and mixed angina; they reduce the incidence of silent ischemia; and they have been shown to reduce postmyocardial infarct angina. Experimental data suggest that they may have certain cardioprotective properties in cases of acute myocardial ischemia and infarction, stunned myocardium, diastolic dysfunction, left ventricular hypertrophy and atherosclerosis. Moreover, they have been shown to improve exercise performance, as well as the diastolic abnormalities in patients with hypertrophic cardiomyopathy. In animals, they may delay or reduce the extent of myocardial necrosis after coronary occlusion or coronary occlusion followed by reperfusion, and in low doses that do not alter the hemodynamic profile, they have been shown to enhance the return of ventricular function in animals with stunned myocardium. However, the early first-generation calcium antagonists (nifedipine, verapamil, diltiazem) have not been shown to reduce myocardial infarct size or to enhance survival in patients with acute myocardial infarction. There now are clinical studies that suggest that, unlike beta blockers or nitrates, nifedipine may slow the development of atherosclerotic progression in humans over a 2-year period, and it seems likely that in the 1990s there will be further expansion of the use of calcium antagonists for not only angina and hypertension but also for aspects of cardioprotection. That calcium antagonists may delay, prevent or possibly regress atherosclerotic lesions is an exciting possibility. ",13 399,"A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells. Malignant spreading of cancer cells requires cell surface proteases that cleave the crosslinked collagenous matrix of connective tissues. From correlating the morphologically defined invasiveness of tumor cells with the presence of specific membrane-associated proteases, we have identified a malignant human melanoma cell line, LOX, that invades crosslinked gelatin films in vitro and contains uniquely a neutral 170-kDa gelatinase in the cell membrane. A similar gelatinase was found in membranes recovered from culture media conditioned with LOX. The 170-kDa gelatinase is a wheat germ agglutinin-binding protein. The proteolytic activity is maximal at neutral pH, enhanced by EDTA and dithiothreitol, inhibited by the cysteine protease inhibitors N-ethylmaleimide, HgCl2, and phenylmethylsulfonyl fluoride, and can bind to an organomercurial adsorbent, suggesting that it is a neutral sulfhydryl-sensitive protease. This 170-kDa gelatinase of LOX cells was not found in a control melanoma cell line, SK-MEL28, or in 32 other tumor cell lines that did not show extracellular gelatin degradation. Thus, we have identified a large membrane-bound protease that may be a specific marker molecule for melanoma cell invasiveness. ",3 685,"Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones. One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm). ",5 1309,"Natural history of low-stage prostatic cancer and the impact of early detection. An expanding and increasingly older population, a rising incidence of prostate cancer, and uncertainties regarding treatment effectiveness have made this disease a target of special concern. The natural history of the cancer must be a consequence of host-tumor interactions, but little is known for sure about this subject. The growth rate of the tumor is determined by many factors, including genetic instability. At present, tumor grade, volume, and ploidy are the most useful techniques for judging the growth rate and metastatic potential. Stage A1 tumors generally are indolent, whereas stage A2 tumors are more aggressive. The natural history of stage B lesions is not well documented. The author asks two questions (Is cure necessary in those in whom it may be possible? Is cure possible in those in whom it may be necessary?) and reviews the problems inherent in screening for prostate cancer at this time. ",11 32,"Use of latex agglutination technique for detecting Legionella pneumophila (serogroup 1) antibodies. Following the outbreak of Legionnaires' disease in Stafford in 1985, 500 serum samples were submitted to the indirect immunofluorescence antibody test and a latex agglutination. Latex agglutination using ultrasonically disrupted Legionella pneumophila antigens coupled to latex particles, proved a rapid, simple method for detecting circulating antibodies to L pneumophila in a one minute slide latex agglutination test. There was good correlation with the indirect immunofluorescence antibody test (IFAT), and the specificity and sensitivity with respect to a diagnostic result were 98.3% and 97.6%, respectively, using a series of well characterised sera. The latex agglutination test seems well suited as a screening test for presumptive cases of Legionnaires' disease; the latex reagent is easy to prepare and seems to remain stable at 4 degrees C for up to six months. ",0 2519,"Increased transcapillary escape rate of albumin in nondiabetic men in response to hyperinsulinemia. Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01). ",18 2033,"Clues to the electrocardiographic diagnosis of subtle Wolff-Parkinson-White syndrome in children. The electrocardiographic diagnosis of Wolff-Parkinson-White syndrome (WPW) may be missed because delta waves can be subtle in children, so we examined 66 electrocardiograms from patients with proven WPW, 24 from those with questionable WPW (""subtle WPW""), and 369 consecutive electrocardiograms from control patients to identify additional clues that WPW might be present. Three features were notable in WPW: no Q wave in left chest leads (88%), PR interval less than 100 milliseconds (80%), and left axis deviation (33%). In subtle WPW these findings were similar: 79%, 67%, and 46%, respectively. By comparison, 5% of control subjects had no Q wave, 16% had a PR interval of less than 100 milliseconds, and 4% had left axis deviation (all p less than 0.001). The coexistence of two of these features was common (74%) in WPW and subtle WPW (63%) but rare (2%) in control subjects (p less than 0.001). A PR interval of less than 100 milliseconds was less specific before 1 year of age, but 89% of patients with WPW had a QRS duration of greater than 80 milliseconds versus 2% of control subjects (p less than 0.001). Obvious WPW disappeared later in 11 patients; however, left axis deviation or lack of a Q wave persisted in eight (p less than 0.01). We conclude that the diagnosis of WPW in children, even when subtle, is suggested by the presence of these four changes. Preexcitation may persist in some patients in whom overt delta waves are no longer present. ",13 34,"A clinical trial of topical terbinafine (a new allylamine antifungal) in the treatment of tinea pedis. Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream compared with placebo vehicle in the treatment of tinea pedis. Of the 20 patients who were evaluated for efficacy, 10 received terbinafine and 10 received placebo. Except for the terbinafine-treated patients being an average of 11 years older than the patients receiving placebo and the median duration of disease being 6 weeks longer in the placebo group, the two groups were demographically and clinically similar. Results of mycologic tests and clinical findings showed terbinafine to be significantly more effective than placebo in the treatment of tinea pedis. Significantly more terbinafine-treated patients than placebo-treated patients showed conversion to negative culture and microscopy at end of therapy and a significant reduction in scored signs and symptoms. Overall efficacy at follow-up (combined mycologic and clinical findings) was also significantly greater in the terbinafine group (78%) than in the placebo group (zero) (p less than 0.001). Unexplained elevation of liver function test results was noted in three placebo-treated patients and in one terbinafine-treated patient, but these changes were not considered clinically relevant or drug related. ",0 291,"Cancer in the families of children with soft tissue sarcoma. The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis. ",3 3001,"Nurse-monitored cardiac recovery: a description of the first 8 weeks. Health problems and related patient management during early recovery after cardiac surgery are not well documented. As part of a larger study of recovery from cardiac surgery 75 patient-care giver pairs received telephone calls from nurses at 1, 2, 3, 4, 6, and 8 weeks after discharge for the purpose of intervening to facilitate early recovery at home. After each call, nurses recorded detailed notes on the patients' progress and concerns. Content analysis of detailed nurses' recordings revealed the following predominant nursing actions: assessment, provision of support, reinforcement of predischarge teaching, referrals, and teaching. The five nursing diagnoses that occurred most frequently across the 8-week recovery period were altered comfort: pain; ineffective coping, individual; activity intolerance; sleep pattern disturbance; and altered nutrition. In response to these problems, patients managed and prevented health-related problems and engaged in health promotional and normalizing activities. By anticipating common problems in recovery, patients and care givers can be better prepared for going home. Similarly nurses can be better prepared to anticipate and respond to common recovery problems. ",22 1434,"Biocompatibility of dialysis membranes is of no importance for objective or subjective symptoms during or after hemodialysis. The clinical importance of biocompatibility of hemodialysis membranes is a matter of controversy. The authors studied the relationship between biocompatibility and acute symptoms during hemodialysis (HD). Twenty-three patients underwent 12 different bicarbonate HD using Cuprophan, Hemophan, or Polyamide membranes for short (2 hr) and long (4 hr) treatments, with small or large membrane areas. Subjective and objective symptoms were registered during HD and 12 and 36 hours thereafter. Type of membrane, membrane area, or Kt/V were of no importance for the occurrence of subjective or objective symptoms. The patients registered fewer symptoms during 2 hr HD with high blood flow than during 4 hr HD with slow blood flow (p = 0.04). Headache was particularly more frequent during the 4 hr HD. Blood pressure, and to some extent subjective symptoms, were influenced by ultrafiltration volume but not by type of membrane. Biocompatibility is not a determinant of acute side effects of hemodialysis. ",11 2788,"Selective monitoring of patients with suspected blunt cardiac injury. Blunt chest trauma can result in cardiac injury with consequent dysrhythmias, valve malfunction, or frank rupture. Typically, patients with blunt chest trauma and suspected cardiac injury have required cardiac monitoring for 48 to 72 hours. Predicting which patients with blunt chest trauma are not at risk for cardiac complications would obviate many patient-hours of monitoring in the intensive care unit. This series examines the sensitivity of two-dimensional surface echocardiography in predicting cardiac complications. Over a 24-month period, 115 patients were admitted with blunt chest trauma and prospectively evaluated for cardiac injury with admission electrocardiograms, serial creatine kinase isoenzyme studies, and two-dimensional echocardiography. Thirty-one patients (27%) had abnormal two-dimensional echocardiograms. In 8 (25.8%) of these patients, cardiac complications requiring treatment developed. Eighty-four patients (73%) had normal two-dimensional echocardiograms, and a cardiac complication requiring treatment developed in only 1 (1.2%) of them. Of the 9 patients who required treatment of cardiac complications, 3 had normal admission electrocardiograms and only 1 had elevated levels of the myocardial-specific isoenzymes of creatine kinase. We believe two-dimensional echocardiography is a sensitive test for evaluating cardiac injury resulting from blunt chest trauma and is helpful in selecting those patients who require monitoring in the intensive care unit. ",20 2638,"Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. We derived a total of 146 T lymphocyte lines specific for human myelin basic protein (MBP) from the peripheral blood of 20 MS patients and from a control group of 12 healthy donors, and determined the reactivities of T cell lines by [3H]thymidine incorporation on exposure to MBP and MBP peptides 1-44, 45-89, and 90-170. We defined HLA restriction of the T lines by using monoclonal antibodies against monomorphic determinants on human HLA-DR, HLA-DQ, and HLA-DP molecules. MBP-specific T cell lines could be isolated with a comparable efficiency from MS patients and healthy individuals. In both groups, MBP-specific T lymphocytes recognized at least 4 different epitopes in the MBP molecule, and specificities showed comparable patterns for different MBP peptides. MBP-specific T cell lines derived from MS patients and controls were restricted by DR products of the human major histocompatibility class II locus. Notable phenotypic differences of T cell lines existed between the 2 groups. Lines isolated from MS patients expressed predominantly the CD3+ CD4+ CD8- phenotype, while some control lines were composed of up to 87% CD3+CD4+CD8+ T lymphocytes. These findings illustrate the presence of MBP-specific T cells in MS patients and controls that are similarly sensitized to MBP and restricted by HLA-DR products. ",19 2637,"Proton magnetic resonance spectroscopy in multiple sclerosis. Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation. ",19 624,"Evaluation of anterior maxillary alveolar ridge resorption when opposed by the transmandibular implant. Fifteen edentulous patients with complaints regarding denture comfort and/or function were treated with the transmandibular implant. All patients were restored with conventional maxillary dentures opposed by implant-supported removable prostheses. Two to 4 years after surgery, these patients were evaluated for vertical and horizontal maxillary bone loss with a radiographic analysis developed by the authors. With this technique, attention was focused on vertical alveolar ridge resorption in the anterior maxilla. Although the sample size was small, the findings from this study indicate that vertical bone loss in the anterior maxilla does occur when a maxillary denture is opposed by an implant-supported overdenture. Comparison of these results with a previous study that evaluated anterior maxillary resorption when a complete maxillary denture opposed natural mandibular anterior teeth and a distal extension removable partial denture demonstrated no statistically significant difference. ",4 2748,"Blunt traumatic pericardial rupture. A ten-year experience 1979 to 1989. Blunt traumatic pericardial rupture is rarely diagnosed preoperatively and is associated with high mortality. During a ten-year period from 1979 to 1989 over 20,000 patients were admitted to a major trauma center and 22 were found to have blunt traumatic pericardial rupture. Sixteen of the 22 (72.7%) were injured in vehicle accidents, 3 (13.6%) in motorcycle crashes, and 2 (9.1%) in falls; 1 (4.5%) was crushed. Eighteen (81.8%) were diagnosed intraoperatively during resuscitation or surgery for associated injuries, and four (18.1%) were diagnosed preoperatively with pericardial window. Eighteen were males and four were females. The median age was 40.14 years (range, 17 to 68). The tears were found at the following sites: left pleuropericardial (14/22 [64%]), diaphragmatic (4/22 [18%]), right pleuropericardial (2/22 [9%]), and superior mediastinal (2/22 [9%]). Associated cardiac injuries were found in only 5 of the 22 (22.7%); all of those patients died. The overall mortality rate was 63.6% (14/22). A high index of suspicion should alert the trauma surgeon to make the diagnosis intraoperatively during emergency surgical resuscitation in the hemodynamically unstable patient and by pericardial window in the stable patient. ",20 111,"Tampon absorbency, composition and oxygen content and risk of toxic shock syndrome. Tampon use has been identified as a major risk factor for toxic shock syndrome, although the etiologic role of tampons is not clearly understood. Two epidemiologic studies conducted to date have reported an association between tampon absorbency and risk of toxic shock syndrome. This finding is not corroborated by laboratory studies, however, which have suggested that absorbency may be a marker for other characteristics that create an environment conductive to the elaboration of toxic shock syndrome toxin 1. We used data from the previously reported Tri-state study to estimate simultaneously the effects of tampon oxygen content, absorbency and chemical composition. Although the data are sparse, oxygen content was more strongly associated with risk of toxic shock syndrome than either absorbency or chemical composition. The results suggest that it may be possible to develop a highly absorbent tampon that is not associated with a high risk of toxic shock syndrome. ",0 3052,"Plasma concentrations of methadone during postoperative patient-controlled extradural analgesia. Plasma concentrations of methadone were measured by gas chromatography in 16 patients receiving extradural methadone by continuous infusion for relief of postoperative pain. Venous blood samples were taken after a loading dose of extradural methadone 2 mg and during infusion of 0.46 mg h-1 plus patient-controlled increments of 0.2-1 mg. Mean (SD) plasma concentration of methadone was 9.8 (2.1) ng ml-1 at 15 min; this did not change significantly during the first 2 h, after which it increased gradually to 32.2 (4.6) ng ml-1 (P less than 0.001) at the end of 24 h. The mean quantity of extradural methadone required to produce effective analgesia was 10.3 (1.8) mg during the first 12 h after operation and 6 (1.0) mg for the subsequent 12 h. The mean amount of methadone for effective analgesia on the second day was 7.6 (1.1) mg. No adverse effects were detected during the 2-3 days of methadone therapy. Plasma concentration of methadone increased significantly during patient-controlled infusion of extradural methadone in the first 24 h after operation, suggesting rapid vascular uptake. Systemic activity of the drug contributes to the analgesic effect of extradural methadone. ",22 692,"Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa. Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. ",5 1497,"Pregnancy and liver transplantation. To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential. ",12 1307,"Nephrotoxicity associated with concomitant ACE inhibitor and NSAID therapy. Angiotensin-I converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) can be nephrotoxic and may synergistically compromise renal function. A computer-assisted study was done to asses the prevalence of compromised renal function and the clinical importance of this drug interaction. A search of the records of all patients seen in the University of Nebraska Medical Center Internal Medicine Clinic was conducted to identify cases involving renal insufficiency, therapy with ACE inhibitors, or therapy with NSAIDs. Records of cases meeting these criteria were reviewed for clinical correlation and revealed 2278 patients treated with NSAIDs, 328 with ACE inhibitors, and 162 with both. No nephrotoxicity was found in conjunction with monotherapy, but three cases of reversible renal failure were found in conjunction with combination therapy. Significant nephrotoxicity during the concomitant use of ACE inhibitors and NSAIDs is not uncommon, and attention should be drawn to this potentially important interaction. ",11 804,"Calcium and calcium binding in human gallstone disease. Precipitation of calcium salts from bile is important in pigment gallstone formation and may serve as a nidus for cholesterol precipitation. We compared gallbladder bile from patients with symptomatic gallstone disease (40 with cholesterol gallstones and 12 with pigment gallstones) with bile from 10 patients undergoing surgery for non-biliary tract disease. Bile from patients with gallstone disease was less concentrated, with decreased sodium, bile salt, and phospholipid concentrations, but elevated biliary calcium concentrations were not observed. The relationship between free ionized calcium and total calcium was similar in all groups, indicating no difference in calcium binding by gallstone-containing bile. We cannot exclude elevated biliary calcium level as a factor in gallstone pathogenesis, as it could be a transient event. The importance of calcium precipitation was supported by our finding that more than half of the samples were saturated or supersaturated with at least one calcium salt, calcium carbonate. ",5 2839,"Conventional radiographic and computed tomographic findings in cases of fracture of the mandibular condylar process. A total of 40 patients with 46 fractures of the mandibular condylar process were examined an average of 47 months after the injury. The conventional radiologic examination consisted of panoramic radiography and lateral transcranial view of the fracture in the mouth-open and mouth-closed positions. Sixteen patients with 21 fractures of the condylar process were examined additionally by computed tomography (CT) because of temporomandibular joint problems in the sagittal and coronal projection. Computed tomography revealed bony changes in the fractured mandibular condyle and its position in the mandibular fossa more exactly than conventional radiographic examinations. Furthermore, the results showed that disturbances in the position and function of the articular disc may be more common than was earlier anticipated, suggesting the more frequent use of CT examinations to evaluate temporomandibular joint changes after condylar process fractures. ",20 476,"Computed tomography and bronchoscopy in chest radiographically occult main-stem neoplasm diagnosis and Nd-YAG laser treatment in 8 patients. We studied 8 adult patients with variable symptoms of cough, dyspnea, stridor, wheezing, or hemoptysis. Fiberoptic bronchoscopy in all showed complete or nearly complete endobronchial obstruction of a main-stem bronchus by neoplasm with a mean bronchial diameter of 1.9 mm +/- 1.6 mm (mean +/- standard deviation). In 4 patients, a lobar bronchus was also completely obstructed. No mass was visible on chest radiographs of any patient; however, computed tomography in each showed main-stem endobronchial obstruction, lobar obstruction (4 instances in 3 patients), and in 6 patients hypoperfusion of the involved lung. Computed tomographic scan showed additional abnormalities that were unsuspected on viewing chest radiographs or at bronchoscopy, including mediastinal adenopathy in 3 patients and an extraluminal tumor component in 4. After therapy with Nd-YAG laser, main-stem airway diameter increased to a mean of 9.6 mm +/- 1.0 mm (P less than .05) and pulmonary functions improved. Results suggest the complementary role of computed tomography and fiberoptic bronchoscopy in the detection and laser-treatment planning of chest radiographically occult severe neoplastic obstruction of the main-stem bronchus. ",3 422,"Granular cell tumor of the esophagus: endoscopic ultrasonographic demonstration and endoscopic removal. A 35-yr-old Japanese man with a granular cell tumor of the esophagus that was removed by endoscopic polypectomy is presented. Radiography and endoscopy showed a 20 x 12 mm sessile protrusion in the distal esophagus. Endoscopic ultrasonography demonstrated the hypoechoic mass in the submucosa without continuity to the muscularis propria. The lesion was successfully treated by endoscopic polypectomy without complications. The cross-sections of the resected specimen were quite in agreement with the ultrasonographic findings. Endoscopic ultrasonography is valuable to assess the exact location and extent of the tumor, and to determine the indication for endoscopic polypectomy. ",3 1570,"Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value. ",13 952,"Pulmonary denervation in humans. Effects on dyspnea and ventilatory pattern during exercise. The role of the pulmonary autonomic nerves in the mediation of respiratory sensation is unclear. Pulmonary neurogenic mechanisms may contribute to dyspnea either directly or indirectly via an influence on the pattern of ventilation. Using human heart-lung transplantation as a model of pulmonary denervation, we studied the ventilatory response, respiratory drive (P0.1), and sensation of breathlessness (modified Borg scale) during maximal incremental bicycle exercise. The subjects were four female heart-lung transplant recipients 3 to 9 months post-transplant and 10 age-matched control subjects. The ventilatory response to increasing CO2 output (VCO2) was higher (p less than 0.001) in transplant recipients than in control subjects, such that ventilation at peak exercise was similar in the two groups despite a lower peak VCO2 in transplant recipients. The ratio of tidal volume to inspiratory capacity increased with increasing ventilation in a similar fashion in both groups. Although the respiratory rate increased more quickly in transplant recipients, it was similar at peak ventilation in the two groups. Ventilatory timing and duty cycle at half-peak and peak ventilation were similar in transplant recipients and control subjects. Dyspnea ratings were not different between the two groups at similar levels of ventilation. Dyspnea as a function of P0.1 was also similar in transplant and control groups. These results indicate that pulmonary neurogenic mechanisms play a role in determining the level, but not the pattern, of ventilation during exercise. Furthermore, these pathways do not appear to contribute significantly to the perception of breathlessness in normal humans. ",7 1089,"Local anesthesia for neonatal circumcisions: are family practice residents likely to use it? Dorsal penile nerve block with lidocaine (DPNB) is a local anesthetic technique for neonatal circumcision which is both effective and consistent with ethical concerns for infant welfare. As such, it should be included in training programs that prepare residents to care for newborns. To assess the current level of DPNB use by residents in a family practice training program and to identify attitudes and other factors that relate to use, a survey was sent to 127 residents in the Department of Family Practice and Community Health, University of Minnesota. Of the 101 respondents, 55% had used DPNB, and 17% could be characterized as high users, employing the technique for over one half of the circumcisions they performed. Residents with comprehensive understanding of the newborn's capacity to feel pain were more likely to be using DPNB than their less well-informed counterparts. Four factors were identified as predicting use: cooperation of nursery staff for the procedure, accessibility of instruction in PNB technique, belief that PNB is effective in reducing infant pain, and likelihood of parents giving consent for PNB. These results suggest strategies which may be implemented by family practice educators who wish to promote the principles and techniques of DPNB. ",9 2854,"Toxicological screening: a three year experience in poisonings in Kuwait. The results of toxicological screening of body fluids (urine, blood and gastric lavage) from pediatric patients were analyzed for the period January 1985 - December 1988. Of the 119 cases, approximately one half were positive for at least one foreign substance. In about one fifth of the cases, multiple substances were detected. The most commonly implicated drugs were those acting on the central nervous system including the barbiturates, tricyclic antidepressants, phenothiazines, benzodiazepines and carbamazepine. ",20 780,"Colonoscopy in critically ill patients. What conditions call for it? Indications for colonoscopy in the intensive care unit include acute lower intestinal bleeding, sigmoid volvulus, pseudo-obstruction of the colon, and suspicion of pseudomembranous colitis. Although the incidence of cardiorespiratory complications may be higher in these critically ill patients, the procedure can be done safely with proper attention to detail. Because of colonic dilatation, endoscopy can often be done without bowel preparation. ",5 535,"Conservative surgery and radiation therapy for soft tissue sarcoma of the wrist, hand, ankle, and foot. Seventy-eight patients with soft tissue sarcoma (STS) arising in the distal extremities--wrist, hand, finger, ankle, foot, and toe--who were treated with conservation surgery and radiation therapy were studied retrospectively with respect to survival, local recurrence, functional limb preservation, complications, and distant metastasis. After a median follow-up of 7.9 years, actuarial 5-year and 10-year survival rates were 80% and 69%, respectively, and disease-free rates were 61% and 51% at the same times. Actuarial local control rates were 80% and 74% at 5 and 10 years, respectively. Fifteen patients (19%) had local recurrence, but 12 of these were salvaged. Ultimately, 53 patients (68%) retained a normal or fairly normal extremity, six (8%) needed amputation for complications, and 13 (17%) needed amputation to control recurrent disease. The functional outcome was significantly better for patients with upper extremity lesions than for those with lower extremity tumors; even for the latter, this treatment strategy was preferable to amputation. The incidence of hematogenous metastases from distal extremity sarcomas depends on the size of the primary tumor. It was concluded that conservation surgery and radiation therapy (XRT) is an acceptable treatment strategy for STS arising in distal extremities; it yielded a high rate of disease control and functional limb preservation. ",3 1666,"Percutaneous excimer laser coronary angioplasty. To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/mm2. The mean number of pulses delivered at 20 Hz was 1,272 +/- 1,345. Acute success was defined as a greater than or equal to 20% increase in stenotic diameter and a lumen of greater than or equal to 1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 +/- 14 to 49 +/- 11% after laser treatment and to 38 +/- 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 +/- 0.4 to 1.6 +/- 0.5 mm after laser treatment and to 2.1 +/- 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses. ",13 363,"Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients. Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug. ",3 607,"Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders. Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P less than 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P less than 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day. ",4 1724,"Effects of n-3 fatty acids in essential hypertension. We examined the effects on blood pressure, plasma lipoproteins, and platelet function when marine oil supplements (rich in n-3 fatty acids) or vegetable oil supplements (rich in n-6 fatty acids) were added to the usual diets of patients with mild essential hypertension. In a randomized, double-blind, parallel-group study, patients received 50 g of either marine oil (n = 8) or vegetable oil (n = 8) daily for 6 weeks following a baseline observation period. Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil. We conclude that large doses of marine oil reduce diastolic blood pressure, lower triglycerides, and increase bleeding time in patients with mild hypertension. ",13 2095,"Novacor left ventricular assist filling and ejection in the presence of device complications. In order to better understand the relationship among certain device related complications and Novacor left ventricular assist system (LVAS) pumping parameters, a Mock Circulatory Loop was utilized to simulate the following clinically realistic conditions: 1) inflow valve regurgitation, 2) inflow cannula obstruction, 3) outflow valve regurgitation, and 4) outflow cannula obstruction. Various pumping parameters (e.g., pump rate, stroke volume, pump output) were recorded at baseline (control) and during each simulation. Additionally, pump volumes were continuously recorded and differentiated for calculation of rates of pump filling (FR) and ejection (ER). The results indicate that perfusion pressures and rates of filling and ejection change significantly in the presence of device complications. The implications of these findings, as relates to assessment of pump operation in LVAS patients, are discussed. ",13 212,"Role of mastectomy in breast cancer. The surgical management of breast cancer continues to evolve in an attempt to define the ideal line between therapeutic efficacy and morbidity. It is clear that breast cancer is a biologically heterogeneous group of diseases, and no single hypothesis explains its behavior. The surgical options proposed to the individual patient must draw from the experience of retrospective clinical studies and prospective randomized trials in an attempt to optimize the treatment plan. Most patients without distant disease are eligible to consider mastectomy, which can accomplish excellent local control and significantly improve survival for earlier stages of disease. However, breast conservation remains an appropriate alternative for a carefully defined subset of patients. Today, with early-stage disease, no patient need leave the operating room without a breast. Recent advances in reconstructive surgery make mastectomy with immediate reconstruction or limited resection plus axillary dissection with postoperative radiation therapy the two principal treatment choices available. Future studies will focus on the integration of other treatment modalities. Clinical research into the use of preoperative chemotherapy to downstage the disease to permit less extensive surgery is of interest. Recent application of molecular biologic techniques such as oncogene analysis, cytogenetic studies, proliferative indices, and the highly sensitive detection of distant micrometastases using monoclonal antibodies may assist in the design of innovative approaches to surgery, radiation therapy, and systemic drug treatment. These advances show great promise for improving the quality of life and the cure rate for patients with breast cancer. Today, surgical treatment options have evolved that fulfill some of the objectives outlined by Dr. James Ewing of Memorial Hospital some 50 years ago. His concerns about breast cancer remain as relevant today as they were half a century ago: ""I have drawn the impression that in dealing with mammary cancer, surgery meets with more peculiar difficulties and uncertainties than with almost any other form of the disease. The anatomical types are so numerous, the variations in clinical course so wide, the paths of dissemination so free and diverse, the difficulties of determining the actual conditions so complex, and the sacrifice of tissues so great, as to render impossible in the majority of cases a reasonably accurate adjustment of a means to an end."". ",3 1329,"Ethical issues in geriatric nephrology: overview. Developments in medical care over the past five to six decades have provided remarkable life-sustaining technologies (LST) that have contributed to prolongation of the life span of patients, as well as to a general increase in health and well-being. End-stage renal disease (ESRD) treatment is a prototype of these LST treatments and of the issues surrounding provision of chronic/catastrophic care. This remarkable progress has been accompanied by ethical dilemmas that include allocation of scarce resources, and initiation and termination of care with LST. Consideration of these ethical dilemmas are especially poignant for the elderly, because they raise ""hard choices"" and there are no easy answers to these ethical dilemmas. ",11 398,"The recombinant immunotoxin anti-Tac(Fv)-Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia. Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin containing the heavy and light variable regions of the anti-Tac monoclonal antibody fused to a mutant form of Pseudomonas exotoxin (PE). Anti-Tac binds to the p55 subunit of the human interleukin 2 (IL-2) receptor, and anti-Tac(Fv)-PE40 kills human or monkey cell lines that contain either the intact IL-2 receptor or its p55 subunit alone. To assess the usefulness of anti-Tac(Fv)-PE40 in treatment of IL-2 receptor-positive leukemia, we tested peripheral blood mononuclear cells from six patients with adult T-cell leukemia. In each of the six patients, anti-Tac(Fv)-PE40 was extremely cytotoxic to the malignant cells. Metabolic activity and sensitivity of the fresh cells improved when a small amount of IL-2 (10 units per ml) was present during incubation. The toxin concentration necessary to inhibit protein synthesis by 50% after 16-hr incubation of cells with immunotoxin varied from 1.6 to 16 ng/ml (2.5-25 x 10(-11) M). In every case, binding was by means of the Tac antigen because anti-Tac(Fv)-PE40 cytotoxicity was prevented by adding excess anti-Tac antibody. Moreover, anti-Tac alone or an inactive mutant of anti-Tac(Fv)-PE40 without ADP-ribosylation activity had very little cytotoxic activity. Peripheral blood mononuclear cells from normal controls, from a patient with Tac-negative leukemia, and from adult T-cell leukemia patients without significant peripheral blood involvement were not sensitive to anti-Tac(Fv)-PE40. These results indicate that anti-Tac(Fv)-PE40 is a potent cytotoxin against adult T-cell leukemia cells in vitro and warrants clinical testing. ",3 2176,"Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting. Serum samples from 398 individuals (270 whites and 128 blacks) exhibiting quantitatively normal amounts of five typically seen fractions (albumin, alpha 1-globulin, alpha 2-globulin, beta-globulin, and gamma-globulin) in serum protein electrophoresis and showing no evidence of multiple myeloma, other immunoproliferative diseases, or any of the other diseases known to produce monoclonal proteins were tested for monoclonal gammopathy of undetermined significance (MGUS) by immunofixation electrophoresis. No individual in the study had a serum protein electrophoresis pattern suggestive of monoclonal protein gammopathy. Except for one 37-year-old woman, all subjects were men. Subjects were divided into seven age groups: 20 to 29 years (I), 30 to 39 years (II), 40 to 49 years (III), 50 to 59 years (IV), 60 to 69 years (V), 70 to 79 years (VI), and all over 79 years (VII) of age. Considering all subjects in a given race, blacks had two times (14.8%) higher incidence of MGUS than whites (7.8%); this difference was statistically significant. An increased incidence of MGUS in blacks when compared with whites prevailed in each age group, and the difference was statistically significant in all age groups except group II. No MGUS was found in groups I and III in either race. Both races showed a threefold increase in incidence of MGUS from group II to group VII. No routine laboratory test such as erythrocyte sedimentation rate in subjects with MGUS was significantly different than that in age- and race-matched individuals without MGUS. These results show that the incidence of MGUS is higher in the group (blacks) also known to have a higher prevalence of multiple myeloma. ",14 1842,"Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts. Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage. ",13 679,"Sterol-dependence of gastric protective activity of unsaturated phospholipids. The major aim of this study was to investigate the gastric protective effect of unsaturated phospholipids and to determine the ability of neutral lipids to enhance this activity. We found that although a liposomal suspension of unsaturated phosphatidylcholine (PC) administered intragastrically failed to protect rats from acid-induced gastric ulcer formation, addition of cholesterol to unsaturated PC induced a dose-dependent protective response with the maximally effective dose, reducing lesion score greater than 70%. This effect also was seen with the plant sterol, beta-sitosterol (reducing lesion score by 81.6 +/- 36%) but was blocked if cholesterol was esterified to fatty acids of varying chain length. Addition of sterols to liposomes of saturated dipalmitoylphosphatidylcholine, in contrast, attenuated the gastric protective action of the saturated PC. It appears that the protective mechanism elicited by sterols and unsaturated PC is not mediated by alterations in gastric emptying rate or prostaglandin biosynthesis, although maintenance of surface hydrophobicity may be involved. These results suggest that the sterol may promote the packing of adjacent unsaturated phospholipid molecules of either the cell membrane or a putative extracellular hydrophobic lining of the gastric epithelium to provide the mucosa with protection against luminal acid. ",5 2494,"Morbidly obese patients' perceptions of social discrimination before and after surgery for obesity. Morbidly obese patients' perceptions of obesity-related prejudice and discrimination were assessed before and 14 months after operation for obesity. Preoperatively, the 57 consecutive patients perceived overwhelming prejudice and discrimination at work, within the family, and in public places. After a weight loss of more than 45.5 kg (100 lb), these patients perceived little or no prejudice or discrimination. We examine factors contributing to the change in patients' perceptions and comment upon patients' perceptions of the negative attitudes held by health professionals toward obese patients. ",17 1105,"Characterization of periventricular edema in normal-pressure hydrocephalus by measurement of water proton relaxation times. The magnetic resonance longitudinal relaxation time (T1) and transverse relaxation time (T2) of the water proton of the periventricular white and cortical gray matter were measured for 17 control patients and 21 patients with suspected normal-pressure hydrocephalus (NPH). Of the latter group, 14 showed good response to shunting (true-NPH group) and seven showed no response (false-NPH group). In the true-NPH group, both the T1 and the T2 of the periventricular white matter were significantly prolonged compared to the control values, and slowly shortened after cerebrospinal fluid (CSF) shunting. The true-NPH group showed significantly longer T1 and T2 of the white matter than did the false-NPH group. The T1 and T2 of the white matter were longer than those of the gray matter in this group, which was the reverse of the relationship observed in the control patients. In the white matter of the false-NPH group, there was a significant prolongation of T1 only; no difference was seen in the T2 compared to control values. There was no change in either T1 or T2 of this region after CSF shunting. The false-NPH group showed no significant difference in either T1 or T2 between the white and the gray matter. There was no difference in either T1 or T2 of the gray matter between the false-NPH and control groups or between preshunt and postshunt measurements in each patient group. It is suggested that a distinction between true- and false-NPH, which cannot be made from the radiographic appearance alone, may be possible from measurement of relaxation times. The mechanism of varied relaxation behavior between two entities may be explained by a difference in properties of the biological water and its environment. ",9 1661,"Simultaneous measurement of myocardial perfusion and ventricular function during exercise from a single injection of technetium-99m sestamibi in coronary artery disease. New radiopharmaceuticals permit simultaneous assessment of myocardial perfusion and left ventricular function using a single tracer injection. The purpose of this study was to quantitate the relation between myocardial perfusion and function at rest and during exercise in patients with documented coronary artery disease (CAD). A rest first-pass radionuclide angiocardiogram (RNA) was recorded in 51 patients with CAD during injection of 10 mCi of technetium-99m (Tc-99m) sestamibi, and tomographic perfusion images were obtained 60 minutes later. A treadmill test was then performed, and on attainment of an exercise end point a second first-pass RNA was recorded with 30 mCi of Tc-99m sestamibi. Tomographic images reflecting myocardial perfusion during exercise were obtained 1 hour later. Tomographic perfusion defect size, quantified using modifications of the Cedars-Sinai program, correlated directly with end-systolic volume and inversely with ejection fraction at rest and during exercise. However, perfusion defect size often varied widely in patients with similar left ventricular function. This independence between measurements of perfusion and function suggests that simultaneous assessment of the 2 physiologic variables could improve the diagnostic and prognostic information of radionuclide tests. ",13 2360,"Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas. The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit. ",17 2502,"Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts. Successful pancreas transplantation in type I diabetic patients restores normal fasting glucose levels and biphasic insulin responses to glucose. However, virtually no data from pancreas recipients are available relative to other islet hormonal responses or hormonal counterregulation of hypoglycemia. Consequently, glucose, glucagon, catecholamine, and pancreatic polypeptide responses to insulin-induced hypoglycemia and to stimulation with arginine and secretin were examined in 38 diabetic pancreas recipients, 54 type I diabetic nonrecipients, and 26 nondiabetic normal control subjects. Glucose recovery after insulin-induced hypoglycemia in pancreas recipients was significantly improved. Basal glucagon levels were significantly higher in recipients compared with nonrecipients and normal subjects. Glucagon responses to insulin-induced hypoglycemia were significantly greater in the pancreas recipients compared with nonrecipients and similar to that observed in control subjects. Glucagon responses to intravenous arginine were significantly greater in pancreas recipients than that observed in both the nonrecipients and normal subjects. No differences were observed in epinephrine responses during insulin-induced hypoglycemia. No differences in pancreatic polypeptide responses to hypoglycemia were observed when comparing the recipient and nonrecipient groups, both of which were less than that observed in the control subjects. Our data demonstrate significant improvement in glucose recovery after hypoglycemia which was associated with improved glucagon secretion in type I diabetic recipients of pancreas transplantation. ",17 680,"Gastric lesions secondary to long-distance running. Gastrointestinal disorders have been reported during long-distance running. The purpose of this study was to evaluate the effects of prolonged exercise on the upper digestive tract. Seven subjects were submitted to a standard endoscopic examination of the upper digestive tract before and after long-distance running (range 18-50 km). Mucosal biopsy specimens were taken during all endoscopies. After running, all runners had histologically pathological features in the stomach. Vascular lesions were present in the chorion in six subjects after running, with the intensity of the lesions ranging from congestion to hemorrhage. Postexercise histological examination also showed a decrease in mucosal secretion. These lesions secondary to prolonged exercise indicate the presence of hemodynamic perturbations in the upper digestive tract. ",5 2032,"Production of thrombi on intact endothelium by use of antiheparin agents in vivo. It had been suggested that antithrombin activity on the surface of intact endothelial cells may play a role in inhibiting platelet adhesion and thrombus formation. The antithrombin activity may be due to thrombomodulin or to activation of antithrombin III by glycosaminoglycans or thrombomodulin, or possibly a combination of these. This inhibitory activity has been shown to be affected by such antiheparin agents as protamine, hexadimethrine bromide (Polybrene; Aldrich Chemical Co., Milwaukee, Wis.) and platelet factor 4, as well as by such enzymes as heparinase and heparitinase. We have used a hamster cheek pouch preparation to observe thrombus formation in vivo in a normal vascular flow, to determine whether the production of thrombi by thrombin can be enhanced by antiheparin agents. After intra-arterial injection or topical application of protamine or hexadimethrine bromide, platelet adhesion and thrombus formation on intact arteriolar endothelium was produced by a dose of thrombin, which when injected alone had no effect. No thrombi were found in venules or capillaries. Injection of heparin before or after the antiheparin agents necessitated a larger dose to enhance the action of thrombin. On electron microscopy the thrombi were found to consist primarily of platelets adherent to an intact endothelium. The possible clinical implications of these observations are discussed. ",13 265,"The technicon H6000 analyzer discriminates chronic lymphocytic leukemia from other B-cell leukemias through automatic assessment of large unstained cells. The separation of chronic lymphocytic leukemia of B-cell origin from other chronic B-cell leukemias is subjective, being largely based on the morphologic features of the lymphoid cells in the peripheral blood. The percentage of large unstained cells determined with a Technicon H6000 analyzer (an automated blood cell differential analyzer, Technicon Instruments Corp, Tarrytown, NY) was used as a cell volume variable in an investigation of 70 cases of chronic lymphocytic leukemia of B-cell origin and of other chronic B-cell leukemias. The significant degree of correlation between the percentage of large unstained cells and morphoimmunophenotypic diagnosis, although obtained for a relatively small number of cases, suggests that this method of cell volume analysis can be used to improve diagnostic reproducibility in chronic B-cell leukemia. ",3 1568,"Plasma epinephrine levels in resuscitation with cardiopulmonary bypass. Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation. ",13 3119,"Observations on the haemopoietic response to critical illness. Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis. ",22 270,"Autologous bone marrow transplantation in high-risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. Fourteen patients with high-risk T-lineage acute lymphoblastic leukemia (ALL) in complete remission underwent autologous bone marrow transplantation (BMT) in an attempt to eradicate their residual disease burden. A combined immunochemotherapy protocol using a cocktail of two immunotoxins directed against CD5/Tp67 and CD7/Tp41 T-lineage differentiation antigens in combination with the in vitro active cyclophosphamide congener 4-hydroperoxy-cyclophosphamide (4-HC) was used to purge autografts. Despite high dose pretransplant radiochemotherapy and effective purging of autografts, 9 of 14 patients relapsed at a median of 2.5 months (range, 1.2 to 16.8 months) post BMT. Two patients remain alive and disease free at 26 and 28 months post BMT. We used a novel quantitative minimal residual disease (MRD) detection assay, which combines fluorescence activated multiparameter flow cytometry and cell sorting with leukemic progenitor cell (LPC) assays, to analyze remission bone marrow (BM) samples from T-lineage ALL patients for the presence of residual LPCs. Notably, high numbers of residual LPC detected in remission BM before BMT constituted a poor prognostic indicator, providing the first evidence for the biologic significance and clinical value of in vitro T-lineage ALL LPC assays. The median value for the residual leukemia burden before BMT, was approximately 8.6 x 10(3) LPC/10(8) mononuclear cells (MNC) (approximately 0.0086% LPC). Patients with a residual leukemia burden less than this median value appeared to have a better outlook for remaining free of relapse after autologous BMT than patients with a greater leukemia burden (53 +/- 25% v 14 +/- 13%, P = .006, Mantel-Cox). By comparison, the log kill efficacy of purging, the remaining numbers of LPC in purged autografts, or the estimated numbers of reinfused LPC, did not correlate with the probability of disease-free survival (DFS). These results indicate that the primary reason for the recurrence of leukemia was inefficient pretransplant radiochemotherapy rather than inefficient purging of autografts. ",3 917,"Tracheostomy in children with Guillain Barre syndrome During the 10-yr period beginning January 1979, 59 infants and children with Guillain Barre syndrome (GBS) were admitted to our hospital. Tracheostomies were performed in 15 patients and their records were reviewed. Fourteen patients were recalled for assessment of pulmonary function and respiratory muscle strength (RMS). The median duration of assisted ventilation (including endotracheal [ET] intubation) was 21 days and the median duration of tracheostomy was 39 days. Only two patients were discharged with the tracheostomy in situ. All patients were successfully decannulated at the first attempt. No tracheostomy-related complications or symptoms were reported apart from croup in two patients. On review, lung volumes and maximal inspiratory and expiratory flows were normal. There was no evidence of tracheal stenosis or significant tracheomalacia. RMS tests were normal. In this hospital, tracheostomy is a safe, well-tolerated procedure in the management of infants and children with GBS who need long-term ventilation. There were no deaths and all patients returned to their normal school or were gainfully employed after their illness, although 12 patients had mild persistent weakness of at least foot dorsiflexion. ",7 30,"Ringer's acetate and dextran-70 with or without hypertonic saline in endotoxin-induced shock in pigs. The effects of Ringer's acetate, 6% dextran-70, 7.5% NaCl, and the combination of 7.5% NaCl and dextran-70 were tested in resuscitation from endotoxin shock induced by continuous iv infusion of Escherichia coli endotoxin in pigs. After about 3 h, a reproducible shock state was achieved and treatment was started, governed by the left atrial pressure. The hypertonic solutions (7.5% NaCl and 7.5% NaCl in dextran-70) did not show any overall advantages over the isotonic solutions (Ringer's acetate and dextran-70). Only transient beneficial hemodynamic effects lasting less than 30 min after infusion were seen. When dextran-70 was administered, cardiovascular function was markedly improved and oxygen delivery (DO2) and survival were significantly higher compared with the crystalloid groups (Ringer's acetate and 7.5% NaCl). Administration of large amounts of Ringer's acetate resulted in an immediate deterioration of pulmonary function. It was difficult to elevate left atrial pressure or even to keep it at baseline level, and cardiac index was only transiently increased. The overall result was a deterioration of DO2 and poor survival compared with the dextran-70 treated pigs. We conclude that dextran-70 is superior to Ringer's acetate in resuscitation from endotoxin-induced shock in pigs. Furthermore, we found no role for the use of hypertonic saline, alone or in combination with dextran, in the treatment of this type of prolonged endotoxin shock. ",0 2436,"The effects of moderate exercise training on nutrient intake in mildly obese women. The relationship between moderate exercise training (five 45-minute sessions per week, brisk walking at 62 +/- 2% VO2 max for 15 weeks) and changes in nutrient intake was investigated in a group of 36 sedentary, mildly obese women. The study was conducted using a 2 x 3 factorial design (two groups of subjects: exercise and nonexercise groups; three periods: baseline, 6-week, and 15-week testing sessions). Data were analyzed using repeated measures ANOVA. The pattern of change in caloric intake over time tended to be different between groups (F[2, 68] = 2.50, p = .089); the exercise group experienced a significant decrease in caloric intake by 15 weeks. Significant group x time interactions were found for intakes of carbohydrate, dietary fiber, thiamin, niacin, vitamin B-6, and folate. Intake tended to decrease in the exercise group and to increase in the nonexercise group. Change in intake of each of these nutrients was significantly correlated with change in bread and cereal consumption. The pattern of change in bread and cereal intake over time was significantly different between groups (Pillais Trace = 0.266, F[2, 33] = 5.99, p = .006); the exercise group had significant decreases in intake at 6 and 15 weeks vs baseline values. These data suggest that mildly obese women reduce energy intake subsequent to initiating an exercise program; concomitantly there is a decrease in the quality of nutrient intake from their diets compared with those of sedentary controls. ",17 1182,"Brainstem auditory evoked response and subcortical abnormalities in autism. Previous studies of the neurobiology of autism that have used the brainstem auditory evoked response have given contradictory results. The authors of this study considered two supplementary aspects; they added an ipsilateral masking procedure, and they compared the results for every subject to the values (corrected for age and sex) of a large number of normal children. Twenty autistic (according to DSM-III-R criteria) and 13 mentally retarded (nonverbal IQ less than 75) subjects were assessed. Eighty percent of the autistic subjects had abnormal interpeak latencies, compared to 15% of the mentally retarded subjects. The I-V and III-V prolonged interpeak latency values were seen only in the autistic subjects. The ipsilateral masking procedure doubled the rate of detection of higher-brainstem abnormalities in the autistic children. ",9 59,"Mycoplasmal pneumonia. Are you thinking of atypical presentations? The presentations of mycoplasmal pneumonia can be varied and sometimes complicated. The atypical nature of this illness, as opposed to the clear pattern of findings in classic bacterial pneumonias, leads the physician to the diagnosis. Appropriate therapy then allows quick improvement as a rule, with few sequelae. ",0 252,"Lymph node metastasis from papillary-follicular thyroid carcinoma in young patients. A total of 117 patients under 20 years of age with papillary and/or follicular thyroid cancer presented to the M. D. Anderson Cancer Center between 1949 and 1987. The most common presenting symptom was a cervical mass. Twenty percent of the patients had a history of prior irradiation. Sixty percent initially had palpable lymph nodes, while 26% who had clinically negative examinations had pathologically positive lymph nodes. Recurrence was highest in regional lymph nodes at 24%, with only a 4% recurrence rate at the primary site and a 3% recurrence rate at distant sites. There were no deaths due to the thyroid cancer. To maintain a low rate of recurrence, near-total thyroidectomy with neck dissection followed by iodine 131 treatment should be considered in these young patients. ",3 1460,"Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. Results are presented of a randomized, double-blinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/- 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/- 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Life-table analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (log-rank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in high-risk populations. ",12 950,"Atypical presentation of pulmonary embolism. Today we have discussed an interesting patient with an atypical presentation of pulmonary embolism. We have outlined a suggested algorithm to aid in the diagnosis and management of this disease. References 8 through 24 in the reference section are suggested readings that offer further insight into the diagnosis and management of this entity. ",7 3105,"Effects of tracheal irritation and hypercapnia on tracheal smooth muscle in humans. Both hypercapnia and tracheal irritation are known to constrict the airways in animals. To see whether similar responses occur in humans, we investigated tracheal smooth muscle (TSM) responses to hypercapnia and tracheal irritation with water in 14 paralyzed and anesthetized humans. TSM tone was monitored by measuring the pressure in the saline-filled cuff of the endotracheal tube. Although, tracheal irritation caused TSM constriction in 10 of 14 patients, 4 patients showed no TSM response. Administration of intravenous atropine attenuated the TSM constriction response. Hypercapnia did not cause any change in TSM tone in any of the 14 patients. These results indicate that in paralyzed and anesthetized humans, there exist interindividual differences in the TSM responses to tracheal irritation and that hypercapnia cannot be an effective stimulus for the TSM constriction. ",22 552,"Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation. ",3 269,"The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer. A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988, 41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases. ",3 3331,"Acellular matrix allograft small caliber vascular prostheses. We have developed an acellular matrix vascular prosthesis (AMVP) made by detergent and enzymatic extraction of natural arteries, yielding a tissue framework of collagen and elastin from the original vessel, with preservation of the natural basement membrane at the blood flow surface. These biografts have excellent handling characteristics and suturability, as well as low thromboreactivity. Whole vessel static testing of circumferential compliance (8.9 +/- 1 [SEM] X 10(-2)% mmHg at 100 mmHg) revealed behavior virtually identical to the paired natural vessel from which each AMVP was derived in nine canine carotid arteries. We implanted 16 canine-origin AMVPs into nine dogs (12 femoral and three carotid arteries, and one infrarenal aorta) with no antithrombotic drugs. Angiographic patency was maintained in 15 of 16 (one occlusion within 3 days) for follow-up from 3 days to 6 years, with no aneurysm formation in three AMVP at over 4 1/2 years. Explant analysis revealed preservation of AMVP elastica and collagen with no inflammation or dystropic calcification of the AMVP, and almost total thrombus free flow surfaces. These results suggest that allograft AMVPs could achieve long-term patency equivalent to saphenous veins. ",22 2982,"The scapegoat effect on food aversions after chemotherapy. The effects of consuming a novel food (halva) versus a familiar food (cookies) before gastrointestinal (GI) toxic chemotherapy on patients' preference for familiar foods consumed after chemotherapy treatment were compared. The development of aversions to the novel and familiar foods was also assessed. Patients with a history of posttreatment nausea consumed either a novel or a familiar food before chemotherapy and were asked to keep a food record through the next breakfast and to rate their preference for these foods. Patients who consumed halva before treatment were significantly more likely to increase their ratings for foods consumed after chemotherapy than patients who consumed familiar cookies. Aversions to the novel food were significantly more frequent than aversions to the familiar food. These findings provide evidence that a novel but not a familiar food consumed before chemotherapy can act as a scapegoat to prevent items in the regular diet consumed after chemotherapy from decreasing in preference. Providing patients with a novel food before chemotherapy is a useful clinical intervention to reduce the likelihood of forming aversions to familiar foods consumed after chemotherapy. ",22 774,"Preliminary report: the antegrade continence enema. The principles of antegrade colonic washout and the Mitrofanoff non-refluxing catheterisable channel were combined to produce a continent catheterisable colonic stoma. The intention was that antegrade washouts delivered by this route would produce complete colonic emptying and thereby prevent soiling. The procedure has been successfully carried out in five patients with intractable faecal incontinence. ",5 193,"Growth of group A rotaviruses in a human liver cell line. Recent observations in children with rotavirus gastroenteritis and in infant mice given rotavirus vaccine by oral administration suggest that this well-known gastrointestinal pathogen may infect the liver. To examine this possibility, the susceptibility of Hep G2 cells to infection with a variety of rotavirus strains was tested. These cells were used because they are considered to be well differentiated and exhibit many liver-specific functions. The Hep G2 cells supported the growth of the simian strain rhesus rotavirus (MMU 18006), a strain currently being used in vaccine trails, but did not support the growth of any human strain (D, DS1, Price or ST3). The rhesus rotavirus infection was cytopathic and resulted in release of lactate dehydrogenase. Rhesus rotavirus growth in Hep G2 cells displayed trypsin-enhanced infectivity and was inhibited by pretreatment of cells with Arthrobacter ureafaciens neuraminidase but not with neuraminidase from Clostridium perfringens. Hep G2 cells were also permissive for another simian strain (SA11), a bovine strain (UK) and single gene substitution reassortants containing VP7 (the major outer capsid neutralization protein) from a human rotavirus strain and the remaining 10 genes from either rhesus rotavirus or UK. In general, UK and its reassortants produced lower levels of antigen than did rhesus rotavirus and its reassortants. Hep G2 cells and other hepatic cell lines may prove to be useful tools to explore the hepatotropic potential of wild-type rotaviruses and candidate vaccine strains. ",3 1409,"The overlooked, retained Double J stent. A series of 4 patients with long overlooked, retained ureteral stents is presented to illustrate the variable, unpredictable, and at times, hazardous course of such patients. These cases are cited to re-emphasize the need for careful documentation, observation, and follow-up of patients in whom stents are placed. ",11 1065,"Apneic oxygenation in apnea tests for brain death. A controlled trial. We performed a prospective controlled study of apneic oxygenation on 15 patients undergoing apnea tests for brain death. All patients were preoxygenated with 100% oxygen at existing respirator settings. During the 10-minute apnea tests, nine patients were given continuous apneic oxygenation by tracheal cannula. The other six patients had tracheal tubes open to room air. The patients given apneic oxygenation had little or no hypoxia by the end of the test. The patients given room air during the test became hypoxic. Many neurologists perform apnea tests with no oxygenation or with preoxygenation alone. This is the first prospective controlled study (to our knowledge) of apneic oxygenation; it shows that preoxygenation alone does not prevent hypoxia during apnea tests for brain death. We recommend that all apnea tests be performed with apneic oxygenation. ",9 2922,"Comparison of resting energy expenditures and caloric intake in children with severe burns. Nutritional support is provided to children after severe burn injuries in amounts derived from empirical formulas or measurements of resting energy expenditure. To scrutinize these methods, indirect calorimetry measurements were performed on 74 survivors of burns (greater than or equal to 40% total body surface area) and compared to their actual caloric intake, percent weight change, and optimal caloric requirements formulated from the Curreri and Shriners' equations. These parameters showed that in spite of an initial deficit in actual caloric intake as compared to formulated goals, weight was maintained, whereas resting energy expenditures ranged from 30% to 40% below the actual caloric intake. Furthermore, a subgroup of patients (n = 42) who met +/- 20% of their formulated needs were stratified by extent of burn; this illustrated a significant weight gain in the more severely burned children. In conclusion, nutritional formulas in popular use overestimate caloric requirements in severe burns, whereas resting energy expenditure measurements require an additional factor of 30% to maintain body weight. ",20 313,"Detection of duodenal gastrinomas by operative endoscopic transillumination. A prospective study. The ability of operative endoscopic transillumination of the bowel wall to detect duodenal gastrinoma was evaluated prospectively in 26 patients with the Zollinger-Ellison syndrome. The results were assessed by exploratory laparotomy and compared with the results of other localization techniques. Twelve duodenal gastrinomas were resected from 10 patients. Operative endoscopic transillumination detected 10 of the 12 gastrinomas, a sensitivity of 83%, which was significantly greater (P less than 0.05) than that for either preoperative imaging (25%) or intraoperative ultrasonography and palpation (42%). The sensitivity of operative endoscopic transillumination was a result of the ability to detect focal areas that did not transilluminate on the serosal side of the duodenum, and not the mucosal appearances seen through the endoscope, which were not helpful. Operative endoscopic transillumination detected gastrinomas less than 1 cm in diameter throughout the duodenum. Of the patients in this study, 39% had duodenal gastrinomas, a greater frequency than previously reported. These results indicate that operative endoscopic transillumination is the most sensitive technique yet described for detecting duodenal gastrinomas and should be performed routinely in all patients with the Zollinger-Ellison syndrome who undergo exploratory laparotomy for cure. ",3 1942,"Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease. The effect of cardiac sympathetic blockade by high thoracic epidural anesthesia (TEA) (T1-T6, bupivacaine) on the luminal diameter of normal and diseased portions of epicardial coronary arteries was determined by quantitative coronary angiography in patients (n = 27) with severe coronary artery disease (CAD). In a separate group of patients (n = 9) with severe CAD, the effects of TEA on coronary arterioles (resistance vessels) were studied, by measuring total and regional myocardial blood flow and metabolism with the retrograde coronary sinus thermodilution technique. At the stenotic segments, TEA induced an increase in luminal diameter from 1.34 +/- 0.11 to 1.56 +/- 0.13 mm (P less than 0.002), but did not change the diameter of the nonstenotic segments (3.07 +/- 0.13 to 2.99 +/- 0.13 mm). In the second group of patients, TEA induced no changes in coronary perfusion pressure, total or regional myocardial blood flow, coronary venous oxygen content, coronary blood flow distribution, regional myocardial oxygen consumption, or lactate extraction or uptake. Two patients had chest pain in the control situation and had regional myocardial lactate production that was attenuated by TEA. We conclude that TEA may increase the diameter of stenotic epicardial coronary artery segments in patients with CAD without causing a dilation of coronary arterioles. These effects may be beneficial when high TEA is used to treat severe ischemic chest pain in patients at rest. ",13 253,"Survival discriminants for differentiated thyroid cancer. Since 1975, the American Cancer Society, Illinois Division, has published end results of major cancer sites drawn from patient data contributed voluntarily by hospital cancer registries throughout the state. The current study was undertaken, in part, to apprehend information regarding contested areas in the management of patients having differentiated (papillary/follicular) thyroid cancer. A total of 2,282 patients with either papillary or follicular carcinoma of the thyroid from 76 different Illinois hospitals and providing 10 years of follow-up information (life-table analysis) were retrospectively analyzed for demographic, disease, and treatment-related predictors of survival. Multivariate analysis using the Cox proportional hazards method was made for stage, age, race, sex, morphology, history of radiation exposure, presence of positive lymph nodes, initial surgical treatment, postoperative iodine 131 therapy, and replacement/suppressive thyroid hormone treatment. Statistically significant (p less than or equal to 0.05) predictors of favorable survival after thyroid cancer were low stage (I and II), young age (less than 50 years), white race, female sex, and the administration, postoperatively, of either thyroid hormone or radioactive iodine. Factors that had no influence on survival were lymph node status, choice of initial surgical treatment, and a history of prior irradiation. We suggest that where a prospective clinical trial is impracticable, a retrospective analysis of a large and detailed database, such as that available from cooperating hospital-based tumor registries, may yet provide useful insights to solutions of cancer management problems. ",3 989,"The adult respiratory distress syndrome. The adult respiratory distress syndrome remains an enigmatic disorder with a high mortality rate, although it can sometimes be managed effectively. Recognizing the conditions with which it is associated is the first step in preventing its occurrence. Decreasing the risk factors of developing ARDS remains the fundamental goal of initial management. Once the syndrome has developed in a particular patient, the clinician's goals in management are to stabilize the patient, avoid further insults, maximize the support therapies available, and be cognizant of and avoid the potential adverse effects of these supportive therapies. ",7 1865,"Everted cervical vein for carotid patch angioplasty. Because of the theoretic benefits of autologous vein we undertook an investigation to evaluate cervical veins (facial, external jugular) as patch material after carotid endarterectomy. A device that stimulated both circumferential fixation by sutures and radial tension exerted on in vivo patches was constructed to measure burst strength of tissue. Mean bursting pressure for groin saphenous vein (n = 10) was 94.5 +/- 15.1 pounds per square inch (psi), 75.5 +/- 8.9 psi for ankle saphenous vein (n = 10), 83.3 +/- 14.5 psi for everted (double layer) cervical vein (n = 5) and 10 +/- 3.3 psi for single layer cervical vein (n = 5). No significant differences between saphenous vein at any level and everted (double layer) cervical vein, but all were significantly different from single layer cervical vein (p less than 0.05). From June 1987 through November 1989, 19 patients underwent 21 carotid endarterectomies complemented with adjunctive everted cervical vein patch angioplasty. Indications for surgery were asymptomatic stenosis (53%), transient ischemic attack (29%), and cerebrovascular accident with recovery (18%). All patients were studied after surgery with duplex scanning. Asymptomatic recurrent stenosis was observed in one patient. Transient hypoglossal nerve dysfunction occurred in one other patient. One postoperative death occurred as a result of massive aspiration. These results indicate that everted cervical vein is comparable to the saphenous vein in resistance to bursting and can yield similar results as patch material after carotid endarterectomy. Accordingly, saphenous vein can be spared and lower extremity incisions avoided. ",13 124,"Cytomegalovirus and Rasmussen's encephalitis In-situ hybridisation with a biotinylated cytomegalovirus (CMV) DNA probe was done on brain biopsy specimens from 10 patients with Rasmussen's encephalitis (RE) and 46 age-matched control patients with other neurological diseases. All 10 patients with RE had intractable epilepsy and focal neurological deficits, and there was perivascular cuffing, microglial nodules, astrogliosis, and neuronal loss. CMV genomic material was demonstrated in 7 of the 10 patients with RE (in neurons, astrocytes, oligodendrocytes, and endothelial cells) and in 2 of the 46 control patients. Probes for herpes simplex virus and hepatitis B virus were negative in all patients and in fibroblast controls. The results suggest that CMV is a likely cause of Rasmussen's encephalitis. ",1 740,"Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. The objective of this study was to determine the changes in systemic hemodynamics (systemic vascular resistance [SVR], cardiac output [CO], systemic blood pressure [SBP]) and cardiac function (pulmonary artery pressure [PAP] and pulmonary wedge pressure [PWP]) during the 96 hours following orthotopic liver transplantation (OLT) and correlate these with changes in hepatic and renal function and patient outcome. The study took place in a 12-bed medical respiratory intensive care unit in a large teaching hospital. Twenty-one patients had OLT performed over a 21.5-month period (January 1988 to October 15, 1989) for end stage liver disease (ESLD) from a variety of causes. A flow-directed right heart catheter and an indwelling arterial cannula were inserted for hemodynamic monitoring over a 96-hour postoperative period. Liver and renal function studies, total serum calcium, serum albumin, and fluid balance were determined daily. The SVR increased significantly to 12.8 +/- 0.6 U at 48 hours compared with immediate (less than 8 hours) postoperative levels (p less than 0.05) and remained elevated for 96 hours. The CO fell progressively and was significantly lower than baseline values from 64 to 96 hours. There was significant inverse correlation between the increase in SVR and the fall in CO (r = .85, p less than 0.01). The SBP was stable except for a small, but significant fall at 16 and 24 hours postoperatively. The PWP increased significantly from a baseline value of 12.5 +/- 0.9 mm Hg to 15 +/- 0.9 mm Hg at 32 hours and remained elevated through 96 hours (p less than 0.05). The serum bilirubin level fell progressively postoperatively and the prothrombin time and partial thromboplastin time (PTT) shortened significantly. Bile flow increased progressively from 107 +/- 120 ml/24 hours at the end of the first 24 hours to 188 +/- 125 ml/24 hours by 96 hours postoperatively. Five patients died from nine to 43 days postoperatively. These patients' hemodynamic parameters were not significantly different from the patients who survived. Successful OLT is associated with a rapid increase in SVR and a fall in CO without changes in SBP. These findings tend to parallel the improvement found in results of liver function tests. However, there is no correlation between the improvement in the hemodynamic state and long-term survival. ",5 747,"24-hour intragastric acidity and plasma gastrin after omeprazole treatment and after proximal gastric vagotomy in duodenal ulcer patients The relationship between suppressed gastric acidity and the increase in plasma gastrin levels after pharmacological and surgical treatment of peptic ulcer disease were compared in this study. Eight patients with chronic duodenal ulcer and referred for proximal gastric vagotomy were studied. 24-hour intragastric acidity and plasma gastrin levels were investigated in the same patients on three consecutive occasions: preentry without any treatment; after 4 weeks of administration of 20 mg of omeprazole daily, and 4-6 months after proximal gastric vagotomy. Intragastric acidity was slightly more reduced by omeprazole (94%) than after proximal gastric vagotomy (78%), with no difference found during the day or night with either. Plasma gastrin levels increased slightly more after proximal gastric vagotomy [284% (median, 2120 pmol.h/L; range, 733-2831 pmol.h/L)] than after omeprazole administration [186% (median, 1586 pmol.h/L; range, 495-2573 pmol.h/L)]. There is strong evidence that the increased plasma gastrin concentration following omeprazole treatment is caused by the reduced intragastric acidity. The slight increase in plasma gastrin concentration following proximal gastric vagotomy despite a lesser reduction in intragastric acidity may be the result of additional effects on gastrin release by the vagotomy. Both treatments resulted in a modest increase in plasma levels of gastrin that were far below the gastrin levels observed in achlorhydric patients, e.g., patients with pernicious anemia. ",5 1233,"Anteromedial tibial tubercle transfer without bone graft. We followed 30 patients for more than 2 years after anteromedial tibial tubercle transfer for persistent patellofemoral pain associated with patellar articular degeneration. Twelve of these patients were followed more than 5 years. We report 93% good and excellent results subjectively and 89% good and excellent results objectively. The quality of improvement was sustained in all 12 of the patients who were evaluated again after more than 5 years from surgery. When examined separately, 75% of those patients with advanced patellar arthrosis achieved a good result; none of these patients achieved an excellent result. Postoperative continuous passive motion has markedly reduced the incidence of stiffness. Serious complications such as compartment syndrome, infection, and skin slough were avoided completely in 51 consecutive cases. Patellofemoral contact pressure studies in five cadaver knees have shown that anteromedial tibial tubercle transfer can provide substantial reduction of patellofemoral contact stress while helping to balance medial and lateral facet pressures. This surgical procedure is mechanically and clinically successful for alleviating intractable pain related to patellar malalignment and articular degeneration. This procedure enables the majority of appropriately selected patients with malalignment and patellar articular degeneration to resume increased levels of activity with substantially diminished pain. ",9 2828,"Nonosmotic stimuli alter osmoregulation in patients with spinal cord injury. Studies on two quadriplegic patients who developed severe hyponatremia during episodes of acute respiratory distress were performed to determine whether differences in osmoregulation of vasopressin release could be identified in these patients compared to other quadriplegic subjects previously studied in a similar manner. Both patients were clinically stable and normonatremic, with no signs or symptoms of respiratory distress, when the studies were performed. However, both exhibited evidence of hemodynamic instability in the sitting posture. Linear regression analysis of the plasma vasopressin/plasma osmolality (Pavp:Posm) relationship during infusions of 0.85 M sodium chloride showed no significant differences in either the slope (sensitivity) or abscissal intercept (osmotic threshold) of this relationship compared to that of other quadriplegic subjects when the patients were supine. In contrast, when the patients were studied in the sitting posture there was a marked shift in the relationship of Pavp:Posm indicative of increased sensitivity and reduced osmotic threshold for vasopressin release. The slopes of the Pavp:Posm relationships were 0.249 and 0.178 for the two patients, respectively, compared to 0.092 +/- 0.03 ( +/- SD) for previously studied quadriplegic subjects. Oral water-loading studies performed on one patient revealed marked impairment of urine-diluting ability and free water clearance in the sitting posture compared with observations in similar studies performed when the patient was supine. Impairment of renal water excretion could not be attributed to an effect of vasopressin, which was reduced to unquantifiable levels by water loading. These studies have shown that hemodynamic stress related to autonomic dysfunction in quadriplegic patients may result in marked alteration of osmoregulation of vasopressin release in more severely affected individuals. Such altered osmoregulation, which may also be associated with vasopressin-independent impairment of renal water excretion in the sitting posture, may be a predisposing factor in the development of hyponatremia, especially in the presence of other potent nonosmotic stimuli. ",20 2091,"Design mediated thrombus reduction in the Utah-100 total artificial heart. The Utah-100 total artificial heart was initially designed and tested in 1983. General design goals, including improved fit for human application, improved reliability, and elimination of thrombus formation, were identified as improvements over the clinically used Jarvik-7 artificial heart, previously developed at the Institute for Biomedical Engineering, University of Utah. Specific design goals included 1) elimination of connector and valve-associated thrombus formation and 2) elimination of gross mineralization, thrombus formation, and creases on the blood-pumping diaphragm of the device. Explant retrieval results from 29 calves and sheep implanted with the Jarvik-7 artificial heart were compared with results from 25 calves and sheep implanted with the Utah-100 artificial heart. Macroscopic thrombus formation was found in 44% of the connectors of the Jarvik-7 artificial-hearts, compared with 2% (p less than or equal to 0.01) in animals with the Utah-100 artificial heart. Subvalvular and supravalvular thrombi were observed in 33% of the valves in the Jarvik-7 artificial heart and 10% (p less than or equal to 0.01) of the valves in the Utah-100 artificial heart. Mineralization of the pumping diaphragm was observed in 12% of the animals implanted with the Jarvik-7 artificial heart and in 4% of the animals with the Utah-100 diaphragms. Thrombus formation in the diaphragm-housing interface occurred in 2% of Jarvik-7 ventricles and in 6% of the Utah-100 ventricles. There were no identifiable diaphragm creases in the Utah-100 diaphragms, but a 10% incidence was found in Jarvik-7 devices. These results validate substantial progress toward improved design and fabrication methods in the Utah-100 total artificial heart. ",13 2416,"Defective free-fatty acid and oxidative glucose metabolism in IDDM during hypoglycemia. Influence of glycemic control. To examine the impact of diabetes and its treatment on plasma free-fatty acid (FFA) and oxidative fuel metabolism during hypoglycemia, we combined indirect calorimetry with [3-3H]glucose during a 4-h low-dose insulin infusion (plasma insulin approximately 2-fold above basal) in six poorly controlled and nine well-controlled insulin-dependent diabetes mellitus (IDDM) patients and in six healthy subjects. Diabetic subjects received insulin overnight to maintain euglycemia before study. Although free-insulin levels and counterregulatory hormone responses were similar, the plasma glucose fall was more pronounced in well-controlled diabetic subjects. In well-controlled diabetic and healthy subjects, the small increment in insulin rapidly suppressed plasma FFA and fat oxidation by approximately 50% and stimulated carbohydrate oxidation by approximately 80%. In contrast, plasma FFA levels did not fall in poorly controlled diabetic subjects, and glucose oxidation was not stimulated. To determine whether this resistance to the antilipolytic effect of insulin occurs in the absence of hypoglycemic counterregulation, we used a sequential low-dose euglycemic insulin clamp (0.2, 0.3, and 0.5 mU.kg-1.min-1). In healthy subjects, plasma FFA was nearly maximally suppressed at the lowest insulin dose. In contrast, plasma FFA remained persistently elevated in poorly controlled diabetic subjects at each insulin dose. However, the insulin dose-response curve for suppression of plasma FFA was near normal in well-controlled subjects. We conclude that poorly controlled IDDM diabetic patients are resistant to the antilipolytic effects of insulin and show impaired stimulation of glucose oxidation during insulin-induced hypoglycemia. Amelioration of these defects in well-controlled patients may be another factor contributing to the higher risk of hypoglycemia during intensified insulin therapy. ",17 2147,"Fluosol DA-20 in the treatment of severe anemia: randomized, controlled study of 46 patients. We evaluated the safety and efficacy of Fluosol DA-20% (FDA) as a blood substitute in the treatment of severe anemia. Thirty-six patients received either FDA (n = 21) or crystalloid/hydroxyethyl starch (CHS) (n = 15) as part of a randomized, controlled trial. Ten patients received FDA as part of a humanitarian protocol. All were Jehovah's Witnesses who refused transfusion, had bled recently, and had average Hgb levels of 4.3 g/dl. After pulmonary artery catheter insertion, each patient was infused with CHS to attain a pulmonary artery wedge pressure (WP) of 10 to 18 mm Hg. FDA was given as a one-time dose of 30 ml/kg. Data were collected at baseline, 12, 24, and 48 h. None of the patients with negative reactions to a 0.5-ml test dose of FDA had adverse reactions to the subsequent infusion. The plasma or dissolved component of oxygen content was significantly higher in the FDA group at 12 h (FDA group 1.58 +/- 0.47 ml/dl, control group 1.01 +/- 0.31 ml/dl, p less than .02, t-test). Nineteen patients died: 12 (37.5%) FDA, seven (46.6%) control. The difference was not significant. We conclude the following: a) FDA can be given safely to severely anemic patients in doses of 30 ml/kg; b) FDA significantly increased the dissolved component of oxygen content after 12 h but the effect did not persist; c) severely anemic patients can survive without transfusion although mortality is high. In this study, inability of FDA to sustain increased oxygen content was due in part to the rapid elimination of FDA and also to the limited amount given. ",14 86,"Group B streptococcus endocarditis following second-trimester abortion. An 18-year-old woman who underwent an elective second-trimester abortion developed Streptococcus agalactiae (group B streptococcus) endocarditis characterized by a large, pedunculated vegetation involving a previously normal tricuspid valve. Polyarthritic symptoms, as well as multiple pulmonary emboli, were experienced, and cure followed a course of treatment using intravenous penicillin G potassium combined with gentamicin sulfate. Endocarditis caused by this pathogen usually occurs among individuals compromised by underlying chronic disorders and, today, is a rare sequela of pregnancy and abortion. When planning therapy, consideration should be given to the possibility of tolerance among clinical isolates and the need for operative intervention in selected patients. ",0 1134,"Steroids induce acetylcholine receptors on cultured human muscle: implications for myasthenia gravis. Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications. ",9 1473,"Current concepts of beta-endorphin physiology in female reproductive dysfunction. beta-Endorphin has a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. We have reviewed the evidence pointing to an alteration in this neuropeptide that may contribute to the pathogenesis of various reproductive dysfunctions. Elevated or high levels of beta-endorphin have been associated with exercise-associated amenorrhea, stress-associated amenorrhea, and polycystic ovarian syndrome. Depressed or low levels of beta-endorphin have been associated with PMS and menopause. Alterations in the levels of beta-endorphin may change the pulsatile release of GnRH via noradrenergic and/or dopaminergic pathways. We have primarily focused on beta-endorphin as representative of the endogenous opioid peptides, but other opioid peptides may also contribute to the pathogenesis of various types of reproductive dysfunction. Perhaps it will become possible to characterize and hone our understanding of the function of beta-endorphin and the other substances composing the endogenous opioid peptides. A better understanding of their role in physiological as well as pathophysiological processes may allow for the development of rational approaches to the treatment of specific disorders pertaining to reproduction. Many questions remain unanswered. Among the most relevant are: what is the precise mechanism of action by which beta-endorphin exerts its influence on pulsatile GnRH release? Is there a functional relationship between CNS and peripheral (serum) levels of beta-endorphin? Are the detected changes in beta-endorphin levels merely associated, or are they a cause of a particular disorder? Since it took almost 40 years between the time prostaglandins were first discovered and eventual realization of their clinical application, it may take some time before the beta-endorphin story is complete. ",12 437,"Systemic therapy in metastatic colorectal cancer. Fluorouracil-based chemotherapy regimens have been utilized in metastatic colorectal cancer for more than 30 years. Early attempts at defining an optimal treatment schedule and use in combination with other drugs failed to significantly improve results. In contrast, the clinical effectiveness of fluorouracil has been improved by continuous infusion administration and modulation with folinic acid. Both approaches have increased the response rate compared with results achieved with traditional bolus schedules; the effect on survival has been less significant. Unfortunately, expense and, in some instances, toxicity have also been increased, which detracts from their overall usefulness. Clinical studies that evaluate fluorouracil chemotherapy in combination with biological-response modifiers are ongoing and will be areas of intense research during the next few years. ",3 709,"Nonmucous glycoproteins as pronucleating agents. Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol-phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients. ",5 2042,"The role of beta-blockade therapy for ventricular tachycardia induced with isoproterenol: a prospective analysis. Isoproterenol is sometimes required for ventricular tachycardia (VT) induction. However, the role of beta-blockade for treatment of such VT has not been critically assessed. The use of beta-blockade was evaluated prospectively in 14 consecutive patients who required isoproterenol 2.4 +/- 1.3 (+/- S.D.) micrograms/min to induce sustained monomorphic VT (greater than 30 seconds, or requiring termination due to hemodynamic collapse) after a negative baseline study. The VT mechanisms were enhanced automaticity (group A, six patients), triggered automaticity (group B, three patients), and reentry (group C, five patients). Groups A and B had serial intravenous electropharmacologic tests with propranolol alone (0.2 mg/kg), verapamil alone (0.15 mg/kg), and propranolol plus verapamil, and group C had serial tests with propranolol alone, procainamide or quinidine (class Ia drug) alone, and propranolol plus a class Ia drug until VT could no longer be induced. All six patients in group A responded to propranolol alone. In group B, one patient responded to verapamil alone, and two patients responded to propranolol plus verapamil. In group C, three patients responded to propranolol alone, one patient responded to a class Ia drug alone, and one patient responded to propranolol plus a class Ia drug. During a follow-up of 7 to 37 (17.9 +/- 10.7) (+/- S.D.) months, VT has not recurred in any patient. Three patients treated initially with propranolol alone have required substitution of amiodarone due to refractory congestive heart failure. In patients requiring isoproterenol for VT induction, beta-blockade alone appears to be effective in preventing reinduction of VT caused by enhanced automaticity. A heterogeneous response occurs when the VT mechanisms are triggered automaticity or reentry. ",13 2824,"Dealing with geographic variations in the use of hospitals. The experience of the Maine Medical Assessment Foundation Orthopaedic Study Group. Orthopaedists and other physicians in Maine organized the Maine Medical Assessment Foundation to deal with the problem of variations in the rates of hospitalization for orthopaedic conditions. Five musculoskeletal injuries and five orthopaedic procedures were selected for study. The variation in decision-making by orthopaedists was least for fractures of the ankle and fractures of the hip and was greatest for fractures of the forearm, derangement of the knee, and lumbosacral sprain. The rates in an area tended to be consistently high or low for the same treatments. The major reasons for the variations appeared to be related to lack of agreement about optimum treatment. Feedback of data to physicians on variations in patterns of practice reduced the variations. ",20 2670,"Mathematical models of HIV infection. I. Threshold conditions for transmission and host survival. This is the second in a series of papers modeling human immunodeficiency virus (HIV) infections at four levels: transmission, interaction with the immune system, gene regulation, and selection of mutants. In the previous paper (1) we described and presented a theory of the HIV cytopathic effect based upon the models (and a review of the literature). In this article we give mathematical equations of threshold conditions that connect infectivity, length of host survival, and frequency of acts conducive to transmission. The formula is derived not only for homogeneous populations but also for populations of an arbitrary number of subgroups with varying frequencies of risk behavior, varying rates of infection and latency periods, and varying frequencies of interaction with other groups. ",19 1426,"Various methods for calculation of Kt/V: a clinical comparison. Analysis of the National Cooperative Dialysis Study (NCDS) showed that dialysis morbidity and mortality was related to Kt/V of urea. Various formulas have been derived to make calculation of Kt/V simpler. We compared the kinetically measured Kt/V (A) to estimated Kt/V derived from approximate total body water (0.6 body weight) and uniform dialyzer clearance (B), Kt/V = 0.04 PRU-1.2 where PRU is % reduction in BUN (C) and Kt/V = In(R-0.03-UF/W) where R is post/pre BUN, UF is ultrafiltration L/HD and W is postdialysis weight (D) in 26 patients. The correlation coefficient (r) was 0.14 (p less than 0.05) for A vs. B; 0.75 (p less than 0.01) A vs. C; 0.77 (p less than 0.01) A vs. D; and 0.97 for C vs. D. In an additional 51 patients, Kt/V was calculated using formulas B, C, and D. The r was 0.91 C vs. D, 0.70 B vs. D, and 0.68 B vs. C. With B, greater than 30% of the patients could have been misclassified using NCDS criteria for adequacy of dialysis. The study suggests that use of formulas C and D, but not B, is appropriate and accurate for Kt/V calculation. Formula C may be simpler and easier than D, as UF and W are not required. Serial Kt/V could be easily and accurately calculated using C and D for quality assurance and quantitation of dialysis. ",11 118,"In situ hybridisation with digoxigenin-labelled DNA probes for detection of viral genomes. The applicability of a recently developed non-radioactive DNA labelling and detection method, which uses the digoxigenin (DIG) enzyme linked immunosorbent assay (ELISA) system, for the detection of viral infections in pathology specimens by in situ hybridisation, was examined. Its efficacy was compared with that of biotin and radioisotope labelling methods. Three cases of progressive multifocal leucoencephalopathy, two of verruca vulgaris, and seven cases of laryngeal papilloma were studied. The sensitivity of the DIG labelled probe was almost the same as that of a 35S-labelled probe in the dot-blot hybridisation test. Using in situ hybridisation with 35S-labelled and DIG labelled probes, the levels of the hybridised signals detected were similar. The biotin labelled probe was less sensitive, particularly in the cases of laryngeal papilloma. The DIG labelling and detection method was highly sensitive and applicable to the detection of viral infection by ISH, and is preferable to a radiolabelled probe, especially when in situ hybridisation is done in the pathology laboratory. ",1 477,"Correlation of free phenytoin to serum albumin in cancer patients. The objectives of this study were to compare the total and free phenytoin serum concentrations of cancer patients with hypoalbuminemia with those of cancer patients with normal serum albumin and to correlate the percentage of free phenytoin with the albumin concentration. A total of 22 patients were studied, 13 with normal albumin concentration and 9 with low albumin. The mean free phenytoin in the normal albumin group was 9.9 (+/- 1.3) percent and 17.6 (+/- 4.6) percent in the low albumin group. With the groups combined, the mean free phenytoin was 13.1 percent (range 8.3-22.2) with the albumin range of 20-45 g/L. There was a significant negative correlation (r = -0.9, p less than 0.001) between the percentage of free phenytoin and the measured serum albumin. In cancer patients, the serum albumin concentration appears to be the key factor that determines the percentage of free phenytoin. In cancer patients with low serum albumin concentration, the total and free phenytoin concentration should be measured for adequate assessment of phenytoin therapy. ",3 1707,"Effects of diltiazem on the functional recovery of the myocardium at organ and cellular level during prolonged hypothermic ischemic cardiac arrest. The effectiveness of diltiazem on the functional recovery of the heart, calcium (Ca++) uptake and binding, Ca++ ATPase of cardiac sarcoplasmic reticulum (SR), and MB fraction of creatine kinase (MBCK) of coronary sinus blood was investigated after one and a half hours of reperfusion following three hours of ischemic cardiac arrest. The dogs were divided into three groups: group I, sham bypass; group II, cold crystalloid cardioplegia; and group III, cold crystalloid cardioplegia with diltiazem. There was a decrease in aortic pressures left ventricular pressure development (dp/dt), left ventricular work index (LVWI), total systemic vascular resistance (TSVR), and left ventricular systolic pressure (LVSP) in the sham bypass group. There was a decrease in cardiac index (CI), LVWI, and mean right atrial pressure (mRAP) and an increase in TSVR and pulmonary vascular resistance (PVR) in group II as compared with group I. Although there was a tendency for a decrease in the indices of myocardial contractility in group II, they were not significantly different from those in group I. The indices of myocardial contractility, CI, and LVWI in group III were slightly higher than in group II, but they were not significantly different from each other. The values for calcium uptake by SR in groups II and III were similar but significantly lower than those in group I. Calcium binding in group III was significantly lower than that in group I. Calcium ATPase of SR in the three groups were similar. Although MBCK increased in all the groups, the increases were not significantly different among the three groups. The results of this study indicate that cold crystalloid cardioplegia with diltiazem was not better than cold crystalloid alone in preserving the cardiac contractility and cellular function during prolonged ischemic cardiac arrest. However, the cardiac function in terms of cardiac index was better preserved with diltiazem. ",13 1640,"Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris. To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil. ",13 2287,"Linear porokeratosis: successful treatment with diamond fraise dermabrasion. A patient with linear porokeratosis was successfully treated with diamond fraise dermabrasion. Follow-up evaluation revealed an excellent cosmetic result with adequate repigmentation, no scarring, and no recurrence of lesions. Long-term follow-up will be necessary to determine whether dermabrasion treatment of linear porokeratosis provides adequate prophylaxis against the subsequent development of malignancy. ",16 2970,"Pathophysiologic events related to thermal injury of skin. Acute thermal injury of skin equivalent to second-degree injury and involving approximately 25% of total body surface results in a series of pathophysiologic events which lead to both local and distant tissue/organ injury. The distant effects involve intravascular hemolysis and acute lung injury, both of which can be attributed to complement activation and intravascular stimulation of neutrophils, resulting in oxygen radical production, which results in injury of red cells and pulmonary vascular endothelial cells. At the local site of thermal injury, the progressive increase in vascular permeability is linked to complement activation and histamine release, the outcome of which is interaction of histamine with xanthine oxidase, resulting in enhanced catalytic activity of the enzyme. Toxic oxygen products of xanthine oxidase, including H2O2 and its conversion product, the hydroxyl radical, appear to be linked to the damage of dermal vascular endothelial cells, resulting in progressive vascular permeability. The increased vascular permeability can be greatly attenuated by the use of inhibitors of xanthine oxidase, the inhibitor of histamine release (cromolyn), catalase, an iron chelator (deferoxamine), or scavengers of the hydroxyl radical. Interestingly, neutrophils appear to play little if any role in dermal vascular injury in this animal model of thermal trauma. Those studies suggest that pathophysiologic events following local thermal trauma are complex and involve a variety of mediator pathways. ",20 2052,"How to select a drug for the long-term treatment of chronic heart failure. First-line drugs for the treatment of chronic congestive heart failure should produce immediate symptomatic benefit, improve exercise tolerance, and thereby improve the quality of life. They should preferentially be active as monotherapy or at least reduce the need for comedication. The drugs must be safe and well tolerated by patients and change, in the end, the natural history of the disease, so that sudden death will be prevented and life expectancy improves. None of the currently available drugs satisfies all these criteria. Diuretics, digitalis, converting-enzyme inhibitors, and ibopamine come close to the described ideal. ",13 2521,"Intraoperative parathormone level measurement in the management of hyperparathyroidism. To investigate the potential use of intraoperative intact parathormone measurements to predict curative parathyroidectomy, we measured ionized calcium (Cai) levels and parathormone levels in 33 patients with hyperparathyroidism who underwent exploratory bilateral neck surgery. Nineteen patients each had a solitary adenoma, 13 patients had hyperplasia, and one patient had four normal parathyroid glands. These results were compared to the results for 37 patients who underwent either thyroid lobectomy (TL) (n = 10) or near-total thyroidectomy (NTT) (n = 27) and of 14 control patients who underwent miscellaneous operations. Parathormone decline after curative parathyroidectomy was 86.4 +/- 1.2% (mean +/- SE), which was significantly greater than a decline of 25.7% +/- 9.8% in three patients with persistent postoperative hyperparathyroidism (p less than 0.01). Declines were 38.5% +/- 8.7% after TL (p less than 0.01), 52.2% +/- 5.9% after NTT (p less than 0.01), and 8.3% +/- 4.3% (p less than 0.01), in the control patients. An intraoperative Cai decline of 4.0% +/- 0.6% after curative parathyroidectomy did not differ significantly from the results after TL, NTT, or miscellaneous operations in the control patients. Patients with persistent postoperative hyperparathyroidism had the greatest decline in Cai levels (7.1% +/- 2.3%; p less than 0.05). From these data we conclude that (1) a decline in parathormone level of 70% or more 20 minutes after parathyroidectomy is predictive of cure, (2) thyroidectomy, even unilaterally, produces a significant decline in parathormone level that affects interpretation of intraoperative parathormone level changes, (3) Cai level because of its slow decline is not useful in predicting effective parathyroidectomy, and (4) measurement of intraoperative parathormone level changes should not be used as a substitute for exploratory bilateral neck surgery. ",18 1703,"Comparison of standard one-minute treadmill exercise and strandness test (absolute walking distance) in relation to site of lesion, walking distance, and diastolic blood flow velocity (Doppler curves). In 215 outpatients suffering from occlusive arterial disease of the lower limbs the authors compared the decrease in the ratio of ankle systolic pressure to brachial systolic pressure according to whether the treadmill exercise was limited to one minute or extended until pain forced the patient to stop. After a one-minute walk the pressure index always decreased significantly, especially when walking was restricted. The decrease in the pressure index was generally greater when the exercise was continued until the absolute walking distance, and the recovery time was usually twice as long. The fall in the pressure index was significantly greater for patients with single and multiple iliac stenoses than for those with stenoses at lower levels. In patients having a diastolic blood flow velocity on Doppler curves at rest, not modified by walking, a maximum drop in peripheral pressure was recorded after walking for one minute. In this instance there was no intensification of the decrease in peripheral pressure, unlike in patients without a diastolic blood flow velocity at rest. This one-minute test is not a maximal hemodynamic response, but it is sufficient for the appreciation of ischemia during exercise, according to the different parameters measured. ",13 46,"Detection of interleukin-3 in the serum of mice infected with Mycobacterium lepraemurium. Infection of mice by Mycobacterium lepraemurium is accompanied by ablation of erythropoiesis in the bone marrow and gross enlargement of the spleen. This, together with increased monocytopoiesis and the earlier demonstration of macrophage colony-stimulating factor in the serum of infected mice, suggested the activity of additional cytokines. Eight weeks after infection of mice by M. lepraemurium, interleukin-3 (IL-3) activity was demonstrated in the serum (titer, 1:3200). The serum titer of IL-3 activity was maximal after 13 weeks (greater than 1:6400) and was slightly reduced after 18 weeks (1:6400). That the IL-3 activity detected in the serum of the M. lepraemurium-infected mice reflected the presence of IL-3 itself was confirmed by a neutralization assay using anti-murine IL-3 antibodies; IL-3 activity in the serum of mice 13 weeks after infection was completely abolished by the anti-IL-3 antibodies. Finally, a 1-kb signal of IL-3 RNA was detected in the spleens of M. lepraemurium-infected mice 13 weeks after infection. ",0 888,"Pneumonia syndromes: a clinical approach in the elderly. Important in the pathogenesis of pneumonia in the elderly patient are chronic diseases, including diabetes mellitus, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and cerebrovascular disease. Also vital are the changes that take place in the immune system and mucociliary clearance mechanisms of the lung. The clinician should be aware of these risk factors, especially since the mortality rate of lower respiratory infections approaches 40% in these elderly patients. Treatment guidelines are included. ",7 635,"The use of liposuction to contour cherubism. Yet another application of suction lipectomy equipment is presented to remove the pathologic tissue in cherubism. Owing to the variations of consistency of the material in this condition, this technique may not be successful in all patients, but it is certainly recommended when indicated. ",4 2498,"An implanted peritoneal oxygen tonometer that can be calibrated in situ. Oxygen tension in the peritoneum has been continuously measured with a Silastic tonometer having an integral oxygen electrode and inlet and outlet tubes for gasequilibrated electrolyte solution. Remote kinetic calibration of the system is periodically performed. Tonometers were implanted in six rabbits. Peritoneal oxygen tension was measured in awake and anesthetized rabbits under various oxygen breathing conditions. ",17 2402,"Recent progress in understanding apolipoprotein B. For the past 5 years, investigators from many different laboratories have contributed to a greatly increased understanding of two very important lipid-carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an extremely large protein composed of 4,536 amino acids, is synthesized by the liver and is crucial for the assembly of triglyceride-rich VLDL particles. Apo B-100 is virtually the only protein of LDL, a cholesteryl ester-enriched class of lipoproteins that are metabolic products of VLDL. The apo B-100 of LDL serves as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and extrahepatic tissues. The LDL receptor-binding region of apo B-100 is located in the carboxyterminal portion of the molecule, whereas its lipid-binding regions appear to be broadly dispersed throughout its length. Apo B-48 contains the amino-terminal 2,152 amino acids of apo B-100 and is produced by the intestine as a result of editing of a single nucleotide of the apo B mRNA, which changes the codon specifying apo B-100 amino acid 2,153 to a premature stop codon. Apo B-48 has an obligatory structural role in the formation of chylomicrons; therefore, its synthesis is essential for absorption of dietary fats and fat-soluble vitamins. Both apo B-48 and apo B-100 are encoded on chromosome 2 by a single gene that contains 29 exons and 28 introns. An elevated level of apo B-100 in the plasma is a potent risk factor for developing premature atherosclerotic disease. In the past 3 years, many different apo B gene mutations that affect the concentrations of both apo B and cholesterol in the plasma have been characterized. A missense mutation in the codon for apo B-100 amino aid 3,500 is associated with hypercholesterolemia. This mutation results in poor binding of apo B-100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL particles to accumulate in the plasma. This disorder is called familial defective apo B-100, and it is probably a cause of premature atherosclerotic disease. Familial hypobetalipoproteinemia is a condition associated with abnormally low levels of apo B and cholesterol; affected individuals may actually have a reduced risk of atherosclerotic disease.(ABSTRACT TRUNCATED AT 400 WORDS). ",17 186,"Oncocytic glomus tumor of the trachea. An oncocytic variant of glomus tumor of the trachea occurred in a 47-year-old woman. She experienced intermittent cough and hemoptysis for about three years. Bronchoscopy and chest CT scan showed a small reddish polypoid tumor on the lower end of the trachea. Bronchoscopic biopsy was carefully done and was diagnosed as oncocytoma. A wedge resection of the tumor was done. Tumor cells were characterized by strongly eosinophilic granular cytoplasm on light microscopy and by numerous closely packed round or ovoid mitochondria with prominent tubular cristae on electron microscopy. They were arranged in a sheet around small vessels, as a result of which the biopsy diagnosis of oncocytoma was changed to oncocytic glomus tumor. To our knowledge, this is the first report of an oncocytic glomus tumor arising from the trachea. ",3 2893,"Endoscopic extraction of an entrapped nasogastric tube. Inadvertent entrapment of a nasogastric tube within a stapled gastrointestinal anastomosis is a preventable and infrequent surgical complication. We report our experience with this complication and describe a successful endoscopic approach to management. ",20 1393,"Applications of prostate ultrasonography. Transrectal ultrasonography is a relatively new imaging modality that may be useful in the evaluation and management of patients with prostate cancer. Although cancer may have a characteristic appearance, it cannot always be reliably differentiated from benign conditions. While this technique has clinical applications in staging, monitoring tumor response to therapy, and assisting in biopsy, it is unclear as to whether useful information is obtained in the evaluation of patients with palpable disease. The role of transrectal ultrasonography in patients with nonpalpable disease or as a screening tool has yet to be determined. Other diagnostic tests in conjunction with ultrasound may in the future prove to be useful. Carefully performed prospective investigations with state-of-the-art equipment are still needed to further define the role of this diagnostic modality. ",11 1474,"Further observations on the doubling time of human chorionic gonadotropin in early asymptomatic pregnancies. The doubling time (DT) of human chorionic gonadotropin (hCG) in serum was investigated retrospectively using serial serum hCG values that had been obtained from asymptomatic pregnant women with a prior history of infertility. The DT of hCG did not increase significantly as pregnancy advanced during the period in gestation when the serum hCG concentration was less than 10,000 mIU/mL (International Reference Preparation). Serum hCG concentrations increased subnormally in 2 of 60 women with normal intrauterine pregnancies, 5 of 8 women with asymptomatic ectopic pregnancies (EPs), and in 2 of 8 asymptomatic women who subsequently aborted their pregnancies. Neither the sensitivity nor the specificity of serial hCG testing for EP was enhanced by adopting different test criteria at different serum hCG concentrations. ",12 1432,"Influence of phosphatidylcholine on ultrafiltration and solute transfer in CAPD patients. Fifteen patients (mean age 59.9 +/- 16.1 years) treated by CAPD for a mean of 21.6 +/- 14 months, underwent peritoneal clearances before and after 15 days of intraperitoneal phosphatidylcholine (PC) treatment (50 mg/L). No difference was observed in urea, creatinine, uric acid, and reverse dextrose clearances. A statistically significant increase in phosphate clearances (4 and 6 hr dwell times) (1.36%) and a reduction in drainage volume (2 hr dwell time) (1.36%) were observed after treatment. Urine output and percent dextrose reabsorption were unchanged. The ultrafiltration (UF) showed a tendency to increase, which lasted for 15 days after discontinuation of treatment. This tendency allowed the patients to reduce, during the same period, the amount of hypertonic solution (23.8 L vs. 21.3 L) required. The tendency to increase UF over time deserves further study. ",11 1826,"Valvular and coronary surgery in renal transplant patients. The Authors report aortic valvular replacement (AVR) and coronary artery bypass graft surgery (CABG) successfully performed in two renal transplant patients. The postoperative blood urea and creatinine levels were comparable to the preoperative values. The first patient underwent isolated AVR. The second patient had an initial AVR combined with CABG followed two years later by a further AVR for prosthetic dysfunction. For many reasons, coronary artery (CAD) and valvular diseases are not uncommon in renal transplant patients. Cardiac surgery is feasible without impairment of the renal function provided some precautions are taken, ie good mean perfusion pressure during cardiopulmonary bypass (CPB), adequate volume replacement, and selected use of mannitol and dopamine. ",13 866,"Improved primary surgical and dental treatment of clefts. The improved combination of surgical and dental teamwork in the primary treatment of clefts presented here is consistent with principles. In fact, this is a staged design for correction of classic clefts of the lip and palate that, based on biological principles, facilitates the continuance of the failed embryonic ""migrations"" toward a normal end point. Positioning of the alveolar segments, dissection of mucoperiosteum out of the cleft, and union of mucoperiosteum across the alveolar and anterior hard palate cleft make it possible to create a periosteal tunnel across the bony gap and set up a condition conducive to bone formation and eventual tooth eruption in the cleft area. Lip closure by adhesion reduces the tension of the primary lip closure and allows gentle molding until solidification of the arch occurs. Thus a complete cleft has been rendered an incomplete cleft. With a balanced, stabilized maxillary platform, the definitive lip and nose corrections can be carried to completion early (by 2 to 4 years of age). These planned actions bypass a persistent cleft, fistulas, raw areas, malposition of alveolar segments, and probably the necessity for later bone grafting. The only question not totally answered is the effect of this approach on final growth. Although most reports seem to indicate that growth has and will proceed within normal limits, another 10 years of careful follow-up is indicated and, in fact, is in progress. ",6 2660,"Bronchial responsiveness to histamine in infants and older children Normal infants have been shown to respond to a relatively low concentration of inhaled histamine. However, those studies used partial maximal expiratory flow volume (PMEFV) curves to assess lung function. In order to directly compare responsiveness between infants and older children, we compared bronchial responsiveness to histamine between a group of 45 normal infants, median age 4 wk (range 2 to 6 wk) and a group of 30 nonasthmatic older children, median age 10 yr (range 5 to 15 yr) using PMEFV curves in both groups to assess lung function. In the infant group, PMEFV curves were generated using the forced expiratory flow volume technique. For the older children, PMEFV curves were generated by voluntary effort. The provocative concentration of histamine that produced a 40% fall (PC40) in maximum flow at functional residual capacity (VmaxFRC) was calculated from the PMEFV curves. The geometric mean PC40 of the infants (1.02 g/L) was lower than the geometric mean of the older children (3.4 g/L) (p less than 0.001). However, these results were then corrected for dilution of the aerosol due to air entrainment (AE). Corrected values of PC40 were not significantly different between infants and older children. These results demonstrate the importance of accounting for AE in the evaluation of histamine responsiveness and suggest that bronchial responsiveness may be similar in normal infants and older children. ",19 3027,"The effect of race on the relationship between fetal death and altered fetal growth. This population study examines racial differences in the relationship between birth weight and fetal death. An earlier report showed that a birth weight that results in a fourfold increased risk of stillbirth is not a constant birth weight percentile (2nd percentile at 25 weeks, 17th percentile at 42 weeks). This analysis was applied to 782,430 white and black births in Illinois from 1980 to 1984. Mean and 10th percentile growth for white and black infants is identical before 34 weeks' gestation and growth diverges by 250 gm at term, with white infants being larger. Race-specific birth weights resulting in quadrupling of the stillbirth rate were determined with an exponential regression analysis of the relationship between birth weight and fetal death rate for each gestational age. The data indicate (1) that the birth weights resulting in quadrupling the stillbirth rate are substantially above the Denver 10th percentile and the previously unpublished race-specific Illinois 10th percentiles and (2) that at term white infants demonstrate this constant risk at the 12th percentile, whereas black infants exhibit the risk at the 18th percentile. From these data we conclude that black fetuses are more sensitive than white fetuses to factors that adversely affect growth and that continued use of ""race-neutral"" data for clinical management in racially heterogenous populations will not accurately predict the risk of stillbirth. ",22 717,"Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach. We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025-0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01-0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5-1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa. ",5 927,"Neuropeptides and nasal secretion. Recent research has disclosed that neurotransmitters and neuropeptides released within the autonomic nervous system exert homeostatic control of nasal secretion. Although cholinergic and adrenergic influences have long been thought to be the predominant mechanisms, the nonadrenergic, noncholinergic responses may have more suitable, longer-lasting effects. Peptides from sensory nerves, such as calcitonin gene related peptide, substance P, and neurokinin A, may participate in axon response-mediated vasodilation and plasma extravasation. Substance P and gastrin releasing peptide may induce glandular secretion. Defensive responses to local mucosal injury may be amplified by axon response, which initiates these vascular and glandular reactions. Cholinergic effects are primarily responsible for mediating parasympathetic reflexes, but vasoactive intestinal peptide may regulate acetylcholine release, augment glandular secretory responses, and have a vasodilatory effect. In the sympathetic nervous system, neuropeptide Y probably functions as a long-acting vasoconstrictor. Integration of sympathetic and parasympathetic influence may regulate the normal nasal cycle, and sensory and parasympathetic defensive reflexes may respond to epithelial and mast cell stimulation. It is possible, then, that the pathophysiology of vasomotor rhinitis involves an exaggeration of these neural influences. ",7 403,"Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each of these six tumors contains aberrant transcripts derived from identical splicing of exon 1 to exon 8 as a consequence of a deletion-rearrangement of the amplified gene, the extent of which is variable among these tumors. In spite of this intertumoral variability, each intragenic rearrangement results in loss of the same 801 coding bases (exons 2-7) and creation of a new codon at the novel splice site in their corresponding transcripts. These rearrangements do not, however, affect the mRNA sequence for the signal peptide, the first five codons, or the reading frame downstream of the rearrangement. ",3 2353,"Complement-fixing antibodies to sympathetic and parasympathetic tissues in IDDM. Autonomic brake index and heart-rate variation. We describe herein complement-fixing anti-adrenal medullary (CF-ADM) and anti-sympathetic ganglia (CF-SG) antibodies in insulin-dependent diabetes mellitus (IDDM). This study describes complement-fixing anti-vagus (CF-V) nerve antibodies and their relationship to the cardiovascular autonomic brake index (a measure of transient decrease in heart rate during the 1st min after a tilt), and R-R interval variation with deep breathing. CF-V was detectable in 7 of 83 (8.4%) subjects with IDDM aged 1.5-65.5 yr (mean +/- SE 28.7 +/- 1.8 yr) and duration of diabetes 0-47 yr (11.8 +/- 1.4 yr). Seventy-six nondiabetic subjects (aged 10-65 yr) all had negative CF-V scores. CF-V scores correlated with CF-ADM (0-16 yr of IDDM, r = 0.61, P less than 0.0001) and CF-SG (r = 0.39, P less than 0.05). Seventy IDDM subjects (aged 28 +/- 5 yr, duration of diabetes 17 +/- 3 yr) without proteinuria or proliferative retinopathy were screened for CF-ADM, CF-SG, and CF-V antibodies. Five of 70 (7.1%) had CF-SG only (negative for CF-ADM and CF-V). Brake indices ranged from 14.7 to 51.3 (37.3 +/- 6.9). Three of 70 (4.2%) had CF-ADM only, with brake indices from 26.9 to 45.1 (32.9 +/- 6.1). Four of 70 (5.7%) had CF-V antibodies only, with brake indices of 12.7-17.3 (15.1 +/- 1.1). Subjects with CF-SG or CF-ADM (anti-sympathetic) had higher brake indices than subjects with CF-V (anti-parasympathetic) antibodies (P less than 0.03). ",17 3230,"Nontraumatic coma. Glasgow coma score and coma etiology as predictors of 2-week outcome. In 1987 and 1988, we carried out a prospective study of patients older than 10 years with nontraumatic coma in the intensive care units of Columbia-Presbyterian Medical Center, New York, NY. Of 188 patients with Glasgow Coma Scale (GCS) determinations within 72 hours, 61% were dead or in persistent coma by 2 weeks from onset. Age, sex, and ethnicity did not influence outcome. The 2-week outcome for patients with initial GCS of 3 to 5 was 14.8% awake; 85.2% were dead or in persistent coma. For the GCS 6 to 8 group, 53.1% were awake and 46.9% were dead or in persistent coma. Hypoxic or ischemic coma had the worst 2-week outcome (79% dead or comatose); coma caused by metabolic disease or sepsis (68%), focal cerebral lesions (66%), and general cerebral diseases (55%) were intermediate, while drug-induced coma had a favorable outcome (27% dead or comatose). The independent predictors of 2-week outcome were the first GCS and drug-induced coma. The predicted probability of waking at 2 weeks was eight times better for drug-induced coma than other causes when GCS was held constant. Patients with an initial GCS score of 6 to 8 were seven times more likely to waken than those with a score of 3 to 5. The motor subscore alone was a significant independent predictor of 2-week outcome. Modification of coma score to include etiology may give more accurate predictions of 2-week outcome after nontraumatic coma. ",22 71,"Evidence for gonococcal transmission within a correctional system. In a study to examine sexually transmissible disease occurring within a large correctional system where sexual activity is prohibited, 27 male inmates acquired culture-proven gonorrhea from in-jail sexual activity during a three-month period. These results provide evidence to encourage inmate education about the acquired immunodeficiency syndrome (AIDS) and to support condom distribution programs in correctional facilities. ",0 1359,"Mohan's urethral valvotome: a new instrument. Electrothermic fulguration of posterior urethral valves with a resectoscope is difficult in newborns, especially in small for gestation date and premature newborns because of a small caliber urethra. This difficulty has prompted the innovation of the valvotome described. The outer diameter of the valvotome is 3 mm. and it can be easily introduced without stretching the urethra. This instrument has been used successfully in 8 patients to date. Patient age ranged from 3 days to 3 1/2 years with varying degrees of hydronephrosis and hydroureter. All patients have a good urinary stream with regression of the hydronephrosis and hydroureter. ",11 2836,"The physician's role in injury prevention: beyond the U.S. Preventive Services Task Force report. Injuries and their prevention have received little attention by the medical community, despite the fact that injuries are the leading cause of premature death. However, much can be done to reduce the number and severity of injuries, and the practicing physician has an important role to play in this process. This report outlines the U.S. Preventive Services Task Force report recommendations for prevention strategies to reduce injuries and then seeks to define a broader role for the physician in prevention injuries that extends beyond the confines of office-based practice. While screening and counseling have proven effectiveness in certain situations, interventions that are passive or automatic in action, such as air bags, have proven to be more effective long-term solutions to reduce both the number and the severity of injuries. The author outlines and provides examples of seven areas where physicians can have a major impact either directly or through implementing effective injury-control strategies. These are: treatment, education, screening, hazard identification, research, advocacy, and policy making. Using all of these approaches, physicians can play a truly effective role in reducing the burden of injuries for their patients. ",20 3257,"Outcome of patients with chronic affective disorder: a five-year follow-up. Patients with major depression, mania, or schizo-affective disorder that had been present without remission for 2 years or more at intake (N = 129) were followed prospectively for 5 years, as were 580 patients who had been ill for shorter periods at intake. Despite very substantial durations of episode, three-quarters of the chronic patients recovered, although recovery occurred much later in the follow-up period than it did among the nonchronic patients. Factors associated with recovery were less severe illness at intake, lack of psychotic features, good friendship patterns in adolescence, and, most important, a relatively high maximum level of functioning in the 5 years preceding intake. ",22 2385,"Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. ",17 3093,"Rapid percutaneous tracheostomy We describe a new method of performing percutaneous tracheostomy rapidly and safely using a specialized instrument kit. The technique permits the safe insertion of a full-sized 7.0 (ID) or 7.5 mm (ID) cuffed cannula into the trachea within 1-2 min, through the membranous second intercartilagenous space. Animal studies have demonstrated a superior healing process compared to that seen after conventional tracheostomy techniques. ",22 425,"Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. The authors studied by immunohistochemistry the intermediate filament (IF) protein profile of 66 frozen samples of breast tissue, including normal parenchyma, all variants of fibrocystic disease (FCD), fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies (MAbs) to cytokeratins included MAb KA 1, which binds to polypeptide 5 in a complex with polypeptide 14 and recognizes preferentially myoepithelial cells; MAb KA4, which binds to polypeptides 14, 15, 16 and 19; individual MAbs to polypeptides 7, 13, and 16, 17, 18, and 19, and the MAb mixture AE1/AE3. The authors also applied three MAbs to vimentin (Vim), and three MAbs to glial filament protein (GFP). Selected samples were studied by double-label immunofluorescence microscopy and by staining sequential sections with some of the said MAbs, an MAb to alpha-smooth muscle actin, and well-characterized polyclonal antibodies for the possible coexpression of diverse types of cytoskeletal proteins. Gel electrophoresis and immunoblot analysis also were performed. All samples reacted for cytokeratins with MAbs AE1/AE3, although the reaction did not involve all cells. Monoclonal antibody KA4 stained preferentially the luminal-secretory cells in the normal breast and in FCD, whereas it stained the vast majority of cells in all carcinomas. Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas. Vimentin-positive cells were found in 8 of 12 normal breasts and in 12 of 20 FCD; in most cases, Vim-reactive cells appeared to be myoepithelial, but occasional luminal cells were also stained. Variable subpopulations of Vim-positive cells were noted in 9 of 20 ductal and in 1 of 7 lobular carcinomas. Glial filament protein-reactive cells were found in normal breast lobules and ducts and in 15 of 20 cases of FCD; with rare exceptions, GFP-reactivity was restricted to basally located, myoepithelial-appearing cells. Occasional GFP-reactive cells were found in 3 of 31 carcinomas. Evaluation of sequential sections and double-label immunofluorescence microscopy showed the coexpression of certain cytokeratins (possibly including polypeptides 14 and 17) with vimentin and alpha-smooth muscle actin together with GFP in some myoepithelial cells. The presence of GFP in myoepithelial cells was confirmed by gel electrophoresis and immunoblotting. Our results indicate that coexpression of cytokeratin with vimentin and/or GFP is comparatively frequent in normal basal-myoepithelial cells of the breast.(ABSTRACT TRUNCATED AT 400 WORDS). ",3 1516,"The rate of rise of corticotrophin releasing factor and endogenous digoxin-like immunoreactivity in normal and abnormal pregnancy. Maternal plasma concentrations of corticotrophin releasing factor (CRF) and endogenous digoxin-like immunoreactivity (EDLI) were estimated in 80 normal and 88 abnormal pregnancies which were sampled sequentially from 24 weeks gestation to delivery. A slope was fitted for each woman's antenatal EDLI and CRF values, both of which rose significantly during gestation, and the mean of the slopes for the normal and abnormal groups for each value compared. There was no evidence of significant mean differences between groups for EDLI but there was evidence of a significant mean difference for CRF (P less than 0.05). After adjustment for other variables which may affect pregnancy outcome, the slopes for CRF were found not to be significantly related to outcome. ",12 1713,"Combined internal mammary artery graft for coronary artery revascularization. Five patients with multiple-vessel coronary artery disease underwent isolated coronary artery bypass grafting with a technique involving both internal mammary arteries and a small piece of interposed saphenous vein. The combined internal mammary artery grafts were used for sequential grafting. A total of 20 anastomoses were performed (average number, 4 anastomoses per patient). There were no operative deaths. Postoperative complications included reoperation for bleeding in 1 patient and diaphragmatic dysfunction in another. Postoperative coronary angiography 2 days before discharge (mean time, 10 days postoperatively) revealed that all the sequential anastomoses with the combined IMA graft were patent. Exercise tolerance tests performed 3 and 11 months postoperatively indicated excellent results and no ischemia. Based on this experience, we conclude that this method appears promising for multivessel coronary artery bypass grafting. ",13 1427,"Evaluation of plasma sodium concentration during hemodialysis by computerization of dialysate conductivity. Kinetics modeling based on sodium mass balance and changes in conductivity at the dialysate outlet compared to that at the dialysate inlet, led to predicting the plasma water conductivity of the blood inlet. Conductivity transducers, with temperature compensation, located at the dialysate inlet and outlet ports of the dialyzer and connected to a conductimeter, were interfaced with a portable computer for data acquisition. In 38 dialysis sessions, a close relationship was found between estimated plasma water conductivity (CdBi) and measured plasma sodium concentration [Na]Bi, according to the formula: CdBi = 0.101[Na]Bi + 0.37 (n = 38; r = 0.922). The study shows that plasma sodium concentration at the dialyzer inlet could be evaluated, with a standard error of +/- 1.5 mEq/L, by continuous measurement of conductivity gradient between dialysate inlet and outlet. ",11 2448,"Asian osteomalacia is determined by dietary factors when exposure to ultraviolet radiation is restricted: a risk factor model Twenty-seven previously osteomalacic and 77 normal Asian women participated in a seven-day survey of dietary intake and daylight outdoor exposure. Individual levels of daylight outdoor exposure discriminated poorly between normal and osteomalacic women. The presence of osteomalacia was strongly related to varying degrees of vegetarianism. Lactovegetarianism (no meat, fish or egg consumption) was associated with significantly greater osteomalacic risk than ovolactovegetarianism (no meat or fish consumption). Unlike Asian rickets, high-extraction wheat cereal as chapatti was not a significant risk factor for osteomalacia in Asian women and dietary fibre was a less important risk factor than absent dietary meat, fish or egg. When exposure to ultraviolet radiation is limited, Asian osteomalacia (and Asian rickets) are determined by dietary factors. ",17 1685,"Overview: renal physiology and pathophysiology of aging. Cross-sectional studies in humans have suggested that there is a progressive decline of renal function with age after 40 years. The decline in various functions (eg, tubular maximums, concentrating and diluting abilities, and acidification) tend to parallel the decreases in glomerular filtration rate (GFR) and renal blood (plasma) flow (RPF). Recent observations from the Baltimore Longitudinal Study of Aging suggest that not all individuals follow this pattern, and that, indeed, many show no decline and some even an increase in their renal function over time. Whether the observed decreases in renal function with aging are the results of intervening pathologic processes, eg, immunologic, infectious, and toxic injury and ischemia, or can be related to hyperperfusion and hyperfiltration with resultant glomerulosclerosis, or to some other relentless involutional process, remains unclear. The purpose of this report is to review the descriptive studies documenting the changes in renal morphology and physiology with age and to discuss what is known about mechanisms involved in these losses of renal substance and function. ",13 1163,"Misdiagnosis in patients with amyotrophic lateral sclerosis. To confirm our impression that a high percentage of patients with amyotrophic lateral sclerosis are initially misdiagnosed, we reviewed records of 33 patients with a definitive diagnosis of amyotrophic lateral sclerosis seen over 10 years. Fourteen patients (43%) were initially misdiagnosed. Mean time to correct diagnosis was significantly greater for the misdiagnosed group (16.0 +/- 9.3 months) than for the rest of the patients (7.6 +/- 4.1 months). Two of three patients with an initial symptom of dyspnea were misdiagnosed. Three patients underwent laminectomies because of misdiagnosis. Age, stage of disease, and unusual presenting symptoms were not identified as causes of misdiagnosis. Most likely causes were physicians' failure to consider the diagnosis and lack of familiarity with the common clinical presentations of amyotrophic lateral sclerosis. Earlier diagnosis of amyotrophic lateral sclerosis may help prevent medical mismanagement and may benefit patients both medically and psychologically. ",9 1199,"Triiodothyronine and brain excitability. We investigated mechanisms involved in thyroid hormone action on brain excitability. The effect of acute exposure of triiodothyronine (T3) to rat hippocampal slices in vitro was studied. No significant changes could be detected in prevolley, field excitatory postsynaptic potentials (fEPSP) and population spike amplitude, while there was a minor, nonsignificant trend toward shortening of the population spike latency time. T3 had no effect on penicillin-induced epileptiform activity. There was, however, an active accumulation of radioactively labeled T3 in the slices. A rat cervaux-isole preparation was used to determine focal seizure thresholds in the visual cortex, and no acute (2-4 h) effects were demonstrated. No significant acute effects of T3 on brain excitability in the hippocampus and visual cortex was observed, despite an active accumulation of T3. Thus, the effect of T3 on brain excitability most likely is due to delayed effects. ",9 1521,"Basal body temperature and endometriosis. This investigation examined the association between pelvic endometriosis and altered basal body temperature (BBT). The study population consisted of infertile women who have been diagnosed as having endometriosis. A significant association was found between the presence of pelvic endometriosis (without previous treatment) and the appearance of a late decline in BBT during the early follicular phase of the menstrual cycle. A temperature greater than 97.8 degrees F on the first 3 days of menses is associated with pelvic endometriosis. The findings of this study support the early clinical diagnosis of endometriosis in infertile women. Basal body temperature chart analysis may be useful as a clinical adjunct when endometriosis is suspected. ",12 2901,"Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval II. Previous studies have demonstrated antagonist-precipitated withdrawal from 45 min to 24 hr after acute opioid administration in nondependent human subjects. The purpose of this study was to examine longer postagonist intervals and to determine the maximum interval between agonist administration and antagonist challenge at which precipitated withdrawal can be observed. During this study 6 nondependent male volunteers who reported using opiates an average of 4 times per week received naloxone challenges (10 mg/70 kg i.m.) at 6, 12, 24, 36, 48, 60, or 72 hr after single i.m. injections of morphine (18 mg/70 kg or 30 mg/70 kg). Each interval was tested independently in random order. Naloxone reliably precipitated withdrawal signs and symptoms at 6 and 12 hr postmorphine. Withdrawal symptoms were greatly diminished in intensity at 24-hr postmorphine and were not elicited at postmorphine intervals longer than 24 hr. Withdrawal precipitation persisted somewhat longer than pupillary constriction because pupils had returned to predrug diameters by 24 hr postmorphine but, generally, there appeared to be correspondence between offset of agonist effects and dissipation of precipitated withdrawal. This study extends observations about the time course of acute physical dependence effects which begin within minutes after acute morphine exposure, dissipate within 36 hr, are associated with the onset and offset of agonist effects and do not require chronic opioid administration. ",20 1524,"Correlation between quantitative antibody titers of sperm immobilizing antibodies and pregnancy rates by treatments. Immunological infertility in women who possessed sperm immobilizing (SI) antibodies made it very difficult to conceive using the usual treatments. We examined SI antibodies by the quantitative Sperm Immobilization Test and found the antibody titers (50% sperm immobilization unit: SI50 unit) associated with pregnancy rates. Patients with high SI50 titers (greater than 10 units) did not conceive by ordinary or repeated artificial inseminations with husband's semen (AIH) except when treated with in vitro fertilization (IVF) and embryo replacement. Patients with relatively low SI50 titers (less than 10 units) could conceive either by repeated or ordinary AIH, though the success rates were lower than by IVF-embryo replacement. It is important to assess the SI50 titers by the quantitative method to select treatments for infertile women with SI antibodies. In follow-up studies of the patients who conceived successfully, it was found that SI50 titers tended to decline as pregnancy proceeded. ",12 3239,"Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin. The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio. ",22 1388,"Use of distal Thiersch-Duplay urethroplasty for proximal hypospadias repairs in conjunction with short island pedicle flap. Experience with 8 boys having proximal hypospadias with severe chordee and a foreshortened dorsal hooded foreskin is presented. Use of a distal Thiersch-Duplay tube was incorporated in addition to an island pedicle flap to achieve the correct meatal location on the glans. One boy with perineal hypospadias required both proximal and distal Thiersch tube with an island flap interposition. Follow-up of nine months to 3.5 years demonstrated excellent cosmetic and functional results with no recurrent chordee or urethral stenosis. The only fistula noted developed at the proximal Thiersch tube-island flap anastomosis in the boy with perineal hypospadias. Advantages of the aforementioned procedure include decreasing the risk of chordee on the basis of a foreshortened island pedicle flap, use of vascularized flaps, and completing the procedure in one stage with a satisfactory result. ",11 2952,"Mineralogic parameters related to amosite asbestos-induced fibrosis in humans. We have previously shown that in the lungs of a group of chrysotile miners and millers, grade of interstitial fibrosis (asbestosis) is directly proportional to tremolite fiber or chrysotile fiber concentration but is inversely proportional to mean fiber length and length-related parameters. To compare the effects of the commercial amphibole asbestos amosite on parenchymal fibrosis, we histologically graded fibrosis in four different sites in the lungs of 20 shipyard and insulation workers with heavy amosite exposure and measured by analytic electron microscopy fiber concentration and size in corresponding portions of lung tissue. Fibrosis grade was found to be strongly positively correlated with amosite concentration and negatively correlated with mean fiber size parameters, including fiber length, width, surface area, and mass. A comparison of our present results with our data on the chrysotile miners and millers showed that the regression lines of fibrosis grade versus concentration for amosite, chrysotile, and tremolite were statistically different. These findings indicate that amosite concentration, like chrysotile and tremolite concentration, is closely and directly related to fibrosis at the local lung level. Furthermore, these observations again raise the possibility that short fibers may be more important than is commonly believed in the genesis of fibrosis in man. Last, the concentration comparison data indicate that, fiber for fiber, amosite is more fibrogenic than is chrysotile or tremolite, and indirectly suggest that tremolite is more fibrogenic than is chrysotile. ",20 325,"Oncogenes and suppressor genes: their involvement in colon cancer [editorial] Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented. ",3 1453,"Epidural analgesia for a parturient with herpes gestationis. A 23-yr-old parturient with herpes gestationis spontaneously delivered a normal healthy infant under epidural analgesia. She received five injections of bupivacaine 0.5 per cent over a ten-hour period. There was no infection at the lumbar region, even though her body was covered with vesicles and bullae including the face and neck. Eight months after delivery the patient still has a vesicular eruption which occurs mainly during her menses. ",12 508,"Technetium-99m(v) dimercaptosuccinic acid planar scintigraphy in head and neck cancer: clinical, scintigraphic and radiological study. Technetium-99m (Tc99m)(v) Dimercaptosuccinic Acid (DMSA) is an imaging agent which has been proposed as a scintigraphic marker for head and neck squamous cell carcinoma. Fifty-four patients were studied of whom 51 had a head and neck tumour. All patients were examined and then imaged using Tc99m(v) DMSA scintigraphy and computerized tomography. Scintigraphy was less sensitive than clinical examination in the detection of patients with cancer, patients with primary tumours and patients with metastatic neck disease. CT was as sensitive and as accurate as clinical examination but more sensitive than Tc99m(v) DMSA in detecting patients with cancer and with primary tumours. CT was more sensitive and more accurate than both clinical examination and Tc99m(v) DMSA scintigraphy in predicting which patients had metastatic neck disease. Although Tc99m(v) DMSA is accumulated by squamous cell carcinoma, its inability to detect low volume disease and apparent low specificity means it has no role to play in the management of patients with head and neck squamous cell carcinoma. ",3 2140,"Primary splenic lymphocyte-depletion Hodgkin's disease. A case of lymphocyte-depletion Hodgkin's disease is described for the purpose of reviewing the criteria currently used to distinguish this disease from other pleomorphic large-cell malignancies. A 76-year-old man with a 3-month history of daily fevers underwent extensive evaluation and exploratory laparotomy, which revealed only two large, separate splenic tumor nodules. Postoperatively, the patient remained asymptomatic. Histologically, the tumor was composed of giant cells, including both typical Reed-Sternberg forms and mononuclear variants with inflammatory stromal response along its borders. Immunoperoxidase showed tumor cells to be strongly reactive for Leu-M1 (CD15), BER-H2 (CD30), Leu-3 (CD4), and T11 (CD2) and weakly reactive for Leu-4 (CD3) but nonreactive for EMA, LCA, lysozyme, Leu-9, Leu-M3, Leu-M5, and immunoglobulin light chains. Southern blot analysis revealed an isolated clonal band for kappa light chain only. Included in the discussion of this case of primary splenic lymphocyte-depletion Hodgkin's disease is a review of clinical, histologic, immunohistochemical, and gene-rearrangement characteristics of what can be defined as lymphocyte-depletion Hodgkin's disease. ",14 3292,"Alterations in brain electrical activity may indicate the onset of malignant hyperthermia in swine. The time course of changes in brain electrical activity during halothane anesthesia was examined in 12 malignant hyperthermia-susceptible (MHS) and 14 normal (nMHS) swine. Power densities in selected frequency bands were calculated from the electroen-cephalogram (EEG). EEG and systemic variables were determined over a period of 60 min after starting halothane (1% inspired). Malignant hyperthermia (MH) was triggered in all susceptible pigs. Initial changes in the EEG during development of MH consisted of a decrease in total power and a shift to lower frequencies (delta-theta activity) in all animals. These EEG alterations were noted when there was an increase in heart rate, but other systemic variables were still normal. EEG changes in all MHS animals started at an arterial oxygen tension (PaO2) greater than 90 mmHg and an arterial carbon dioxide tension (PaCO2) less than 50 mmHg. In 5 MHS animals EEG became isoelectric at a PaO2 of 61-82 mmHg and a PaCO2 of 53-68 mmHg. Mean arterial blood pressure at this time was 54-66 mmHg. To determine the effects of hypoxia on the EEG in 7 nMHS animals, oxygen was decreased over a period of 45-60 min to 7% inspired. In 7 other nMHS animals, hypercarbia was produced by admixture of carbon dioxide to the fresh gas supply to achieve incremental increases of PaCO2 to 110-120 mmHg. Significant EEG changes during hypoxia comparable to those seen at the onset of MH were noted at a PaO2 below 40 mmHg and during hypercarbia at a PaCO2 greater than 68 mmHg. ",22 2565,"Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis: its identification as sulfatide. Sera from patients with autoimmune chronic active hepatitis were found to contain IgG-class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid-phase enzyme-linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thin-layer chromatography and negative ion fast atom-bombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide-6-sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune-type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane. ",19 876,"Basis for defective proliferation of peripheral blood T cells to anti-CD2 antibodies in primary Sjogren's syndrome. Anti-CD2-induced T cell proliferation was analyzed in the peripheral blood samples of 31 primary and 8 secondary untreated Sjogren's syndrome patients. Anti-CD2-stimulated PBMC proliferation was very low in about one-third of primary Sjogren's syndrome samples, despite the number of CD2+ cells being similar in primary and secondary Sjogren's syndrome and normal PBMC samples. The depressed response to anti-CD2 was mainly found in anti-Ro+/La+ patients. Experiments on purified T cells demonstrated that a defect at the T cell level was responsible for the anti-CD2 unresponsiveness. Cell proliferation failure was associated with poor IL-2 and IL-2 receptor mRNA expression and, consequently, IL-2 and IL-2 receptor synthesis. Since defective anti-CD2-induced mitogenesis could be reversed by phorbol myristate acetate, but not calcium ionophore A23187, it is probably correlated with impaired protein kinase C activation. Comparison of anti-CD2-triggered PBMC proliferation in treated and untreated patients and a long-term study of nine patients showed that the defect is a stable characteristic in primary Sjogren's syndrome patients, but that it can be reversed by pharmacological immunosuppression. ",6 1240,"Fetal homotransplants (ventral mesencephalon and adrenal tissue) to the striatum of parkinsonian subjects. Fetal ventral mesencephalon and fetal adrenal tissue grafted to the caudate nucleus of four and three parkinsonian patients, respectively, have been shown to be an alternative treatment for the amelioration of the signs of the disease. The ventral mesencephalon patients had a significant amelioration of rigidity, bradykinesia, postural imbalance, gait disturbance, and facial expression. Three of these four patients have returned to work. The fatal adrenal group only showed amelioration of rigidity and bradykinesia. Though these patients are now able to perform their basic daily living activities, and one of them has renewed her household tasks, the other two have not yet been able to return to work. The differences observed between the ventral mesencephalon- and the fetal adrenal-transplanted patients may be related to the heterogeneity of their disease and/or the type of graft implanted. However encouraging our results may be, this experimental procedure obviously requires further studies, and should not be practiced outside of highly qualified clinical research centers. ",9 54,"A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease BACKGROUND. Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children. The capsular polysaccharide vaccine does not protect children at greatest risk (those under the age of 18 months), but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group. METHODS. We enrolled 114,000 infants in Finland in an open, prospective, randomized trial of a H. influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]). Children born on odd-numbered days were vaccinated at the ages of 3, 4, 6, and 14 to 18 months; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months. RESULTS. After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination, as compared with 64 cases in the control group, between the ages of approximately 7 and 24 months. The protective efficacy of the vaccine was thus 94 percent (95 percent confidence interval, 83 to 98). No serious adverse effects were reported. The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants. The primary immunization series resulted in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months, and the fourth dose evoked an anamnestic response, with a mean antibody concentration of 45.22 micrograms per milliliter. CONCLUSIONS. A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier (PRP-D), administered to infants beginning at the age of 3 months, is highly effective in protecting young Finnish children (7 to 24 months old) against invasive H. influenzae type b infections. ",0 1542,"The value of hysteroscopy in elderly women prior to in vitro fertilization-embryo transfer (IVF-ET): a comparative study. Two hundred eighty-four hysteroscopies were performed in 312 (91%) candidates for in vitro fertilization and embryo transfer (IVF-ET) who were divided into two groups. Group I consisted of elderly women over 40 years, and group II of women below this age. Although visualization revealed uterine abnormalities in 29.9% of all patients, abnormal findings were significantly increased in the former group in comparison to the latter (P less than 0.001). This difference was attributed mainly to uterine rather than cervical pathology. Furthermore, in elderly women age-related uterine pathology such as submucous myomata, endometrial hyperplasia, and polyps were more prominent, while in younger patients other uterine lesions such as adhesions and tubal ostia occlusion were more common. Moreover, treatment prior to IVF-ET resulted in 7 clinical pregnancies (8.9%) in group I and in 41 clinical pregnancies (19.9%) in group II, all of which failed in one to three cycles previously. It seems that hysteroscopic evaluation may reduce the IVF-ET failure rate due to intrauterine abnormalities in elderly as well as young patients, thus it becomes an absolute prerequisite for all patients scheduled for an IVF program. ",12 2121,"Effects of nicardipine, a calcium antagonist, on myocardial salvage and high energy phosphate stores in reperfused myocardial injury. The current study determined the effectiveness of nicardipine, a 1,4-dihydropyridine calcium antagonist, in preserving reperfused myocardium in a cat model of temporary coronary occlusion and ascertained if replenishment of myocardial phosphate stores during reperfusion as defined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was indicative of salvage. Twenty open chest, anesthetized cats were studied with use of a snare ligature around the proximal left anterior descending coronary artery, with a coil sutured to the epicardial surface overlying the distribution of the artery. Peak areas of phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP) NMR signals were measured during 1 h of occlusion followed by 1.5 h of reperfusion. Infarct size and jeopardy area were determined in vitro by simultaneous infusion of phthalocyanine blue dye and triphenyltetrazolium chloride into the aorta and the left anterior descending coronary artery, respectively, after 5 h of myocardial reperfusion. Nicardipine-treated and control groups had similar jeopardy area values (41.2 +/- 1.6% versus 47.4 +/- 3.1% of the left ventricle), but infarct area was significantly reduced in the nicardipine-treated group (3.2 +/- 1.1% versus 24.9 +/- 7.5% of jeopardy area, p less than 0.01). High energy phosphate compounds remained markedly altered during reperfusion in both groups. No significant improvement in phosphocreatine or inorganic phosphate recovery was observed in animals pretreated with nicardipine despite an 87% reduction in infarct size. Myocardial ATP was greater during reperfusion in the nicardipine-treated compared with the control group (average over initial 90 min of reperfusion 58 +/- 6% versus 46 +/- 3% of baseline values, p less than 0.05), suggesting improved recovery of ATP. However, the measured levels of high energy phosphate compounds during reperfusion and their ratios did not correlate with infarct size and thus were not predictive of myocardial salvage. ",13 1939,"No finding of increased myocardial ischemia during or after carotid endarterectomy under anesthesia with nitrous oxide. Nitrous oxide (N2O) has been implicated as a cause of myocardial ischemia. We investigated whether substitution of N2O for a portion of the anesthesia supplied by isoflurane increased myocardial ischemia in patients at risk for such ischemia. Seventy patients having carotid endarterectomies (63 patients) or other carotid surgery (seven patients) were prospectively, randomly assigned to an anesthetic regimen that included or excluded N2O. All other aspects of anesthetic management were similar, except for greater concentrations of oxygen and isoflurane in patients not given N2O. Perioperative monitoring for myocardial ischemia and infarction included 12- or 5-lead electrocardiography, transesophageal echocardiography, and creatine kinase isoenzyme levels. By transesophageal echocardiographic or electrocardiographic criteria, 44% of patients given oxygen but only 21% of those given N2O had myocardial ischemia intraoperatively (P = 0.065). Similarly, myocardial infarction, identified by changes in creatine kinase isoenzymes, occurred in only one patient given N2O but in three given oxygen (not significantly different). Thus we found no trend indicating a greater incidence of myocardial ischemia or infarction associated with the use of N2O. ",13 2284,"Management of onychomycosis with oral terbinafine. The safety and efficacy of oral terbinafine in the treatment of finger onychomycosis caused by Trichophyton rubrum were evaluated in an open study including 11 patients. Treatment consisted of 125 mg of terbinafine given twice daily for 6 months or until the infection cleared. At the end of the treatment period, all patients were clinically and mycologically normal, with the drug acting as a fungal barrier to prevent further distal fungal invasion into the nailplate. Mild gastric discomfort in one patient was the only side effect reported during this study. No laboratory abnormalities were detected. ",16 2711,"AIDS-related knowledge, sexual behavior, and condom use among men and women in Kinshasa, Zaire. This study was conducted in 1988 among a random sample of 6,625 men and women of reproductive age in all 24 administrative zones of Kinshasa, the capital city of Zaire, to determine existing levels of knowledge regarding AIDS (acquired immunodeficiency syndrome), sexual behavior, knowledge and use of condoms in marital and extramarital relations; perceived risk of AIDS, and attitudes toward testing for the human immunodeficiency virus (HIV). Awareness of AIDS is almost universal, and the vast majority know the four main modes of transmission. Almost half believed in transmission by mosquitoes and in a vaccine or cure for AIDS. The majority of male respondents knew of condoms, but negative attitudes toward condom use are widespread, and few respondents perceived them to play a central role in combatting AIDS. ",19 1989,"Iliac artery stenosis and occlusion: preliminary results of treatment with Gianturco expandable metallic stents. Ten patients with atherosclerotic stenosis or occlusion of the iliac artery were treated with Gianturco expandable metallic stents. In the five cases of stenosis, only balloon dilation was performed prior to placement of stents. The five patients with occluded arteries were given intraarterial infusions of urokinase before balloon dilation and stent placement. Clinical symptoms improved in all patients, and no technical failures or complications occurred. Doppler ankle-brachial index studies were performed in nine cases, and in all nine cases the indexes improved after stent placement. During follow-up of 2-18 months (mean, 10.3 months), all arteries remained patent. Follow-up angiograms showed slight intimal thickening and no restenosis. Long-term follow-up and more clinical experience will be necessary to evaluate the efficacy of this stent. However, preliminary results suggest that the Gianturco expandable metallic stent is of value in the treatment of arterial occlusive disease. ",13 905,"Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. In summary, these findings indicate the importance of designing future experiments that delineate between opioid and nonopioid forms of respiratory disease and dysfunction, and the need to identify means of diagnosing them in order to achieve successful recovery. Apparently there is great diversity between animal species in terms of contributions of endogenous opioids to tonic control of ventilation, and future work should strive to identify which species is most appropriate as a model of human ventilatory control and disease. Certain opioid receptor types appear to be linked to independent respiratory functions. For instance, mu receptors in the brain stem produce strong inhibitory actions on respiratory parameters, including RR, VT, VE, and CO2 sensitivity. These effects have been observed in vivo and by electrophysiologic recordings in vitro. Delta receptors may also exert some inhibitory effect on respiration, especially in the NTS. In the CNS, the ventral surfaces of the medulla and pons, especially the NTS and NA, seem to be important sites for opioid-induced inhibition of respiration, whereas the spinal cord probably is not involved in opioid-mediated ventilatory depression. Kappa receptors appear to be devoid of respiratory depressant activity, whereas sigma receptors may stimulate some ventilatory parameters. Morphine and similar pure mu agonists, such as fentanyl and oxymorphine, probably produce their analgesic and respiratory depressant effects through stimulation of mu receptors. Mixed agonists/antagonists that have mu antagonist (or partial agonist) activity plus kappa agonist and/or sigma agonist activity show a ceiling effect for respiratory depression. Future tests need to determine which opioid receptor may be responsible for the ceiling effect. In addition, the effects of mu, delta, kappa, and sigma selective agonists on hypoxic drive should also be determined, as a drug that stimulates hypoxic sensitivity in the face of hypercapnic depression may produce less overall respiratory depression due to counteractive effects. In the future, clinically optimal opiates should have more specificity of action than those available now. This may be achieved by creating drugs selective for single receptors or by creating drugs with desirable combinations of receptor selectivities. The combinations of mixed agonists/antagonists with pure mu agonists currently in use today are promising, as they provide analgesia with reduced respiratory depression. In the early days of opiate research and development, combination drug regimens were thoroughly tested to determine the ""ideal ratios"" that would retain analgesic properties but not the other undesirable effects such as respiratory depression (196).(ABSTRACT TRUNCATED AT 400 WORDS). ",7 974,"Utility of fiberoptic bronchoscopy in nonresolving pneumonia Although fiberoptic bronchoscopy (FOB) has been traditionally used to evaluate nonresolving pneumonia, its efficacy is unknown. We, therefore, reviewed FOB in 35 consecutive patients who had (1) a roentgenographic infiltrate, (2) cough, (3) either temperature greater than 38.1 degrees C, leukocytosis, sputum production, (4) symptoms present for at least ten days, and antibiotic therapy for at least one week. Known lung cancer and AIDS were excluded. Fiberoptic bronchoscopy was diagnostic in 86 percent (12/14) in whom a specific cause was found. No patient had endobronchial cancer. Two patients with nondiagnostic FOB and persistent systemic symptoms had open lung biopsy specimens showing Wegener's granulomatosis and bronchiolitis obliterans with organizing pneumonia (BOOP). Twenty-one patients with nondiagnostic FOB had no final diagnoses other than community-acquired pneumonia. We conclude that FOB is extremely useful in finding a specific diagnosis for a nonresolving pneumonia when a specific diagnosis can be made. Fiberoptic bronchoscopy was most likely to yield a specific diagnosis in nonsmoking patients with multilobar infiltrates of long duration and could have been avoided in older, smoking, or otherwise compromised patients with lobar or segmental infiltrates with no decrease in diagnostic yield in our series. ",7 3156,"Influence of the menstrual cycle on systemic diseases. Physiological changes associated with the menstrual cycle influence the clinical course of some diseases such as bronchial asthma, allergies, anaphylaxis, epilepsy, migraine, dermatoses, and porphyria. Hormonal manipulation can be beneficial in some patients. ",22 983,"Intraluminal irradiation for the palliation of lung cancer with the high dose rate micro-Selectron. Fifty patients with inoperable, symptomatic endobronchial carcinoma were treated by a single exposure of intraluminal radiotherapy. A high dose rate afterloading system (the micro-Selectron-HDR) was used to minimise radiation exposure for staff. Haemoptysis was relieved in 24 of 28 patients, breathlessness in 21 of 33 patients, and cough in nine of 18 patients. Radiological collapse resolved in 11 of 24 patients. Treatment was given on an outpatient basis and was well tolerated. Intraluminal radiotherapy appears to offer an effective alternative to conventional fractionated external beam radiotherapy. ",7 2725,"Naturally occurring HIV-1 isolates with differences in replicative capacity are distinguished by in situ hybridization of infected cells. Replication of human immunodeficiency virus type 1 (HIV-1) isolates in peripheral blood mononuclear cells (PBMC) has been studied by in situ hybridization using the riboprobe BH10-R3 from HTLV-IIIB. Two series of isolates were tested: (a) 20 isolates from individuals with varying severity of HIV-1 infection and (b) sequential isolates from 5 subjects showing signs of clinical progression over a 45 month observation period. The results show that HIV-1 isolates with distinct replicative capacity can be distinguished by the intensity of radioactive labeling over single infected cells after in situ hybridization. Sequential isolates from patients with clinically progressive HIV-1 infection show a gradual increase in replicative capacity over time. In PBMC cultures infected with such sequential isolates, intensity of radioactive label over single infected cells increases and is strongest with isolates obtained at the time of low CD4 counts in blood. The results suggest that the restriction of virus replication that operates in the early stages of HIV-1 infection is gradually lost with progression of the disease. ",19 1,"Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. We studied the infectious risk of different methods of managing vascular catheters during long-term use. Consecutive surgical ICU patients requiring triple lumen catheters, pulmonary artery catheters, or arterial catheters for greater than 7 days were prospectively randomized to one of three management groups: a) percutaneous (PERC) puncture with every 7-day catheter change at a new site, b) no weekly change (NWC) with a new site when changed, or c) guidewire exchange (GWX) with every 7-day catheter change at the same site. In all groups, a catheter change was mandatory for a positive blood culture, skin site infection, or sepsis without a likely source. Cultures were obtained when clinically indicated and at the time of every catheter change. Catheter-related sepsis (CRS) was defined as a positive blood culture and catheter culture with the same organism. A total of 112 patients met evaluation criteria. There were no intergroup differences in age, primary diagnosis, severity of injury or illness, number of study days, number of protocol violations, route of catheterization, number of catheters present/patient day, catheter sepsis rate, or bacteremia rate. The NWC group demonstrated an increased number of days/catheter, fewer catheter/subcutaneous tract segment cultures/patient, and a reduced incidence of catheter tip colonization. These results occurred in a setting where the number of CRS episodes/patient was 0.17 for GWX, 0.22 for PERC, and 0.16 for NWC. We conclude that there is no difference in infectious risk between these three methods of long-term catheter management. The method with the least complications and expense should be used. ",0 878,"Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin. We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient, indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals, because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase, catalase, or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18, the common beta-subunit of structurally related adhesion receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals, myeloperoxidase, and elastase. ",7 3071,"Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years. Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve-related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation. ",22 2702,"Putative tyrosine kinases expressed in K-562 human leukemia cells. Tyrosine phosphorylation is important in the transmission of growth and differentiation signals; known tyrosine kinases include several oncoproteins and growth factor receptors. Interestingly, some differentiated cell types, such as erythrocytes and platelets contain high amounts of phosphotyrosine. We analyzed tyrosine kinases expressed in the K-562 chronic myelogenous leukemia cell line, which has a bipotential erythroid and megakaryoblastoid differentiation capacity. Analysis of 359 polymerase chain reaction-amplified cDNA clones led to the identification of 14 different tyrosine kinase-related sequences (JTK1-14). Two of the clones (JTK2 and JTK4) represent unusual members of the fibroblast growth factor receptor gene family, and the clones JTK5, JTK11, and JTK14 may also belong to the family of receptor tyrosine kinases but lack a close relationship to any known tyrosine kinase. Each of these different genes has its own characteristic expression pattern in K-562 cells and several other human tumor cell lines. In addition, the JTK11 and JTK14 mRNAs are induced during the megakaryoblastoid differentiation of K-562 cells. These tyrosine kinases may have a role in the differentiation of megakaryoblasts or in the physiology of platelets. ",19 365,"Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. Previous studies in animals have demonstrated liposome-encapsulated doxorubicin (LED) has substantially less cardiac toxicity than free doxorubicin but retains antitumor activity. In a phase I clinical study of LED, the maximum tolerated dose was 90 mg/m2 and dose-limiting toxicity was considered to have been reached when granulocytopenia was produced. We used LED to treat 20 patients with advanced, measurable breast cancer. LED was given at doses of 60-75 mg/m2 every 3 weeks as an intravenous infusion. Regression of disease was objectively measured in nine patients; in five of these patients, complete regression of the index lesion occurred. The mean duration of the responses was 7 months. Hematologic toxicity consisted of grade 1-2 leukopenia in some patients. Gastrointestinal toxicity and mucositis were generally mild and tolerable. Alopecia occurred in all patients and usually was complete. Twelve patients received cumulative doses of LED of greater than 400 mg/m2 and were evaluated with radionuclide ventriculograms. In eight patients, the cumulative dose was greater than 500 mg/m2, and five had endomyocardial biopsies. Four of these biopsy results were Billingham grade 0, while one (cumulative LED dose, 750 mg/m2) showed grade 1 changes with mild myofibrillar loss and dilatation of the sarcoplasmic reticulum involving less than 5% of cardiac myocytes. Two patients had decreases in left ventricular ejection fraction. One of these patients had received a total dose of LED of 630 mg/m2 and had a decline of 13% in left ventricular ejection fraction, but had no clinical evidence of congestive heart failure and had a Billingham grade 0 endomyocardial biopsy. ",3 1547,"Flow patterns in dilated cardiomyopathy: a pulsed-wave and color flow Doppler study. In 48 patients with dilated cardiomyopathy, pulsed-wave and color Doppler examination were performed. In addition, 14 normal patients served as control subjects. Peak inflow velocity at the level of the mitral valve, middle left ventricle, and apex and outflow velocity at the level of the apex, middle left ventricle, and subaortic area were measured. In normal patients there was brisk propagation of inflow velocity to the apex. Patients with dilated cardiomyopathy demonstrated delayed propagation and prolongation of the duration of inflow compared with control subjects (p less than 0.04). Continuous apical flow was visualized in 25% of dilated cardiomyopathies and in no normal patients. Apical velocities were significantly increased in cardiomyopathies with significant mitral regurgitation. Outflow velocities were decreased in dilated cardiomyopathy. In patients with dilated cardiomyopathy and apical dyskinesis, flow directed toward the base was measured in the middle left ventricle during isovolumic relaxation secondary to dyskinetic rebound. Patterns of abnormal flow in dilated cardiomyopathies are readily apparent by color M-mode and two-dimensional color Doppler. ",13 49,"Tumor necrosis factor-alpha plays a role in host defense against Histoplasma capsulatum. Tumor necrosis factor-alpha was detected in supernatants collected from BALB/c mouse peritoneal macrophages incubated continuously with Histoplasma capsulatum. The levels of TNF alpha measured by actinomycin D bioassay peaked within hours after exposure and then greatly declined by 24 h. TNF alpha was also measured in bronchoalveolar lavage fluid from BALB/c mice challenged intranasally with H. capsulatum. Lavage fluid TNF alpha levels exhibited the same pattern as the in vitro supernatants; they peaked within hours after challenge and lower levels were detected at 24 h. Treatment of mice with anti-TNF alpha antibody accelerated mortality in response to systemic infection and significantly increased tissue colony counts in the liver and spleen. In the murine model, TNF alpha is produced in response to H. capsulatum and appears to play some role in host defense to infection. ",0 763,"Rosacea and ulcerative colitis: a possible association. Although rosacea was formerly believed to be associated with gastrointestinal upsets, no one any longer finds a significant association between rosacea and the intestinal tract. We describe four patients with a combination of ulcerative colitis and rosacea. In all four, ulcerative colitis preceded the onset of severe papulopustular rosacea, and we therefore feel that the severity of rosacea could have been due to the associated bowel disorder. In one, the severity and poor initial response of rosacea to treatment was clearly related to the activity of the ulcerative colitis, and the rosacea improved only after proctocolectomy. While it is possible that this purported association is fortuitous, we report these cases in the hope that others may have seen this combination of diseases, to our knowledge previously unreported. ",5 647,"Gallium nitrate for advanced Paget disease of bone: effectiveness and dose-response analysis. OBJECTIVE: To evaluate whether a brief course of treatment with gallium nitrate can reduce biochemical parameters of accelerated bone turnover in patients with advanced Paget disease. DESIGN: Unblinded trial, decreasing dose schedules of gallium nitrate. SETTING: University hospital with primary orthopedic and metabolic bone disease specialty. PATIENTS: Ten patients with advanced Paget disease who had previously received conventional therapy consisting of calcitonin, etidronate, or mithramycin. INTERVENTIONS: Five patients were entered into each of three dose schedules: 2.5 mg/kg body weight per day by continuous intravenous infusion for 7 days; 0.5 mg/kg per day for 14 days by subcutaneous injection; and 0.25 mg/kg per day for 14 days by subcutaneous injection. Several patients were treated with different dose schedules. Patients were followed until relapse. RESULTS: Fifteen courses of treatment were administered to ten patients. Reductions in serum alkaline phosphatase and urinary hydroxyproline excretion were observed after treatment with each dose schedule. After treatment with high, intermediate, and low doses, the median maximum decreases in serum alkaline phosphatase activity were 49%, 39%, and 18%, respectively. The median maximum decreases in urinary hydroxyproline excretion were 50%, 52%, and 16%, respectively. The maximum decrease in urinary hydroxyproline excretion occurred within a median of 2 weeks from the start of treatment, whereas the maximum decrease in serum alkaline phosphatase activity occurred substantially later at a median of 6 weeks. All treatment schedules were well tolerated. Response duration was highly variable (range, 6 to 42 weeks). CONCLUSIONS: Short-term treatment with gallium nitrate can reduce biochemical parameters of disease activity in patients with advanced Paget disease of bone. Larger trials using low-dose intermittent treatment schedules are required to evaluate the safety and effectiveness of this therapy. ",4 1839,"Efficacy of propafenone in preventing ventricular tachycardia: inverse correlation with rate-related prolongation of conduction time The efficacy of propafenone in preventing induction of ventricular tachycardia was evaluated in 25 consecutive patients (mean age 62 +/- 8 years) with remote myocardial infarction who underwent programmed electrical stimulation for ventricular arrhythmia using up to three extra-stimuli after basic drive at the right ventricular apex. In nine patients (Group A), propafenone prevented induction of sustained ventricular tachycardia (noninducible in four, nonsustained [less than 30 s] in five). In the other 16 patients (Group B), sustained ventricular tachycardia was still inducible; in 11 of the 16, the tachycardia configuration was unchanged but the cycle length was significantly longer (431 +/- 99 versus 284 +/- 44 ms, p less than 0.001). Propafenone did not significantly affect either sinus cycle length or AH and HV intervals. However, it prolonged QRS duration during sinus rhythm equally in both groups of patients. With ventricular pacing, propafenone also prolonged right ventricular effective and functional refractory periods and surface QRS duration. There was greater lengthening of the paced surface QRS duration when drug therapy was ineffective (for example, +35 +/- 12 ms in Group A versus +69 +/- 23 ms in Group B at a basic drive of 400 ms, p less than 0.01). Drug-induced prolongation of a paced QRS complex greater than 40 ms had a 94% positive predictive value for drug failure to prevent induction of ventricular tachycardia. Drug-induced percent prolongation of ventricular tachycardia cycle length in Group B did not correlate well with percent QRS prolongation. ",13 1650,"Transient left ventricular filling abnormalities (diastolic stunning) after acute myocardial infarction. A variety of experimental studies suggest that diastolic left ventricular (LV) function changes after acute myocardial infarction (AMI), but limited data exist on these changes in humans. To assess diastolic filling after AMI, 60 patients underwent Doppler echocardiographic examination within 24 hours of AMI. Of 54 patients who also underwent catheterization, 45 (83%) were successfully reperfused. A subgroup of 17 patients underwent a follow-up Doppler examination at 7 days after infarction, whereas 15 patients with stable exertional angina served as control subjects. There was no significant difference in age, gender, incidence of systemic hypertension or diabetes mellitus, heart rate, mean arterial pressure or severity of coronary artery disease between the infarct and control groups. The infarct group had a lower velocity time integral total (9.9 +/- 0.4 cm vs 12.0 +/- 0.9 cm, p less than 0.001), a lower velocity time integral E (5.8 +/- 0.3 cm vs 6.8 +/- 0.5 cm, p less than 0.01) and a lower velocity time integral 0.333 (3.5 +/- 0.4 cm vs 6.1 +/- 0.5 cm, p less than 0.01) than the control group. In addition, velocity time integral A/total was significantly greater in the infarction group (0.44 +/- 0.03 vs 0.35 +/- 0.04, p less than 0.01) compared to the control group. The follow-up subgroup showed an increase in velocity time integral total (p less than 0.01), velocity time integral E (p less than 0.05) and velocity time integral 0.333/total (p less than 0.05) over the first 7 days after infarction. The final recovery values at 7 days were not significantly different from those of the coronary artery disease group. ",13 3038,"Cochlear implant flap complications. In a series of 52 patients who received cochlear implants, 4 patients suffered flap complications (7.7%). The problems encountered involved the postauricular flap and were usually minor in nature. None required explantation as a direct result of these complications. Flap ischemia in a patient with Cogan's syndrome and vasculitis, two cases of suture extrusion with one having exposure of the implant, and a case of receiver unit magnet extrusion repaired with a vascularized pericranial flap based upon temporalis muscle are presented. Flap design in patients who have had postauricular incisions demands special consideration. Principles useful for avoiding complications as well as their management are discussed. ",22 1287,"Possible significance of cilioretinal arteries in low-tension glaucoma. Cilioretinal arteries arise from the short posterior ciliary artery circulation or directly from the choroidal circulation. The presence of a cilioretinal artery may in compromised discs steal flow from the peripapillary circulation and account for worsening glaucoma damage. We reviewed the records of 33 patients with unilateral cilioretinal arteries admitted for investigation of low-tension glaucoma. We looked for absolute difference between the affected and unaffected eyes as well as percent difference relative to the mean value for the two eyes and to the value for the unaffected eye in the following variables: mean defect, corrected loss variance or corrected pattern standard deviation, and adjusted neuroretinal rim area. No statistically significant differences were found. The mean disc area for the eyes with cilioretinal arteries was significantly larger than that previously reported for normal eyes. The results suggest that if vascular steal exists because of the presence of this artery, it is not of major clinical importance. ",10 2700,"Care of the infant born exposed to human immunodeficiency virus. The expanding epidemic of HIV infection in reproductive-age women, the availability of antiretroviral therapy for children, and recommendations for increased case identification activities augur a time when more and more pediatricians are going to be called on to care for HIV-exposed infants. This article outlines a comprehensive medical framework for the care of these children from the labor and delivery setting to the nursery, outpatient clinic, and the emergency room. It includes issues of infection control; medical, developmental, and psychosocial care; and laboratory evaluations. Finally, it address the need for long-term follow-up of all children born exposed to HIV. ",19 343,"Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature. ",3 2047,"Can heart failure be prevented, delayed, or reversed? A review of the clinical course of chronic heart failure demonstrates that current outcomes remain highly unsatisfactory both in mortality and perhaps more important in morbidity. The extraordinary satisfactory functional responses seen in patients who undergo cardiac transplantation clearly identify the primary cause as the status of the heart itself, whatever the pathophysiologic adjustments of the neuroendocrine system, and interventions of the wide variety of drugs. Since donor hearts are unlikely to be available even from younger sufferers of these clinical syndromes, prevention must be the hallmark. Protection of the viability of myocytes, such as in acute myocarditis and acute infarction, is essential. Myocardial collagen undergoes continual synthesis, and production is greatly stimulated in the presence of hypertrophy caused by increased wall stress. It is possible that excess collagen is intimately involved with diastolic ventricular dysfunction, but that this may be a reversible process if the collagen-producing stimulus is removed. Thus reduction in wall stress and reversibility of ventricular hypertrophy appear to be promising directions. However, to limit the catastrophic effects of chronic heart failure, early recognition of the precursors of these syndromes, prevention of progression, and surgical intervention in valvular heart disease at an optimal point in time are essential. ",13 2604,"Non-Hodgkin's lymphoma in the elderly. I. Pathologic features at presentation. The pathologic findings of 118 patients aged 70 years or older with non-Hodgkin's lymphoma (NHL) are reported. These patients formed 27.2% of 433 consecutive cases of NHL seen in a single institution over a 5-year period. Thirty-one of 433 NHL cases were histologically not classified, whereas the remaining 402 could be classified according to the International Working Formulation (WF) of NHL for clinical usage. Immunophenotypic analyses were carried out in 112 NHL cases; of this group 28 were NHL in elderly patients. Of the 95 elderly NHL that could be classified in the histologic categories of the WF 28 cases were in the low-grade, 41 in the intermediate-grade, and 26 in the high-grade categories. Eighty-one cases had diffuse histologic types and 14 had follicular/nodular histologic types. Thirty-five cases were of the G (diffuse large cell) + H (large cell, immunoblastic) categories. No significant differences in the prevalence of the different subtypes were observed among patients younger or older than 70 years. Immunohistologically, most NHL cases in the elderly expressed B-cell phenotype. Sixty-two NHL in the elderly were extranodal at presentation. The results of this study indicate that elderly patients form a relevant proportion of patients developing NHL and thereby present a very difficult management problem. The pathologic features of NHL in the elderly does not differ significantly from those of their younger counterparts, although an increase in diffuse versus follicular histologic patterns, and in extranodal versus nodal disease was observed with advancing age. ",19 1717,"Liver transplantation with atrioatrial anastomosis for Budd-Chiari syndrome. We report the case of a young woman with Budd-Chiari syndrome in whom mesentericoval shunt was first performed, followed by transcaval liver resection and hepatoatrial anatomosis 3 years later. Liver transplantation became necessary 5 years later because of deterioarating liver function with portal hypertension and bleeding. Successful transplantation was performed with atrioatrial anastomosis with help of cardiopulmonary bypass, simplifying considerably the technical procedure and reducing dramatically blood loss. ",13 1705,"Underestimation of treatment effect in crossover trials. In crossover trials each subject serves as his own control. For the study of cardiovascular diseases such as hypertension and angina pectoria, properly designed crossover studies are preferred to parallel studies. There is a considerable between-subject variability of symptoms in some of these conditions. Bias due to this is eliminated by the use of a crossover design. However, a problem is the so-called treatment-by-period interaction. The present study analyzes the potential influences of this on the outcome of the trial. Physical carryover effect, defined as a physical effect of the first treatment period carrying on into the second, tends to minimize differences between two consecutive treatment periods. So does the frustrating experience of an inactive agent in the first treatment period. Outside influences such as the change of the seasons may affect lengthy crossover trials in a similar way. The author concludes that the treatment effect in a crossover trial tends to be underestimated. The current concept that reports of clinical trials are generally biased toward an exaggeration of treatment effects does not seem to apply to crossover trials. ",13 3023,"Sudden unexpected nocturnal death syndrome in the Mariana Islands. Sudden unexpected nocturnal death syndrome (SUNDS) is a distinct clinical entity in previously healthy, young, Southeast Asian males. It is well known in the Philippines and more recently recognized in the U.S. by nonspecific autopsy findings, with no evidence of underlying disease and absence of toxic drug or alcohol levels. In 1973-89, 14 cases of apparent SUNDS came to coroner's autopsy in the Commonwealth of the Northern Marianas (CNMI) and Guam. All 14 cases, with the exception of one Yapese, were previously healthy, male Filipinos, aged 23 to 55, who were either found dead in bed, or described by their colleagues as having nocturnal seizure activity consisting of gurgling, frothing, and tongue biting immediately prior to death. Autopsy findings showed no anatomic findings to account for death. Comprehensive serum and urine drug analyses were negative. All decedents showed absence of significant atherosclerosis or grossly detectable structural cardiac anomaly, while four showed cardiomegaly. Migrants from Southeast Asia carry with them a pre-disposition to this syndrome, which appears to decline with longer residence in the new country. The mechanism of death in SUNDS is believed to be ventricular fibrillation, possibly precipitated by sudden sympathetic discharge. Studies suggest at least some deaths may be associated with an abnormal cardiac conduction system. Acute pancreatitis has been a finding in some series, but not our cases. Why the condition is virtually limited to males and seemingly sleep-triggered, has not been adequately explained. Stress and depression are believed to be predisposing factors. ",22 2192,"William Glenn lecture. The cavopulmonary shunt. Evolution of a concept. A bold and imaginative development, the cavopulmonary anastomosis, appeared to originate in several centers almost simultaneously. After extensive research on right heart bypass, Glenn was the first in North America to perform a successful experimental cavopulmonary shunt, and it became known by his name. In properly selected patients, palliation success was excellent, and mortality rates were low. From 1961 through 1988, we used a cavopulmonary anastomosis for palliation in 139 infants and children. There were eight hospital deaths, and most occurred early in the series. Palliation generally lasted 6-8 years-until the child outgrew the blood supply to the contralateral lung. Palliation could be restored by increased flow to that lung with another shunt. Six otherwise inoperable patients received benefit from the addition of an axillary arteriovenous fistula. Late pulmonary arteriovenous fistulas were identified in 11% of our patients by angiography, but with more sensitive testing, the incidence rate may be as high as 21%. The occurrence of pulmonary arteriovenous fistulas caused general concern and less frequent use of the shunt. Recent application of an end-to-side anastomosis, creating a bidirectional shunt, has restored interest. A major legacy of the cavopulmonary anastomosis was demonstration of the feasibility of partial right heart bypass, which paved the way for the Fontan operation, and it is frequently constructed as part of that operation. Currently, the Glenn shunt is most often used as a temporary or permanent alternative to a Fontan repair if there appears to be significant risk. The risk factors usually encountered include small pulmonary arteries, young age, poor ventricular function, atrioventricular valve incompetence, and myocardial hypertrophy-sometimes alone but often in combination. ",15 1056,"Spectral electroretinography in thioridazine toxicity. In three patients with thioridazine toxicity, the electroretinogram (ERG) to red light was found to be below the average normal range. A significant increase in its amplitude appeared with cessation of therapy in two cases. A further deterioration of the ERG amplitude to all stimulus conditions (white, blue, and red lights) occurred when the dose of the medication was increased in the third patient. ",9 1487,"Hyperemesis gravidarum as conversion disorder. Psychosocial factors have long been believed to be important in the pathogenesis of emesis gravidarum (morning sickness) and hyperemesis gravidarum (HG). Although this has been confirmed during extensive studies over the last 30 years, HG has never been described as a conversion reaction. We describe two women presenting with hyperemesis who clearly fulfill diagnostic criteria for conversion. We suggest that strong psychodynamic conflicts are expressed by this potentially dangerous symptom in a subset of individuals and that dynamic interventions have a role in treating certain patients with HG. ",12 2170,"Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. A membrane-bound cytochrome b, a heterodimer formed by a 91-kD glycoprotein (heavy chain) and a 22-kD polypeptide (light chain), is an essential component of the phagocyte NADPH-oxidase responsible for superoxide generation. Cytochrome b is absent in two subgroups of chronic granulomatous disease (CGD), an inherited disorder characterized by the lack of oxidase activity. Mutations in the cytochrome heavy chain gene, encoded by the CYBB locus in Xp21.1, result in the X-linked form of CGD. A rare subgroup of autosomal recessive CGD also lacks cytochrome b (A- CGD), but the genetic defect has not previously been identified. In order to search for possible mutations in the cytochrome light chain locus, CYBA, the structure of this gene was characterized. The CYBA locus was localized to 16q24, and the approximately 600-bp open reading frame determined to be encoded by six exons that span approximately 8.5 kb. Three unrelated patients with A- CGD were studied for evidence of mutations in the light chain gene. One patient, whose parents were first cousins, was homozygous for a large deletion that removed all but the extreme 5' coding sequence of the gene. The other two patients had a grossly normal light chain transcript on Northern blot of mononuclear cell RNA. The light chain transcript was amplified by the polymerase chain reaction and sequenced. One patient was a compound heterozygote for two alleles containing point mutations in the open reading frame that predict a frame shift and a nonconservative amino acid replacement, respectively. The second patient, whose parents were second cousins, was homozygous for a different single-base substitution resulting in another nonconservative amino acid change. These results indicate that A- CGD can results from defects in the gene encoding the 22-kD light chain of the phagocyte cytochrome b. ",14 1632,"Hypertensive heart disease: relationship of silent ischemia to coronary artery disease and left ventricular hypertrophy. ECG evidence of silent ischemia occurs commonly in patients with systemic hypertension, but its relationship to left ventricular hypertrophy (LVH), large-vessel coronary artery disease (CAD), and neurohumoral factors remains unclear. Accordingly we validated the results of the echocardiographic method used to measure left ventricular (LV) mass in the Soviet Union by comparison with necropsy measurements in 30 patients, and we examined the relationships in 46 men with essential hypertension among ST segment depression during ambulatory monitoring, exercise stress and transesophageal pacing (n = 38), and LV mass, catheterization evidence of CAD (n = 25), and neurohumoral factors (plasma catecholamines and platelet aggregability). Echocardiographic measurements of LV mass by both the Soviet and Penn methods were closely correlated with necropsy values (r = 0.78 and 90, respectively; both p less than 0.001). During ambulatory monitoring from 1 to 17 episodes of greater than or equal to 1 mm ST depression occurred in 26 of 46 (65%) patients with hypertension; ischemia was also provoked by exercise or pacing stress in most but not all of these patients (65% and 80%, respectively). Neither ST depression nor the occurrence of additional episodes of symptomatic angina was related to the presence of coronary obstruction at catheterization; patients with and without ST depression did not differ in age, blood pressure, or LV mass. ",13 2938,"Reporting of occupational injury and illness in the semiconductor manufacturing industry. In the United States, occupational illness and injury cases meeting specific reporting criteria are recorded on company Occupational Safety and Health Administration (OSHA) 200 logs; case description data are submitted to participating state agencies for coding and entry in the national Supplementary Data System (SDS). We evaluated completeness of reporting (the percentage of reportable cases that were recorded in the company OSHA 200 log) in the semiconductor manufacturing industry by reviewing company health clinic records for 1984 of 10 manufacturing sites of member companies of a national semiconductor manufacturing industry trade association. Of 416 randomly selected work-related cases, 101 met OSHA reporting criteria. Reporting completeness was 60 percent and was lowest for occupational illnesses (44 percent). Case-description data from 150 reported cases were submitted twice to state coding personnel to evaluate coding reliability. Reliability was high (kappa 0.82-0.93) for ""nature,"" ""affected body part,"" ""source,"" and ""type"" variables. Coding for the SDS appears reliable; reporting completeness may be improved by use of a stepwise approach by company personnel responsible for reporting decisions. ",20 1075,"Does primary fibromyalgia exist? Twenty-one of 25 consecutive primary fibromyalgia or fibrositis patients, identified during a 5-year period in a tertiary care day-ward for pain syndromes, were re-examined. Fifteen fulfilled criteria for fibromyalgia but unexpectedly, all cases had either psychiatric disturbance or thyroid dysfunction. Of the four patients not seen at follow-up, two had developed neurological diseases, another rheumatoid arthritis and one other hypothyroidism. Thus, after 5 years no patient fulfilled the criteria for primary fibromyalgia. Women occupied as manual workers were over-represented. Most patients reported beneficial effects of physiotherapy. None of the patients has been able to return to full time work. ",9 1861,"The costs of prevention. A prevention program is cost-effective if it yields more health benefits than do alternative uses of health care resources. Some prevention programs meet this standard: either they actually save more health care resources than they utilize, or their net costs per healthy year of life gained are lower than those of alternatives such as curative or palliative medicine. Other prevention programs, however, are less cost-effective than are medical treatments for the same disease. One lesson for public policy is that generalizations about the cost-effectiveness of ""prevention"" are unwise. Another lesson is that prevention programs should not be subjected to a higher standard than other health programs: they should not be expected to save money, but they should be expected to yield improved health at a reasonable price. ",13 3108,"Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion. We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max. ",22 2913,"Removal of blunt foreign bodies from the esophagus. Historically, removal of blunt foreign bodies from the esophagus by esophagoscopy under general anesthesia has been considered to be relatively safe and effective. In recent years, alternative techniques of blind removal with balloon catheters or bougies have been advocated. This paper reports 246 esophagoscopies performed over a 19-year period to remove blunt esophageal foreign bodies. Eighty-one percent of the foreign bodies were coins and 74% were in children under 3 years of age. There were no deaths, no perforations, and no instances of mediastinitis. The only complications encountered were those due to esophageal erosion and/or respiratory problems secondary to long-standing foreign bodies. In the author's opinion, esophagoscopy is the best method for removal of all esophageal foreign bodies. There simply does not seem to be a need for alternative methods involving blind removal. ",20 1035,"Anencephaly: clinical determination of brain death and neuropathologic studies. Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation. ",9 181,"Mucinous adenocarcinoma of the submandibular gland. A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported. The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes. Histopathologically, cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern. Many cystic spaces surrounded by tumor cell strands were seen, mucus substance filled in the cystic spaces, and the tumor cells seemed mucus-secreting, but neither epidermoid cells nor papillary appearance could be observed. Electromicroscopically, numerous mucous droplets of low electron density were prominent in the cytoplasm, and the tumor cells had sparse irregular microvilli on the luminal surface. Mucin histochemistry, including paradoxical concanavalin A staining, revealed that the tumor cells contained neutral and acid mucins, and these were identified as class II and III mucosubstances. No other neoplastic lesion, except recurrent metastatic neck nodes, has been detected 6 years after the first examination, and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland. ",3 2359,"Sulfonylureas. Why, which, and how? Although controversies remain as to the usefulness of sulfonylureas, most evidence is in favor of their use in many if not patients with non-insulin-dependent diabetes mellitus. When used properly, sulfonylureas improve insulin secretion and action, and these effects may be maintained for years. If combined with hypocaloric dietary regulation, rapid- and short-acting sulfonylureas may help patients reach and maintain euglycemia without provoking chronic hyperinsulinemia or weight increase. There is no evidence that sulfonylurea treatment causes beta-cell exhaustion; instead, the antihyperglycemic effect helps improve beta-cell function. Sulfonylurea ""failures"" are often dietary failures or may be due to late introduction of these drugs, i.e., when beta-cell function is already attenuated. Desensitization of the insulinotropic effect of sulfonylureas may occur but might be avoided by discontinuous (less than 24 h/day) sulfonylurea exposure, i.e., once-daily administration of a short-acting sulfonylurea in a moderate dose. The most important adverse effect of sulfonylureas is long-lasting hypoglycemia, which may lead to permanent neurological damage and even death. This is mainly seen in elderly subjects who are exposed to some intercurrent event, e.g., acute energy deprivation or a drug interaction, i.e., aspirin. Long-acting sulfonylureas may be more likely to promote long-lasting hypoglycemia. The dose-response relationships of sulfonylureas have been poorly investigated, and sulfonylurea therapy should always be initiated and maintained at the lowest possible dose. ",17 1506,"Continuous or interrupted fascial closure: a prospective evaluation of No. 1 Maxon suture in 402 gynecologic procedures. During a 14-month period of using a long-term absorbable suture (No. 1 Maxon), 402 patients were entered into a prospective, randomized trial of fascial closure. Patients were randomized between a continuous closure (201 patients) and an interrupted en bloc (201 patients) technique. Each patient was subjected to a preoperative and intraoperative protocol for wound management. There were no acute wound failures. Wound infection rates and risk of hernia were not apparently affected by closure technique. ",12 3171,"Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions. The c-myb protooncogene codes for a sequence-specific DNA-binding protein that appears to act as a transcriptional regulator and is highly conserved through evolution. The DNA-binding domain of Myb has been shown to contain three imperfectly conserved repeats of 52 amino acids that constitute the amino-terminal end. Within each repeat, there are three tryptophans that are separated by 18 or 19 amino acids and are flanked by basic amino acids. To determine the role of tryptophans and the flanking basic amino acids in the DNA-binding activity of Myb proteins, we have selectively mutagenized individual tryptophans as well as some of the amino acid residues that flank these tryptophans. Replacement of these tryptophans with glycine, proline, or arginine abolished the DNA-binding activity whereas replacement with other aromatic amino acids or leucine or alanine did not appreciably affect this activity. On the other hand the replacement of two amino acids, asparagine and lysine, that flank the last tryptophan with acidic amino acids completely abolished their DNA-binding activity. These results are consistent with a model we present in which the tryptophans form a hydrophobic scaffold that plays a crucial role in maintaining the helix-turn-helix structure of the DNA binding domain. Basic and polar amino acids adjacent to these tryptophans seem to participate directly in DNA binding. ",22 2456,"Physical growth and development of children with type 1 glycogen-storage disease: comparison of the effects of long-term use of dextrose and uncooked cornstarch. Thirteen patients with type 1 glycogen-storage disease (GSD-1) were studied to compare the effects on biochemical control and growth of 2 y of therapy with intermittent feedings of uncooked cornstarch (UCS) at the fasting glucose production rate and therapy with continuous overnight glucose (COG) and dextrose feedings during the day. Mean biochemical abnormalities for the groups were minimized but not normalized by either COG or UCS. Growth progressed normally when COG was started by 1.2 y of age and normal growth rate was maintained by UCS. Weight increased from 101 +/- 3% ideal body weight at onset of COG to 127 +/- 5% during COG and the first year of UCS therapy but did not increase further in the second year. When growth failure occurred before onset of COG [-3.7 SD score for chronological age (SDSCA)], only partial correction (-1.9 SDSCA) to genetic potential for height occurred. Intermittent feeding of UCS provides an effective alternative to COG for the treatment of GSD-1. ",17 1462,"Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma. We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma. ",12 2815,"Continuous suprascapular nerve block for analgesia of scapular fracture. Fracture of the scapular is uncommon but painful. A case is described in which a comminuted scapular fracture was treated with a continuous suprascapular nerve block. With the patient lying supine an epidural needle was directed towards the scapular notch via a superior approach and an epidural catheter was placed when the notch was believed to have been identified. Repeat injections of 10 ml bupivacaine 0.25 per cent with 1/200,000 epinephrine provided analgesia within minutes and a duration of 8-10 hr. Injection of 10 ml radio-opaque dye demonstrated the catheter to be lateral to the scapular notch. However, dye dispersed throughout the supraspinous fossa including the scapular notch thus blocking the suprascapular nerve. This case demonstrates that continuous suprascapular nerve block can be performed for five days and that location of the scapular notch is less important than previously thought. ",20 1433,"Chronic nightly tidal peritoneal dialysis. Nightly tidal peritoneal dialysis (NTPD) is a technique in which, after an initial fill of the peritoneal cavity, only a portion of dialysate is rapidly cycled. Five anuric, stable, PD patients entered a 4 month study to determine the NTPD session length necessary for clinically adequate dialysis and creatinine clearance similar to those on four daily 2 L CAPD exchanges. NTPD was performed using a modified PAC-X-2 cycler, with the drain phase regulated by a target volume. One patient completed 3.5 months of study, one 4 months, three 6 months, and one patient each continued on NTPD for 13, 14, and 32 months. The mean NTPD session time was 9 hr 24 min (range 8 hr 35 min to 9 hr 55 min) at the end of 4 months. All patients had clinically adequate dialysis. Three patients preferred NTPD over CAPD, particularly because of an empty abdomen during the daytime. One patient required an increase in NTPD time, and an addition of one daytime exchange, because of low creatinine clearance. In conclusion, NTPD provides weekly creatinine clearances comparable to CAPD, with an acceptable duration of nightly dialysis sessions in most anuric patients. A new PD machine providing inexpensive dialysis solution in large quantities, as well as safe and false alarm free dialysis sessions, is needed for practical NTPD implementation. ",11 708,"Gallbladder mucin as a pronucleating agent for cholesterol monohydrate crystals in bile. Mucin is a densely glycosylated macromolecule secreted by the gallbladder epithelium as the principal constituent of gallbladder mucus. Hypersecretion of gallbladder mucus occurs in response to a lithogenic diet in experimental animals, and mucus accumulates as a viscous gel within the gallbladder lumen before gallstone formation. In both animals and man, the initial stage of cholesterol gallstone formation, the nucleation of cholesterol monohydrate crystals, occurs within the mucus gel. Inhibition of mucus secretion with aspirin prevents gallstone formation in the cholesterol-fed prairie dog, indicating the importance of mucus in gallstone formation. Mucin contains domains that bind cholesterol and lecithin transported as vesicles in supersaturated bile. Furthermore, mucin accelerates the nucleation of cholesterol crystals in both supersaturated model and native biles. Binding of cholesterol-enriched vesicles to hydrophobic domains on the mucin protein core appears to be critical for the acceleration of cholesterol crystal nucleation by mucin. Further study of the structure and function of gallbladder mucin should help to elucidate the pathogenesis of cholesterol cholelithiasis. ",5 706,"Biliary cholesterol transport and precipitation: introduction and overview of conference. Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this ""maturation"" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed. ",5 1173,"The use of obstetric analgesia in Sweden 1983-1986 The use of obstetric analgesia was investigated in a Swedish population-based prospective study of 335,207 births, which represents almost all women who had vaginal deliveries in Sweden between 1983 and 1986. Lumbar epidural analgesia (EDA) was used in 16%, paracervical block (PCB) in 12%, pethidine or morphine in 49% and pudendal block in 62%. All four types of analgesia were much more commonly used by nulliparae than multiparae. Variables such as maternal age, smoking, nationality, relationship with the infant's father and gestational age had only moderate influence on the rates of different types of analgesia. EDA and PCB were more frequently used in larger than in smaller hospitals and in the daytime than at night. No such differences were found for pethidine or morphine, or pudendal block, which were administered routinely by midwives. ",9 3195,"Recombination between two 14-bp homologous sequences as the mechanism for gene deletion in factor IX Seattle 1. Factor IXSeattle 1 is a 10-kb intragenic deletion identified in a family that has hemophilia B. By sequencing across the site of the deletion, we discovered at the deletion junction a 13-bp sequence (5' . . . TAGAA-GTTCACTT . . . 3') that was homologous to two 14-bp sequences 10 kb apart in introns D and F of the normal factor IX gene. The presence of these homologous sequences in two different regions of the normal gene allows us to propose that genetic recombination has occurred between the sequences, resulting in the gene deletion. The precise recombination site was able to be localized to one of 5 bp (5' . . . AGTTC . . . 3') in the middle of the homologous sequences. The exact length of the deletion is 10,000 bp. ",22 3334,"Functional heart replacement with the spindle pump: first results. The spindle pump is a nonpulsatile blood pump with a double function, i.e., it works centrifugally and represses simultaneously. The first experiences with this type of pump used as a biventricular assist device in four short-term animal experiments (up to 13 hours) are described. It can be demonstrated that in cases of a normally beating heart, this BVAD decompresses both ventricles by 60-70%, while the aortic pressure is slightly increased; on the other hand, in case of ventricular fibrillation, the BVAD with two spindle pumps maintained the entire circulation, at an arterial pressure between 80 and 90 mmHg with a flow volume between 3.5 and 4 L/min. ",22 82,"Postneonatal mortality in Norway: a study of recent trends and comparison with other mortality rates in Norwegian children. Postneonatal mortality in Norway decreased rapidly from 1956 to 1980 but subsequently remained stable. In recent years the postneonatal death rate appears to be increasing, primarily due to greater numbers of deaths attributed to the Sudden Infant Death Syndrome. During the same period, mortality among older children has also decreased, with the decline evident in all leading causes. Only among people aged 15 to 19 years have recent trends been less than encouraging, with the number of fatal traffic accidents in particular remaining stable or increasing. Although there is room for continued improvement, the widely held belief that the health status of Norwegian children is good is supported by the trends in mortality. ",0 516,"Cholangiocarcinoma. The diagnosis of cholangiocarcinoma can now be made with greater rapidity and accuracy. In the clinical setting of obstructive jaundice, a CT scan or sonogram may suggest cholangiocarcinoma if dilated intrahepatic ducts are seen with a nondilated extrahepatic biliary tree. The diagnosis is confirmed by cholangiography, and the tumor is staged by the combination of cholangiography and angiography. If the tumor extensively involves both lobes of the liver or involves the main portal vein or hepatic artery, the lesion is considered unresectable. These patients are best palliated nonoperatively, but they should still have an attempt at a tissue diagnosis, as various other lesions can masquerade as cholangiocarcinoma. In comparison, if the tumor is confined to or is distal to the hepatic duct bifurcation, extends into only one lobe of the liver, or involves only the right or the left portal vein or hepatic artery, the lesion may be resectable, and exploration is indicated. As many as half of all patients explored with curative intent will have a successful resection. Various surgical options are appropriate for patients undergoing tumor resection, depending on the site and extent of the lesion. Similarly, several surgical options are possible for palliation in patients with unresectable cholangiocarcinoma. The role of radiotherapy in the management of cholangiocarcinoma is uncertain. Our results, like those of many other retrospective analyses, suggest that radiotherapy prolongs survival after curative resection as well as after palliative stenting. However, further data from randomized studies are necessary to support or refute this impression. Further studies of adjuvant chemotherapy or hormonal therapy will also be necessary to improve patient survival. ",3 2500,"Management of ""brittle"" diabetes with a preprogrammable implanted insulin pump delivering intraperitoneal insulin. OBJECTIVE--Glycaemic control in a young woman with ""brittle"" diabetes. DESIGN--Use of a preprogrammable fully implanted pump (Infusaid) to deliver insulin intraperitoneally at variable rates, giving a total dose of about 60 units/24 h. SETTING--Endocrinology department in a teaching hospital. PATIENT--Thirty year old woman with 15 years' history of ""brittle"" diabetes. MAIN OUTCOME MEASURES--Glycated haemoglobin concentration; plasma glucose concentration. RESULTS--After implantation of the pump there was an immediate and sustained improvement in diabetic control. The patient's glycated haemoglobin concentration decreased from 15.2% to 9.2% over seven months. Her daily glucose concentrations were in the range 3.5-12 mmol/l. She has not been admitted to hospital since implantation of the pump, which was eight months before the time of writing. CONCLUSION--The implanted programmable intraperitoneal insulin pump may be of value in the management of patients with ""brittle"" diabetes in whom other attempts at glycaemic control have failed. ",17 1061,"Slow release carbamazepine in treatment of poorly controlled seizures. Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled. ",9 290,"Multiple spinal metastases from paraganglioma. Isolated vertebral body metastases from paraganglioma are exceedingly rare. They have been reported to occur in the presence of active primary tumor in the neck, local recurrence, or widespread metastases. A unique case of carotid body tumor (paraganglioma) is reported with the following features: (1) multiple vertebral body metastases (C6, T9, and L3) presenting with spinal cord compression, and no evidence of local recurrence or other metastatic disease; (2) absence of mitoses on the original specimen or the metastatic deposit; and (3) a prolonged interval (9 years) to the development of symptomatic metastases. ",3 2372,"Differences in lipoprotein subfraction composition and distribution between type I diabetic men and control subjects. Subfractions of very-low-density and low-density lipoproteins were examined in 10 male normolipidemic type I (insulin-dependent) diabetic patients before and after improvement of metabolic control and were compared with subfractions from male control subjects matched to the diabetic patients at entry for age, body mass index, plasma cholesterol, and plasma triglycerides. Two consistent differences in subfraction composition were noted between the diabetic patients at entry and the control subjects. First, subfractions from diabetic patients tended to be cholesterol-ester poor and triglyceride rich; this was particularly marked for the low-density lipoprotein subfractions. Second, the subfractions from pretreatment diabetic patients contained higher proportions of non-apolipoprotein B apolipoproteins. This compositional anomaly, but not the lipid modifications, responded to but was not completely normalized by improved glycemic control, which was also accompanied by reductions in the plasma concentrations of all subfractions. Treatment modified subfraction distribution so that the lipoprotein profile of posttreatment diabetic patients more closely resembled the profile observed in the control subjects. These changes were achieved without significant modification of daily insulin dose. In the context of blood lipid risk factors, the results argue for the need to maintain optimal insulinization even in apparently normolipidemic diabetic patients to avoid modifications of the lipoprotein pattern toward a potentially more atherogenic profile. ",17 2388,"Assessment of cardiac function in patients who were morbidly obese. Cardiac function of 30 patients who were morbidly obese was studied before bariatric surgery. Twelve patients were studied 13 +/- 4 months after surgery. These patients had a mean age of 37.1 +/- 2.9 years and a body mass index of 50.0 +/- 1.4 kg/m2. Cardiac function was measured by echocardiography, radionuclide angiography scanning, and right heart catheterization. To determine the degree of cardiac dysfunction, the patients were studied with exercise and intravenous fluid challenges. Ultrasonography produced evidence of myocardial thickening with an increased interventricular septum in eight patients (32%) and increased left ventricular mass in 17 patients (53%). The radionuclide scan suggested that morbid obesity was associated with a significantly (p less than 0.05) increased end-diastolic volume and decreased left ventricular ejection fraction as compared with patients who were of normal weight. With exercise the patient who was of normal weight had an increase in the end-diastolic volume, stroke volume, and heart rate, but the patient who was morbidly obese only increased heart rate to produce the necessary increase in cardiac output. Right heart catheterization indicated that the relationship of the pulmonary wedge pressure and the left ventricular stroke work index was abnormal in 14 of 29 patients (48.3%) and depressed in six of 29 patients (20.7%) with exercise. One liter of fluid caused an abnormal relationship of the pulmonary wedge pressure and the left ventricular stroke work index in 12 of 30 patients (40%) and a depressed response in 10 of 30 patients (33.3%). Cardiac studies were repeated in 12 patients after a 54.8 +/- 1.9 kg weight loss. Echocardiography indicated a decrease in dilatation (27.3% to 9.1%) and a significant (p less than 0.05) decrease in hypertrophy (45.5% to 0%). After the weight loss, radionuclide and right heart catheterization studies indicated improved cardiac function with reduced filling pressures and increased left ventricular work during fluid and exercise challenges. These results support the presence of obesity-related cardiomyopathy with ventricular dysfunction, which appears to be caused by a noncompliant ventricle. Significant weight loss achieved with gastroplasty results in increased ventricular compliance and improved cardiac function. ",17 1225,"Health locus of control, gender differences and adjustment to persistent pain. Locus of control (LOC) beliefs, long thought important in adjustment to persistent pain, were studied among 160 subjects (67 males and 93 females) referred to a comprehensive pain rehabilitation program. The subscale structure of the Multidimensional Health Locus of Control (MHLC) was factorially replicated in our sample. Three unique MHLC profile clusters were identified for both males and females. Among men, cluster assignment was related to age only. The younger male patients reported a stronger internal attributional style. Older male patients relied more heavily on both chance and powerful other factors. Among women, cluster assignment was related to the use of coping strategies. For example, patients with high internal scores only, reflecting a strong internal orientation towards self-management of health care needs, were more likely to utilize Information-Seeking, Self-Blame, and Threat Minimization coping strategies than patients with high scores on both the Internal and Powerful Other factors. It appears that the presence of both Internal and Powerful Other health attributional styles is associated with less frequent use of cognitive self-management techniques. In understanding the LOC scores it is important to rely on pattern analysis of scores. Implications for clinical treatment are discussed. ",9 1377,"Cell injury associated calcium oxalate crystalluria. Renal tubular cell damage, resulting in membranuria, was induced by the administration of subcutaneous gentamicin to male Sprague-Dawley rats. One group of rats received gentamicin only, while a second group was given gentamicin plus ethylene glycol in drinking water at a concentration which increased urine oxalate but alone did not cause calcium oxalate crystalluria. Crystalluria occurred early in the combined treatment groups and persisted for the duration of the experiment. Crystalluria was not present in animals receiving gentamicin or ethylene glycol only. These results suggest that cellular fragments can serve as heterogeneous foci for the nucleation of calcium oxalate crystals. ",11 1015,"Mucosal thickening on sinus X-rays and its significance. Mucosal thickening is commonly seen on X-rays of the paranasal sinuses taken in the ENT department. This sometimes leads to a sinus washout, which is clear, even though the X-rays were strongly suggestive of disease. This paper examines the prevalence of sinus X-ray anomalies in a general population, having facial X-rays for conditions other than possible sinus disease. The study suggests that up to 50 per cent of the so-called normal population may have sinus X-ray appearances consistent with sinus disease, and this may partly explain clear returns on sinus washout. ",8 1435,"Clinical effects of a polyethylene glycol grafted cellulose membrane on thrombogenicity and biocompatibility during hemodialysis. The biocompatibility and thrombogenicity of polyethylene-glycol (PEG)-grafted cellulose hemodialysis (HD) membranes (PEGC) were investigated in cross-over HD of five HD patients with ordinary cellulose (OC). The PEGC significantly suppressed transient leukocyte and thrombocytopenia, and release of C3a, beta-thromboglobulin and platelet factor 4, in corresponding with the quantity of grafted PEG. HD with PEGC resulted in lower granulocyte elastase production, protein and blood cells adsorption on the membrane surface than those with OC. Minimum heparin in HD with PEGC was three times lower than that with OC, with the thrombin-antithrombin III complex elevation lower than that in HD with OC. The results indicate that the grafted PEG effectively suppresses blood and membrane interaction, thus improving biocompatibility and reducing thrombogenicity in clinical HD. ",11 1304,"Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction. The globozoospermic condition has provided a unique opportunity to determine how the abnormal mitochondrial organization and acrosomal loss associated with this syndrome, influence sperm function. Despite the abnormal midpiece architecture, the movement characteristics of the spermatozoa, in terms of the curvilinear, path, and progressive velocities, amplitude of head displacement, and hyperactivation were all within the normal range. Similarly, the behavior of the spermatozoa on Percoll gradients was normal, although the capacity of the isolated fractions to generate reactive oxygen species was negligible. Of particular significance was the fact that the globozoospermic spermatozoa were incapable of sperm-oocyte fusion or binding the human zona pellucida, even after an intracellular calcium signal had been generated with the ionophore A23187. The sudden induction of sperm-zona interaction could, however, be achieved by the use of a ferrous ion promoter system to induce limited lipoperoxidation. This result demonstrates that the enhancing effect of peroxidation on sperm-zona adhesion involves a direct action on the properties of the sperm-plasma membrane, rather than an indirect consequence of acrosomal damage and acrosin leakage. Such findings emphasize the value of specific teratozoospermic conditions, such as globozoospermia, in dissecting the mechanisms that regulate human sperm function. ",11 2108,"Increase of intraplatelet free calcium ion during extracorporeal circulation with a hollow fiber oxygenator: arterial filter and dynamics of platelet thrombosis on oxygenator and filter in a pig model. Intraplatelet free calcium (IPFC) ions provide a common pathway for platelet activation leading to thrombosis and embolization. IPFC levels were determined by chlorotetracycline fluorometry during extracorporeal circulation (ECC) with systemic heparin in eight Yorkshire pigs (weighing 30-40 kg; 3 control and 5 ECC); the ratio of slow phase organelle calcium sequestration to fast phase platelet-membrane binding is an index of free calcium. During 3 hr of ECC with a hollow fiber oxygenator (HFO) (Bentley CM-50) and AF (Bentley 1025), seven blood samples were collected 5 min before and during ECC. The platelet deposition (CPM/microCi) on HFO (PDHFO) was simultaneously measured with In-111-labeled autologous platelets (300-400 microCi) and a Geiger probe detector at -5, 0, 5, 30, 45, 60, 120, and 180 min. During ECC, IPFC and HFO thrombus increase significantly (p less than 0.05) at 45 min with respect to control IPFC values of 0.4 +/- 0.1, suggesting direct participation of calcium activated platelets in thrombosis on HFO. The decline of IPFC is due to extrusion and sequestration by dense granules, and decline in HFO thrombus is due to embolization. On the other hand, the embolus in the arterial filter was trapped in a linear fashion, with a consistent increase with time of ECC. ",13 2021,"Clinical antecedents to in-hospital cardiopulmonary arrest. While the outcome of in-hospital cardiopulmonary arrest has been studied extensively, the clinical antecedents of arrest are less well defined. We studied a group of consecutive general hospital ward patients developing cardiopulmonary arrest. Prospectively determined definitions of underlying pathophysiology, severity of underlying disease, patient complaints, and clinical observations were used to determine common clinical features. Sixty-four patients arrested 161 +/- 26 hours following hospital admission. Pathophysiologic alterations preceding arrest were classified as respiratory in 24 patients (38 percent), metabolic in 7 (11 percent), cardiac in 6 (9 percent), neurologic in 4 (6 percent), multiple in 17 (27 percent), and unclassified in 6 (9 percent). Patients with multiple disturbances had mainly respiratory (39 percent) and metabolic (44 percent) disorders. Fifty-four patients (84 percent) had documented observations of clinical deterioration or new complaints within eight hours of arrest. Seventy percent of all patients had either deterioration of respiratory or mental function observed during this time. Routine laboratory tests obtained before arrest showed no consistent abnormalities, but vital signs showed a mean respiratory rate of 29 +/- 1 breaths per minute. The prognoses of patients' underlying diseases were classified as ultimately fatal in 26 (41 percent), nonfatal in 23 (36 percent), and rapidly fatal in 15 (23 percent). Five patients (8 percent) survived to hospital discharge. Patients developing arrest on the general hospital ward services have predominantly respiratory and metabolic derangements immediately preceding their arrests. Their underlying diseases are generally not rapidly fatal. Arrest is frequently preceded by a clinical deterioration involving either respiratory or mental function. These features and the high mortality associated with arrest suggest that efforts to predict and prevent arrest might prove beneficial. ",13 582,"Association between extent of colonic mucosal sialomucin change and subsequent local recurrence after curative excision of primary colorectal cancer. Two interrelated studies were carried out to determine whether extent of sialomucin change adjacent to a primary colorectal carcinoma predicted local tumour invasiveness and risk of local recurrence. In the first, depth of tumour penetration was correlated with the length of the sialomucin band adjacent to 72 primary colorectal cancers. There was a significant (P less than 0.05) increase in sialomucin band length adjacent to tumours invading adjacent structures compared with those which had not (Mann-Whitney U test), although there was no overall correlation between depth of penetration, Duke's classification or degree of differentiation (Kruskal-Wallis test). A sialomucin band of greater than 3 cm was associated with a 70 per cent probability of adjacent structure (T4) invasion. These observations were then tested prospectively in a second study involving 256 patients to determine whether the presence of a greater than 3 cm sialomucin band could predict local recurrence. Presence of a greater than 3 cm sialomucin band was a significant (x2 = 7.12, d.f. = 1, P less than 0.001) and independent predictor of local but not distant recurrence. In addition both the interval to local recurrence and survival were significantly shorter if a greater than 3 cm sialomucin band was present. However the accuracy of greater than 3 cm sialomucin band as a predictive test for local recurrence was only 70 per cent. The extent of sialomucin adjacent to a primary colorectal cancer does provide a crude assessment of tumour invasiveness and risk of local recurrence. ",3 1090,"Serious migraine: a study of some epidemiological aspects. Data are scant concerning some epidemiological aspects of those severe headaches which cause serious personal and economic morbidity. Our purpose was to study the incidence and other epidemiological features of patients suffering from severe migraine exacerbations, in an unselected population. The 64 patients who suffered from severe migraine bouts represented 10.5% of all the new walk-in neurological consultations in the area covered in this study. 70% of these patients were between 10 and 39 years old. Although females clearly predominated in all ages after fifteen, below this age there was a slight male predominance. The calculated incidence of serious migraine exacerbations was 90 per 100,000 people per year, the corrected incidence for females being 143/100,000 and for males 37/100,000. The highest incidence for females was in 15-19 year-olds (377/100,000) and for males in 10-14 year-olds (166/100,000). Our data seem to confirm the periodic nature of this condition since in 80% of patients the migraine bouts (ie: groups of attacks) lasted between two and nine months. Also they support the reported existence of genetic and hormonal factors in the susceptibility to migraine exacerbations. Our results may help in planning the public health aspect of migraine and add some light to the natural history of this common condition. ",9 979,"Effects of prostaglandin E1 on platelet attenuation of oxidant-induced edema in isolated rabbit lungs. Numerous studies suggest that platelets may contribute to preservation of normal endothelial cell permeability in models of lung injury. We have previously shown that washed human platelets prevent xanthine oxidase-induced edema in the isolated perfused lung and that protective mechanisms depend on the platelet glutathione redox cycle. It is uncertain, however, whether platelets preserve endothelial function by reducing toxic oxygen metabolites or by aggregating and releasing endothelial cell supportive factors-an activity that may require the glutathione redox cycle. In this study, we present data demonstrating that platelet prevention of oxidant lung injury occurs independent of platelet aggregation and release. Isolated rabbit lungs perfused with a cell-free medium were instilled with purine (2 mmol/L) and xanthine oxidase (0.003 U/ml) to generate oxidant lung edema. The infusion of washed human platelets (1 x 10(10) cells) prevented lung edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, and lung histology. Incubation of platelets with prostaglandin E1 (PGE1), a potent inhibitor of platelet aggregation and release, did not inhibit platelet attenuation of lung edema. Additionally, with the instillation of PGE1 into the perfusate to further inhibit platelet aggregation, no prevention of lung protection by PGE1-treated platelets was seen when these results were compared with those from studies in which lungs were infused with xanthine oxidase and PGE1. Aggregometry studies documented that the inhibitory effect of PGE1 on platelet aggregation persisted for up to 60 minutes, which was the duration of the isolated lung protocol. We conclude that platelet aggregation and release of platelet factors is not required for platelet attenuation of oxidant lung edema. ",7 1814,"Characteristics of biliary lipid metabolism after liver transplantation. Biliary lipid metabolism was studied after 10 liver transplantations with continuous drainage of bile. Within 3 wk after transplantation, the new liver produced bile with concentrations of biliary lipids in agreement with those reported for T-tube bile in cholecystectolized nontransplanted subjects. Although changes in biliary lipid composition occurred swiftly in response to various forms of disturbed liver function, they did not provide substantially more information than did standard serum tests or simple measurements of bile flow in most patients. Secretion rates of phospholipids and cholesterol were found to be completely bile acid dependent. For each micromole of bile acids, 0.22 and 0.08 mumol of phospholipids and cholesterol were secreted, respectively. When bile flow was related to bile acid output, a linear relationship was found (r = 0.89), with a positive intercept indicating a bile acid-independent bile flow of approximately 44 microliters/min. Analysis of individual bile acids showed almost exclusively primary bile acids. The relative proportion of chenodeoxycholic acid was more prominent during the first days after transplantation. Different explanations for this are discussed. ",13 1176,"Early cerebral infarction: gadopentetate dimeglumine enhancement Gadopentetate dimeglumine was administered prospectively to 50 patients who presented for magnetic resonance (MR) imaging within 2 weeks after a cortical cerebral infarction. Twenty-two patients (44%) were imaged within 3 days after clinical ictus. Abnormalities detected with gadopentetate dimeglumine enhancement were observed in 46 (92%) of 50 patients. Classic parenchymal enhancement was a late finding, observed in all patients (17 of 17) imaged at 7-14 days after infarction. Before this time, three additional phases of contrast material-related abnormalities were observed. Enhancement of vessels supplying the infarct (""intravascular enhancement sign"") was the earliest finding, seen in 17 (77%) of 22 infarcts aged 1-3 days. From day 2 to day 6, abnormal enhancement of meninges adjacent to the infarct was frequently noted (""meningeal enhancement sign""). Finally, a transition phase that combined intravascular or meningeal enhancement with early parenchymal enhancement was seen from day 3 to day 6. Gadopentetate dimeglumine-enhanced MR imaging in early stroke reveals evidence of vascular engorgement and sluggish flow, which precede the development of classic parenchymal enhancement. ",9 3138,"Outcome of renal transplantation after urinary diversion and enterocystoplasty: a retrospective, controlled study. A total of 17 patients with intestinal urinary diversion of enterocystoplasty underwent renal transplantation between 1970 and 1988. Patient age ranged from 4 to 35 years (mean age 20 years). The patients were divided into 2 groups. In group 1 (10 patients, 2 of whom required retransplantation) the ureter of the transplanted kidney was implanted into an ileal (7) or colonic (1) conduit or enterocystoplasty (2). In group 2 (7 patients, 1 of whom required a second transplant) the diversion was taken down and the transplanted ureter was implanted into the defunctionalized bladder. There were 14 living related and 6 cadaveric kidneys transplanted. Graft survival rates were 58 and 87% in groups 1 and 2, respectively, with an over-all rate of 70% (14 of 20 kidneys). There was no statistical difference in the graft survival rate between the 2 groups. The complications in group 1 included ureteroileal anastomotic leak (3 patients), ureteroileal stenosis (1), calculus formation (1), urosepsis (1), hyperchloremic metabolic acidosis (1), and wound infection and dehiscence (1). There were no complications in group 2. Renal transplantation into a pre-existing urinary intestinal conduit or augmented bladder does not statistically adversely affect patient or graft survival. However, the complication rate is much higher when the ureter is implanted into an intestinal segment. Therefore, it is preferable whenever possible to implant the ureter into the native bladder. ",22 1010,"Unterberger stepping test: a useful indicator of peripheral vestibular dysfunction? Deviation of gait in a stepping test has been proposed as a useful indicator of peripheral labyrinthine dysfunction. A prospective study of 26 patients suspected of having uncompensated peripheral labyrinthine dysfunction and 49 normal patients with normal labyrinthine dysfunction showed no significant difference in performance of the Unterberger stepping test between patients with electronystagmographically significant canal paresis and those with normal vestibular function. ",8 1555,"Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland. ",13 2706,"Histopathologic, immunophenotypic, and genotypic analysis of Ki-1 anaplastic large cell lymphomas that express histiocyte-associated antigens. CD30/Ki-1 antigen expression in 243 cases of malignant lymphomas was examined using Ber-H2 monoclonal antibody. Among them 20 cases were categorized as Ki-1 anaplastic large cell lymphoma. In two of these cases histiocyte-associated markers were also expressed. In these cases histopathologic and extensive in situ immunophenotypic analyses were used with genotypic studies in the determination of cell lineage. A sinusoid histologic pattern of involvement with partial lymph node infiltration by pleomorphic neoplastic cells was noticed in the nodes from both patients. Solid areas of node replacement resembling metastatic carcinoma were seen in Patient 1. Immunohistologically, tumor cells of both cases were positive for CD30, CD25, CD71, LN3 (HLA-DR), EMA, CD45, CD74, vimentin, alpha-1-antichymotrypsin, and CD68. Patient 1 was also CD45RO+, CD43+, whereas Patient 2 was positive for alpha-1-antitrypsin and CD4 tumor cells. Genotypic studies revealed that TCR beta and TCR gamma chain genes were clonally rearranged in Patient 1, whereas no rearrangements were detected in Patient 2. This study supports the view that some Ki-1 anaplastic large cell lymphomas may express multiple histiocyte-associated antigens and confirms that this group of neoplasms have immunophenotypic heterogeneity. The results of genotypic analyses used with immunophenotyping does not exclude that the tumor cells in these cases may be of true histiocytic origin despite the Ki-1-positive phenotype. ",19 408,"Survey of Alabama physicians' use of mammography, 1989. In early 1989 we surveyed by questionnaire Alabama primary care physicians (N = 1800) concerning their attitudes toward and use of mammography. There were 681 respondents (37.8%). The majority (83%) recommend mammograms for their patients according to the American Cancer Society guidelines and obtain baseline studies in asymptomatic women between the ages of 35 and 40 years. It appears that the cost of mammograms is decreasing in Alabama; a screening study was available for $50 or less to 34% of responding physicians. Almost one half (48%) of the physician respondents believe that more than 50% of their patients have had at least one mammogram. ",3 2887,"Relationship of oxygen dose to angiogenesis induction in irradiated tissue. This study was accomplished in an irradiated rabbit model to assess the angiogenic properties of normobaric oxygen and hyperbaric oxygen as compared with air-breathing controls. Results indicated that normobaric oxygen had no angiogenic properties above normal revascularization of irradiated tissue than did air-breathing controls (p = 0.89). Hyperbaric oxygen demonstrated an eight- to ninefold increased vascular density over both normobaric oxygen and air-breathing controls (p = 0.001). Irradiated tissue develops a hypovascular-hypocellular-hypoxic tissue that does not revascularize spontaneously. Results failed to demonstrate an angiogenic effect of normobaric oxygen. It is suggested that oxygen in this sense is a drug requiring hyperbaric pressures to generate therapeutic effects on chronically hypovascular irradiated tissue. ",20 2280,"Prolonged remission after cyclosporine therapy in pemphigus vulgaris: report of two young siblings. We report the clinical evolution of two young siblings with severe pemphigus vulgaris treated with cyclosporine for 30 and 12 months, respectively. One was resistant to treatment with high-dose corticosteroids and azathioprine. A good clinical response was achieved in both cases. No major side effects were observed. The patients have remained disease free for more than 20 months after stopping cyclosporine therapy. ",16 2895,"Management of tracheobronchial foreign bodies in children: an update. Tracheobronchial foreign bodies continue to be a source of morbidity and mortality in the pediatric population. Technical advances in anesthesia and equipment have made the removal of these troublesome objects more feasible. Diligence must still be exercised and a coordinated team effort must be employed in order to achieve a satisfactory and safe outcome for the patient. The appropriate use of diagnostic studies and management techniques are discussed. ",20 2848,"Organ injury scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. The Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A.A.S.T.) has been charged to devise injury severity scores for individual organs to facilitate clinical research. Our first report (1) addressed O.I.S.'s for the Spleen, Liver, and Kidney; the following are proposed O.I.S.'s for Pancreas (Table I), Duodenum (Table II), Small Bowel (Table III), Colon (Table IV), and Rectum (Table V). The grading scheme is fundamentally an anatomic description, scaled from 1 to 5, representing the least to the most severe injury. We emphasize that these O.I.S.'s represent an initial classification system which must undergo continued refinement as clinical experience dictates. ",20 1344,"Hypophosphatemia in infants on continuous ambulatory peritoneal dialysis. Three infants with irreversible renal failure and treated with continuous ambulatory peritoneal dialysis (CAPD) developed hypophosphatemia. In one of them rachitic lesions were observed on X-ray and bone biopsy showed osteomalacic osteodystrophy. Different mechanisms may have been at the origin of the hypophosphatemia: high doses of phosphate binders, low phosphorus intake, phosphate loss with the dialysate and possibly nutritional repletion. Dietary phosphorus restriction and use of phosphate binders should be applied with caution and serum phosphate should be monitored regularly in infants treated with CAPD. ",11 1327,"The elderly on dialysis: some considerations in compliance. Compliance with scheduled treatments, dietary and fluid restrictions, and multiple medications is an important component in the care and well-being of end-stage renal disease (ESRD) patients. Given the rigorus and complex demands of dialysis, it is important to examine the issue of compliance, focusing on a large and ever-increasing segment of our patient population, the elderly. The ESRD literature reflects efforts to define and measure levels of compliance, identify factors that influence and predict compliance, and develop intervention strategies to improve adherence to treatment regimens. While limited attention has been focused specifically on the elderly, there are studies suggesting that age may be a factor associated with improved adherence and that social support may be a significant contributor to compliance in this patient group. In an effort to examine the current status and needs of the dialysis elderly, research is in progress at Chromalloy American Kidney Center, Washington University, which replicates a study of 5 years ago. Eighty-four patients age 60 and over, on dialysis for a minimum of 6 months, were identified. Sociodemographic, treatment, compliance, and functional capacity data were collected; additional mental and psychological testing was completed on patients willing and able to participate. Preliminary data suggest the current elderly population is larger and significantly older than that of 5 years ago. Other sociodemographic data indicate the population is increasingly female, black, and more socioeconomically disadvantaged. In regard to compliance, the vast majority of elderly demonstrate good compliance as measured by serum potassium, fair to good compliance with phosphorus, and fair to poor compliance with fluid restrictions. ",11 24,"In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents. The susceptibilities of 45 clinical and 3 environmental isolates of Xanthomonas maltophilia to 14 antimicrobial agents was determined by broth microdilution. The newer quinolones PD117596, PD117558, PD127391, A-56620, amifloxacin, and fleroxacin were the most active agents tested, with 70 to 99% of isolates being susceptible to these agents. All isolates were resistant to trospectomycin. The new aminoglycosides SCH24120 and SCH22591 were active against 12 and 1% of isolates, respectively. ",0 1819,"Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction. The treatment of acute myocardial infarction has changed tremendously in the past decade because thrombolytic therapy has become the treatment of choice for the patient with acute myocardial infarction. Although many issues have been resolved, several controversial issues remain unresolved. This article addresses thrombolytic agents in terms of their superiority in achieving infarct vessel patency and mortality reduction as well as the role of thrombolysis in patients who present with chest pain of greater than 6 hours' duration, who are elderly, and who have an inferior infarction. ",13 1723,"Ventricular arrhythmias in hypertensive left ventricular hypertrophy. Relationship to coronary artery disease, left ventricular dysfunction, and myocardial fibrosis. Ventricular arrhythmias occur with increased frequency in hypertensive patients with left ventricular hypertrophy (LVH). The relationships, however, between ventricular arrhythmias and coexistent coronary artery disease, left ventricular dysfunction and left ventricular fibrosis have not been examined in hypertensive LVH. We carried out coronary arteriography on fifteen hypertensive patients with LVH and nonsustained ventricular tachycardia (greater than or equal to 3 consecutive ventricular complexes) of whom nine (60%) were free of significant (greater than 50% stenosis) coronary disease. To identify other possible correlates of left ventricular arrhythmias, 28 patients with LVH, comprising 17 with ventricular tachycardia and 11 without ventricular arrhythmias, underwent quantitative assessment of left ventricular function (angiographic ejection fraction), left ventricular mass (echocardiography), and left ventricular fibrosis (endomyocardial biopsy). Ejection fraction was not significantly different between the two groups (53 +/- 8% v 62 +/- 2%, P = NS). However, left ventricular mass was significantly greater (442 +/- 28 g v 339 +/- 34 g, P less than .05) and percentage fibrosis significantly higher (19 +/- 4% v 3 +/- 1%, P less than .001) in those patients with ventricular tachycardia. Thus ventricular arrhythmias in hypertensive patients with LVH cannot be entirely attributed to coexistent coronary disease, nor to left ventricular dysfunction, but are related to the degree of cardiac hypertrophy and subendocardial fibrosis. ",13 235,"Selenium. Nutritional, toxicologic, and clinical aspects Despite the recent findings of environmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because of the growing public interest in selenium as a dietary supplement and the occurrence of environmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element. ",3 1613,"Fate of patients undergoing transluminal angioplasty for lower-limb ischemia. A prospective study of 370 patients who underwent 500 percutaneous transluminal angioplasties (PTAs) for lower-limb ischemia over a 7-year period was performed. A 97% follow-up rate was achieved. The first PTA was successful in 188 patients (51%). Of the failures, 31% were failed attempts at dilation and 73% occurred within 1 month of intervention. Of the patients with failed PTA, 39% underwent bypass surgery and 24% underwent amputation. The 30-day mortality rate was 3%, with 1% of the deaths attributed to PTA. The survival rate at 5 years for the successes was double that for the failures (P less than .0005). The best results were in femoropopliteal stenoses with two or three patent calf vessels (cumulative patency rate, 78% at 3 years) and the worst in femoropopliteal occlusions with one or no patent calf vessels (cumulative patency rate, 25% at 3 years). Log rank tests on the life-table data were used to show factors favoring a good outcome. It is concluded that PTA is the treatment of first choice in suitable patients and, although the failure of intervention in critical ischemia has a significant risk, it is a valuable addition to the therapeutic options in patients with little chance of surgical treatment. ",13 397,"Adult T-cell leukemia-derived factor/thioredoxin, produced by both human T-lymphotropic virus type I- and Epstein-Barr virus-transformed lymphocytes, acts as an autocrine growth factor and synergizes with interleukin 1 and interleukin 2. Interleukin 1 (IL-1) has been obtained from the Epstein-Barr virus-infected B-lymphoblastoid cell line 3B6 and shown to be involved in autocrine growth of 3B6 B cells. Independently, adult T-cell leukemia-derived factor (ADF) was purified from human T-lymphotropic virus I-infected leukemic T-cell line (ATL-2) and reported as an interleukin 2 (IL-2) receptor-inducing factor. We have previously reported the same molecular mass, pI, and NH2-terminal amino acid sequence for both 3B6-derived IL-1 and ADF. cDNA cloning of ADF demonstrated high homology with the prokaryotic disulfide reducing enzyme thioredoxin. We show here that ADF and 3B6-derived IL-1 are identical. By RNA blot, 3B6 and ATL-2 cells were shown to contain high levels of 0.6-kilobase mRNA corresponding to ADF. Such message was not detected in resting peripheral blood lymphocytes but could be weakly induced by lymphocyte activation. Antibodies have been raised against synthetic peptides corresponding to the NH2 terminus and the COOH terminus of ADF. Immunoblotting and sequential immunoprecipitation with these antibodies revealed the same 13-kDa protein in 3B6 and ATL-2 cells. Recombinant ADF could sustain growth of 3B6 and ATL-2 cells at low cellular concentration without fetal calf serum; ADF, thus, appears involved in their autocrine growth. Similarly, recombinant ADF could enhance growth of other B-cell lines, including the Epstein-Barr virus-negative Burkitt lymphoma line BL41 and the lymphoblastoid cell lines CRAG8, CRB95, and 1G8. Finally, recombinant ADF exhibits marked synergism with other cytokines, such as IL-1 and IL-2, allowing virally infected lymphocytes to respond to suboptimal amounts of a variety of growth factors. ",3 2531,"Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. Although minimal model analysis of frequently sampled iv glucose tolerance tests (FSIGTs) to measure insulin sensitivity is well recognized, application has been limited by the need for endogenous insulin secretion. In the present study we determined whether use of exogenous insulin could permit minimal model assessment of insulin sensitivity (SI) to be extended to diabetic subjects. Normal volunteers had separate FSIGT assessments supplemented with both tolbutamide and insulin to accelerate glucose disappearance, while diabetics had a FSIGT supplemented only with insulin. There was a strong and highly significant correlation between the two assessments in normal subjects (r = 0.87; P less than 0.001), and the rank order of SI generally was maintained with the two assessments over a 3-fold range of SI; however, insulin-determined SI was 16% lower (3.4 +/- 0.4 vs. 4.1 +/- 0.4 x 10(-4) min/microU.microL; P less than 0.01). Diabetic subjects had markedly lower insulin sensitivity than controls (SI = 0.61 +/- 0.16; P less than 0.0001). Across all subjects, the level of fasting serum glucose was correlated inversely with both insulin sensitivity (r = -0.62; P less than 0.05) and acute insulin responses (r = -0.72; P less than 0.02); however, insulin sensitivity in diabetic subjects with little insulin secretion (0.6 +/- 0.2) was comparable to insulin sensitivity in diabetic subjects with near-normal responses (0.6 +/- 0.3). In subjects with fasting hyperglycemia, there were significant correlations between insulin sensitivity and body mass index, percent fat mass, and waist/hip ratio (all P less than 0.03). Among all female subjects, there was also a strong correlation between insulin sensitivity and upper body obesity, as measured by waist/hip ratio (r = -0.68; P less than 0.02). Model parameters also permitted glucose uptake to be estimated in diabetic vs. normal subjects at comparable hyperglycemia (11.1 mmol/L). Total glucose uptake was decreased in diabetic subjects (5.2 +/- 0.8 vs. 12.7 +/- 1.7 mg/min.kg in normals; P less than 0.001), insulin-dependent glucose uptake was diminished to a greater extent (1.3 +/- 0.4 vs. 6.2 +/- 1.2) than noninsulin-independent glucose uptake (3.9 +/- 0.5 vs. 6.4 +/- 0.9; both P less than 0.02). Administration of insulin permits minimal model FSIGT analysis to be applied to diabetic as well as normal subjects, yielding information about both insulin- and noninsulin-mediated glucose uptake as well as insulin sensitivity and insulin secretion. ",18 2844,"Studies on B-lymphocyte dysfunctions in severely burned patients. We studied in vitro functional parameters of peripheral blood B-lymphocytes from severely burned patients (n = 10; burn injuries ranging from 25 to 72% TBSA). While the number of B-cells remained unchanged, B-cell proliferation induced by Staphylococcus aureus strain Cowan I (SAC) was normal or even enhanced at early and late phases postburn, but showed a marked suppression during the second to fourth week. A similar pattern was observed for the pokeweed mitogen (PWM)- or SAC-stimulated synthesis of immunoglobulin M (IgM), whereas IgG production was decreased over the whole postburn period monitored. Cytokine (interleukin 4)-induced B-cell activation as indicated by the expression of the CD23 surface antigen was impaired throughout the second to fifth week. In parallel, the release of the proteolytic cleavage product sCD23 which represents a B-cell growth and differentiation factor was reduced. Our data provide evidence that activation, proliferation, and differentiation processes of B-lymphocytes are impaired in severely burned patients, which may contribute to their enhanced susceptibility to infection and sepsis. ",20 317,"Transthyretin receptors on human astrocytoma cells. Transthyretin (TTR), a transport protein for T4 and retinol-binding protein, is the principal T4-binding protein of cerebrospinal fluid. Its function in regard to the delivery of its ligands and in other respects is unclear. The binding of [125I] TTR to cultured human astrocytoma cells was studied to determine whether these cells carry receptors for TTR. Scatchard analysis was consistent with a single class of binding sites with a Kd of 3 nM. No significant cross-reactivity with transferrin or serum albumin was observed. Internalization of TTR was temperature dependent and proportional to receptor occupancy. Dilutions of cerebrospinal fluid displaced [125I]TTR in proportion to their content of radioimmunoassayable TTR and in parallel with purified TTR. The uptake and internalization of TTR increased in the presence of high T4 or T3 concentrations. These results demonstrate that TTR binds to specific high affinity receptors on human astrocytoma cells. Receptor binding of TTR provides a potential mechanism for the delivery of its ligands within the central nervous system. ",3 278,"Premorphological metabolic changes in human breast carcinogenesis. Malignant breast tissue is characterized by morphological and metabolic changes when compared with normal breast tissue. In this study, the cytochemical measurement of glucose-6-phosphate dehydrogenase (G6PD) activity was used to detect abnormal metabolism in breast tissue and to determine whether abnormal metabolic activity precedes morphological change during human breast carcinogenesis. Normal and benign breast tissue, morphologically normal tissue from cancer-containing breasts, and malignant breast tissue were studied. In malignant tissue, mean(s.e.m.) G6PD activity was significantly increased when compared with normal and benign tissue (9.69(2.3) versus 27.02(1.7) mean integrated extinction (MIE) x 100, P less than 0.01). G6PD activity was increased in morphologically normal tissue from cancer-containing breasts when compared with normal and benign breast tissue from breasts with no known cancer (27.02(1.7) versus 18.42(2.6) MIE x 100, P less than 0.05). These findings suggest that metabolic abnormalities precede morphological changes in breast carcinogenesis. Abnormal metabolism can be detected widely within a cancer-containing breast. The detection of such abnormality may prove helpful in identifying patients at high risk of developing breast cancer. ",3 945,"The contributions of John B. Murphy to thoracic surgery. John B. Murphy was a prominent surgeon who lived in Chicago from the 1880s until his death in 1916. During his career, he was associated with both Rush Presbyterian and Northwestern Medical Schools. He was responsible for popularizing the use of an artificial pneumothorax as an effective adjunct in the treatment of pulmonary tuberculosis. This modality was not, however, his original concept. In addition to all of the fields of general surgery, Murphy undertook the management of empyema and lesions of the chest wall and also performed thoracoplasty procedures. Although he had done several thoracotomy procedures in his laboratory, he rarely undertook this operation in a clinical setting. Drop ether anesthesia was used for all surgical procedures. Murphy did not use closed water seal drainage of the chest. His oration on thoracic surgery, given at the annual meeting of the AMA, in 1898, was an excellent monograph on the subject and undoubtedly contributed to the increased interest and progress in this field of surgery. Murphy was a wise surgeon, an able technician and a scholarly teacher. The high regard in which he was held by his contemporaries is best expressed by the remark of William Mayo, ""...he was the surgical genius of our generation"". ",7 2639,"Pediatric acquired immunodeficiency syndrome: an unusually high incidence of twinning. Surveillance data on incidence of twins among reported cases of pediatric AIDS in New York City are presented. Most pairs are concordant for HIV infection. Three discordant pairs have been described elsewhere. Possible reasons for the association are discussed, including the most likely explanation that twins show symptoms early and are overrepresented in the early years of surveillance of pediatric AIDS. ",19 3271,"Liver transplantation: the shadow side. For a relatively large number of patients with liver disease, a liver transplant does not always provide a successful solution. What does confrontation with this modern technology mean for those involved? We interviewed 30 relatives of patients who had died after they had been turned down for a transplant, or during or shortly after a liver transplant operation performed in the Groningen Liver Transplant Programme. Quantitative data were obtained by means of a questionnaire. One-third of the respondents were of the opinion that the patient would have been better off if he/she had not entered the programme. Over half found the loss more difficult to accept because the patient had been involved in the programme. Nevertheless, many had the feeling of satisfaction that everything possible had been done. However fruitful transplantation technology may be for a specific group of patients, it also involves undesirable side-effects which should be included in the careful judgement of this technology. ",22 1923,"Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia. The effects of oral mexiletine on left ventricular (LV) ejection fraction (EF) and ventricular arrhythmias--and a possible relation between these effects--were evaluated during 3 months of therapy in 29 patients with chronic ventricular premature complexes (VPCs) and a moderately reduced to normal LVEF by 24-hour Holter monitoring and by radionuclide ventriculography at rest and during maximum tolerable exercise testing. After an average titration period of 13 days, a mean daily mexiletine dose of 739 mg was maintained throughout the treatment. At the end of titration and after 3 months of treatment, patients with a baseline LVEF less than or equal to 40% (group 2) responded with a median reduction of the hourly VPC rate by 90 and 81%, respectively, compared with 79 and 72% in those with a baseline LVEF greater than 40% (group 1). Couplets and runs of ventricular tachycardia were almost completely suppressed in nearly all patients. A single patient had a proarrhythmic increase in VPCs during treatment. Compared with baseline, there were no significant changes in resting or exercise LVEF after 1 or 3 months of treatment in either of the 2 groups of patients. No correlation was found between treatment-induced changes in arrhythmia frequency and in resting EF. No symptoms of congestive heart failure developed. The study confirms that long-term use of mexiletine is efficacious and relatively free of cardiac depressant effects even in patients with diminished LV function. ",13 2712,"The impact of HIV-related illness on employment. We used structured telephone interviews to determine the extent of work loss following onset of symptoms, the interval between onset of symptoms and cessation of work, and the risk factors for work loss among 193 persons with symptoms of human immunodeficiency virus (HIV)-related illness attending the AIDS Clinic at the University of California, San Francisco, between October 1, 1988, and September 30, 1989. Estimates of the duration of time between onset of HIV-related symptoms and work loss derive from the life table method of Kaplan and Meier. A Cox proportional hazards model is used to estimate the effect of risk factors on the probability of withdrawing from work in each time interval. Eighty-six percent of the respondents worked prior to onset of the first symptom of HIV-related illness; 40 percent were working at the time of the most recent interview, a mean of 958 days later. The total number of hours worked declined by 59 percent during this time. Kaplan-Meier analysis indicates that 50 percent who worked prior to onset of HIV-related illness stopped working within two years and all had stopped within 10 years after onset of the first symptom. ",19 256,"Significance of positive margins in oral cavity squamous carcinoma. Three hundred ninety-eight consecutive, previously untreated patients undergoing surgery for epidermoid carcinoma of the oral cavity from 1979 to 1983 were reviewed. One hundred twenty-nine patients were classified as having positive surgical margins. Of these, 83 patients had tumor within 0.5 mm of the surgical margin, 9 had premalignant changes at the margin, 9 had in situ carcinoma at the margin, and 28 had invasive cancer at the margin. The remaining 269 patients had uninvolved margins. The significance of positive margins relating to survival, subsequent clinical course, local recurrence, and patterns of treatment failure was examined, along with the impact of adjuvant postoperative radiotherapy on positive margins. The percentage of patients having positive margins progressively increased with increasing T stage: 21% in T1 versus 55% in T4 primary cancer. The overall 5-year survival for patients with negative margins was 60%. For patients with positive margins, 5-year survival was 52%. This difference was statistically significant. The incidence of local recurrence in patients having positive surgical margins was twice as much as in those with negative margins (36% versus 18%). Metastasis rates in the neck and at distant sites were not significantly influenced by the status of the surgical margin. Of the 129 patients with positive margins, 49 received postoperative radiotherapy. In those patients so treated, a trend toward lower recurrence rates was noted. Differences were not statistically significant. This retrospective review confirms the importance of adequate resection of the primary tumor as well as the relative ineffectiveness of adjuvant postoperative radiotherapy in the improvement of local control in patients with positive surgical margins. ",3 410,"Time to recurrence varies inversely with thickness in clinical stage 1 cutaneous melanoma. The thickness of a tumor has been identified as the principal prognostic factor in cutaneous malignant melanoma. However, time to recurrence has not conclusively been related to thickness. A retrospective study of 216 patients with a primary cutaneous malignant melanoma that recurred was conducted to clarify this relationship and investigate possible independent relationships between age at diagnosis and sex of patients to time to recurrence. The results of analysis of linear regression revealed an inverse linear relationship between thickness and time to recurrence (p less than 0.001). Patients more than 50 years of age at the time of diagnosis were shown to relapse sooner than those less than 50 years of age (p = 0.014). Sex was not a significant factor in predicting time to recurrence (p greater than 0.10). These results suggest that thickness of tumor provides an indication of time to recurrence in those patients destined to recur and stress the need for long term surveillance in patients with a history of malignant melanoma because of the possibility of late relapse even with thin lesions. ",3 568,"The role of attitudes, beliefs, and personal characteristics of Italian physicians in the surgical treatment of early breast cancer. The influence of Italian physicians' attitudes, beliefs, and personal characteristics on medical decision making is examined in the case of surgical treatment of early breast cancer. Responses to a mail survey of 657 physicians from different specialties were analyzed comparing doctors recommending a radical procedure (9%) to those preferring a conservative procedure for younger patients only (25%), and those considering conservative surgery the treatment of choice regardless of patients' age (66%). The findings suggest that the likelihood of physicians' preferring a conservative procedure is influenced by their specialty and the extent to which they feel that a patient should have a role in the treatment decision more than by differences in the beliefs of treatment outcomes. Only preferences of the small group indicating radical surgery as the sole admissible treatment can be accounted for by ignorance or distrust of results of recent trials. These findings suggest that other than scientific factors guide many doctors in their decision making; they may help to explain why the diffusion of research results into clinical practice is often disappointingly slow. ",3 1897,"Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease. To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease. ",13 1466,"Maternal genetic effects on ethanol teratogenesis and dominance of relative embryonic resistance to malformations. Maternal genetic factors and/or fetal genetic factors contribute to variations in response to prenatal alcohol exposure. To assess the contribution of maternal genotype to ethanol teratogenesis, a reciprocal cross study was conducted in an animal model using C57BL/6J (B6) and long-sleep (LS) mice. B6 mice are more susceptible than LS mice to prenatal ethanol-induced malformations but both mouse stocks are susceptible to fetal weight deficits following in utero alcohol exposure. B6 and LS dams were reciprocally mated to B6 or LS males producing four embryonic genotype groups: the true-bred B6B6 and LSLS genotypes, and the genetically similar B6LS and LSB6 genotypes (the F1 genotype). Dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of sucrose (S) on day 9 of pregnancy. Fetuses were removed on gestation day 18, weighed, and assessed for soft tissue or skeletal malformations. Results showed a greater litter weight deficit and increased total malformation rate in ethanol-exposed F1 litters carried by B6 mothers compared to ethanol-exposed F1 litters carried by LS mothers. This result would be expected only if maternal genetic factors contribute significantly towards susceptibility to ethanol teratogenesis. The influence of the LS mother was to decrease susceptibility to ethanol teratogenesis compared to the B6 mother while the influence of the B6 mother was to increase susceptibility to ethanol teratogenesis compared to the LS mother. The average malformation rate for F1 litters was significantly less than the predicted midparental value. This shows that the F1 genotype exhibited dominance towards resistance to prenatal alcohol effects. ",12 1742,"Contribution of calmodulin and protein kinase C to renin release in spontaneously hypertensive rats. This study was designed to evaluate the contribution of calmodulin and protein kinase C to renin release from isolated glomeruli of spontaneously hypertensive rats (SHR, Okamoto and Aoki). Male 7-week-old SHR and age-matched control Wistar-Kyoto rats (WKY) were used in this study. Isolated glomeruli were sealed in the superfusion chamber and perfused with Krebs-Ringer solution at a constant flow of 0.3 mL/min. Renin release was increased by calmodulin inhibitor, W-7, and protein kinase C inhibitor, H-7, in both SHR and WKY. SHR showed higher maximal levels of renin release by W-7 and lower maximal levels by H-7 compared to WKY. These results indicate that calmodulin and protein kinase C play inhibitory roles in renin release from juxtaglomerular cells. The calmodulin-mediated suppression mechanism in renin release appears to be augmented in the SHR, whereas the protein kinase C-mediated system is attenuated. ",13 671,"The molecular basis of hereditary 1,25-dihydroxyvitamin D3 resistant rickets in seven related families. Hereditary 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] resistant rickets (HVDRR) is an autosomal recessive disease caused by target organ resistance to the action of 1,25(OH)2D3, the active form of the hormone. The defect in target cells is heterogenous and commonly appears to be a mutation in the gene encoding the vitamin D receptor (VDR). We have studied cultured skin fibroblasts and Epstein-Barr virus transformed lymphoblasts of seven family branches of an extended kindred having eight children affected with HVDRR. We have previously shown that cells from three affected children in this group contain an ""ochre"" nonsense mutation coding for a premature stop codon in exon 7 within the steroid-binding domain of the VDR gene. In the current studies, we found that cells from affected children failed to bind [3H]1,25(OH)2D3 and had undetectable levels of VDR as determined by immunoblots using an anti-VDR monoclonal antibody. Measurement of VDR mRNA by hybridization to a human VDR cDNA probe showed undetectable or decreased abundance of steady-state VDR mRNA. Parents, expected to be obligate heterozygotes, showed approximately half the normal levels of [3H]1,25(OH)2D3 binding, VDR protein, and mRNA. The mutation at nucleotide 970 (counting from the mRNA CAP site) results in the conversion of GTAC to GTAA, which eliminates an Rsa I restriction enzyme site and facilitates identification of the mutation. We found that polymerase chain reaction (PCR) amplification of exons 7 and 8 from family members and subsequent Rsa I digestion allows detection of the specific genotype of the individuals. When Rsa I digests of PCR-amplified DNA are subjected to polyacrylamide gel electrophoresis, children with HVDRR exhibit a homozygous banding pattern with loss of an Rsa I site. Parents exhibit a heterozygotic DNA pattern with detection of both normal and mutant alleles. In summary, our data show that the genetic abnormality is a point mutation within the steroid-binding domain of the VDR in all seven related families with HVDRR. Analysis of restriction fragment length polymorphism at the 970 locus of PCR-amplified DNA fragments can be used to diagnose this mutation in both affected children and parents carrying the disease. ",4 616,"Soft tissue rheumatism of the upper extremities: diagnosis and management. Upper extremity tendinitis and bursitis are usually the result of repetitive microtrauma, probably resulting in disruption of fibers. A focus of inflammation often occurs, producing pain, spasm, and disability. With a careful history and physical exam, the diagnosis can be made, distinguishing soft tissue rheumatism from arthritis. Treatment consists of rest, heat or ice, and frequently, the use of non-steroidal anti-inflammatory drugs or injections to control the inflammatory response. Protection from repeated trauma may be beneficial in preventing recurrence. ",4 1912,"Potential usefulness of combined thromboxane A2 and serotonin receptor blockade for preventing the conversion from chronic to acute coronary artery disease syndromes. Evidence suggests that unstable angina, non-Q-wave myocardial infarction and Q-wave myocardial infarcts represent a continuum, such that transient reduction in coronary blood flow associated with platelet aggregation and dynamic vasoconstriction at sites of coronary artery stenosis and endothelial injury lead to abrupt development of unstable angina. Factors potentially responsible for the conversion from chronic to acute coronary artery disease include endothelial injury at sites of stenosis. The endothelial injury may be the result of plaque fissuring or ulceration, hemodynamic factors (including systemic arterial hypertension or flow shear stress), infection, smoking, coronary arteriography or balloon angioplasty. Clinical and experimental animal studies suggest that interference with thromboxane and serotonin contributions to platelet aggregation and dynamic coronary artery constriction may prevent chronic coronary artery disease syndromes from converting to acute disease. To protect against this process may require both thromboxane and serotonin receptor antagonists or a combination of thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist. Further studies are needed to test this hypothesis. ",13 815,"Should safety concerns with available ulcer treatment influence drug selection? With the identification of the parietal cell receptors for gastric acid secretion coupled with the introduction of cimetidine in 1977, treatment of acid-peptic diseases was transformed from empiric therapy to an approach based on a clearer understanding of human physiology. Today, physicians are confronted with an array of antiulcer agents that differ within their drug class (e.g., the H2-receptor antagonists) as well as in their mechanisms of action (e.g., neutralize acid, alter mucosal defensive factors, or suppress acid secretion). With minor exceptions, the clinical efficacy of the available antiulcer drugs can be regarded as comparable. Thus, the safety profile becomes the next consideration when choosing among similarly effective drug products. Of the available antiulcer agents, the H2-receptor antagonists as a class have an excellent safety profile, as indicated by more than 25 years of cumulative clinical experience and postmarketing surveillance. Important safety issues with currently available antiulcer drugs, i.e., H2-receptor antagonists, sucralfate, prostaglandin E analogues, and the newest antiulcer agent, omeprazole, are reviewed to place them into perspective for the clinician. ",5 771,"Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid. ",5 819,"Gallstone dissolution. Many methods are available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin or methyl tert-butyl either; and calcium or pigment solvents such as EDTA and polysorbate. Which of these approaches will be appropriate for an individual patient depends on the type of stones; whether they are in the gallbladder or the bile ducts; whether access to the biliary tree is available; the patient's age and general medical condition; and the availability of necessary expertise. In the US, both chenodeoxycholate and ursodeoxycholate are now available. Ursodeoxycholate is more expensive but appears to produce fewer side effects and may be more efficacious. These agents are most effective in thin women with small floating, radiolucent cholesterol stones in a functioning gallbladder. Only about half of the small subset of patients will experience partial or complete dissolution of stones within a year. Stone recurrence and the potential toxicity of long-term therapy are problems with this approach. Therefore, for most patients, cholecystectomy, either in the traditional fashion or using a laparoscopic approach (see article later in this issue by Gadacz et al), is the most cost-effective and perhaps the safest option. Intragallbladder instillation of methyl tert-butyl ether probably will be applicable only to a small subset of patients, and treatment is likely to be followed by a high recurrence rate. In patients with retained common duct cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be initiated as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90% success rate with this technique can be expected within 7 days. ",5 203,"Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered ""sunspots."". ",3 295,"Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the Study Group of Japan. One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid-line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high-dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2-year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT. ",3 3269,"Measurements of right ventricular volumes during fluid challenge. The effects of fluid loading on RV function were studied in 41 acutely ill patients monitored with a modified pulmonary artery catheter equipped for measuring RVef. Hemodynamic evaluation was performed before and after infusion of 300 ml of 4.5 percent albumin solution in 30 min. Changes in SI did not correlate with Pra or Ppao but did with RVEDVI. For the entire group, RVef was unchanged (27 +/- 9 vs 27 +/- 9 percent). In the eight patients with an initial RVEDVI greater than 140 ml/m2, the fluid challenge increased Pra and Ppao and reduced LVSWI without any other significant effect. There was no significant correlation between RVEDVI and Pra and only a weak correlation between RVESVI and Ppa. However, there was a highly linear correlation between both RVEDVI and RVESVI and changes in RVEDVI and in RVESVI, suggesting that in the absence of severe pulmonary hypertension RV output is primarily dependent on RV preload. ",22 596,"Healing of non-vascularised diaphyseal bone transplants. An experimental study. Four different experiments were performed to study the healing of a large, non-vascularised, diaphyseal, bone segment in adult cats. In the first experiment, a 4 cm segment of tibia with its periosteum was excised and replaced in its bed. The other experiments were similar, except that in the second, the periosteum of the segment was removed, in the third its medullary canal was blocked with a Silastic rod, and in the last group the segment was isolated from its muscle bed by a Silastic sheet. The reparative processes were quantified by estimating the resorption index, the cortical new bone formation index, the callus encasement index, and the osteocyte count. Bone resorption and apposition occurred in the segment even when the periosteum was absent or the medullary canal was blocked, with osseous union at both ends by eight to 12 weeks, provided the segment was not isolated from its muscle bed. Thus, the muscle bed played a significant role in these reparative processes. ",4 1436,"Difference in beta 2-microglobulin removal between cellulosic and synthetic polymer membrane dialyzers. Several kinds of dialyzers, with highly permeable membranes (HPM), have been designed to specifically remove beta 2-microglobulin (BMG). To clarify their solute transport characteristics, nine types of HPM dialyzers were evaluated during in vivo and in vitro studies using human plasma and aqueous solutions. No BMG membrane adsorption and/or plugging was seen with cellulosic membrane dialyzers during in vitro experiments using human plasma. On the other hand, all synthetic polymer membrane dialyzers had adsorptive properties, and in a dialyzer with a polymethylmethacrylate membrane, a large amount of BMG was removed by adsorption alone. Dialyzers with cellulose triacetate and polyacrylonitril membranes showed higher values of BMG diffusive dialysance (greater than 20 ml/min) and sieving coefficient (greater than 0.9). From in vitro experiments using an aqueous solution containing several solutes with relatively small or middle molecular weights, all HPM dialyzers had a higher overall mass transfer coefficient than any conventional membrane dialyzer. ",11 1737,"Calciotropic hormones in human and experimental hypertension. Although altered cellular calcium handling plays a critical role in the pathophysiology of hypertension, little attention has been focused on the impact of calcium regulating hormones on this process. Recent research provides evidence that parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D, as well as newly described factors such as calcitonin gene-related peptide (CGRP), exert target-organ-specific actions in cardiac and peripheral vascular tissues, are linked to the renin-aldosterone system, and thus to the control of sodium metabolism, and may directly participate in the hypertensive process, especially in low renin and salt sensitive forms of hypertensive disease. The metabolic set-point of these linked renin and calcium hormone systems, which serve to transduce environmental dietary mineral signals at the cellular level, determines the blood pressure consequences of sodium and calcium loading and/or restriction, and helps to explain the heterogeneous and seemingly inconsistent effects of these dietary maneuvers on blood pressure. Measurement of renin and calcium factors in hypertension thus provides a physiological basis for individualized therapeutic recommendations in human hypertension. ",13 669,"Effect of a pulsing electromagnetic field on metabolically derived osteoporosis in rats: a pilot study. The literature suggests that a pulsating electromagnetic field (PEMF) is effective against bone loss in disuse osteoporosis. This study was conducted to evaluate the effects of PEMF on metabolically derived osteoporosis in rats. Sixteen 5 month old female Sprague-Dawley rats were divided into three groups (G-1,2,3). G-1 was given a normal diet and no exposure to PEMF; G-2,3 were oophrectomized and fed a low calcium diet for 8 months; and G-3 was also exposed for 24 hr/day to PEMF generated by applying a 15 Hz, 5.6 A peak to peak square wave to Helmholtz coils (64 cm I.D., 200 turns/coil). The rats were sacrificed at 4, 6, and 8 months. Skeletal changes were analyzed by measurements of acid extracted bone calcium and bone mineral content (BMC) using single photon absorptiometry (SPA). Although all animals started at approximately the same weight (mean of 290.0 g), G-2 showed a more progressive increase. While the mean weight after 8 months in G-1 was 350.0 g, and 352.5 g for G-3, that in G-2 was 400.0 g. The calcium content of the femur in G-2 and G-3 at 8 months was lower than that of G-1, but there were no significant differences among the three groups. ",4 1190,"Selective spatial attention in patients with visual extinction. The present study was designed to verify the attentional performance of patients with parietal lesions in the experimental condition in which they had to pay attention to 3 spatial positions located on the left, on the right and directly above the fixation stimulus (Experiment 1) and to only 1 of the 3 spatial positions at a time (Experiment 2). Twelve patients (6 subjects with right parietal lesions and 6 subjects without neurological deficits) participated in the experiment. The results of Experiment 1 showed that in patients with right parietal lesions the speed and accuracy of response to horizontally aligned stimuli increased gradually from right to left, whereas the control group showed only the effect due to the different retinal eccentricities of the 3 stimuli, that is, responses to central stimuli were faster and more accurate than responses to left and right stimuli. The results of Experiment 2 showed that both the neurological and control groups were faster to respond to central than to left and right stimuli, and that the neurological group was faster to respond to right than left stimuli, whereas no difference in RTs between two visual fields was obtained in the control group. Furthermore, when the patients had to respond to 3 spatial locations aligned horizontally (Experiment 1), the speed and accuracy of response to the right stimulus were the same as when they had to focus attention on it (Experiment 2). These results showed that the focus of attention in patients with visual extinction is on the rightmost stimulus and that the increased attention to the right is accompanied by a decreased attention to the left. ",9 1837,"Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: a combined hemodynamic and Doppler echocardiographic study of varying loading conditions. To explore the mechanisms of change of left ventricular diastolic filling associated with preload and afterload reduction, the influence of nitroprusside on the transmitral flow velocity pattern, pulmonary capillary wedge pressure and left ventricular pressure interaction was studied in 11 patients with end-stage heart failure. Pulsed Doppler echocardiographic recordings of mitral inflow were obtained with simultaneous high fidelity left ventricular and phase-corrected pulmonary capillary wedge pressure recordings before and during levels of nitroprusside infusion. With nitroprusside, left ventricular systolic and end-diastolic pressures decreased by 14% and 41% (p less than 0.05, p less than 0.05), respectively, and cardiac output increased by 67% (p less than 0.05). The pulmonary capillary wedge-left ventricular crossover pressure decreased by 41% (p less than 0.05), but the time constant of isovolumetric left ventricular pressure decrease T was insignificantly changed. Isovolumetric relaxation time and acceleration and deceleration times of the early diastolic filling wave were significantly prolonged with nitroprusside infusion (p less than 0.05, p less than 0.05 and p less than 0.05, respectively). Peak early diastolic filling velocity was maintained (65 +/- 11 to 62 +/- 13 cm/s, p = NS) in spite of the decreased absolute crossover pressure. Changes in peak early diastolic filling velocity correlated weakly with changes in the crossover pressure (r = 0.48, p less than 0.05) and correlated better with the crossover to left ventricular minimal pressure difference (r = 0.78, p less than 0.05). Peak early diastolic filling velocity appears to be most affected by the early diastolic pulmonary capillary wedge to left ventricular pressure difference rather than the absolute pulmonary capillary wedge pressure. The lack of peak flow velocity change during nitroprusside infusion could be explained by either the associated decrease in left ventricular minimal pressure or downward shift of left ventricular diastolic pressure by the same amount as the decrease in pulmonary capillary wedge pressure. This may reflect a reduction of external constraint to ventricular distensibility produced by a reduction in filling volume in patients with a markedly dilated ventricle. Thus, a prolonged early diastolic filling period and preserved peak early diastolic filling velocity in spite of decreased left ventricular filling pressure and constant relaxation rate are associated with the beneficial effects of nitroprusside on left ventricular function in patients with severe congestive heart failure. ",13 2858,"Alcohol consumption and problem drinking in Vietnam era veterans and nonveterans. The relationship between Vietnam era veteran status and 13 indicators of alcohol consumption and problem drinking is examined using data from the 1977, 1983 and 1985 National Health Interview Surveys conducted by the National Center for Health Statistics. Compared to a group of nonveterans frequency matched on age, a greater proportion of Vietnam era veterans are currently heavy drinkers and a smaller proportion are abstainers, after simultaneous adjustment for seven demographic factors (age, region of the U.S., urbanization, ethnicity, marital status, education and income). Further, both white veterans and white nonveterans demonstrate an effect of increasing abstention with increasing age across the 3 interview years. In all race and veteran groups the proportion of lifetime abstainers can be ranked in increasing order as follows: white veterans, white nonveterans, non-white veterans and non-white nonveterans. This ranking is reversed for lifetime heavy drinking. Nearly half of the white veterans report drinking heavily at some point in their lives. Among both whites and non-whites, a significantly greater proportion of veterans than nonveterans report alcohol-related motor vehicle crashes or violations. ",20 565,"Breast cancer: the military's experience at Wilford Hall USAF Medical Center. We reviewed the experience with breast cancer at Wilford Hall USAF Medical Center for the years 1978 through 1988. A total of 868 cases were identified in the Wilford Hall Tumor Registry; overall 5-year and 10-year survivals were 63% and 39%, respectively. Infiltrating ductal carcinoma represented the principal histologic category. The other predominant variants included invasive lobular carcinoma, lobular carcinoma in situ, and ductal carcinoma in situ. Until recently, most of these patients (90%) had modified radical mastectomy as their definitive surgical therapy, with chemotherapy reserved primarily for patients with advanced disease. ",3 2371,"Family of glucose-transporter genes. Implications for glucose homeostasis and diabetes. Glucose transport by facilitated diffusion is mediated by a family of tissue-specific membrane glycoproteins. At least four members of this gene family have been identified by cDNA cloning. The HepG2-type transporter is the most widely distributed of these proteins. It provides many cells with their basal glucose requirement for ATP production and the biosynthesis of sugar-containing macromolecules. The liver-type transporter is expressed in tissues from which a net release of glucose can occur and in beta-cells of pancreatic islets. A genetic defect resulting in reduced activity of this transporter could hypothetically lead to the two principal features of non-insulin-dependent diabetes mellitus, insulin resistance and relative hypoinsulinemia. The adipocyte/muscle transporter is expressed exclusively in tissues that are insulin sensitive with respect to glucose uptake. This protein is an excellent candidate for a highly specific genetic defect predisposing to insulin resistance. ",17 660,"The effect of stem stiffness on femoral bone resorption after canine porous-coated total hip arthroplasty. Bilateral noncemented total hip arthroplasty (THA) was produced in dogs to determine the effect of stem stiffness on stress-related bone resorption. Two porous-coated femoral implants of substantially different stiffnesses were designed for direct comparison. One was manufactured from cobalt-chromium (CoCr) alloy, the other from titanium alloy. The titanium stem was hollowed out to a wall thickness of 1 mm to further reduce its stiffness. The cumulative stiffness differences were about 5.4-fold axially and 3.6-fold in bending and torsion. Staged bilateral THA was performed on eight dogs. Each dog received a stiff CoCr stem on one side and a flexible titanium stem on the other. After death, the femora were removed and processed for undecalcified thin-section histology. Bone ingrowth and remodeling were quantified by computer-aided image analysis and compared between stem designs. All femoral specimens showed bone ingrowth fixation of both stiff and flexible stems along the implant length. Tetracycline labeling indicated active bone turnover in the femoral cortex and in regions of ingrowth. However, gross differences in femoral bone remodeling were observed both roentgenographically and histologically. Femora with the flexible stems consistently showed much less bone resorption than those with the stiff stems. Quantitative analysis of paired cross-sections indicated an average of 25%-35% more cortical bone area in the femora with flexible stems. Severe resorption of the cortex in the midstem region occurred in three of the femora with the stiff stems but in none with the flexible stems. Stem stiffness strongly influences bone remodeling. The flexible stem results in more uniform load transfer and less stress shielding. ",4 1301,"Comparison of albumin excretion rate obtained with different times of collection. This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient. ",11 831,"Breast-feeding and diarrheal morbidity. This study used a unique longitudinal survey of more than 3000 mother-infant pairs observed from pregnancy through infancy. The sample is representative of infants from the Cebu region of the Philippines. The sequencing of breast-feeding and diarrheal morbidity events was carefully examined in a longitudinal analysis which allowed for the examination of age-specific effects of feeding patterns. Because the work controlled for a wide range of environmental causes of diarrhea, the results can be generalized to other populations with some confidence. The addition to the breast-milk diet of even water, teas, and other nonnutritive liquids doubled or tripled the likelihood of diarrhea. Supplementation of breast-feeding with additional nutritive foods or liquids further increased significantly the risk of diarrhea; most benefits of breast-feeding alone or in combination with nutritive foods/liquids became small during the second half of infancy. Benefits of breast-feeding were slightly greater in urban environments. ",5 2480,"Mild hypoglycemia and impairment of brain stem and cortical evoked potentials in healthy subjects. To evaluate the impact of mild hypoglycemia on CNS function in healthy adults, we measured brain stem auditory evoked potentials and P300 potentials (elicited by cognitive processing of auditory stimuli) during hypoglycemic or euglycemic insulin clamps (80 mU.m-2.min-1). In the hypoglycemic clamp study (n = 8), plasma glucose was allowed to fall from 4.6 to 3 mM in hourly approximately 0.5-mM steps and subsequently returned to euglycemic baseline levels. In the euglycemic clamp study (n = 8), plasma glucose was maintained at baseline levels throughout. Neither brain stem nor P300 responses changed during the euglycemic control study; symptoms and counterregulatory hormones were also unaffected. During the hypoglycemia study, epinephrine and growth hormone rose once plasma glucose reached 3.4 +/- 0.1 mM. Brain stem and P300 potentials remained unchanged until the 3-mM glucose step, when neurophysiological changes suddenly developed in conjunction with reported symptoms. At this glucose level, the wave V component of the brain stem potential was selectively altered in 7 of 8 subjects. Furthermore, P300 latency significantly increased, and amplitude diminished. Changes in both brain stem and cortical (P300) responses reversed when euglycemia was restored. We conclude that modest reductions in plasma glucose (to 3 mM) produce marked alterations in both brain stem and cortical responses to auditory stimuli. These changes in neural function appear at the same time as symptoms and follow rather than precede the rise in counterregulatory hormones during hypoglycemia. Our data suggest that the adverse effects of mild hypoglycemia on brain function are not limited to higher centers but also involve the brain stem. ",17 386,"Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure. The Brain Tumor Study Group has shown procarbazine (PCB) to be as effective an adjuvant treatment as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We treated 35 patients with recurrent malignant astrocytomas after radiation and nitrosourea failure with successive courses of PCB 150 mg/m2/d for 28 days every 8 weeks. After 2 courses, 2 patients had complete responses, 7 had partial responses, 11 had stable disease, and 15 had progression. Significantly more patients receiving PCB had complete or partial responses or stable disease than a similar group of patients in a previous trial who received intra-arterial (IA) cisplatin (DDP). There is a significant advantage in time to disease progression for those receiving PCB compared with those receiving IA diaziquone (AZQ). Our results suggest that PCB is a more effective 2nd agent than IA DDP or AZQ following radiation and nitrosourea failure. ",3 3172,"Mutations in src homology regions 2 and 3 of activated chicken c-src that result in preferential transformation of mouse or chicken cells. src homology regions 2 and 3 (SH2 and SH3) of proteins encoded by src and closely related genes are conserved domains believed to modulate the protein-tyrosine kinase activity of this class of proteins, perhaps through interactions with other proteins. To explore the possibility of using src mutants as probes for such interactions, we have compared mouse NIH 3T3 cells with chicken embryo fibroblasts as host cells for 24 previously described substitution and deletion mutants with lesions in the SH2- and SH3-encoding regions of a transformation-competent allele of chicken c-src. Although several of these mutants are equally competent or equally defective for transformation of the two cell types, four mutants (three of which map within SH3) preferentially transform NIH 3T3 cells, and seven mutants (all of which map within SH2) preferentially transform chicken cells. Some of the SH2 mutants least able to transform mouse cells exhibit augmented transforming activity in chicken cells. In general, the in vitro protein-tyrosine kinase activities of the mutants correlated with transforming activities. Thus, in many cases, the catalytic activity of a mutant protein depended upon the host cell in which the protein was made. Such host-dependent mutants may be especially useful reagents for biochemical and genetic studies of the src gene family. ",22 613,"The inwardly pointing knee. An unrecognized problem of external rotational malalignment. Twelve patients with inwardly pointing knees had chronic knee pain and disability suggestive of patellofemoral subluxation. None had responded well to conservative measures or surgical correction at the level of the soft tissues. Their pattern of limb alignment was studied roentgenographically and was found to differ significantly from the control group of 49 healthy young adults. The deformities primarily related to the tibia were external tibial torsion, excess varus angulation of the tibial plateau, and varus knees. Angulation of the femoral condyles was normal and femoral anteversion did not appear to contribute significantly to the deformity. Surgery in seven cases (nine knees) was by derotation valgus Maquet osteotomy of the tibia and lateral release realignment of the patellae. Outcome assessments after a three-year follow-up period (five knees) were excellent. Early results on the remaining cases were satisfactory. ",4 776,"Binding to human jejunum of serum IgA antibody from children with coeliac disease. Jejunal histology and the presence of serum IgA antibodies (JAB) binding to human jejunum in vitro were studied in 139 children with severe malabsorptive symptoms. Among 33 children with confirmed coeliac disease (ESPGAN criteria), 13 (93%) of 14 sampled before starting on a gluten-free diet had JAB, none of 21 sampled had JAB while on a gluten-free diet of long duration, and 90% of 30 sampled during gluten challenge had JAB. 53 children had severe jejunal villous atrophy (probable coeliac disease): 71% of those younger than 2 years and 94% of those aged 2-18 years had JAB during gluten intake. JAB could not be detected in 53 disease control patients (normal jejunal histology) and in 3 coeliac disease patients with selective IgA deficiency. Simultaneous determination of antigliadin (AGA) and antiendomysium (EMA) levels, and gliadin and tissue absorption studies, showed that JAB and AGA are different, whereas JAB and EMA are probably identical. IgA JAB could be the target-organ-related autoantibodies in coeliac disease. ",5 3326,"The distribution of enkephalins in human carotid bodies showing cellular proliferation and chronic glomitis. Human carotid bodies obtained at necropsy that showed prominence of either the sustentacular cell or the dark variant of chief cell or chronic carotid glomitis were studied by an immunogold labeling technique. The peptides methionine and leucine enkephalin had a similar distribution to that found in the normal human carotid body. They were localized prominently and predominantly in the dark and progenitor variants of chief (type I) cells. The sustentacular (type II) cells showed no immunoreactivity for the enkephalins. Cell counts on immunolabeled chief cells in cases of sustentacular cell hyperplasia and chronic carotid glomitis were found to be at the lower end of the normal range, whereas those in dark cell prominence occurred nearer the upper limit. ",22 821,"Nonoperative management of bile duct stones. The treatment of choice for most retained bile duct stones is by nonoperative means. If a T-tube is in place, percutaneous techniques via the T-tract are indicated. Percutaneous access via puncture of a Roux-en-Y loop is also practical. In the absence of a T-tube, retrograde endoscopic techniques should be used. Both techniques are very effective and safe. Stones in the intrahepatic and extrahepatic ducts also can be treated nonoperatively. Endoscopic sphincterotomy has a role in the treatment of selected patients with gallstone pancreatitis, acute cholangitis, and choledocholithiasis with in situ gallbladders. In difficult cases, endoscopic and percutaneous techniques are employed in combination. ",5 339,"Clinical evaluation of a side entry access port: a novel dual-lumen venous access device. The initial clinical experience with a low-profile side entry access (SEA) dual-lumen implantable venous access port for cancer chemotherapy administration is summarized in this report. The catheter material is polyurethane. The overall experience in 35 patients in this study was a total of 6,224 patient days, with a mean of 178 days per patient. A variety of chemotherapeutic agents, biologic response modifiers, and antibiotics were administered. In 26% of the patients, the device chambers were in simultaneous use during the treatment period. A 6% incidence of clinical subclavian vein thrombosis was noted. There was no infectious complications. Inconsistencies in blood withdrawal and temporary catheter dysfunction were comparable to other access ports in clinical use. The novel design of this side entry port and the catheter material of low thrombogenicity make this device a good option in patients requiring a low-profile system and dual access. Nursing staff should be made aware of the side entry design and that in-service training for accessing the septum is required in centers where such devices are not routinely used. ",3 1831,"Endothelin family in human plasma and cerebrospinal fluid. To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable. Similarly, big endothelin-1, endothelin-1, and endothelin-3 were identified in human plasma. Although big endothelin-1 was the most abundant, a substantial amount of endothelin-1 and endothelin-3 was found in plasma with a resultant lower molar ratio of big endothelin-1 to endothelin-1 than in CSF. In all CSF samples from 17 patients requiring diagnostic lumbar puncture or lumbar anesthesia, endothelin was detectable, with a preponderance of big endothelin-1 relative to endothelin-1 and endothelin-3. The mean concentrations of endothelin-1 and endothelin-3 in simultaneously collected plasma were significantly (P less than 0.01) higher than those in CSF, while there was no significant difference between the mean big endothelin-1 concentration in plasma and that in CSF. There was no significant correlation among concentrations of big endothelin-1, endothelin-1, and endothelin-3 in each paired sample. These results indicate that endothelin is present in human CSF that is differently processed from endothelin in vascular endothelial cells and suggest a possible role for endothelin as a modulator of neuronal functions. ",13 1859,"Quantification of the reversibility of stress-induced thallium-201 myocardial perfusion defects: a multicenter trial using bull's-eye polar maps and standard normal limits A multicenter trial was performed on 140 patients from four centers to determine the accuracy of quantitative analysis of stress/delayed thallium-201 myocardial tomograms using normal limits to assess the relative amount of reversibility of stress-induced defects. The patients were found to have 85 fixed and 124 reversible defects, as determined by visual interpretation. Reversibility bull's-eye polar maps were compared to gender-matched normal limits from 36 normals. Regions were identified as reversible if their normalized difference between stress and 4 hr greater than 1.5 s.d.s. from the mean normal limits. Overall agreement between experts at multicenter sites and reversibility maps was 73% for reversible defects and 80% of fixed defects. Sensitivity in detecting reversibility was highest for the left circumflex (88%) and lowest for the right coronary (60%). These results indicate that reversibility polar maps and normal limits offer an objective, accurate technique for determining the reversibility of stress-induced perfusion defects. ",13 625,"Polymyositis: a case history approach to the differential diagnosis and treatment. A wide range of conditions can mimic polymyositis. Thus, diagnosing this condition can be a challenge. Although no single criterion is diagnostic of polymyositis, the following criteria have been proposed and widely used: (1) symmetric proximal muscle weakness; (2) characteristic violaceous rash on the hands, elbows, and knees; (3) increased muscle enzymes in the serum; (4) characteristic electromyographic findings (insertional activity, fibrillation potentials, motor unit potentials of increased frequency and decreased duration, and normal conduction velocity in nerves); and (5) muscle biopsy specimen with characteristic inflammatory and myopathic changes. Although polymyositis primarily involves muscle, up to 20% of patients may have extramuscular problems. The main treatment for polymyositis is high-dose corticosteroids. In corticosteroid-resistant patients, methotrexate is often effective. In this report, case histories are presented to highlight the usefulness and the limitations of the common diagnostic criteria for polymyositis. ",4 2544,"The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. The effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a randomised, double-blind, cross-over study. Paroxetine was given as a fixed dose of 40 mg/day, while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400-600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer- and self-rating, but was somewhat less effective than imipramine. However, patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs. On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study reported withdrawal symptoms after discontinuing imipramine. On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported. Self-rating showed no depressive symptoms at baseline, and no changes during the study. Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function. In conclusion, 40 mg paroxetine/day significantly reduced the symptoms in peripheral diabetic neuropathy, and it was suggested that by dose adjustment on the basis of drug level monitoring, paroxetine may become as effective as imipramine. Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients. ",18 2594,"Full-length recombinant CD4 and recombinant gp120 inhibit fusion between HIV infected macrophages and uninfected CD4-expressing T-lymphoblastoid cells. Human immunodeficiency virus-(HIV) infected monocyte-macrophages may contribute to the pathogenesis of HIV-associated immune deficiency and dysfunction by acting as a target and potential reservoir for the virus in vivo, and by functioning abnormally following infection. We have shown that HIV-infected macrophages fuse with uninfected CD4-expressing lymphoid cells in vitro; this may provide an additional mechanism for CD4 lymphocyte depletion in vivo. We report here the inhibition of syncytium formation between HIV-infected macrophages and uninfected CD4-expressing T-lymphoid cells by monoclonal antibody S3.5, directed against an epitope of CD4 involved in binding HIV gp120, by a recombinant protein that comprises the full-length extracellular domain of the CD4 molecule, and by recombinant full-length HIV envelope glycoprotein, gp120. These results indicate that both molecules (gp120 and CD4) are critical to the fusion process, and suggest that gp120 is expressed on the surface of HIV-infected monocyte-macrophages. ",19 2211,"Effect of maternal smoking and age on congenital anomalies. The incidence of congenital anomalies was examined by the level of maternal and paternal smoking during pregnancy for 17,152 infants. A multiple regression analysis was used to control for the possible confounding effects of maternal age, formal education, ethnic origin, religion, marital status, parity, social class, and work outside the home. Neither maternal nor paternal smoking habits were significantly associated with the occurrence of congenital malformations. Maternal age was significantly (P less than .005) related to the incidence of major anomalies. Mothers aged 35 years and older who smoked were found to have a significantly (P less than .002) higher risk for minor malformations and a nonsignificantly increased rate of major malformations. Maternal cigarette smoking may be an important preventable risk factor for congenital anomalies among mothers aged 35 years or older. ",15 1727,"Randomized trials in the study of antihypertensive drugs. Heterogeneity in response to antihypertensive drugs can be addressed by randomized trials in individual subjects. In such a trial a patient receives pairs of treatment periods (one period of each pair active drug, one matched placebo, in random order); patient and clinician are blinded to allocation, and treatment targets are monitored. These trials can optimize antihypertensive therapy in clinical practice and facilitate the investigation of new drugs and the study of pathophysiology. Such trials also have potential in helping decide whether common, nonspecific symptoms reported by patients are really drug related. ",13 2087,"An analysis of outcome following percutaneous transluminal coronary artery angioplasty. An autopsy series. We analyzed autopsy findings on 26 patients who died following percutaneous transluminal coronary angioplasty (PTCA). Twenty-one patients died within 3 weeks of undergoing PTCA; demonstrable cardiac complications were found in 19 patients: platelet-fibrin thrombi (10 patients [48%]), coronary artery dissections (17 patients [81%]), thromboemboli (13 patients [62%]), atheroemboli (seven patients [33%]), and myocardial infarcts (17 patients [81%]). An increased incidence of coronary platelet-fibrin thrombi was noted when compared with a non-PTCA cardiac autopsy population (five of 53 patients). Apparently there was an increased incidence of coronary atheroemboli and thromboemboli in the patients with coronary platelet-fibrin thrombi (eight patients) when compared with patients who did not have platelet-fibrin thrombi (five patients), although this was not statistically significant. There was no evidence of a systemic hypercoagulable state or of disseminated intravascular coagulation. The pathogenesis of this is unclear; however, vasospasm and a disruption of the endothelial surface induced by PTCA with subsequent platelet activation are possible causes. Although not statistically significant, there was a proponderance of female subjects (seven patients) and an increased incidence of diabetes mellitus (six patients) and hypertension (13 patients) when compared with a control population of all patients undergoing PTCA at The Cleveland (Ohio) Clinic Foundation in 1987, suggesting that diabetes mellitus, hypertension, and female sex may be clinical risk factors for fatal complications following PTCA. ",13 2745,"Corticocancellous grafting and an AO/ASIF lag screw for nonunion of the scaphoid. A retrospective analysis. We report our experience in 42 patients, using corticocancellous bone grafts and lag screw fixation for un-united scaphoid fractures. Using a grading system, we analysed the suitability of the method for three types of nonunion. We recommend the operation for the treatment of scaphoid nonunion, except where there is avascular necrosis of the proximal pole. ",20 2307,"Immunosuppressive effects of clonidine on the induction of contact sensitization in the balb/c mouse. The clonidine transdermal therapeutic system (clonidine-TTS) has been associated with a significant incidence of allergic contact sensitization. This incidence was not predicted by premarket skin sensitization testing in animals or humans. One possible explanation lies in recent findings in guinea pigs that clonidine exposure could inhibit the elicitation of skin reactions to unrelated strong contact sensitizers. However, these studies also showed that clonidine pretreatment did not appear to affect the induction of contact sensitization. On this basis, we sought to specifically evaluate the induction phase of sensitization to clonidine as an alternative means of assessing its sensitization properties. The method selected was the assay of in situ lymphocyte proliferation in lymph nodes draining the sites of clonidine exposure, a method recently promoted as an alternative means to assess contact allergenic potential. Utilizing various induction application techniques and regimens, we were consistently unable to demonstrate clonidine's allergenic potential through such an assessment of lymphocyte proliferation. We were also unable to demonstrate sensitization by in vivo ear swelling or in vitro lymphocyte blastogenesis assay techniques. However, a subsequent assessment of the effect of clonidine exposure on the induction of sensitization to unrelated strong contact allergens demonstrated a consistent 40-70% inhibition of the proliferative response to the contact allergens oxazolone and trinitrochlorobenzene. This was similar to the degree of suppression produced by the corticosteroids fluocinonide and hydrocortisone when they were tested at 80 and 10 times lower concentrations. In addition, we observed a comparable inhibition of the ear swelling response to oxazolone. These data extend our knowledge of the immunomodulatory effects of clonidine and offer additional mechanistic insights into the failure of short-term predictive patch-test methods to detect this chemical's potential to induce allergic contact sensitization. ",16 1827,"Successful surgical treatment of subaortic stenosis caused by an accessory mitral valve. A 22-month-old boy with subaortic stenosis was found to have relatively mature mitral valve tissue beneath the aortic valve, associated with a hypertrophic and prominent interventricular septum. This tissue caused obstruction of the left ventricular outflow tract and resulted in a pressure gradient of 70 mmHg between the aorta and the left ventricle. Surgical treatment was successfully performed to excise the tissue and part of the hypertrophic ventricular septum. Results of microscopic examination of the resected specimen are shown and discussed. ",13 2716,"Effect of digitalis on clinical symptoms and conduction variables in patients with multiple sclerosis. Digitalis has been shown to reverse conduction block in demyelinated nerve fibers in experimental animals. In the search for a symptomatic treatment of multiple sclerosis, digoxin (0.02 mg per kilogram of body weight) was given intravenously to 7 patients with probable or clinically definite multiple sclerosis. All of these patients had temperature-dependent symptoms. In 3 patients, improvement of clinical deficits was observed concurrent with significant changes in evoked potential findings. Digitalis derivatives may be useful in ameliorating symptoms in selected patients with multiple sclerosis. ",19 3324,"An evaluation of the Level 1 blood warmer series The Level 1 blood warmer series comprises three infusion sets and two blood warmers of different power outputs. All systems were found to be extremely efficient, with the larger 500 series capable of warming the equivalent of 80 units of blood an hour almost to body temperature. ",22 3063,"Temporary cardiac pacing using a new, steerable, balloon-tipped pacing catheter. A new balloon-tipped, flow-directed, steerable pacing catheter for unipolar temporary ventricular pacing is presented. It was successfully and uneventfully tested in 25 patients with acute myocardial infarction in the coronary care unit. The main advantage of the new catheter is the ease with which a stable contact may be achieved between the pacing electrode and the endocardium. ",22 55,"Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group BACKGROUND. The prevention of invasive Haemophilus influenzae type b disease requires a vaccine that is effective when administered during the first six months of life. The infants of Alaska Natives are at particularly high risk of invasive H. influenzae type b disease. METHODS. To evaluate the protective efficacy of a H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]), we enrolled 2102 Alaska Native infants in a randomized, double-blind, placebo-controlled trial in which either the vaccine or a saline placebo was administered at approximately two, four, and six months of age. RESULTS. After 3969 subject-years of follow-up and 32 episodes of H. influenzae type b disease, the overall incidence of invasive disease was not reduced significantly in the vaccinated subjects (6.0 cases per 1000 patient-years), as compared with the placebo controls (9.6) or with other Alaska Native infants (6.0). After one, two, or three doses there was no significant protective efficacy with the vaccine; after three doses the efficacy was only 35 percent (95 percent confidence interval, -57 to 73). The lack of efficacy was not related to the age at onset of disease, age at immunization, type of disease, degree of Alaska Native heritage, time after immunization, or year of the study. Levels of H. influenzae type b anticapsular antibody in recipients of the vaccine became significantly higher than levels in those who received placebo only after the second and third doses. Even after the third dose, only 48 percent of the vaccinated infants had antibody levels of more than 0.1 microgram per milliliter (geometric mean titer, 0.18). Antibody responses did not vary with the level of maternally acquired antibody, degree of Alaska Native ancestry, or age at time of the first or second immunizations, but they increased with increasing age at time of the third dose (P less than 0.001). CONCLUSIONS. We found no evidence that the PRP-D vaccine provides significant protection, at least for Alaska Native infants, against invasive diseases caused by H. influenzae type b. The ineffectiveness of the vaccine paralleled its limited immunogenicity. ",0 699,"Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment. ",5 1611,"Vena caval flow: assessment with cine MR velocity mapping. The authors used cine magnetic resonance (MR) velocity mapping to study flow in the superior vena cava (SVC) and inferior vena cava (IVC) of 13 healthy control subjects and 13 patients with right-sided cardiac disease. In the control subjects, peaks of flow in systole and diastole were observed, and mean SVC flow was 35% of the cardiac output. Respiratory gating was used in six control subjects to acquire images at end inspiration and end expiration, and although the systolic peak was reduced at end expiration, total flow was unchanged. A reduced systolic peak and retrograde flow in the IVC were observed in patients with tricuspid regurgitation. A reduced diastolic peak was seen in patients with pulmonary hypertension, pericardial constriction, and right ventricular dysplasia, reflecting reduced diastolic compliance of the right ventricle. In the patient with obstruction of the SVC, absence of flow was confirmed, and retrograde flow was seen in the azygos vein. The authors believe that cine MR velocity mapping is a reliable method of studying vena caval flow noninvasively and that it has important potential applications for the investigation of disorders of the right side of the heart. ",13 2079,"Left ventricular filling impairment in asymptomatic chronic alcoholics. Systolic left ventricular dysfunction is relatively common in even asymptomatic alcoholics, but whether diastolic function is also altered is much less well-studied. We used M-mode and Doppler echocardiography to study left ventricular size, mass, systolic function and diastolic filling in 32 alcoholics free of clinically detectable heart disease and in 15 healthy control subjects. Left ventricular mass index and posterior wall thickness were higher in alcoholics than in controls, but there was no statistically significant difference either in end-diastolic size or in systolic ventricular function. More abnormalities were found in the Doppler indexes of diastolic function, however. The alcoholics had a prolonged relaxation time (200 +/- 6 vs 184 +/- 5 ms [mean +/- standard error], p less than 0.05), a decreased peak early diastolic velocity (52 +/- 2 vs 60 +/- 3 cm/s, p less than 0.05), a slower acceleration of the early flow (410 +/- 18 vs 552 +/- 43 cm/s2, p less than 0.01), and a higher atrial-to-early peak velocity ratio (0.74 +/- 0.04 vs 0.60 +/- 0.05, p less than 0.05). This pattern of changes suggests a primary abnormality in the relaxation of the left ventricle. In multivariate analyses, the abnormalities in the Doppler indexes were independent of the duration of alcoholism, the quantity of the most recent ethanol exposure and the increased mass of the left ventricle. Impaired early filling of the left ventricle due to delayed relaxation is common in asymptomatic alcoholics and may in fact be the earliest functional sign of preclinical alcoholic cardiomyopathy. ",13 822,"Surgical management of bile duct stones. The biliary surgeon in the 1990s must be familiar with all of the available techniques for the treatment of bile duct stones. Experience and judgment are important in the successful management of the individual patient with intrahepatic or extrahepatic stones. Knowledge of the nonsurgical methods of stone removal is important in the decision-making process. However, the biliary surgeon must resist the temptation to do less than a thorough removal of all stones at the operation lest the patient be subjected to additional procedures, which carry their own risks of morbidity and death. The goal should be to clear the stones from the biliary system with the fewest procedures offering the lowest morbidity and mortality risks to the patient. ",5 1720,"Financial impact of a rapid CK-MB-specific immunoassay on the diagnosis of myocardial infarction. The purpose of this study was twofold. First, we evaluated the financial impact of a rapid, monoclonal antibody-based CK-MB mass assay (Stratus, Dade Division, Baxter Laboratories, Miami, Fla) for the direct measurement of CK-MB in serum samples from 65 patients admitted to the coronary care unit with the possible diagnosis of acute myocardial infarction. Second, we evaluated retrospectively the Stratus assay and an activity assay (electrophoresis) for CK-MB in the following patient categories: acute myocardial infarction treated with and without thrombolytic therapy, angina, congestive heart failure, skeletal muscle trauma, and the acutely ill without acute myocardial infarction. The advantageous features of the Stratus mass assay were as follows. First, the laboratory was able to perform the assay more frequently because of the short assay time per specimen (less than 10 minutes) without additional personnel. This had a substantial impact on the clinician's ability to diagnose acute myocardial infarction and to move patients out of an intensive care unit at substantial financial savings to the patient, the hospital, or the third-party payer. Second, the Stratus assay was able to detect low levels of CK-MB (1 to 2 micrograms/L) in the presence of low total creatine kinase activity (less than 100 U/L). Third, the Stratus assay showed no interference due to very-high-total creatine kinase activities (greater than 100,000 U/L), CK-BB, macro-creatine kinase, and mitochondrial creatine kinase. ",13 177,"Immunophenotypes in ""classical"" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings. This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of ""classical"" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease. ",3 803,"A pitfall in azygos vein cannulation in cirrhotic patients: mistaken cannulation of the mammary vein. Azygos venous flow can be measured by a thermodilution catheter in patients with cirrhosis. This is a useful technique since azygos flow is thought to reflect the superior portosystemic collateral flow in these patients. The authors report 3 cases in which mistaken internal mammary vein cannulation mimicked azygos vein cannulation in the supine fluoroscopic view. A lateral fluoroscopic view confirmed internal mammary cannulation. They suggest that if the azygos arch is unpronounced or flow measurements are unexpectedly low in patients with portal hypertension due to cirrhosis, a lateral view be performed to rule out internal mammary vein cannulation. ",5 700,"Pancreatic function in Crohn's disease. We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. ",5 2381,"Practical nutritional advice for the elderly, Part I: Evaluation, supplements, RDAs. A geriatrics panel discussion. By the time someone reaches old age, he or she thinks they know everything they want, or need, to know about nutrition. Yet malnutrition and its many effects are a rising danger. In this first of two installments of a panel discussion, nutritional experts review practical concerns for the treating physician, including assessment, interpretation of weight loss, use of supplements, and the relevance of RDAs to the elderly. ",17 904,"Selective IgG subclass deficiencies and antibody responses to pneumococcal capsular polysaccharide antigen in adult community-acquired pneumonia. We measured the serum concentrations of IgG subclasses in healthy subjects (n = 26) and in patients with community-acquired pneumonia (CAP) on admission (n = 38), at recovery (n = 21), and 9 months after admission (n = 19). Then, in 8 of the control subjects and 15 of the patients, we measured IgG subclasses and mean serum antibody concentrations of pneumococcal capsular polysaccharides before and 3 wk after immunization with a pneumococcal vaccine. Compared to the control subjects, the serum concentration of the IgG2 subclass was lower at admission in patients with CAP of bacterial or unknown cause (p less than 0.005). Concentrations of IgG subclasses in patients did not differ between admission and recovery, or between admission and 9 months later. After vaccination, in both control subjects and patients, there was an increase in the concentrations of IgG2 subclasses (p = 0.01) and antipneumococcal antibodies (p less than 10(-4)). We show that serum IgG2 concentration in patients with CAP of bacterial or unknown cause is lower than in healthy subjects and remains lower for several months. After immunization with a pneumococcal vaccine, the increase in serum concentrations of IgG subclasses and antipneumococcal antibodies in patients does not differ from those in control subjects. ",7 3320,"Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion. The prevention of graft occlusion by aspirin (100 mg/day) or heparin followed by phenprocoumon was investigated in a randomized trial in 235 patients after aortocoronary bypass operation. Aspirin treatment started 24 hours before, and heparin 6 hours and phenprocoumon 2 days after surgery. The results of the vein graft angiography and the clinical outcome 3 months postoperatively did not differ: 22% of 218 vein graft distal anastomoses in the aspirin group and 20% of 272 in the anticoagulant group were occluded. At least 1 occluded distal anastomosis was present in 38% of 74 patients in the aspirin-treated group and in 39% of 86 in the anticoagulant group. Worst-case analysis of all randomized patients showed graft occlusions, cardiovascular complications or lost to follow-up in 42% of 122 aspirin-treated patients compared with 41% of 113 patients treated with anticoagulants. For grafts with endarterectomy the occlusion rate was lower in the aspirin (12% of 49) than in the anticoagulant (22% of 41) group (p less than or equal to 0.05). Increased perioperative blood loss in the aspirin group (1,211 +/- 814 ml in the first 48 hours vs 874 +/- 818 ml in the anticoagulant group [p less than or equal to 0.001]) without a higher reoperation rate indicates effective platelet inhibition with low-dose aspirin. Because occlusion rates were equal but high in these patients with advanced stage of coronary artery disease, a combination of low-dose aspirin and anticoagulation should be investigated to reduce graft occlusion rates further. ",22 1196,"Lack of change in neurochemical markers during the postepileptic phase of intrahippocampal tetanus toxin syndrome in rats. The chronic epileptic syndrome induced by injecting tetanus toxin into rat hippocampus causes functional changes that essentially are permanent, outlasting the period of active seizures by at least 1 year. These long-term changes have been characterized by an impaired performance on a range of behavioral tasks, which in turn have been associated with a physiologic depression of hippocampal evoked responses but not with any discernible histopathology. In the present study, we examined the hippocampi of rats in the postseizure phase of the tetanus toxin model and observed no significant changes in the concentration of neurochemical markers for six neurotransmitters. Therefore, the long-term reduction in hippocampal excitability cannot be attributed to any major loss of afferents or hippocampal neurons using aspartate, acetylcholine, gamma-aminobutyric acid (GABA), glutamate, norepinephrine (NE), or serotonin as their transmitters. ",9 260,"Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. There is no consistently reliable treatment for endocarditis resulting from chronic Coxiella burnetii infection, the causative agent of Q fever. Although certain antibiotics are recommended on the basis of their in vitro bactericidal activities, results of therapy with these antibiotics are often disappointing. To evaluate whether the currently recommended antibiotic susceptibility tests for C. burnetii give misleading results because of continued division of uninfected cells, thereby resulting in the dilution of infected cells and, hence, a false picture of antibiotic efficacy, we blocked cell division during antibiotic susceptibility testing with cycloheximide. Using this new method, we found that the currently recommended antibiotics for the treatment of Q fever, doxycycline, pefloxacin, and rifampin, did not reduce the ratio of infected to noninfected cells (either L929 or P388D1) by 9 days postinfection. To test the hypothesis that this lack of antibacterial activity is due to antibiotic inactivation by the low pH of the phagolysosomes in which C. burnetii is found, we used alkalinizing lysosomotropic agents (chloroquine or amantadine) concurrently with doxycycline. This resulted in the sterilization of C. burnetii infection in P388D1 cells. This finding seems to confirm our suspicion that the acidic conditions of the phagolysosomes in which C. burnetii is located inhibit antibiotic activity. This inhibition can be reversed in vitro when lysosomotropic alkalinizing agents are used. ",3 2591,"D-penicillamine-induced lupus erythematosus. We describe a patient who presented with polyarthritis, pleurisy, rash, and a positive antinuclear antibody result after 5 years of D-penicillamine therapy. D-penicillamine-induced antinuclear antibodies were mainly high-titer IgG directed against the (H2A-H2B)-DNA complex. Weak IgM activity with H1 and H2B was also observed. Withdrawal of D-penicillamine therapy resulted in improvement in clinical symptoms and gradual resolution of serologic abnormalities. ",19 556,"Gamma-detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX-1 colon xenografts. Nude mice bearing CX-1 colon tumors were injected with 50 microCi 125I-labeled monoclonal antibody (MAb) B72.3. Radioactivity in tumors was studied with the gamma detecting probe (GDP) on days 1, 3, 7, and 10 after MAb injection. On each day, two mice were sacrificed and sections were examined with autoradiography (ARG), immunoperoxidase methods (IMP), and routine stains. Mean probe counts showed increasing tumor to background ratios and ARG demonstrated a progressive increase in radionuclide in the tumors. The distribution of 125I was primarily around the vascular spaces on day 1, but by day 3 and progressively it appeared in tumor gland lumina and necrotic areas. A regional correlation was shown between radionuclide in vascular spaces and its sequestration in tumor elements. ",3 2322,"A substitution at a non-glycine position in the triple-helical domain of pro alpha 2(I) collagen chains present in an individual with a variant of the Marfan syndrome. A substitution for a highly conserved non-glycine residue in the triple-helical domain of the pro alpha 2(I) collagen molecule was found in an individual with a variant of the Marfan syndrome. A single base change resulted in substitution of arginine618 by glutamine at the Y position of a Gly-X-Y repeat, and is responsible for the decreased migration in SDS-polyacrylamide gels of some pro alpha 2(I) chains of type I collagen synthesized by dermal fibroblasts from this individual. Family studies suggest that this substitution was inherited from the individual's father who also produces abnormally migrating pro alpha 2(I) collagen chains and shares some of the abnormal skeletal features. This single base change creates a new Bsu36 I (Sau I, Mst II) restriction site detectable in genomic DNA by Southern blot analysis when probed with a COL1A2 fragment. The analysis of 52 control individuals (103 chromosomes) was negative for the new Bsu36 I site, suggesting that the substitution is not a common polymorphism. ",16 3057,"Hormone implants and tachyphylaxis. The serum oestradiol levels of 1388 women treated with hormone implants at a menopause clinic were reviewed in 1988. Thirty-eight (3%) were found to be above 1750 pmol/l. Of these 38 women with supraphysiological oestradiol levels 23 had started therapy for menopausal symptoms and 15 for the premenstrual syndrome (PMS). Of the 23 women treated for menopausal symptoms 11 had a history of psychiatric referral for depression and nine had undergone a surgical menopause. Nine of the 15 women with PMS had a history of psychiatric referral for depressive symptoms. We conclude that the women who attain supraphysiological levels of oestradiol on implant therapy have a high frequency of psychopathology or surgical menopause and may require higher oestradiol levels for adequate control of symptoms. ",22 2050,"Medical management of chronic heart failure: inotropic, vasodilator, or inodilator drugs? On the basis of pathophysiologic mechanisms, the medical therapy of today for chronic heart failure is reviewed. The advantages and disadvantages of the vasodilator drugs and the inotropic drugs are presented. Finally, the therapeutic value of the inodilator drugs, which combine the central myocardial effects of positive inotropic agents with those of peripheral vasodilators, is discussed. In particular, the orally available dopaminergic agents, such as ibopamine, which interact with beta-receptors in the heart (mediating a positive inotropic effect) as well as with dopaminergic receptors in the peripheral vessels (mediating a systemic vasodilator effect) and in the kidneys (potentiating the natriuretic effect of diuresis), seem to be an advancement in the modern medical therapy of chronic heart failure. Data are shown during long-term treatment with ibopamine, in which the sustained clinical benefit in heart failure was not diminished, despite a decrease of the adrenergic receptors in blood cells. Dopamine plasma concentration was permanently normalized during long-term treatment. The discrepancy between clinical improvement and the measured adrenergic downregulation may be due to the interference of the inodilator with neurohormonal systems at multiple sites and is probably independent of receptor activation. It is suggested that the biosynthesis of noradrenaline is improved by increasing intracellular dopamine transport. ",13 3235,"Aplasia cutis congenita and arteriovenous fistula. Case report and review. We describe a child with congenital aplasia cutis congenita of the scalp and an occult giant posterior fossa arteriovenous fistula. Previous case reports of central nervous system malformations associated with aplasia cutis congenita are reviewed. The exact incidence of such malformations is unknown. All patients with aplasia cutis congenita should undergo a neurologic evaluation, and their families should be examined for similar lesions. Early central nervous system imaging and other workup may be required, especially if plastic surgery in the head region is being planned. ",22 1578,"Two-way factorial study of alcohol and salt restriction in treated hypertensive men. The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a ""low sodium"" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01). ",13 1958,"Cardioplegia-induced damage to ischemic immature myocardium is independent of oxygen availability. The known benefits of hypothermic pharmacological cardioplegia in protecting the ischemic adult heart may not extend to children. Protection of the ischemic immature rabbit heart with hypothermic Krebs-Henseleit bicarbonate buffer is better than with hypothermic St. Thomas' II cardioplegic solution. We investigated whether the availability of oxygen in the preischemic perfusate is responsible for the increased tolerance to ischemia of immature (7- to 10-day-old) hearts perfused with Krebs buffer in comparison with St. Thomas' II solution immediately before ischemia. After obtaining preischemic control data in the ""working"" mode, we perfused hearts (n = 8 per group) for 3 minutes with hypothermic (14 degrees C) Krebs buffer or hypothermic St. Thomas' II solution saturated with 0%, 25%, or 95% oxygen. This was followed by 2 hours of global ischemia at 14 degrees C. Hearts were reperfused for 15 minutes in the Langendorff mode and 35 minutes in the working mode, and recovery of function was measured. For preischemic oxygen concentrations of 0%, 25%, and 95%, recovery of aortic flow in hearts protected by hypothermia alone during ischemia was 74% +/- 9%, 82% +/- 4%, and 99% +/- 2% of preischemic values, respectively. In hearts protected by hypothermia plus cardioplegia, the values were 69% +/- 6%, 72% +/- 3%, and 86% +/- 5%, respectively. Thus, at equal oxygen concentrations, recovery of postischemic function was better in hearts protected by hypothermia alone compared with hypothermia plus cardioplegia. We conclude that factors other than oxygen availability are responsible for the damaging effect of St. Thomas' II solution on the ischemic immature rabbit heart. ",13 3117,"Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation. The purpose of this study was to compare the reproducibility of two approaches to the evaluation of GH secretion: the integrated concentration of GH (IC-GH), a physiological test of GH secretion, and pharmacological stimulation tests. IC-GH was determined in 40 poorly growing children twice within 4 weeks. The first and second IC-GH were highly correlated r = 0.859, P less than 0.001. One hundred and thirteen poorly growing children underwent pharmacological GH stimulation tests twice within 6 weeks. A moderate correlation was found between the first and second pharmacological test r = 0.524, P less than 0.01. Among the three pharmacological stimuli studied, clonidine (n = 81) had the highest reproducibility followed by arginine (n = 20), and insulin (n = 12). We conclude that IC-GH is more consistently reproducible than the GH response to repeated pharmacological stimulation. ",22 1563,"Left main percutaneous transluminal coronary angioplasty with the autoperfusion catheter in an animal model. Left main coronary angioplasty is associated with high risk because of interruption of blood flow to much of the left ventricle during balloon inflation. An ""autoperfusion"" balloon angioplasty catheter that allows blood to flow passively distal to an inflated balloon was tested in dogs and compared with inflations with standard balloon catheters. During 3 min occlusions of the left main coronary artery with the autoperfusion catheter, regional myocardial blood flow was preserved at 0.60 +/- 0.14 ml/min/g, compared with 0.07 +/- 0.03 ml/min/g during inflation with standard balloon catheters (P less than 0.01). Similarly, at the end of 3 min of inflation, left ventricular systolic pressure and dP/dt were maintained with autoperfusion catheter inflation, but they were severely depressed after standard angioplasty balloon inflation. All seven dogs survived autoperfusion balloon inflation, whereas five of seven developed sustained ventricular tachycardia and/or ventricular fibrillation during or after standard balloon inflation. Thus, distal blood flow, hemodynamics, and survival were preserved during autoperfusion balloon inflation in the left main coronary artery. ",13 2123,"Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist. To determine if alterations in regional coronary vascular resistance could occur in the type of myocardial ischemia present in severe angina pectoris, regional perfusion and function were studied in 35 conscious sedated dogs. A stenosis producing severe hypokinesia of the perfused segment was created for 2 h on the left anterior descending coronary artery and 10 episodes of 1 min of high demand ischemia (atrial pacing at a rate sufficient to induce dyskinesia in the hypoperfused segment) were superimposed before reperfusion. The dogs were randomized into three treatment groups: control (n = 13), dipyridamole (n = 10) or WEB-2086 (n = 12), an antagonist of the effects of the endogenous platelet-activating factor. During stenosis, residual endocardial blood flow in the ischemic but nonnecrotic area averaged 0.72 +/- 0.14, 0.38 +/- 0.13 and 0.68 +/- 0.17 ml/min per g in the control, WEB-2086 and dipyridamole groups, respectively. Twenty-four hours after reperfusion, endocardial blood flow in the ischemic area was significantly lower in control dogs (1.04 +/- 0.15 ml/min per g) than in dogs treated with WEB-2086 (1.44 +/- 0.28 ml/min per g; p less than 0.03) or dipyridamole (3.00 +/- 0.83 ml/min per g; p less than 0.01). Accordingly, in control dogs, endocardial coronary vascular resistance in the ischemic area was increased after reperfusion from 85 +/- 11 to 124 +/- 27 mm Hg/(ml/min per g) (p less than 0.05) after 24 h. In contrast, coronary vascular resistance in the ischemic area remained unchanged in dogs receiving WEB-2086 (77 +/- 8 to 79 +/- 9 mm Hg/(ml/min per g); p = NS) and it decreased significantly in dogs receiving dipyridamole (72 +/- 8 to 44 +/- 8 mm Hg/(ml/min per g); p less than 0.01). Regional function after 24 h remained depressed in all three groups. These data indicate that low flow, high demand ischemia induces alterations in the subendocardial microvasculature. Such alterations in regional coronary vascular resistance might play a role in several forms of ischemic heart disease such as in severe angina, but they appear susceptible to improvement by therapeutic interventions that influence granulocyte and platelet activation. ",13 928,"Platelet-activating factor- and leukotriene B4-induced release of lactoferrin from blood neutrophils of atopic and nonatopic individuals. We found increased accumulation of neutrophils and their components, lactoferrin (Lf) and elastase, as well as platelet-activating factor (PAF) and leukotriene B4 (LTB4) at sites of ongoing human allergic reactions. To determine whether PAF or LTB4, could be the stimulus for in vivo Lf release, blood neutrophils of 17 subjects were incubated with PAF, LTB4, or the phorbol ester, phorbol myristate acetate (PMA), and the released Lf (ELISA assay) was compared with spontaneous release. Significantly increased Lf release was induced by PAF, 10(-5) to 10(-8) mol/L (p less than 0.002); LTB4, 10(-7) to 10(-8) mol/L (p less than 0.004); and PMA (0.05 micrograms/ml) in a dose-dependent reaction. Cytochalasin was not required for Lf secretion but did enhance such responses. PAF-induced Lf secretion was inhibited by the specific PAF antagonist, BN 52063. More Lf was released from neutrophils of atopic than from nonatopic subjects in response to PAF, 10(-6) mol/L (4.2 micrograms/ml +/- 0.2 versus 2.6 micrograms/ml +/- 0.2; p less than 0.001) but not to LTB4, PMA, or buffer (p, not significant). We conclude that (1) PAF and LTB4 released in vivo could stimulate local neutrophils to release Lf with possible pathogenic effects and (2) neutrophils of atopic subjects are more responsive to PAF than neutrophils of nonatopic subjects in this regard. ",7 2818,"Hypophosphatemia--incidence, etiology, and prevention in the trauma patient. Hypophosphatemia is associated with a number of undesirable physiologic consequences and has been reported to occur frequently in trauma patients. We studied patients in the immediate posttraumatic period to document a) the decrease in serum P, b) renal P excretion, and c) the response to prophylactic PO4 administration. In both group 1 (n = 12) and group 2 (n = 10) patients, we measured serum P, creatinine, ionized Ca, urinary P excretion, and creatinine clearance daily for the first 3 to 4 days postinjury. Patients in group 2 also received 0.5 mmol/kg.day of PO4 for the first 48 h after admission. Group 1 patients exhibited a significant (p less than .05) decrease in serum P over the first 24 h (1.00 +/- 0.30 to 0.75 +/- 0.23 mmol/L). In contrast, group 2 patients did not demonstrate a decrease in serum P. Urinary P excretion in group 1 accounts for the observed decrease in serum P. The results of our study show that the immediate posttraumatic period is associated with a decrease in serum P and massive urinary P excretion. We also showed that prophylactic administration of 0.5 mmol PO4/kg.day prevents serum P decrease. ",20 813,"NSAID-induced gastrointestinal damage. A critical review of prophylaxis and therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute diffuse injury to the gastroduodenal mucosa, and also cause chronic focal ulcers that may bleed or perforate without warning symptoms. Acute and chronic lesions are distinct, are pathogenetically different, respond differently to drugs, and require different management strategies. The principal rationale for antiulcer therapy in NSAID users is to prevent or reduce potentially fatal outcomes; to date no evaluated drug meets this criterion for efficacy. Antacids and H2-receptor antagonists, based on open uncontrolled studies, appear to heal both gastric and duodenal ulcers, and maintain them healed during continued NSAID use; larger gastric ulcers show delayed healing with conventional doses of H2-receptor antagonists during NSAID therapy. No such delay occurs with omeprazole therapy. The suggests that if NSAID-associated gastric ulcers are treated with H2-receptor antagonists, larger doses should be given for longer periods. In patients with no pre-existing ulcer disease, H2-receptor antagonists given prophylactically prevent duodenal but not gastric ulcers; sucralfate does the same. In individuals without peptic ulcer disease taking NSAIDs, misoprostol, given as prophylaxis, reduces the development of gastric ulcers; its beneficial effects on ulcer healing or symptoms during continued NSAID therapy, or its ability to prevent duodenal ulcers or ulcer complications, are not established. Because of diarrhea, the 400 micrograms/day dosage is recommended, especially in the elderly. ",5 621,"Musculoskeletal impairments and physical disablement among the aged. This article summarizes the results of a longitudinal investigation of the progression of sight, hearing, and musculoskeletal impairments and their association with change in physical disability, in 10 ADLs among members of the Massachusetts Health Care Panel Study. The findings confirm widely held clinical beliefs that specific types of musculoskeletal decrement are an important cause of physical disability among older persons. Decrement in hand function is a significant musculoskeletal impairment influencing limitations in Basic ADL, and progression of Instrumental ADL dysfunction is influenced by progression of lower extremity impairments. Progression of sight and hearing impairments was not associated with change in physical disability. Musculoskeletal impairments, one of the most prevalent and symptomatic chronic complaints of middle and old age, deserve increased attention from epidemiologists, disability researchers, and clinicians seeking ways to prevent disablement among the aged. ",4 2946,"Trend toward nonoperative management of splenic injuries. Treatment of splenic injuries has evolved over the past decade to reflect more effort to conserve function of the spleen. Records of 169 patients admitted over a 6-year period were identified as documenting the treatment of splenic injuries. We collected data regarding patient age, gender, degree of hemodynamic stability, number of units of blood required, severity of splenic injury, Injury Severity Score, and results of treatment. There were 143 adults (age greater than 16 years) and 26 pediatric patients (age less than 17 years), with mean age in the 2 groups of 31.6 and 11.4 years, respectively. Males comprised 72% of the group, and blunt injury occurred in 154 of the 169 patients. In the adults, splenectomy, splenorrhaphy, laparotomy without operative treatment of the spleen, and nonoperative management were observed 48%, 30%, 14%, and 8% of the time and in the pediatric group 31%, 27%, 19%, and 23% of the time, respectively. By using operative splenic repair techniques and increased use of nonoperative management, the splenic salvage rate has increased in the last 6 years from 41% to 61% without an increase in morbidity and mortality. Incidence of spleen salvage correlated with severity of spleen and overall injury and cardiovascular stability. ",20 68,"Epidemiology of Lyme disease in Virginia. Prior to January 1986, only one case of Lyme disease was reported from Virginia. In 1986-87, however, the Virginia Department of Health observed an increase in reports of suspected Lyme disease by physicians, despite the fact that Ixodes dammini is not highly prevalent in the Virginia tick population. Twenty-eight cases of Lyme disease were identified in Virginia, of which eight cases occurred in 1986 and 20 in 1987. Lyme disease appears to be increasing in frequency in Virginia and moving southward along the Eastern Atlantic Seaboard. ",0 2535,"Training obstetrics-and-gynecology residents to manage breast disease. Incorporation into a breast care clinic. The American Board of Obstetricians and Gynecologists recently issued a directive that education in breast disease be incorporated into all residency training programs. At the University of Michigan Medical Center, the Comprehensive Breast Care Center (BCC) provides the vehicle for the education and training of residents in the area of breast disease. The department of obstetrics and gynecology is fully integrated and participates actively in the care of patients in the BCC. ",18 490,"Lack of relationship between perioperative blood transfusion and survival time after curative resection for gastric cancer. To better comprehend the relationship between perioperative blood transfusion and survival time after curative gastrectomy for advanced gastric cancer, the authors reviewed retrospectively data on 568 patients treated in their clinics from 1965 to 1983. Of these 568, 195 (34.3%) required no blood transfusion and 373 (65.7%) required transfusions within the perioperative period. Univariate analysis indicated that the survival time of the transfusion recipients was significantly less than that of the patients who had no transfusions (P less than 0.01). In subgroups of the authors' patients stratified to adjust for stage of disease, there was, however, no significant difference between the survival rates. Subsequently, multivariate analysis, using the Cox regression analysis, which adjusted for sex, age, and other covariates, indicated that perioperative blood transfusion was not a useful factor for predicting survival time. Multivariate analysis suggested that tumor size (P less than 0.01), degree of invasion into the gastric wall (P less than 0.01) and status of lymph node metastasis (P less than 0.01) were the most important covariates after curative gastrectomy for advanced gastric cancer. The authors' findings revealed the lack of any relationship between perioperative blood transfusion and survival time of patients who underwent curative resection for advanced gastric cancer. ",3 1962,"Current status of antitachycardia devices. With the limitations of currently available modalities for treating clinically important tachycardias, the role of implanted antitachycardia devices will continue to expand. The challenge of the future will not only involve continued technological advances but the socioeconomic impact of this efficacious but expensive mode of therapy in an era of increasing financial restraints. Further studies to definitively prove the efficacy of more widespread use of antitachycardia device therapy will be needed. ",13 1318,"Current options in the management of clinical stage C prostatic carcinoma. The evaluation of clinical stage C prostatic cancer has been enhanced by advances in staging modalities over the past 15 years. Better staging of the local lesion is possible with transrectal ultrasound-guided multiple biopsies of the prostate and its vicinity. Biopsies of suspect pelvic lymph nodes guided by CT (or lymphangiography) may obviate pelvic lymphadenectomy, particularly in patients with high-grade stage C lesions. Advances in the understanding of serum markers have supplemented other staging information. No single therapeutic modality is appropriate for all cases of clinical stage C cancer. In C1 lesions, radical prostatectomy with adjunctive radiation or hormonal therapy seems to produce the best 5- and 10-year survival rates. External-beam radiation alone, or in combination with interstitial radiation, may have equivalent success. In clinical stage C2 disease, external-beam radiotherapy seems at present to be the best therapeutic modality. Interstitial radiation as a sole method of management in stage C disease carries a high local recurrence rate and a significant risk of metastatic progression. Transurethral prostatectomy and hormonal treatment continue to have a place in the management of selected poor-risk patients. The current results with surgery or radiation therapy alone are less than ideal. It is recommended that aggressive combination treatment be compared with monotherapy in randomized clinical trials monitored jointly by radiation and urologic oncologists. ",11 1978,"Fibrinopeptide A is released into the coronary circulation after coronary spasm. To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system. ",13 1579,"Diurnal cardiovascular patterns in spontaneously hypertensive and Wistar-Kyoto rats. This study was designed to determine whether diurnal patterns of blood pressure, heart rate, or locomotor activity differed among two substrains of Wistar-Kyoto rats, derived originally from Charles River or Taconic Farms stock, or the spontaneously hypertensive rat. Cardiovascular parameters were continuously monitored over 24 hours. Resting systolic and diastolic blood pressure values were statistically different among the three groups both during the lights-on (rest) and lights-off (active) phases of the cycle with blood pressure of spontaneously hypertensive rats greater than that of Wistar-Kyoto rats from Taconic Farms, which was greater than that of Wistar-Kyoto rats from Charles River. The largest difference in arterial pressure between Wistar-Kyoto/Taconic Farms and Wistar-Kyoto/Charles River was during the lights-on period. Heart rates of all rats decreased during the lights-on period; Wistar-Kyoto/Charles River had the largest decrease (-70 +/- 5 beats/min), Wistar-Kyoto/Taconic Farms had the least (-17 +/- 2 beats/min), and in spontaneously hypertensive rats the decrease was intermediate (-29 +/- 3 beats/min). The pronounced diurnal variation in pressure and heart rate exhibited by Wistar-Kyoto/Charles River was not present in either Wistar-Kyoto/Taconic Farms or spontaneously hypertensive rats. Blood pressure magnitude correlated with locomotor activity during both periods, although all groups showed minimal activity during the rest period. Observed differences between Wistar-Kyoto/Charles River and Wistar-Kyoto/Taconic Farms were not due to a lack of or an abnormality in baroreceptor reflex function. ",13 2613,"Characteristics of patients with food-related complaints. Forty-five patients with classic food-allergic symptoms and/or subjective food-related complaints not traditionally associated with food allergy underwent evaluation. On the basis of a comprehensive clinical history, skin testing, and placebo-controlled, double-blind food challenges, patients were assigned to one of two groups: patients with reactions highly suggestive of IgE-mediated food hypersensitivity (group A, N = 22) and patients with atypical adverse food reactions that could not be confirmed by double-blind food challenge (group B, N = 23). Most patients in both groups were female, 77.3% and 91.3% of patients in group A and B, respectively. In group B, onset of symptoms occurred at an older age than in group A, 28.9 years +/- 17.2 versus 17.1 +/- 12.1 (p = 0.0015), respectively, and involved more foods, 25.6 +/- 22.1 versus 5.2 +/- 5.5 (p = 0.0002). Foods causing most prominent symptoms among patients in group A included legumes, tree nuts, crustaceans, and fish. In group B, milk, white sugar, wheat, egg, smoked/cured meat, and yeast were among the most troublesome foods. All but one patient in group A gave a positive skin test response to food; only four patients in group B had a positive response. We conclude that a subset of patients with food-related complaints can be accurately predicted to have a negative double-blind challenge with suspected foods on the basis of information obtained by history and skin testing. ",19 589,"Photopheresis for the treatment of cutaneous T cell lymphoma. We investigated the use of extracorporeal chemotherapy (photopheresis) in eight patients with cutaneous T cell lymphoma. Initially described by Edelson et al. for the treatment of erythrodermic cutaneous T cell lymphoma, we have expanded the treatment to include patients with extensive patch/plaque disease as well as tumor-stage disease. Four of five patients with erythrodermic stage disease had either a complete or a partial clinical remission with photopheresis alone. One patient with extensive patch/plaque disease continued to have a partial clinical remission of 7 months' duration with photopheresis alone. Of the two patients with tumor-stage disease, one remained without evidence of clinical disease at 10 months with photopheresis alone, whereas the second patient had a partial clinical remission of 5 months with a combination of local radiation therapy followed by monthly photopheresis. The skin biopsy specimen obtained from the patient with tumor-stage disease in complete clinical remission did not show cutaneous T cell lymphoma. We conclude that photopheresis is an effective modality alone or in combination with adjunctive therapy for erythroderma, extensive patch/plaque disease, and some tumor-stage disease. ",3 1032,"Localized antigen challenge of the nasal mucosa. We describe a localized nasal antigen challenge and the measurement of mediators found at the same site. Eight ragweed-allergic subjects were challenged on 2 days, 1 week apart. Challenges consisted of six sequential provocations, beginning with two control challenges (diluent for antigen-phenol-buffered saline) followed by four increasing antigen doses (0.6, 6, 60, and 160 protein nitrogen units) (antigen day) or an additional four control challenges (control day). The number of sneezes and the symptom scores increased significantly with increasing antigen doses. The levels of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased in the eluted secretions on the antigen day, but not on the control day. The amount of secretions collected also increased per unit of time on the antigen day. We found no significant increase in the concentration level of either histamine or N-alpha-tosyl-L-arginine methyl ester-esterase in nasal secretions on either day. We conclude that the total amount of histamine and N-alpha-tosyl-L-arginine methyl ester-esterase activity increased per unit of time while their concentration did not. ",8 2222,"Persistent right umbilical vein: an ominous prenatal finding? The persistence of a right umbilical vein is an uncommon finding, with only a dozen cases reported since 1826. The persistent right umbilical vein may replace the normal left umbilical vein or be supernumerary. The anomaly is associated with numerous and occasionally lethal malformations. In this series, only three of six fetuses (and another two in the literature) had no associated anomalies. All the others had a variety of associated lesions ranging from minor to lethal. The appearance at ultrasound is easy to recognize: The intrahepatic portion of the umbilical vein is lateral to the gallbladder, and the portal vein curves toward the stomach, instead of parallel to it. Since the recognition of the persistent right umbilical vein is simple and does not require additional scanning (it is visible in the section used to measure the abdominal perimeter), the author suggests using it as an indicator for more in-depth scanning. ",15 2377,"Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin. Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits. ",17 716,"Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps. Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer. ",5 1888,"Coarctation of the aorta. Coarctation of the aorta is a common cardiovascular disorder with an unknown etiology. In the preductal type, blood flows from a patent ductus into the distal aorta. When the coarctation is juxtaductal or postductal, blood flows to the lower extremities by way of the subclavian arteries and collaterals. Plain films may show the reverse sign in postductal coarctation. Arteriography is the gold standard for making the diagnosis. However, magnetic resonance imaging will probably become an increasingly important diagnostic tool. The treatment of choice is surgery, with complete resection of the stenosed segment. ",13 618,"Evaluation of an electrogoniometric instrument for measurement of laxity of the knee. Eight lower extremities from cadavera were tested for anterior-posterior laxity in two positions before and after transection of the anterior cruciate ligament. At critical points in the tests, electrogoniometric and radiographic measurements of tibiofemoral translation were compared. By direct measurement, we determined the accuracy of the radiographic method to +/- 0.4 millimeter (95 per cent) in measuring anterior-posterior translations of the tibia with respect to the femur. The electrogoniometer estimated displacement of the tibia with respect to the femur during the anterior drawer test to be 3.5 +/- 8.2 millimeters at 90 degrees of flexion of the knee and 11.1 +/- 16.1 millimeters at 30 degrees of flexion. Direct comparison of these measurements with those obtained by means of the radiographic technique showed that the electrogoniometer tended, on average, to overestimate the tibial translation. The amount of overestimation was 0.7 millimeter for intact knees and 1.9 millimeters after sacrifice of the anterior cruciate ligament. Despite this small average error in measurement of tibial translation, the difference between individual electrogoniometric and radiographic measurements varied greatly, with a 95 per cent confidence limit of +/- 5.5 millimeters. The error of the electrogoniometric measurements varied with the angle of flexion of the knee during testing, both the accuracy and the reliability of the electrogoniometric measurements being greatly diminished at 30 degrees of flexion. The electrogoniometric method also tended to overestimate tibial internal rotation (by an average of 10.5 degrees) and external rotation (by an average of 9.3 degrees); the reliability of these measurements was +/- 6.9 degrees. ",4 2596,"Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody. Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement. ",19 1291,"Hemihang-back recession: description of the technique and review of the literature. We describe a modification of the hang-back and loop techniques that we call the hemihang-back recession, in which the muscle is reattached to the sclera posterior to the original insertion with a single, absorbable suture. We recommend it for difficult strabismus cases, specifically when recessions of 7 mm or more are required. ",10 1294,"Role of communities in decision-making eye care programs. The concept of primary health care involves educating people to live their lives in ways beneficial to their health. Communities as a whole must participate in the decision-making that is involved in such education, be it promotive, preventive, curative, or rehabilitative. I refer to this participation as ""participatory communication."" It is based on two fundamental tenets: 1) Everyone in a community has some special knowledge to contribute to the development of the health of that community; and 2) No person is superior to another. Subsequent to sociological and anthropological studies of communities in the Southern Sudan by the Norwegian Church Aid, the Norwegian Association of the Blind and Partially-Sighted conducted village workshops based on this concept. ",10 95,"A general model of sexually transmitted disease epidemiology and its implications for control. Achieving control of STDs may be possible by integrating the activities discussed previously with further research to provide additional empiric data on sex behavior, to develop innovative strategies to access and communicate with those most at risk of STD (i.e., core-group members), and to foster biologic study of STD pathogens with the goal of vaccine development. New strategies to identify core-group members aside from the currently used STD-repeater status would be of immense help in targeting educational efforts, laboratory screening, and vaccines. Achieving more complete control of STDs may be possible if recent advances in our understanding of their epidemiology and transmission dynamics can be translated into effective new interventional strategies. ",0 1592,"Transesophageal Doppler color flow mapping assessment of atrial septal defect. Transesophageal Doppler color flow imaging was performed in 19 adult patients (mean age 35 years) with an atrial septal defect demonstrated by cardiac catheterization or at surgery, or both. The transesophageal study correctly identified and classified 19 of 19 shunts in contrast to 16 of 18 shunts identified by the transthoracic approach. The area of the atrial septal defect was calculated by assuming it to be circular and taking the maximal Doppler color flow jet width at the defect site as its diameter. The pulsed Doppler sample volume was placed parallel to the shunt flow direction at the defect site to obtain the mean velocity and flow duration. From these values, the shunt volume was calculated as a product of the defect area, mean velocity, flow duration and heart rate. The calculated shunt flow volume obtained by transesophageal study showed a good correlation with shunt flow volume (r = 0.91, p less than 0.001) and pulmonary to systemic blood flow ratio (r = 0.84, p less than 0.001) obtained at cardiac catheterization. The size of the defect by transesophageal Doppler color flow mapping correlated fairly well with the size estimated at surgery (r = 0.73, p = 0.004). It is concluded that transesophageal Doppler color flow imaging is useful in the detection and classification of atrial septal defects and in the assessment of shunt volumes. ",13 2548,"Reappraisal of thyroxine treatment in primary hypothyroidism. The optimum daily dose of thyroxine was calculated for 13 children aged 3-16 years with primary hypothyroidism by titrating their doses at monthly intervals. The condition of the thyroid was assessed by sensitive assay of thyroid stimulating hormone concentrations, as well as measurement of total and free thyroid hormone concentrations and systolic time interval ratios. Serum thyroid stimulating hormone concentration was found to be the most responsive to small changes in thyroxine. The calculated optimum daily replacement dose of thyroxine (102 micrograms/m2 or 3.5 micrograms/kg) was fractionally lower than that previously recommended, and was more closely related to surface area (coefficient of variation 8.2%) than to body weight (coefficient of variation 16.2%). Our results suggest that though monthly may be the optimal time interval for increases in the dose of thyroxine, any reduction in the dose should be made more gradually. ",18 3350,"Predictors of quitting smoking: the NHANES I followup experience. There are no published prospective studies on the predictors of spontaneously quitting cigarette smoking in a nationally-representative U.S. population. This paper describes such a study, using a cohort taken from the First National Health and Nutrition Examination Survey (NHANES I, 1971-1975) and traced by the NHANES I Epidemiologic Followup Survey (1982-1984). ""Successful"" quitting (for at least 1 year at time of followup) was ascertained among 4779 adults (age 25-74 years) who were smokers at the time of NHANES I and not disabled at followup. Independent predictors of quitting (by proportional hazards multiple regression) were: (1) older age; (2) White race; (3) fewer cigarettes smoked/day; (4) higher household income; and (5) hospitalization in the followup period. Predictors of relapse (ex-smokers at NHANES I who were smoking again at time of followup) were: (1) younger age; (2) urban residence; and (3) female gender. These findings have implications for intervention strategies, public health projections and further research. ",22 2133,"Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease. ",14 2096,"A novel mechanical cardiac assist device for reversing left ventricular failure. Diastolic augmentation of aortic pressure is an efficacious means of improving coronary perfusion in heart failure. A novel mechanical cardiac assist device (MCAD), that has advantages over a conventional intraaortic balloon pump and left ventricular assist devices, has been developed. It consists of a high efficiency rotary solenoid, coupled to a pair of actuator plates that clamp on a shunt aortic graft section, and operates in a diastolic counterpulsation mode. The system has been evaluated in six anesthetized, thoracotomized dogs with myocardial ischemia. The MCAD was activated 30-40 min after coronary artery occlusion and synchronized with the R-wave. As illustrated by a representative sample of the data obtained from one of several trials, the preliminary experimental results demonstrated that the MCAD worked effectively to fulfill the primary functions of a counterpulsation assist device, i.e., augmentation of coronary perfusion and reduction in the vascular impedance to ventricular ejection. ",13 2066,"Pineal hyperactivity in spontaneously hypertensive rats: muscarinic regulation of indole metabolism. 1. Choline acetyltransferase activity and [3H]quinuclidinyl benzylate-binding sites were detected in the pineal gland of normotensive Wistar-Kyoto rats and of spontaneously hypertensive rats. 2. In vitro, muscarinic activation by pilocarpine increased the pineal metabolic production of hydroxyindole derivatives up to 5-hydroxytryptamine and produced a less marked stimulation of melatonin biosynthesis. 3. Electrical field stimulation of pineal gland slices caused similar metabolic effects. 4. Muscarinic blockade with atropine inhibited the effects on hydroxyindole metabolism. 5. [3H]Quinuclidinyl benzylate-binding sites, indicative of muscarinic receptors, were more numerous, and basal 5-hydroxytryptamine and melatonin levels were higher, in the pineal gland of spontaneously hypertensive rats compared with Wistar-Kyoto rats. 6. The atropine-sensitive metabolic effects of pilocarpine and electrical field stimulation on the pineal gland were increased in spontaneously hypertensive rats compared with Wistar-Kyoto rats. ",13 1710,"Intravascular ultrasound: a new potential modality for angioplasty guidance. Current angioplasty devices are limited by significant rates of arterial perforation and dissection, due to inadequate techniques of guidance, and by restenosis, which may be partly attributed to inadequate debulking of lesions. This paper describes the authors' initial experience in-vitro and in-vivo with intravascular ultrasound as a possible method of enhancing the three-dimensional guidance of devices through atherosclerotic obstructions. Using an in-vitro model they correlated the dimensions and histologic morphology of animal and human arteries with ultrasound images of the specimens. Additional in-vivo evaluations of this technology in canine arteriosclerotic and human atherosclerotic arteries preliminarily support the hypothesis that intravascular ultrasound defines the transmural arterial morphology and may enhance the accuracy of angioplasty procedures. Simultaneous imaging with angioscopy and intravascular ultrasound is demonstrated as a potential method of accurately defining both intraluminal and transmural arterial wall characteristics. ",13 951,"A family study of the variability of pulmonary function in alpha 1-antitrypsin deficiency. Quantitative phenotypes. A group of 52 alpha 1-antitrypsin-deficient individuals of phenotype Pi Z and 117 of their relatives underwent a protocol including pulmonary function testing, completion of a questionnaire, and blood donation. Our population permitted a minimum frequency estimate (7 x 10(-4)) for Pi null alleles. Five quantitative phenotypes were measured, including FEV1, FEF25-75, total serum alpha 1AT, oxidized serum alpha 1AT, and total serum IgE. We found that (1) total alpha 1AT levels were higher in Pi Z subjects with lung function impairment (FEV1 less than or equal to 65% of predicted) than in Pi Z subjects who were not impaired; (2) Pi Z subjects with lung function impairment had elevated serum levels of oxidized alpha 1AT; and (3) IgE levels were relatively elevated in first-degree Pi MZ relatives of impaired Pi Z subjects. Moreover, FEV1 tended to be relatively reduced in heterozygous parents of impaired Pi Z subjects, suggesting that a subset of Pi MZ individuals are at risk for development of lung disease because of familial factors. These results represent an initial step toward the development of intermediate phenotypes that will be predictive of a severe course in alpha 1AT deficiency; they suggest that, in addition to cigarette smoking, atopic predisposition and undetermined familial factors may be important codeterminants of lung disease progression. ",7 1236,"pH-adjustment and discomfort caused by the intradermal injection of lignocaine [published erratum appears in Anaesthesia 1991 Mar;46(3):242] One hundred adult day-case patients who required intravenous access had cannulae inserted using local anaesthesia with 1% lignocaine, 1% lignocaine with adrenaline or the corresponding pH-adjusted solutions. The local anaesthetic solutions were modified by the addition of 1 ml 8.4% sodium bicarbonate to 10 ml lignocaine. Pain scores at different stages of cannulation were noted and showed a significant reduction after use of pH-adjusted solutions (p less than 0.02 for the plain lignocaine, and less than 0.001 for the lignocaine with adrenaline). Modification of the pH of lignocaine solutions by the addition of sodium bicarbonate is a simple method significantly to reduce the discomfort caused by the infiltration of the local anaesthetic. ",9 2690,"Effect of thromboxane antagonists on ozone-induced airway responses in dogs. Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness. ",19 139,"Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection. Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable. Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection. In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children. Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis. After 2 years, the prevalence of infection in 5-year-old children decreased by 21%. The annual incidence in an uninfected cohort of children decreased by 35% and, after age-specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%. Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection. These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis. ",2 245,"The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction. Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059). ",3 2253,"Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen. Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. ",16 562,"Vaccination against tumor cells expressing breast cancer epithelial tumor antigen. Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts. ",3 1193,"Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. In patients with acute liver failure and hepatic coma, an increase in the abnormal ""middle molecules"" seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived greater than 3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant. ",9 1055,"A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department STUDY OBJECTIVE: To determine the effectiveness of IV metoclopramide as sole therapy for relieving the pain of acute migraine in the emergency department. DESIGN: Prospective study. Fifty patients were divided randomly into subjects and placebo controls with blinding of the treating physician and the patient. PARTICIPANTS: Patients presenting to the ED with migraine requiring parenteral treatment. INTERVENTIONS: Subjects received 10 mg IV metoclopramide and controls received IV normal saline; patient assessment of relief was followed by means of a numerical scale. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of subjects compared with 19% of controls had effective pain relief within one hour (P less than .001). Subjects achieved mean relief scores of 2.46 compared with 1.69 for controls (P less than .02). No significant side effects were observed. CONCLUSION: IV metoclopramide as a single agent is effective and safe therapy for migraine in the ED. ",9 863,"The prevalence of periodontitis in a military treatment population. A group of 1,984 males and females (age range 13 to 84) at a military dental clinic were given oral examinations with full-mouth circumferential periodontal probing. Diagnoses were made both for individual quadrants and for the entire mouth using clearly defined diagnostic criteria. The results showed 37% of the subjects had gingivitis only, 33% had early periodontitis, 14% had moderate periodontitis, 15% had advanced periodontitis, 0.5% had juvenile periodontitis, and 0.5% had necrotizing gingivitis. The prevalence of periodontitis increased with age to a peak in the 45- to 50-year-age group. The proportion of periodontitis-affected quadrants, although initially lagging behind the overall case diagnoses, also increased with age. ",6 2983,"Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this small change was not statistically significant. These estimations of myocyte cellular hyperplasia, however, were complicated by the fact that cell loss continued to take place with age. The volume fraction of collagen in the tissue, in fact, progressively increased from 8% and 7% at 4 months to 16% and 22% at 29 months in the left and right ventricles, respectively. In conclusion, myocyte cellular hyperplasia tends to regenerate the ventricular mass being lost with age in the adult mammalian rat heart. ",22 2720,"Genomic divergence of an HIV-2 from a German AIDS patient probably infected in Mali. The complete nucleotide sequence of an HIV-2 isolate derived from a German AIDS patient with predominantly neurological symptoms is reported. The HIV-2BEN sequence is highly divergent from those of previously described HIV-2 and SIV strains. Evolutionary tree analysis of eight HIV-2 sequences reveals the existence of three HIV-2 groups. HIV-2BEN belongs to a group with two isolates from Ghana and The Gambia. Based on a comparison of HIV-2BEN with six HIV-2 isolates, SIVsmm and SIVmac, the variability of the structural env and gag proteins is similar within the HIV-2/SIVsmm/mac and HIV-1 groups. In contrast, the regulatory HIV-1 proteins are more highly conserved than those from HIV-2 strains. Multiple sequence alignments reveal that some domains of the envelope and regulatory proteins are well conserved among HIV-1, HIV-2/SIVsmm/mac, SIVagm and SIVmnd. The identification of conserved domains within the external glycoprotein could help to develop broadly active vaccines. ",19 2155,"Immunoglobulin G subclasses in serum and circulating immune complexes in patients with Kawasaki syndrome. IgG subclass concentrations in sera of 17 patients with Kawasaki syndrome were determined. Significantly increased IgG1 (P less than 0.001) and IgG3 (P less than 0.001) were found in the patients compared with 22 age-matched healthy children, whereas IgG2 and IgG4 were normal or slightly decreased. IgG immune complexes were measured by protein A-enzyme-linked immunosorbent assay (ELISA) combined polyethylene glycol precipitations. Eight of 17 patients (47.1%) were found to have circulating immune complexes (CIC) values above the normal control range (geometric mean +2 SD). IgG subclass composition in CIC was analyzed. The subclasses in CIC were predominantly IgG1 and IgG3. Because the antibody responses to different antigens exhibit IgG subclass restriction, it would suggest that the change of serum and CIC IgG subclasses in Kawasaki syndrome may have relevance to the pathogenesis of the disease. ",14 2329,"Induction of ornithine decarboxylase following sellotape stripping in normal and psoriatic skin. Ornithine decarboxylase (ODC) was measured in the epidermis of healthy volunteers and the uninvolved skin of psoriatic patients at various times after sellotape stripping. Basal levels were less than 1 pmol/min/mg protein. Activity peaked to a maximum of 86 pmol/min/mg protein after 8 h; this was followed by an abrupt decline to a lower level which remained relatively constant for at least 36 h. No difference was seen between the response of controls and psoriatic patients. Pretreatment with topical corticosteroids reduced peak ODC levels to about one-half, but oral indomethacin had no effect. ",16 3341,"Effect of complement and arachidonic acid pathway inhibition on white blood cell count and deposition on vascular grafts. To determine the role of complement and arachidonic acid metabolites in the decrease in peripheral white blood cell count (pWBC) observed with graft implantation, Dacron aortic grafts were implanted in control rabbits (Group I, n = 13), or rabbits pretreated with cobra venom factor (80 U/kg) to deplete complement (Group II, n = 13), indomethacin (2.5 mg/kg) to inhibit cyclooxygenase (Group III, n = 7), or diethylcarbamazine (DEC, 90 mg/kg) to inhibit leukotriene synthesis (Group IV, n = 7). pWBC was measured 15 min and 1 hr after graft implantation. After graft removal, the WBC count on grafts (gWBC) was determined by light microscopy (LM) and scanning electron microscopy (SEM). One hr after graft implantation, pWBC decreased significantly in Groups I-IV to 46%, 52%, 40%, and 45% of preoperative pWBC, respectively. There was no significant difference among the groups. LM revealed gWBC per 63x field of 8.0, 12.3, 5.8, and 6.8 in Groups I-IV, respectively. Similarly, SEM showed gWBC per 2000x field of 2.5, 5.6, 0.7, and 1.5 in Groups I-IV, respectively. SEM gWBC was significantly greater in Group II than I (p less than 0.01), and significantly less in Group III than I (p less than 0.05). Results suggested that complement and arachidonic acid pathways alone do not affect the fall in pWBC, but may influence gWBC. ",22 2684,"Transfusion-induced graft-versus-host disease in patients with malignant lymphoma. A case report and review of the literature. A case of transfusion-induced graft-versus-host disease (GVHD) occurring in a 31-year-old female with Hodgkin's disease in complete remission is reported. Clinical features are similar to 19 other reported cases of transfusion-induced GVHD associated with malignant lymphoma. The lack of relationship with underlying histology or disease stage and the nearly uniformly fatal outcome underscores the importance of prophylactic irradiation of blood products given to patients with malignant lymphoma undergoing therapy. ",19 1452,"Pathophysiology of prolonged penile erection associated with trazodone use. Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence. ",11 765,"Frequency of recovery of Blastocystis hominis in clinical practice. We examined the frequency of isolation of Blastocystis hominis from stools of patients seen in an indigent-care teaching hospital. Over a 2-year period, 2,744 stool specimens were examined prospectively. B. hominis was found in 262 stools (9.5% of all stool specimens and 53.5% of the positive specimens). Clinical data were obtained from 80 patients with stools positive for B. hominis. B. hominis was the only parasite isolated in 39 of 47 (83%) of the adults, compared with 17 of 33 (52%) of the children (p = 0.006). All but 2 of 52 patients without concomitant parasitic infection or bacterial pathogens in stool had gastrointestinal symptoms (41 abdominal pain, 26 diarrhea, and 5 vomiting), but no association was seen with fever, peripheral leukocytosis, stool occult blood, fecal leukocytes, or endoscopic or radiologic evidence of colitis. Therefore, B. hominis was frequently recovered from stools examined in a hospital clinical parasitology laboratory. The clinical presentations of patients in our series did not suggest that B. hominis was invasive. Most patients with B. hominis probably do not require treatment since they will either have spontaneous resolution of symptoms or will be found to have an alternative explanation for their problem. ",5 991,"Intact epithelial barrier function is critical for the resolution of alveolar edema in humans Within 15 min of endotracheal intubation, the resolution of pulmonary edema was studied over the next 12 h in 34 mechanically ventilated patients by (1) serial measurements of the alveolar-arterial oxygen difference, (2) the extent of edema on the initial and follow-up chest radiograph, and (3) by an initial and final measurement of total protein and albumin concentration in sequential samples of pulmonary edema fluid. Based on the oxygenation and chest radiographic data, 24 patients clinically improved and 10 patients did not improve. In the 10 patients who did not clinically improve (3, hydrostatic edema; 7, permeability edema), there was no change in the final edema fluid protein concentration (4.1 +/- 1.1 g/100 ml) compared with the initial edema fluid protein concentration (4.2 +/- 1.0 g/100 ml) (p = ns). However, in the 24 patients who clinically improved (15, hydrostatic edema; 9, permeability edema), there was an increase in every patient's final edema protein concentration (5.6 +/- 2.3 g/100 ml) compared with their initial edema protein concentration (3.8 +/- 1.2 g/100 ml) (p less than 0.01). In 13 of these 24 patients, the final edema fluid concentration (7.3 +/- 1.6 g/100 ml) exceeded the final plasma protein concentration (5.6 +/- 0.8 g/100 ml) by a mean value of 1.7 g/100 ml protein. The data provide the first evidence in humans to support the hypothesis that active ion transport across the alveolar epithelial barrier is the primary mechanism for clearance of edema fluid from the air spaces of the lung. ",7 1073,"Double-blind comparison of topical lignocaine-prilocaine cream (EMLA) and lignocaine infiltration for arterial cannulation in adults. In a double-blind, double-dummy study, the efficacy of topical 5% EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation. Forty unpremedicated adults were allocated randomly to four groups to receive EMLA cream alone, EMLA and 0.9% saline infiltration, EMLA and 1% lignocaine infiltration or placebo cream and 1% lignocaine infiltration. Following arterial cannulation, pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score. Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient (P less than 0.01) and observer (P less than 0.001) assessments. There were no significant differences between the three EMLA groups. ",9 2510,"Metabolic control and complications over 3 years in patients with insulin dependent diabetes (IDDM): the Stockholm Diabetes Intervention Study (SDIS). In a planned 5-year study, 97 patients with insulin dependent diabetes mellitus (IDDM), non-proliferative retinopathy and unsatisfactory blood glucose control were monitored for 3 years. The patients were randomized to an intensified conventional treatment (ICT, n = 44) or a regular treatment (RT, n = 53) group. HbA1c (normal range 3.9-5.7%) was reduced from 9.5 +/- 0.2 (mean value +/- SEM) to 7.4 +/- 0.1% in the ICT group (P = 0.0001), and from 9.5 +/- 0.2 to 9.0 +/- 0.2% in the RT group (P = 0.004). Nerve conduction velocities in the sural and peroneal nerves (P = 0.01-0.0001) were impaired in the RT group, but not in the ICT group. Retinopathy increased in both groups. The condition of 22 ICT patients (50%, 95% confidence interval 34-66%) and 37 RT patients (73%, 61-84%) deteriorated with regard to at least one microvascular complication (retinopathy, nephropathy, neuropathy) (P = 0.024). Lower HbA1c levels during the study significantly reduced the risk of deterioration (P = 0.01). In total, 57% of the ICT patients had at least one episode of serious hypoglycaemia, compared with 23% in the RT group (P = 0.001). The patients in the ICT group also gained weight (P = 0.0001). Improved blood glucose control slowed down the progression of microangiopathy during a 3-year period in patients with non-proliferative retinopathy, but at the price of an increased frequency of serious hypoglycaemic episodes, and some gain in body weight. ",17 1268,"Caspar Stromayr: sixteenth century ophthalmologist. Caspar Stromayr, ophthalmologist and hernia surgeon, is credited with writing the first German ophthalmic work of known authorship. Written in about 1559 as an appendix to Practica Copiosa, a larger work on hernia surgery, the ophthalmic chapters describe Stromayr's thoughts on the etiology and treatment of cataract. Stromayr, a master craftsman, also expresses his hostility to the shams and ignorance of the charlatan eye surgeons of his day. This interesting historical article provides a biographical sketch of Stromayr, a description of his book, and a translation of two chapters, ""On Cataract of the Eye: How They Take Their Beginning and Whence they Come"" and ""How You Recognize the Cataract, When It is Ripe to Recline or to be Taken Away."". ",10 2898,"Age effect on prognosis for functional recovery in acute, traumatic central cord syndrome. The purpose of this study was to determine if age is significant in functional recovery in acute, traumatic central cord syndrome (CCS). Recovery of ambulation, ADL status, and bowel and bladder function were evaluated. A retrospective study tested the hypothesis that functional recovery in 51 consecutive CCS patients was better in younger patients than in older patients. Four patients, all more than 50 years, died. Ability to ambulate independently at discharge was compared in 30 patients younger than 50 years with 21 patients 50 years or older. Results showed that 29 of 30 (97%) of the younger patients were ambulatory compared to seven of 17 (41%) of the older patients (p less than .002). The younger patients were also able to achieve independence in self-care and bowel and bladder function in a significantly greater proportion. The prognosis for functional recovery in acute traumatic CCS should consider the patient's age. The prognosis is less optimistic in older patients, but it is considerably more favorable in younger patients than previously reported. ",20 2585,"Effects of deep inhalation during early and late asthmatic reactions to allergen [published erratum appears in Am Rev Respir Dis 1991 Feb;143(2):451] Eighteen asthmatic patients with a biphasic asthmatic reaction to house dust mite were studied. The effect of deep inhalation (DI) was quantitated by comparing the maximal expiratory flow at 40% (MEF40) of vital capacity from partial (P) and maximal (M) flow-volume curves, and specific airway conductance (SGaw) before and after DI (SGawDI). At baseline, the ratio MEF40M/P was significantly larger than unity (1.45 +/- 0.26 SD), whereas the ratio SGawDI/SGaw was not significantly different from unity (0.92 +/- 0.24). During early phase reaction, both MEF40M/P and SGawDI/SGaw were significantly increased to 2.66 +/- 0.97 and 1.96 +/- 0.47, respectively. During late phase reaction, when the FEV1 values were similar to those observed during early phase reaction, MEF40M/P and SGawDI/SGaw were 1.86 +/- 0.46 and 1.43 +/- 0.29, respectively, significantly higher than the values at baseline but significantly lower than those during early phase reaction. Similar results were obtained in a subgroup of nine patients when SGaw values during the late phase reaction were similar to those during the early phase reaction. We conclude that DI has a different effect during early and late asthmatic reactions, suggesting a different ratio of airway to parenchymal hysteresis. This may result from an increased parenchymal hysteresis (more peripherally located bronchial obstruction) or a decreased airway hysteresis (prominent airway inflammation) during the late phase reaction. ",19 1523,"Cryopreserved/thawed semen for in vitro fertilization: results from fertile donors and infertile patients. We evaluated the in vitro fertilization (IVF) outcome in 54 cycles using cryopreserved/thawed semen from fertile donors. Controls were other IVF patients matched by time frame, female age, stimulation protocol, number of pre-embryos transferred, and absence of a male factor using freshly ejaculated normal semen samples. In the study group and controls, respectively, post-thaw swim-up motility was 83.1% and 89.5%; fertilization rate of preovulatory oocytes (91.8%, 95.7%) and ongoing pregnancy rate (PR) per transfer (21.1%, 25.0%) were similar. The excellent fertilization rate with frozen/thawed semen was achieved through high-concentration insemination (0.5 x 10(6) motile sperm/mL). With use of frozen/thawed samples from infertile men (normal and subfertile samples), PR was similar but fertilization rate was lower. Cryopreserved semen is a valuable option for infertile couples in IVF therapy. ",12 769,"Morphological study of cholesterol hepatolithiasis. Report of three cases. Three cases of pure cholesterol intrahepatic stones are compared morphologically to those of calcium bilirubinate stones. Cholesterol stones were found in the intrahepatic bile duct of the left lateral lobe in two cases and in both the left lateral and the right posterior lobe in one. Although the chronic inflammatory reaction and fibrous thickening of bile duct wall were similar in both types of hepatolithiasis, the proliferation of intrahepatic periductal glands and the production of mucin were rather mild, compared to that is the liner containing calcium bilirubinate stones. Multiple intramural cholesterol calculi and cholesterin granulomas (cholesterin crystals surrounded by foreign-body giant cells) were found within the cystically dilated small bile duct branches and/or conduits of periductal glands. The calculi and granulomas were characteristic for cholesterol hepatolithiasis. These findings suggest that the formation of the cholesterol stones differs from that of calcium bilirubinate stones; the perturbation of factors influencing cholesterol nucleation in the hepatic bile may be related to the changed microenvironment of the intrahepatic bile ducts, which is followed by the formation of cholesterol stones. ",5 2267,"Severe phototoxic burn following celery ingestion. A 65-year-old woman developed a severe, generalized phototoxic reaction following a visit to a suntan parlor. History taking revealed that she had consumed a large quantity of celery root (Apium graveolens) 1 hour earlier. With the use of thin-layer chromatography, methoxsalen (8-methoxypsoralen) and 5-methoxypsoralen were identified in the extract from a similar celery root. The biologic activity of this extract, as evaluated with the semiquantitative Candida albicans inhibition technique, indicated a total psoralen dose of approximately 45 mg. Substantial amounts of psoralen may be absorbed from vegetables, such as celery, and under unusual circumstances, this may constitute a health hazard. ",16 2846,"Bilateral sacroiliac joint fracture-dislocation: a case report. Bilateral sacroiliac joint fracture-dislocation of the sacrum with displacement is a rare injury. We found only four such injuries previously reported in the literature. Nonoperative management in this case led to complete functional return and acceptable alignment. ",20 3220,"Management of premature removal of the percutaneous gastrostomy. Percutaneous endoscopic gastrostomy (PEG) has become the preferred method of enteral access for nutritional support. With increased use of this modality, complications are encountered more frequently. Premature withdrawal, inadvertent removal of the gastrostomy tube within the first seven days after insertion, before adherence of the gastric serosa to the parietal peritoneum, has been an indication for laparotomy. This report describes the treatment of premature withdrawal by immediate endoscopic replacement. Over an 18-month period, 271 patients underwent insertion of a PEG. Five patients (1.8%) who inadvertently removed their gastrostomy tube within seven days of insertion were treated with immediate replacement using the retrograde string technique, avoiding laparotomy. All five PEGs were successfully replaced through the same gastrostomy site. Despite the presence of pneumoperitoneum, no patient developed peritonitis or other septic complications. Premature gastrostomy tube withdrawal is safely managed by endoscopic replacement and observation. Laparotomy is unnecessary and potentially meddlesome. ",22 633,"Diastrophic dysplasia gene maps to the distal long arm of chromosome 5. We have used polymorphic DNA markers to map the gene for a clinically well-characterized form of osteochondrodysplasia, diastrophic dysplasia (DD), an autosomal recessive disorder of unknown pathogenesis. Linkage was analyzed in 13 families with two or three affected sibs comprising a total of 84 individuals. Positive two-point logarithm-of-odds (lod) scores were obtained between the DD locus and three polymorphic markers on chromosome 5. The highest pairwise lod score estimate of 7.37 with zero recombination to locus D5S72 suggests very tight linkage. There was no evidence of heterogeneity. Multipoint linkage analysis against the published order of the three loci gave the result centromere-D5S84-(DD, D5S72)-D5S61-terminus with a four-point lod score of 9.11. The present findings place the DD locus distal to the gene for adenomatous polyposis coli on the distal part of the long arm of chromosome 5. Our results provide a basis for refining the map position of the DD locus followed by physical localization, isolation, and characterization of the gene. ",4 1806,"Respiratory muscle strength in congestive heart failure. In experimental animals, conditions which drastically decrease cardiac output may reduce the strength and endurance of respiratory muscles leading to hypercapnic respiratory failure. Because patients with chronic CHF have reduced cardiac output and vital capacity (FVC), we measured PImax and PEmax and maximal handgrip force in 16 patients with CHF and 18 AMNs. The patients with CHF had a mean left ventricular ejection fraction of 26 +/- 7 percent. Maximal respiratory pressures were significantly reduced; group mean values (+/- SD) for PImax at FRC were 41.4 +/- 5.6 cm H2O (CHF) and 102.1 +/- 27.4 cm H2O (AMN) (p less than 0.001), with PImax values in five patients with CHF as low as 20 to 30 cm H2O. In most patients, PEmax was comparably reduced. Handgrip force was less dramatically reduced, suggesting selective respiratory muscle weakness. Possible explanations include reduction in respiratory muscle blood flow or generalized muscular atrophy and weakness related to cardiac cachexia. ",13 773,"Assessment of functional gastrointestinal disease: the bowel disease questionnaire. A need exists for a self-report questionnaire that reliably and accurately measures symptoms and that distinguishes patients with functional gastrointestinal disease from those with other conditions. We have developed such an instrument, the bowel disease questionnaire, and herein describe details of its discriminatory validity. Data from 399 subjects were analyzed. Patients with gastrointestinal symptoms were ultimately diagnosed as having functional gastrointestinal disease (82 with the irritable bowel syndrome and 33 with functional dyspepsia) or organic gastrointestinal disease (N = 101). There were 145 healthy control subjects and 38 patients with a psychiatric disease, somatoform disorder (which includes those with a diagnosis of hypochrondriasis, psychogenic pain, and somatization or conversion disorder). All subjects completed the questionnaire before undergoing an independent diagnostic assessment by experienced physicians. Functional gastrointestinal disease could be distinguished from organic disease, somatoform disorder, and health by using models derived from logistic discriminant analysis. With use of these models, the estimated probability of functional gastrointestinal disease was then calculated. Descriptive symptom scores were of less value than the scores derived from the data sets by logistic discriminant analysis. Age did not significantly affect the responses to the questionnaire items. We conclude that, in the population studied, the bowel disease questionnaire is a valid measure of symptoms of functional gastrointestinal disease, and this instrument may have clinical and research applications. ",5 2145,"Enhanced endogenous leukotriene biosynthesis in patients treated with granulocyte-macrophage colony-stimulating factor. The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is being used in clinical trials for its potential in the treatment of hematopoietic insufficiency due to various causes. Involvement of leukotrienes in the effects of GM-CSF is suggested by analytical and pharmacologic evidence obtained in vitro. However, until now no data in support of a role of leukotrienes in GM-CSF action in vivo have been presented. In the present investigation this question was approached by measurement of endogenous cysteinyl leukotriene formation in patients treated with the cytokine for cytopenia induced by cytostatic drugs or for refractory anemia with excess of blasts (RAEB). Endogenous cysteinyl leukotriene formation was assessed by determination of urinary leukotriene metabolites using combined high-performance liquid chromatography and radioimmunoassay analysis. After GM-CSF administration a distinct increase in urinary cysteinyl leukotrienes was found in the cytopenic and the RAEB patients that ranged from 2.3- to 57-fold and 2.4- to 333-fold, respectively. In the cytopenic patients the increase in leukotriene production was correlated to an expansion of peripheral blood leukocytes; RAEB patients responded to GM-CSF with enhanced leukotriene biosynthesis even if the peripheral leukocytes decreased, possibly due to an abnormal number and/or irritability of leukotriene-producing cells. The increase in endogenous leukotriene production during therapy with GM-CSF may indicate that leukotrienes play a role in GM-CSF action in vivo. ",14 728,"Healing or amelioration of esophagitis does not result in increased lower esophageal sphincter or esophageal contractile pressure [published erratum appears in Am J Gastroenterol 1991 Feb;86(2):253] There is conflicting evidence regarding whether lower esophageal sphincter and esophageal contractile pressures are affected by changes in the severity of gastroesophageal reflux disease. We compared the manometric and endoscopic findings from 30 patients before and after treatment for esophagitis. Before treatment, the grade of esophagitis (I-III) was significantly correlated (r = -0.37; p less than 0.05) with lower esophageal sphincter pressure, but not with esophageal contractile pressure. After treatment, the grade of esophagitis did not change or became worse in 15 patients, and became better in 15 patients. Of these, seven healed. The group that showed no endoscopic improvement demonstrated no change in lower esophageal sphincter or esophageal contractile pressures. The group that did show endoscopic improvement also demonstrated no increase in lower esophageal sphincter or esophageal contractile pressures, and this was particularly evident in those whose esophagitis healed. These data suggest that healing of esophagitis does not result in improvement of esophageal motor function. ",5 1250,"Histopathologic study of the Molteno glaucoma implant in three patients. Three eyes with the Molteno glaucoma implant (one eye with epithelial downgrowth, one eye with iridocorneal endothelial syndrome, and one eye with aphakia and glaucoma) were enucleated two to six years after implantation. Histopathologic examinations disclosed no evidence of erosion of sclera or conjunctiva of the eye by the glaucoma implant device. In the outer layers of the bleb wall, few and mostly degenerated inflammatory cells were present, which represented a minimal inflammatory reaction. Scanning electron microscopy of the tubes in these three patients showed that the tube was intact, patent, and without signs of degradation. The tube entering into the anterior chamber caused no appreciable inflammation and maintained its patency even when downgrowth epithelial cells lined the anterior chamber. The Molteno plate induced little or no inflammatory reaction. Therefore, the Molteno glaucoma implant is a useful device for patients with high risk for failure after surgery for glaucoma. ",10 3032,"Isoenzymes of aldehyde dehydrogenase in human lymphocytes. The types of isozymes of aldehyde dehydrogenase (ALDH) present in human lymphocytes has been investigated using isoelectric focusing of polyacrylamide gels followed by substrate-specific staining. Lymphocytes obtained from most individuals were found to contain both types I and II ALDH. This group of 'typical' individuals reported that they did not develop marked facial flushing or rapid heart rate after drinking alcohol nor did they develop an erythema to cutaneously applied ethanol. Lymphocytes obtained from 'atypical' individuals who do suffer from alcohol-induced flushing and rapid heart rate and who developed erythema to cutaneous ethanol displayed type II, but not type I, ALDH. Lymphocytes thus appear to be an easily accessible and suitable tissue for determining type I ALDH phenotype. ",22 2803,"Methylene chloride: report of five exposures and two deaths. Five patients presented to the emergency department (ED) following exposure in an enclosed space to methylene chloride (dichloromethane), used for removing paint. Two workers and three rescuers were involved. Two rescuers complained only of dizziness and mild nausea, and were subsequently discharged from the ED. One rescuer was asymptomatic. Worker no. 1 arrived in cardiac arrest and eventually died in the ED despite resuscitation efforts. Worker no. 2 also presented to the ED in cardiac arrest, and was successfully resuscitated to pulse and blood pressure. However, he never regained consciousness or spontaneous respirations, and died on the fourth day. Of interest is that worker no. 2's carboxyhemoglobin level increased from 2% to 8% over the 9 hours following admission, despite administration of 40% to 50% oxygen by endotracheal tube. Among the conclusions that can be drawn are (1) the cause of death in these patients was not carbon monoxide poisoning, but solvent-induced narcosis; (2) carboxyhemoglobin levels may continue to rise following cessation of exposure, despite administration of high flow oxygen; (3) rescuers can easily become victims if proper protective clothing and respirators are not worn. ",20 1786,"Surgical repair of postinfarction ventricular septal defect. Thirty-one patients underwent repair of postinfarction ventricular septal defect (VSD) from 1980 to 1989. All patients were in New York Heart Association functional class IV, and 15 of them were in cardiogenic shock when operated on. Coronary arteriography was performed in all patients before surgery: nine had one-vessel, 11 had two-vessel, and 11 had three-vessel disease. The VSD was anterior in 15 patients and posterior in 16. The operative technique evolved over the years from a fairly extensive infarctectomy and reconstruction of the septum and right and left ventricular walls with a double Dacron patch, to minimal or no infarctectomy and closure of the VSD by excluding the infarcted muscle from the left ventricular cavity. This is accomplished by suturing a single patch of bovine pericardium to healthy endocardium surrounding the infarcted muscle. The right ventricle is left intact. Overall mortality was 10%, with three operative deaths. All deaths occurred in patients in cardiogenic shock who had three-vessel coronary artery disease. Thus, the mortality for patients in shock was 20%, and the mortality for patients with three-vessel disease was 27%. The operative mortality for patients with posterior VSD was twice as high as in patients with anterior VSD. However, univariate analysis of various clinical, hemodynamic, and operative variables indicated that only three-vessel disease was predictive of operative mortality. Because the number of patients was small and the overall operative mortality relatively low, the results of this analysis may not be valid. ",13 2811,"Brief intervention strategies for harmful drinkers: new directions for medical education. Recent advances in the technology of behavioural interventions for harmful drinkers have created a new role for clinical practice and new challenges for medical education. Several reports from expert committees have recommended new initiatives in the secondary prevention of alcohol problems through physician-based interventions at the primary care level. The conceptual and scientific bases for these recommendations are discussed in terms of recent studies of harmful and hazardous drinkers. The behavioural principles thought to account for the effectiveness of brief interventions are explained. Despite these promising developments, difficulties are inherent in the introduction of new technologies, especially behavioural technologies, into medical practice. A major challenge to medical education will be the development of academic programs that not only teach skills and competencies in secondary prevention but also deal with the socialization of physicians as behavioural practitioners. ",20 61,"Comparison of species distribution and antimicrobial susceptibility of aerobic actinomycetes from clinical specimens. To compare the species distribution and antimicrobial susceptibility of aerobic actinomycetes, we evaluated 366 isolates referred to the Centers for Disease Control from October 1985 through February 1988. We used conventional biochemical tests to identify the various species. Four species accounted for 191 (52%) of aerobic actinomycete isolates: Nocardia asteroides (98 isolates), Actinomadura madurae (42 isolates), Streptomyces griseus (28 isolates), and Nocardia brasiliensis (23 isolates). Sputum and wounds were the most common sources. No isolate was resistant to amikacin, no N. brasiliensis isolate was resistant to sulfamethoxazole or trimethoprim-sulfamethoxazole, and no A. madurae isolate was resistant to ceftriaxone or imipenem. In summary, our findings show that unusual species of aerobic actinomycetes can cause infection, colonization, or both and that antimicrobial resistance varies markedly by species. ",0 3332,"Development of a soft, pliable, slow heparin release venous graft. To prevent their collapse, a certain amount of stiffness is generally required for prosthetic venous grafts, so EPTFE grafts have been used. However, the native vein is pliable without any stiffness. We developed a soft and pliable graft that can maintain patency of the lumen because of its compliance. Fresh porcine ureter was incubated in a ficin solution to remove cell components and noncollagenous proteins. One percent protamine sulfate solution was injected into the ureter lumen to impregnate the inner surface. The ureter was then crosslinked with a 1% glutaraldehyde solution, dipped into a 1% heparin solution for 5 hours, and rinsed with distilled water. This procedure made the ureter very soft and pliable, and also conferred antithrombogenicity to the graft by heparinization. The grafts were implanted into the posterior vena cavae of 20 dogs and were removed from 1 to 878 days after implantation. Eighteen grafts were patent, but two grafts were occluded at the anastomotic site at 218 and 107 days, respectively. As a control experiment, nonheparinized grafts were implanted into 15 dogs; all were occluded with fresh thrombi. All the patent grafts kept their original elasticity, which allowed them to heave in unison with the heartbeat, and were similar in appearance to the native vena cava. Heparinization was effective in preventing thrombus formation. These results indicate that this type of graft is an ideal prosthesis as a venous graft, having physiologic properties such as compliance and antithrombogenicity. ",22 2657,"Evaluation of the efficacy and cost effectiveness of health education methods to increase medication adherence among adults with asthma. We randomized 135 adult asthma patients to a control group, and 132 patients to an experimental group which received a special health education intervention. Four adherence measures were documented at baseline and 12-month follow-up: correct inhaler use, inhaler adherence, medication adherence, and total adherence rating. Costs to routinely deliver the intervention were $32.03/patient. Experimental group patients exhibited a significantly higher level of improvement in adherence (44 percent) than control group patients (2 percent). ",19 406,"Interventional radiology of the biliary tract. Intraductal radiation. One palliative method of treating patients with a high duct cholangiocarcinoma is the use of 192Ir wire. This is placed through the tumor, which has been previously intubated, and delivers a high local dose of radiation. The mean survival time in 30 patients treated with intraductal radiation was 16.8 months, an improvement compared to surgical bypass or endoscopic and radiologic drainage procedures. ",3 2216,"Autosomal dominant retinitis pigmentosa: absence of the rhodopsin proline----histidine substitution (codon 23) in pedigrees from Europe. In exon 1 at codon 23 of the rhodopsin gene, a mutation resulting in a proline-to-histidine substitution has previously been observed in approximately 12% of American autosomal dominant retinitis pigmentosa (ADRP) patients. The region around the site of this mutation in the rhodopsin gene has been amplified and analyzed in affected individuals from 91 European ADRP pedigrees. The codon 23 mutation has been found to be absent in all cases, including a large Irish pedigree in which the disease gene has previously been shown to be closely linked to the rhodopsin locus. This indicates the presence of either allelic or nonallelic heterogeneity in ADRP. ",15 1077,"Patellar resurfacing in total knee arthroplasty. Technical errors in patellar resurfacing at the time of total knee arthroplasty (TKA) are responsible for many of the complications that affect the patellofemoral joint. Instability, patellar fracture, and wear of metal-backed patellar implants are significantly affected by errors of patellar resurfacing. A review of 50 TKAs using a condylar prosthesis and a standardized technique for patellar resurfacing was performed to evaluate the accuracy of the technique. The patients were evaluated at a mean of 2.5 years (range, two to five years) after surgery. The Hospital for Special Surgery Knee Score improved from a preoperative mean of 56 to 92 at the last evaluation. The Hospital for Special Surgery Knee Scores were excellent in 92% and good in 8%. The Knee Society Knee Score improved from a preoperative mean of 28 for pain and 49 for function to a last evaluation mean of 96 for pain and 85 for function. None of the patients had symptoms referable to the patellofemoral joint. There were no patellar fractures, dislocations, or instances of implant loosening of the patella. Roentgenograms revealed nine asymmetrically resurfaced patellae and five tilted patellae. There were no patellar subluxations. Patellar thickness was maintained at the preoperative level of 21 mm. Joint-line height was elevated 1 mm. The patellar height was decreased 2 mm from the preoperative height. Using a standard technique, satisfactory clinical results can be achieved, but minor errors in resurfacing and alignment will still occur. ",9 2843,"Basophil releasability in severely burned patients. Thermal injury is known to induce dysregulation of the immune system; however, the precise mechanisms have to be clarified. We investigated the histamine release of basophil granulocytes from severely burned patients (n = 12) after stimulation with anti-IgE or the Ca-ionophore A 23187, respectively. The anti-IgE-induced basophil histamine release of all patients was reduced in comparison to healthy donors beginning at day one postburn (p.b.) (5.0 +/- 2.3% vs. 30.5 +/-3.4%), while the Ca-ionophore-induced release was not decreased before day two p.b. Basophils of patients who finally succumbed to their injuries showed poor responsiveness (to zero levels) over the total time. In contrast, the basophil releasability of surviving patients returned to nearly normal levels (fifth to seventh week p.b.). Already in the second week p.b. there was a significant difference in histamine release between survivors and nonsurvivors [e.g., days 6-9 p.b.: 23.7 +/- 4.0 vs. 6.9 +/- 2.7 (p less than 0.005) after Ca-ionophore stimulation]. The altered basophil histamine release was neither due to a diminished dose- or a delayed time-response to the stimuli nor due to differences in the basophil counts or the cellular histamine content. Our data indicate that the decrease of the basophil releasability, which may be secondary to altered signal transduction pathways in severely burned patients correlates with the clinical outcome. ",20 1234,"Community hospital carotid endarterectomy in patients over age 75. We compared the prevalence of stroke and death in 133 patients aged 75 and older in whom 170 carotid endarterectomies were performed with that in 501 patients less than age 75 in whom 640 carotid endarterectomies were performed. There were three strokes (2%) in patients aged 75 and older and nine strokes (1%) in younger patients (p = 0.7). There were 8 deaths (5%) in patients aged 75 and older and 14 deaths (2%) in younger patients (p = 0.1). After controlling for the possible confounding effects of diabetes, prior stroke, history of angina, prior carotid artery disease, previous vascular surgery, history of myocardial infarction, preoperative hypertension requiring medication, and female gender, a logistic regression model showed that patients aged 75 and older were no more likely to have a stroke or death than patients under age 75. We conclude that age alone is not a contraindication to the safe performance of carotid endarterectomy in the community hospital. ",9 2470,"The need for accurate nutrition survey methodology: the South Carolina experience. Assessment of two nutrition-related risk factors, obesity and fat intake, was completed on a representative sample of South Carolina adults. Obesity estimates determined from self-reported heights and weights were less than prevalences determined from direct measurements (white males 21.4% vs. 28.2%; white females 20.8% vs. 24.5%; black males 29.2% vs. 30.1%; black females 43.6% vs. 50.6%; and total 24.9 vs. 29.8%). Nine fat-intake habits were identified from dietary mannerisms involving the consumption of red meat, fat on meat, fried fish/chicken, butter, eggs, whole milk, bacon/sausage, and cheese and the use of solid fats when cooking vegetables. The mean number of the nine habits exhibited was four. The total number of habits did not correlate well with serum cholesterol, as 27% of the individuals with none of the nine fat intake habits had blood cholesterol values greater than 6.2 mmol/L (239 mg/100 mL), while only 17% of the individuals with seven habits had the high level of cholesterol. These nine habits explained less than 10% of the variability of serum cholesterol values. ",17 1130,"Late juvenile-onset Krabbe's disease. Krabbe's disease is an autosomal recessive leukodystrophy characterized by a lack of galactocerebroside beta-galactosidase activity. In contrast to the classic early infantile-onset form of Krabbe's disease, less recognized, late-onset variants exist. The authors present a case of late juvenile-onset Krabbe's disease, including the associated magnetic resonance imaging (MRI) findings. Most patients with late-onset Krabbe's disease present with visual loss due to optic atrophy. Associated gait abnormalities and parental consanguinity should increase the clinician's suspicion that a child may have late-onset Krabbe's disease. Because of the prolonged survival in late-onset Krabbe's disease, the recent development of bone marrow transplantation for these patient makes diagnosis of this disorder particularly important. ",9 79,"Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus. The native capsular polysaccharide of type III group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human subjects. ",0 1280,"Immunohistologic study of epiretinal membranes in proliferative vitreoretinopathy. We performed an immunohistologic study on 11 specimens of epiretinal membranes surgically obtained from patients who had rhegmatogenous retinal detachment with proliferative vitreoretinopathy. Immunostaining procedures were used to identify immunoglobulin and complement deposits, to visualize class II antigen expression by proliferating cells, and to determine eventual infiltration by cells of the immune system. Diffuse deposits of IgG, IgA, IgE, C1q, C3c, and C3d were found in epiretinal membranes, whereas numerous cells, including glial or pigmented epithelial cells, expressed HLA-DR and HLA-DQ antigens. Some macrophages and B or T8 lymphocytes were identified. These results suggest activation of the immune system during the course of proliferative vitreoretinopathy. Class II antigen expression could be dependent upon growth-promoting factors and interferon gamma and could play a crucial role in this immune reaction, which resulted in immunoglobulin deposition and activation of complement. However, the eventual role of immune phenomena in the extension of proliferative processes remains to be determined. ",10 2357,"Development of IDDM after donating kidney to diabetic sibling. The goal of this study was to describe a patient who developed insulin-dependent diabetes mellitus (IDDM) after donating a kidney to his sibling and to suggest a possible solution to prevent such an occurrence. A 42-yr-old man was found to have islet cell autoantibodies (ICAs) as part of a screening program of first-degree relatives with IDDM. Two years previously, he had donated his kidney to his HLA-identical sibling with long-standing IDDM. Both oral and intravenous glucose tolerance tests demonstrated a gradual loss of insulin secretion and increasing glucose intolerance until the patient developed IDDM 6 yr after the nephrectomy. Whether the presence of ICA is an absolute contraindication to being a kidney donor could be debated. Nonetheless, ICA should be used as a screening test to identify individuals at risk for subsequent IDDM. For those found to be positive, counseling should be provided. ",17 457,"The Cancer Prevention Reminder System. The Cancer Prevention Reminder System is a computer-based system designed to increase the delivery of periodic health maintenance procedures. The program provides printed reminders that identify patients' overdue procedures, prints summary reports of the percentage of patients who are eligible and overdue for a procedure, and prints mailing labels for patients. We performed a randomized, controlled trial in which the effects of computer-based reminders were compared with those of two other interventions among residents in a university-based group practice. ",3 2223,"Parenchymal and vascular magnetic resonance imaging of the brain after extracorporeal membrane oxygenation. Three-dimensional (volume) magnetic resonance angiography is a new and noninvasive method for imaging the intracranial vasculature. The combination of magnetic resonance angiography and conventional magnetic resonance imaging was used to evaluate brain parenchyma and vessels in 30 survivors of extracorporeal membrane oxygenation. Magnetic resonance imaging findings were abnormal in 33% of the patients, with no increased frequency of right hemispheric lesions. Magnetic resonance angiography demonstrated good intracranial flow in all infants and demonstrable right internal carotid arterial flow in 35% of those patients with permanent carotid ligation. An abnormal magnetic resonance imaging study was found more often in infants with abnormal predischarge neurologic examination results. These techniques have several advantages over other neuroimaging modalities, including better definition of deep structures, myelin formation, and intracranial vasculature, the absence of bone artifact, and the elimination of catheter or contrast use. ",15 634,"Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy. The hyperuricemia responsible for the development of gouty arthritis results from a wide range of environmental factors and underlying genetically determined aberrations of metabolism. 31P magnetic resonance spectroscopy studies of children with hereditary fructose intolerance revealed a readily detectable rise in phosphomonoesters with a marked fall in inorganic phosphate in their liver in vivo and a rise in serum urate in response to very low doses of oral fructose. Parents and some family members heterozygous for this enzyme deficiency showed a similar pattern when given a substantially larger dose of fructose. Three of the nine heterozygotes thus identified also had clinical gout, suggesting the possibility of this defect being a fairly common cause of gout. In the present study this same noninvasive technology was used to identify the same spectral pattern in 2 of the 11 families studied with hereditary gout. In one family, the index patient's three brothers and his mother all showed the fructose-induced abnormality of metabolism, in agreement with the maternal inheritance of the gout in this family group. The test dose of fructose used produced a significantly larger increment in the concentration of serum urate in the patients showing the changes in 31P magnetic resonance spectra than in the other patients with familial gout or in nonaffected members, thus suggesting a simpler method for initial screening for the defect. ",4 3042,"Pharmacokinetics of paracetamol after cardiac surgery. Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children. ",22 119,"Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection. Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients. ",1 741,"Enteroglucagon and peptide Y-Y response after construction of a pelvic reservoir in humans. The results of an investigation of plasma levels of gastrointestinal hormones in patients after the construction of a pelvic reservoir are reported. Enteroglucagon (EG) and peptide tyrosine-tyrosine (PYY), two hormones believed to play a relevant role in the adaptive response to bowel resection, were investigated using a specific radioimmunoassay in basal conditions and after a standard meal. Pouch patients showed a statistically significant increase in basal levels of both enteroglucagon and PYY compared with control subjects (P less than 0.02 and P less than 0.001, respectively). The response of enteroglucagon to food ingestion, evaluated by means of the total integrated response, was similar in patients and controls. Conversely, the response of PYY was significantly increased in pouch patients compared with control cases (P less than 0.02). Results of this investigation suggest that gut hormones may be involved in mediating the adaptive response of the intestine to pouch construction. Changes of gut peptides may explain, at least in part, the functional results observed after pouch construction. ",5 1270,"Assessment of tear drainage after canalicular obstruction using fluorescein dye disappearance. Assessment of tear drainage impairment after monocanalicular obstruction can be difficult. The authors used fluorescein dye disappearance to evaluate tear drainage after experimental obstruction of upper, lower, neither, or both canaliculi in 20 subjects. Marked impairment was noted in all subjects when both canaliculi were occluded (P less than 0.004). Monocanalicular obstruction (either upper or lower) generally resulted in minimal or no impairment, though 10% of subjects showed marked impairment. Fluorescein dye disappearance proved a reliable, rapid method for assessing tear drainage and detecting lacrimal obstruction. ",10 2683,"Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected. ",19 1171,"Ultrasonography and magnetic resonance imaging in Leigh disease. An infant with Leigh disease, who was the younger sister of a similarly affected infant, had been examined before the onset of the disease. Ultrasonography revealed hyperechoic lesions in the putamen and caudate nucleus during the preclinical stage. At onset, these changes extended into the cerebral cortex and medulla. These lesions were also detected by T2-weighted magnetic resonance imaging (MRI) as areas of increased signal intensity. Her brother demonstrated the same ultrasonographic results; cranial computed tomography disclosed low-density areas in the basal ganglia which were detected as hyperechoic lesions by ultrasonography. These findings suggest that ultrasonography is useful in detecting early intracranial lesions in Leigh disease. ",9 2303,"Psoriasis: the application of genetic technology and mapping. Recent progress in molecular genetics has led to the creation of a map of the human genome utilizing RFLP. Given a sufficient family structure, genetic diseases can now be placed on this map. Genetic studies of psoriasis can both help resolve and be confounded by problems of disease heterogeneity, environmental effects on disease expression, and lack of a clear model of inheritance. ",16 554,"Cryoprobe as a ""handle"" for resection of metastatic liver tumors. Resection of metastatic liver tumors can be a difficult and risky procedure. Using a cryoprobe as a ""handle"" can greatly facilitate resection by providing a taut surface for transection and improving visualization of ductal and vascular structures. In addition, this technique may decrease the risk of contaminating surrounding tissues with cancer cells, and may inhibit tumor recurrence within the margins of resection. ",3 2550,"In vitro and in vivo testing of an electrocatalytic glucose sensor. A prerequisite for the development of an implantable artificial pancreas is the availability of a stable, long-life glucose sensor. Platinum (Pt) catalyzed electrodes have been demonstrated in vitro to show high sensitivity to glucose and long cycle life but are more sensitive to co-reactants compared with enzymatic methods. The authors developed a special data processing method (compensated net charge ratio, or CNCR) in which the measured electrode response is very sensitive to glucose, completely insensitive to urea, and only moderately sensitive to amino acids. Other endogenous and exogenous co-reactants show only minor interferences. The CNCR method involves the determination of the ratio of net oxidation charge to total charge during one complete cycle of a cyclic voltammogram. Prototype electrodes tested in vitro in spiked plasma have shown typical sensitivities of greater than 2 x 10(-4) CNCR units per 1 mg/dl change in glucose concentration, with linear response up to 400 mg/dl. For in vivo testing, a modified 5 F vascular catheter with membrane covered surface mounted electrodes was used at a vena cava site in swine. Several sensor designs were tested in vivo, with sensitivities of 1-5 x 10(-4) CNCR units (mg/dl). ",18 3155,"Does indomethacin alter the hemodynamic response to magnesium sulfate infusion and hemorrhage in gravid ewes? The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes. ",22 850,"Diagnosing periodontal diseases. At present, the diagnosis of periodontal disease requires a clinical evaluation of the patient including visual findings, the use of the periodontal probe, and radiographs. No test is available to evaluate disease activity. In specific cases, adjunctive procedures may also be useful. The identification of pathogenic microorganisms may aid in evaluating the periodontal status of special patients. However, these are not required for an adequate diagnosis of the common adult form of chronic periodontitis. ",6 2128,"Prevalence of Raynaud phenomenon in the adult population of South Carolina. A prevalence estimate for Raynaud phenomenon among adult residents of South Carolina was based on data obtained from respondents in a statewide health survey, followed by face-to-face interviews and clinical screening for Raynaud phenomenon, using a screening procedure developed by the authors. The survey obtained 5246 personal interviews from a probability sample of over 3000 households, and 494 survey subjects participated in the clinical screening. The prevalence estimates and their standard errors were computed using survey case weights, design-based estimation, and logistic modelling techniques. The prevalence of Raynaud phenomenon among adult residents of South Carolina was determined to be 3.5%, with a standard error of 0.6%. Prevalence was higher for females (4.3%, SE = 0.7%) than for males (2.7%, SE = 0.6%). These figures are much lower than most estimates in the existing literature on Raynaud phenomenon. ",13 2589,"Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona. The age-adjusted prevalence ratio for Bombay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States. ",19 2300,"Lymphocyte trafficking in psoriasis: a new perspective emphasizing the dermal dendrocyte with active dermal recruitment mediated via endothelial cells followed by intra-epidermal T-cell activation. Prominent within the inflammatory infiltrate of psoriasis are HLA-DR positive T lymphocytes and factor XIIIa positive dermal dendrocytes. Many investigators studying psoriasis have assumed that the HLA-DR positive T cells are activated, and thereby capable of producing lymphokines such as gamma interferon. However, by immunohistochemical analysis, greater than 95% of the dermal T cells in psoriatic lesions are Ki-67 negative, which suggests that they are in a resting or non-cycling (Go) state. In contrast to the dermal T-cell population, the epidermal T-cell population contains a greater population of Ki-67 positive lymphocytes. The entry of the T cells into the epidermis is, therefore, apparently associated with an important activation event, which in all likelihood involves interaction with the keratinocyte. The presence of activated intraepidermal T cells has been substantiated by the ability to detect gamma interferon mRNA by polymerase chain reaction in epidermal sheets of psoriatic lesions. The pathophysiologic implication in psoriasis for these distinctions and compartmentalization involving dermal and epidermal T cells are placed into the context of a cascade of cellular trafficking events, which are further dissected into a specific network of molecular mediators of inflammation. This report suggests that more attention should be placed on the microenvironment of the skin, with specific emphasis on the mechanism by which T cells accumulate in the dermis and epidermis, and elucidation of the selective inductive and recruitment capabilities of endothelial cells, perivascular dermal dendrocytes, and keratinocytes. ",16 915,"Trimming of the inferior turbinates: a prospective long-term study. The aim of this study was to determine whether the initial benefits of radical trimming and anterior trimming of the inferior turbinates on nasal airflow persisted in the long term. Radical trimming significantly reduced nasal resistance at 2 months following operation (n = 12) (P less than 0.005). There was no significant change in nasal resistance over the next 20 months. Symptom scores for nasal obstruction also showed a significant reduction (n = 16) (P less than 0.005), at 2 months, and did not change significantly over the next 20 months. Radical trimming of the inferior turbinates is a highly effective operation in patients with hypertrophy of the inferior turbinates with few initial complications. However, further analysis of the data revealed that up to 20% of patients lose the initial subjective benefit of relief of nasal obstruction within 2 years of follow-up. Late onset crusting occurs in some patients though this is not directly attributable to an increase in nasal airflow. This study also concludes that anterior trimming of the inferior turbinates cannot be recommended as a form of treatment. ",7 1825,"The effect of enoximone and dobutamine on hemodynamic performance after open heart surgery. A clinical comparison. In a prospective, randomized study the phosphodiesterase inhibitor enoximone was compared to dobutamine after open heart surgery. In either group 25 patients were treated with enoximone and dobutamine, respectively, beginning immediately after weaning from cardiopulmonary bypass until 4 hours postoperatively. The drug was administered as a continuous infusion of 5 micrograms/min/kg body weight. Under enoximone a significant increase of cardiac output [enoximone (E): + 100%; dobutamine (D): + 38%] and a significant decrease of pulmonary vascular resistance (E: -34%, D: +65%) and of total systemic vascular resistance (E: -59%, D: -7%) was achieved. Systemic blood pressure and heart rate were not different. Side effects were not observed. Enoximone proved to be safe and superior to dobutamine in low cardiac output states after open heart surgery. ",13 3170,"MyoD induces growth arrest independent of differentiation in normal and transformed cells. MyoD is a gene involved in the control of muscle differentiation. We show that MyoD causes growth arrest when expressed in cell lines derived from tumors or transformed by different oncogenes. MyoD-induced growth inhibition was demonstrated by reduction in the efficiency of colony formation and at the single-cell level. We further show that MyoD growth inhibition can occur in cells that are not induced to activate muscle differentiation markers. The inhibitory activity of MyoD was mapped to the same 68-amino acid segment necessary and sufficient for induction of muscle differentiation, the basic-helix-loop-helix motif. Mutants with alterations in the basic region of MyoD that fail to bind or do not activate a muscle-specific enhancer inhibited growth; mutants with deletions in the helix-loop-helix region failed to inhibit growth. Thus, inhibition of cell growth by MyoD seems to occur by means of a parallel pathway to the one that leads to myogenesis. We conclude that MyoD is a prototypic gene capable of functionally activating intracellular growth inhibitory pathways. ",22 151,"Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum. During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity. We determined the minimal infective dose of the P. falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P. falciparum strains. A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge. These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P. falciparum. ",2 3161,"Histologic evaluation of the width of soft tissue necrosis adjacent to carbon dioxide laser incisions. This study evaluated the width of tissue necrosis lateral to carbon dioxide laser incisions on human intraoral excisional biopsy specimens. Measurements were made on specimens including epithelium, muscle, dense and loose connective tissue, and salivary gland. Results showed a mean width of tissue necrosis of 86 microns in epithelium, 85 microns in muscle, 51 microns in loose connective tissue, 96 microns in dense connective tissue, and 41 microns in salivary gland. The range of thermal necrosis in different tissue types is probably based on the water content within each type. A cellular partially homogenized zone of reversible thermal damage up to 500 microns in width was visible adjacent to the zone of thermal necrosis. The relatively narrow width of tissue necrosis with this technique may account for the claimed superior properties of laser-induced wounds compared with those created by electrosurgery. ",22 836,"Plasma fatty acid profile in advanced cirrhosis: unsaturation deficit of lipid fractions. Fatty acid (FA) profile of plasma total lipids, phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG) were measured in 101 patients with advanced liver cirrhosis and in 44 age- and sex-matched healthy controls. Plasma levels of lipidic phosphorus, esterified cholesterol, and TG also were measured, and the unsaturation index (UI) was calculated for each fraction. Total plasma concentrations of saturated FA, linoleate, and polyunsaturated FA (PUFA) were lower in cirrhotics than in controls. This profile was also found in plasma levels of PL- and CE-associated FA. No detectable amounts of C20:3n9 were found in cirrhotic patients. Percent FA distribution of lipid fractions showed a lower percentage of linoleate and PUFA and a higher relative amount of saturated and monoenoic FA in cirrhotics than in controls. As a consequence, the UI of PL and CE was diminished in liver cirrhosis. Linoleate and PUFA deficiency was more marked in CE than in PL, as shown by the number of patients with values below the 5th percentile of the control group, suggesting an attempt to maintain the unsaturation of PL as the most important component of cell membranes. Hepatic failure, poor essential FA intake, and malnutrition are some of the possible etiologic factors for PUFA deficiency in cirrhosis. Their relative contribution to plasma FA abnormalities, as well as the clinical and pathophysiological consequences of PUFA deficit in cirrhotic patients, requires further investigation. ",5 1308,"The absence of nephrotoxicity and differential nephrotoxicity between tobramycin and gentamicin. We conducted a prospective, double-blind, randomized trial of gentamicin and tobramycin to evaluate differences in nephrotoxicity. We evaluated levels of creatinine, creatinine clearance, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) as indicators of nephrotoxicity, and attempted to correlate them. Forty patients met the criteria for evaluation; 14 were given tobramycin and the remaining 26 received gentamicin. Significant nephrotoxicity, as defined by an increase in creatinine of 0.5 mg/dL, did not occur in either group. Increases in beta 2-microglobulin values were seen in 67% of the patients in the tobramycin group, and 52% of those in the gentamicin group. Elevations in NAG levels occurred in 54% of those in the tobramycin group and 52% of those in the gentamicin group. Elevation of NAG and beta 2-microglobulin levels was congruent in only 40% of the cases. We conclude that there was no significant difference in nephrotoxicity between gentamicin and tobramycin. Elevations of NAG and beta 2-microglobulin occurred at rates similar to those reported in the literature, but they did not correlate with significant nephrotoxicity. ",11 354,"Implementation of cancer prevention guidelines in clinical practice. Data from several sources, including consumer surveys, physician surveys, and medical record audits, indicate that consumers do not receive cancer screening tests as recommended by the National Cancer Institute, the American Cancer Society, and the U.S. Preventive Services Task Force. Performance rates are consistently below published standards for all tests except Pap tests. Major reasons physicians do not perform the recommended tests include physician forgetfulness, disagreement with recommendations, lack of time, and patient refusal. Physicians also tend to overestimate their own performance rates. Barriers to screening test performance can be categorized into patient factors, physician factors, test factors, and health care delivery system factors. Interventions, such as computerized reminder systems, physician audits with feedback, and patient education and reminders, can be effective in promoting performance of such screening. Interventions that target both physician and patient may be particularly effective. ",3 2399,"S-antigen. Identification of human T-cell lymphocyte proliferation sites. Immune responses to normal retinal proteins, including S-antigen, have been demonstrated in patients with a variety of retinal disorders, as well as in those who have received panretinal laser photocoagulation. T-cell lymphocytes (T cells) have been implicated in the pathogenesis of several ocular inflammatory diseases of possible autoimmune etiology. We used synthetic peptides that correspond to the amino acid sequence of S-antigen in lymphocyte proliferation assays to identify specific sites in the molecule recognized by human T cells. Ten patients with type II diabetes were studied before and after initial panretinal laser photocoagulation for proliferative diabetic retinopathy. T-cell responses, expressed as a stimulation index, to S-antigen and peptides were negative in all patients before treatment. Three weeks after panretinal laser photocoagulation, eight of 10 assays were positive (stimulation index greater than 2; P less than .01) when lymphocytes were stimulated with peptide BSA(273-292); six of nine were positive (P less than .01) with peptide BSA(303-332); and six of six were positive (P less than .001) with peptide BSA(343-362). Our study identifies several specific sites in S-antigen that elicit human immune responses. The implications of these findings with regard to the pathogenesis and treatment of autoimmune uveitis are discussed. ",17 3041,"Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death The pathophysiology of recurrent cyanotic episodes has been investigated in 51 infants and children. Episodes began at a median age of 7 weeks (range 1 day to 22 months, 39 at less than 4 months). They were characterised by the rapidity of onset and progression of severe hypoxaemia with early loss of consciousness from cerebral hypoxia. The most common precipitating factor was a sudden naturally occurring stimulus from pain, fear, or anger. In uncontrolled trials, cyanotic episodes were reduced in frequency and severity by tetrabenazine (n = 15) and additional inspired oxygen (n = 10). Eight patients died suddenly and unexpectedly (four during cyanotic episodes). Twenty eight patients underwent physiological studies during cyanotic episodes. There was no evidence of seizure activity at the onset and although prolonged absence of inspiratory effort with continued expiratory efforts was common, breathing sometimes continued. Episodes were not caused by upper airway obstruction and sometimes occurred during positive airway pressure ventilation. The rapidity of fall in arterial oxygen pressure and continued breathing suggested a right to left shunt of sudden onset. The results of contrast echocardiography and lung imaging studies confirmed that this was occurring within the lungs. These cyanotic episodes included both intrapulmonary shunting and prolonged expiratory apnoea. They are best explained by interactions between central sympathetic activity, brainstem control of respiration and vasomotor activity, reflexes arising from around and within the respiratory tract, and the matching of ventilation to perfusion in the lungs. They are a cause of sudden unexpected death in infancy and early childhood. ",22 165,"Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus. Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas. ",3 3228,"Aortic occlusion and vascular isolation allowing avascular hepatic resection. Occlusion of the supraceliac abdominal aorta and hepatic vascular isolation were employed in a series of 15 patients as a definitive method to allow avascular hepatic resection. The series was compared with an earlier group of patients treated conventionally. In the avascular hepatic resection group there was no mortality; hypotension did not occur at the time of hepatic vascular isolation; rapid, accurate excision of the hepatic lesions could be achieved in a bloodless field; resection of midline lesions and those involving the great veins was possible; and ""segmentectomies,"" or resections crossing segmental boundaries, could be performed where previously formal hepatic lobectomies were required. Concomitantly, the greatest amount of uninvolved hepatic parenchyma remained in situ. There was increased ease of operative management, reduced blood loss, and reduced operating time (mean, 2.8 hours). ",22 2233,"Neonatal ethics: development of a consultative group. Experience of a neonatal ethics advisory group in a tertiary care setting was reviewed to identify which aspects of the experience have been most valuable in the development of a consultative group. Consultations were requested for 31 patients seen from August 1984 through December 1988. Review of these patients indicated that 21 of 31 infants were born after full-term gestations, 11 of 31 infants were seen beyond the neonatal period, and some type of congenital anomaly was the principal diagnosis for 64.7% of the patients. The reasons for seeking consultation primarily involved decisions regarding withdrawal or withholding of treatment. For 22 of the 31 patients, the consensus of the group supported the decision of the health care team. In the remaining consultations, the recommendation of the group was that more information and/or communication was needed. In the analysis of the neonatal ethics advisory group's experience with consultations the characteristics of neonatal patients were identified and the value of having a forum for discussing the difficult ethical issues facing members of the health care team were validated. ",15 1126,"The opposite pupil in herniation. I serially examined the pupil opposite the one already enlarged from transtentorial herniation in 13 patients. The main abnormalities, stereotyped in most patients, were an initially diminished light reaction with a 2.5- to 4-mm-diameter pupil, followed by slight reduction in size, and then reenlargement to greater than original size, all with preserved roundness. Subsequent deterioration varied among patients, but a transitional oval shape was infrequent and oculomotor function was preserved until both pupils were enlarged and fixed. Once the pupil on the side of a mass enlarges, heralding herniation, subsequent deterioration can be appreciated through changes in reactivity and size of the opposite pupil. ",9 855,"Dental implants used for periodontal patients. For those performing implant treatment, continued research and reports of long-term successful results are essential to evaluating the validity of implants, especially when variables such as design and surface treatment are introduced. The dental profession has enthusiastically embraced the clinical results of implant treatment and its benefits to the patient. However, just as patients who undergo periodontal and restorative treatment must continue a regular long-term routine of maintenance therapy to ensure their dental health, so must those patients who receive dental implants. Both the periodontist who places the implants and the dentist who fabricates the prosthetic replacement must work cooperatively to deliver a healthy restoration that will function for many years. ",6 2343,"Specificity of anti-Scl-70 antibodies in scleroderma: increased sensitivity of detection using purified DNA topoisomerase I from calf thymus. A large scale purification of DNA topoisomerase I from calf thymus was obtained using the combinations of 62% ammonium sulfate precipitation, Biorex 70, hydroxylapatite and phenylagarose chromatography. Silver staining of the preparation separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed 2 bands of apparent molecular weight of 70 and 60 kDa. Immunoblotting with a serum of anti-Scl-70 specificity also recognized both proteins. Anti-Scl-70 antibodies were detected in 24/32 (75%) patients with diffuse scleroderma by ELISA and 28/32 (87%) had the ability to neutralize the topoisomerase I activity. All of 14 sera with anticentromere antibodies did not react with DNA topoisomerase I by both assays. The presence of anti-Scl-70 antibodies remained disease specific despite the increase in sensitivity of both assays. ",16 2325,"Spinal synovial cyst: case report using magnetic resonance imaging. The case of a 65-year-old woman who developed a spinal synovial cyst at the L4-5 disk space is reported. Her clinical signs and symptoms are presented. A comparison among her preoperative myelogram, computed tomography scan, and magnetic resonance imaging showed magnetic resonance imaging to be more accurate in detailing both the intraoperative and pathological findings. ",16 1115,"Responses of intercostal muscle biopsies from normal subjects and patients with myasthenia gravis. In order to evaluate the mechanisms of weakness in muscles of patients with myasthenia gravis (MG), intercostal muscle biopsies were obtained from 9 normal subjects and 6 MG patients, and the compound muscle action potential (AP) and tension responses to nerve and muscle stimulation, and contracture responses on exposure to caffeine, were monitored in vitro. In normal muscle, on stimulation of the nerve or muscle at 30 to 100 Hz, the AP responses showed decrement in amplitude, one-third of which was attributable to failure of neuromuscular transmission and two-thirds to failure of muscle membrane excitation. On stimulation at 1 to 5 Hz, the AP responses showed very little decrement, while the contractile responses showed significant fade in tension, due to failure of E-C coupling or contractility. In muscle from patients with generalized MG, stimulation of the nerve at all frequencies (1 to 100 Hz) caused much greater decrement in APs and fade in tension responses than in normal muscle, due mainly to failure of neuromuscular transmission. However, at 100 Hz, 40% of the decrement in APs was due to failure of muscle membrane excitation, and at 1 to 5 Hz, 40% of the fade in tension was due to failure of E-C coupling or contractility, as in normal muscle. On direct stimulation the contraction and half-relaxation times were slower and the tetanic tension was smaller than in normal muscle, especially in the MG patient with thymoma. Caffeine-induced contractures were smaller in MG muscle than in normal muscle. These results indicate that while the weakness of MG muscle is due mainly to failure of neuromuscular transmission, it is also partly due to reduced E-C coupling or contractility. ",9 3302,"Effect of indomethacin on pain relief after thoracotomy. The effect of indomethacin on postoperative pain was studied in 60 adult patients undergoing thoracotomy in a prospective, randomized, double-blind manner. Patients receiving indomethacin required significantly less opioid after operation and had significantly lower pain scores compared with the control group. Pain on movement and on coughing were reduced also. No major adverse effects were encountered. ",22 1447,"Immunotherapy of murine bladder cancer by irradiated tumor vaccine. This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone. ",11 2647,"Epidemiology of cytomegalovirus infections. The determinants of cytomegalovirus (CMV) infection and disease can now be understood from studies of newborns, recipients of organ or bone marrow transplants, subjects infected with human immunodeficiency virus, and recipients of blood transfusions. CMV is transmitted to the neonate transplacentally, by passage through a contaminated birth canal, or by ingestion of infected breast milk; to the adult by heterosexual and homosexual sex with an infected partner; and to the transplant recipient by infected organs. A major unsolved problem in the study of CMV is the nature of viral latency. Knowledge regarding the requirements for activation of latent infection at the molecular, cellular, or host level is incomplete. Both viral and host factors may contribute to the successful transmission of CMV by latently infected cells in transplanted organs and transfused blood. ",19 2065,"Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates. 1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume. ",13 2628,"Serial studies of evoked potentials and circulating lymphocyte subsets for multiple sclerosis: attempts to monitor progress. A concurrent change in evoked potential measurements and quantitation of circulating T-suppressor (CD8) lymphocyte subpopulations might indicate increased subclinical disease activity. Eight untreated patients with clinically definite multiple sclerosis were monitored monthly for changes in the numbers of cells positive for CD8 markers, and hence in the ratio of CD4: CD8 positive cells. Such changes were found not to be associated with changes in evoked potentials or clinical status. ",19 1847,"Relation between beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure. The Multicenter Diltiazem Post-Infarction Research Group. This study examined the relations among beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure in patients after myocardial infarction. The study was performed with the placebo group of the Multicenter Diltiazem Post-Infarction Trial. Ejection fraction data were available in 1,084 patients; of these, 557 were receiving a beta-blocker and 527 were not. In addition to ejection fraction, other correlates of left ventricular function included the presence or absence of pulmonary rales, chest X-ray film evidence of pulmonary congestion and the presence of an S3 gallop. Beta-blocker use was less frequent in patients with an ejection fraction less than 30%, rales, an S3 gallop and pulmonary congestion on chest X-ray film. Twenty-one percent of patients with an ejection fraction less than 30%, 42% of patients with rales, 28% of patients with an S3 gallop and 28% of patients with pulmonary congestion were receiving beta-blocker therapy. For every correlate of left ventricular function, the chance of developing congestive heart failure was greater in patients with diminished left ventricular function than in those without. For each level of left ventricular function, the chance of developing congestive heart failure requiring treatment was greater in patients not taking a beta-blocker. ",13 655,"Magnetic resonance imaging and the nonoperative treatment of spinal epidural abscess. This report describes three patients with spinal epidural abscess diagnosed by magnetic resonance imaging and treated nonoperatively. Prior to treatment, one patient was neurologically intact, one patient demonstrated a moderate neurological deficit, and one patient was severely paraparetic with loss of bladder and bowel control. Following identification of the pathogenic organism, antibiotic therapy was continued until the patients demonstrated clinical improvement and radiological resolution of the abscess. All patients remained stable or improved neurologically. Analysis of 33 previously reported patients treated with antibiotics suggests that nonoperative treatment may be a reasonable alternative therapy under certain clinical conditions. These include (1) identification of the pathogenic organism, (2) a stable neurological condition, (3) access to magnetic resonance imaging or computed tomography for potentially rapid reevaluation, and (4) appropriate neurosurgical consultation and nursing care. Nonoperative treatment may also be considered as a reasonable alternative for patients who have severe concurrent medical illness. ",4 3040,"Meropenem pharmacokinetics and penetration into an inflammatory exudate. The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose. ",22 1739,"Vascular and calcemic effects of plasma of spontaneously hypertensive rats. Circulating substances that increase intracellular calcium, and other circulating substances that increase blood pressure, have been described in hypertensive animals and humans. In this study, we report the existence of a factor of the plasma of spontaneously hypertensive rats that does both. These effects were dose-dependent, and the time course for such effects was correlated with the time course for potentiation of pressor agents by the plasma. In addition, the plasma of spontaneously hypertensive rats was found to inhibit the depressor effects of parathyroid hormone. Our results confirm the presence of a circulating hypertensive factor in the plasma of spontaneously hypertensive rats, which may act by increasing calcium uptake in vascular smooth muscle. These findings may also help explain the secondary increase in parathyroid hormone noted in some forms of human and experimental hypertension. ",13 1604,"Early and late effects of captopril treatment after large myocardial infarction in rats. The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months. ",13 1633,"Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Family history of CAD, defined as parental death by CAD, was found to be a significant independent predictor of CAD in a logistic regression model controlling for standard risk factors and length of follow-up among the 5209 participants in the Framingham Study. Persons with a positive parental history have a 29% increased risk of CAD, and the strength of the association between parental history and CAD is similar to that found for other standard risk factors such as systolic blood pressure, cholesterol level, and cigarette smoking. No evidence was found that persons with a family history of CAD have a decreased capacity to cope with the deleterious effects of known risk factors; that is, no significant interaction was found between any of the risk factors and parental history of CAD. Among men with low risk for CAD by risk-factor profile (i.e., nonsmoking, thin, nonhypertensive persons), more than two thirds of those who experience CAD have a positive parental history. This study suggests that CAD among persons who are predicted to be at low risk by standard risk factors may have a substantial genetic component and that the risk associated with parental history may not be reduced by modification of these factors. Nevertheless, among persons with a positive family history, those with a favorable risk profile are at substantially less risk for CAD than those with an unfavorable risk profile. ",13 3189,"Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease. Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up. ",22 2778,"Inpatient treatment of employed alcoholics: a randomized clinical trial on Hazelden-type and traditional treatment. The first randomized clinical trial on the Hazelden-type of treatment showed that this AA-oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment. One hundred forty-one employed alcoholics were randomized to either Hazelden-type treatment (N = 74) or to traditional-type treatment (N = 67). The treatment groups were highly comparable. The bimonthly follow-up lasted one year. According to the COPES-questionnaire (short form), the treatment at the Hazelden-type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional-type institute. In accordance the treatment drop-out rate was 7.9% at Hazelden-type institute and 25.9% at traditional-type institute (p less than 0.02). The participation in outpatient treatment was significantly better after the Hazelden-type treatment. The proportion of those abstinent (admitted ethanol consumption, 0 g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden-type institute during the last (8-12 months) follow-up period (26.3% vs. 9.8%, p = 0.05). Fourteen percent of the Hazeldon-type institute patients and 1.9% of the traditional-type institute patients stayed abstinent during the whole 1-year follow-up period (p less than 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden-type treatment obtained better results in 1-year abstinence rate than a more traditional-type treatment. ",20 2875,"Simultaneous reconstruction of cervical soft tissue and esophagus with a gastro-omental free flap. A microvascular transfer of gastric tube and omentum was used to simultaneously reconstruct cervical soft-tissue and esophageal defects in five patients. All patients had previous high-dose radiation and multiple flap reconstructions. The largest esophageal and soft-tissue defects were 10 cm and 160 cm2, respectively. All wounds healed primarily except for one orocutaneous fistula. There was one death from an intraoperative stroke. The gastro-omental flap is useful in cases where the reconstructive surgeon is faced with both esophageal and soft-tissue defects--particularly in heavily irradiated patients who have few reconstructive options. ",20 2616,"The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. The pathophysiologic effects of histamine in anaphylaxis have been shown to be mediated through H1 and H2 receptors, individually and in combination. H1 receptors mediate coronary artery vasoconstriction, wheezing, cutaneous vascular permeability, and possibly an increase in pulse rate. H2 receptors stimulate ventricular and atrial inotropy, arterial chronotropy, coronary vasodilation, and rises in basophil cyclic adenosine 3':5' monophosphate (cyclic AMP). (Neither receptor mediates increases in cyclic AMP in mast cells.) H1 and H2 receptors in combination seem to be most potent in mediating flush, headache, increases in pulse pressure, and decreases in diastolic blood pressure. Clinical trials have been conducted to determine the efficacy of H1 and H2 antagonists in preventing anaphylactic reactions to plasma expanders, anesthesia-inducing agents, morphine, and radiocontrast material. Concurrently, retrospective observations of the prevention of anaphylactic reactions to chymopapain have been recorded. Despite some conflicting and inconclusive data, the sum of these studies indicates that pretreatment with a combination of H1 and H2 antagonists is more effective than H1 antagonists alone in preventing reactions to these agents. These results, when added to the available knowledge of the physiology of histamine release, support the preferential use of H1/H2 antagonist combinations in the prevention and treatment of anaphylaxis and anaphylactoid reactions. ",19 2305,"Sodium lauryl sulphate for irritant patch testing--a dose-response study using bioengineering methods for determination of skin irritation. The dose-response relationship in patch testing with sodium lauryl sulphate (SLS) was studied. The irritant skin response was quantified by visual scoring as well as by the following noninvasive methods: measurement of transepidermal water loss (TEWL) by an evaporimeter, measurement of skin color by a colorimeter, measurement of superficial blood flow by laser Doppler flowmetry, and measurement of edema in the skin by ultrasound A-scan. Twelve volunteers were patch tested with 0.12, 0.25, 0.50, and 1.00% SLS, and the skin response was evaluated after 24 and 48 h, respectively. We found a statistically significant linear dose-response relationship between dose of SLS and skin response evaluated by measurement of TEWL, skin color, superficial blood flow, and edema. Statistical evaluation by regression analysis proved measurement of TEWL to be the method best suited overall for quantification in relation to patch testing with SLS, whereas colorimetry was found to be the least sensitive of the applied methods. Ultrasound A-scan was found to be a promising method for quantification of the inflammatory response, being consistently more sensitive than measurement of skin color. ",16 1161,"IgM deposits at nodes of Ranvier in a patient with amyotrophic lateral sclerosis, anti-GM1 antibodies, and multifocal motor conduction block. We studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti-GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath. When injected into rat sciatic nerve, the serum IgM bound to the nodes of Ranvier, and the binding activity was removed by preincubation with GM1. These observations suggest that anti-GM1 antibodies may have caused motor dysfunction by binding to the nodal and paranodal regions of peripheral nerve. ",9 503,"Use of Mohs micrographic surgery to establish quantitative proof of heightened tumor spread in basal cell carcinoma recurrent following radiotherapy. We compared 27 basal-cell carcinomas (BCCs) recurrent following radiotherapy and subsequently excised by Mohs micrographic surgery to a control group of BCCs recurrent following other treatment modalities and similarly excised. Mohs technique permitted precise, quantitative tumor assessment, obtained via a novel method utilizing three parameters: the number of surgical stages required for complete excision, the percentage increase between clinical preoperative tumor area and final postoperative defect area, and the presence of deep subcutaneous tissue invasion. Figures for the postradiation group were larger in all three categories, with the latter two revealing statistically significant differences versus the nonradiation group. This study gives strong, direct quantitative support to the clinical impression that BCC recurrent following radiotherapy is a uniquely aggressive, invasive subset of recurrent BCC. ",3 3222,"Hiccups and breathing in human fetuses. Serial recording in 45 low risk fetuses throughout the second and third trimesters showed that hiccups were the predominant diaphragmatic movement before 26 weeks' gestational age and that there was a significant negative correlation with gestational age. There was a pronounced reduction between 24 and 26 weeks, which was the result of a decrease in the number of episodes of hiccups rather than a change in the duration of episodes. In contrast, fetal breathing was positively correlated with gestational age, the greatest increase in breathing occurring between 26 and 32 weeks' gestation. This was the result of both an increase in the number and duration of episodes. From the time that rest-activity cycles of behaviour could be determined in recordings, both breathing and hiccups were dependent on behavioural state or cycle, occurring predominantly during active episodes. This association between quiet and active behaviour and breathing did not alter with increasing gestational age, and the variables in fetal behavioural state became increasingly closely linked. The importance of prolonged and repeated recording, and also the need to take account of other variables in fetal behaviour, before any sinister conclusions can be drawn about the absence of fetal breathing is emphasised. ",22 2926,"Gasoline burns: the preventable cause of thermal injury. Gasoline related burns are a significant cause of thermal injuries each year in the United States. In this retrospective review of 1858 admissions to our Regional Burn Center from 1979 to 1988, 270 (14.5%) were persons with gasoline-related injuries. Natural gas and other distillates were excluded. Most victims were male (228 of 270); mean age was 27 years; mean burn size was 25% total body surface area. There were 299 skin grafts performed on 172 patients, and there were 16 deaths. The mean length of stay decreased from 38 to 17 days (p less than 0.001) between the first and second 5-year time periods, even though there was no significant change in age or mean burn size. The majority (59%) of gasoline-related burns were the result of inappropriate or unsupervised use of gasoline. The general public is largely unaware of the dangers of gasoline, and further education in this area is needed. ",20 665,"The effects of parathyroid hormone (PTH) and PTH-related peptide on osteoclast resorption of bone slices in vitro: an analysis of pit size and the resorption focus. The mechanism whereby PTH, a potent stimulator of bone resorption, may under certain circumstances exert anabolic effects on bone is not known, but it is possible that it involves reduction of the size of osteoclast resorption lacunae. We have therefore made a detailed in vitro study of the effects of PTH and PTH-related peptide (PTHrP) on resorption by neonatal rat osteoclasts paying particular attention to the plan area of resorption pits. In order to distinguish between increased resorption at a particular site and increased numbers of sites, we have used an eyepiece graticule to define a focus of resorption, namely an area occupying 1/116th of the bone slice, which may contain either one or several pits. In addition we have studied the relationship between the number of pits in a resorption focus and the total area of bone resorbed at the focus. We found that PTH and PTHrP, at doses between 2 x 10(-10) M and 2 x 10(-8) M, while exerting significant stimulatory effects on bone resorption, caused a reduction in the median plan area of pits. An increase in the number of resorption foci was the primary stimulatory effect of PTH and PTHrP, occurring within 6 h in the case of PTH. However, the plan area of bone resorbed at a focus showed no significant increase, despite an increase in the number of pits per focus, because as more pits were formed at a focus, the pits were smaller, thus partially dissipating the stimulatory effect of PTH on resorption. These results are consistent with the activation of new remodeling sites by PTH in vivo. Furthermore, the formation of smaller pits under the resorptive influence of PTH may, together with the maintenance of coupling between formation and resorption, play a role in the preservation of cancellous bone recorded in cases of primary hyperparathyroidism and the anabolic effect of exogenous PTH. ",4 3282,"Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction. To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height. ",22 2698,"Biology of retroviruses. Detection, molecular biology, and treatment of retroviral infection. Although human retrovirology can trace its roots to the early part of this century, it has been within the last decade that the field has seen its greatest advances, including the description of the first human retroviruses, HTLV-I, and the subsequent discovery of HTLV-II and the AIDS retroviruses, HIV-1 and HIV-2. The growth this field has undergone in recent years would not have been possible had it not been for key advances in the fields of cell biology, immunology, biochemistry, and molecular biology. Nowhere has this been more evident than in the description of HIV as the etiologic agent of AIDS. In the relatively short time since the disease was initially described, the agent responsible has been isolated, much of its complex biology has been defined, and a drug that helps combat it has been licensed for use. The rapidity with which these events have transpired is largely unprecedented. There remain many unanswered questions regarding HIV and AIDS, and there still is no effective vaccine or cure. Significant questions regarding the immune response to HIV and the HIV response to immune or chemotherapeutic challenge, the establishment and maintenance of HIV latency, and the all-important mechanisms of HIV cytopathicity remain unanswered. It is clear that HIV offers no easy answers, and that significant work remains to be done before death from AIDS can be halted. ",19 470,"Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation. ",3 359,"Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia. Because trimethoprim-sulfamethoxazole (TMP-SMX) causes neutropenia in children with leukemia, we investigated the possibility that pharmacokinetic interaction between methotrexate (MTX) and TMP-SMX causes accumulation of the antileukemia agent. We studied the pharmacokinetics of MTX given intravenously or orally to nine children with acute lymphoblastic leukemia, once with and once without TMP-SMX. There was an increase in free MTX fraction during TMP-SMX therapy in all patients, from (mean +/- SD) 37.4 +/- 11% without TMP-SMX to 52.2 +/- 6.4% with TMP-SMX (p less than 0.01). Plasma clearance of total MTX did not change significantly, whereas clearance of free MTX decreased significantly (from 12.5 +/- 4 to 7.6 +/- 1.5 ml/kg/min; p less than 0.05). There was a consistent decrease in the renal clearance of free MTX (from 12.1 +/- 6.8 to 5.6 +/- 2.4 ml/kg/min; p less than 0.05). Elimination half-life of MTX was not affected significantly by TMP-SMX. There was a significant correlation between serum concentrations of TMP-SMX and the percentage of decrease in the renal clearance of free MTX (r = 0.91; p less than 0.05). These changes in protein binding and tubular clearance of MTX, caused by competition with TMP-SMX, result in a mean 66% increase in systemic exposure to MTX and may explain the myelotoxicity often observed with the coadministration of the two drugs. ",3 1175,"Effect of normal MSAFP screening on maternal age for genetic amniocentesis. Routine maternal serum alpha-fetoprotein (MSAFP) screening for neural tube defects is considered by many to be standard obstetrical care, and recently many have encouraged this test to screen for Trisomy-21 (Down's syndrome). We questioned whether, after a normal MSAFP screen, the risk of Trisomy-21 decreases enough to warrant modifying the recommended age for genetic amniocentesis for Down's syndrome. A logistic regression was developed which, using reported values for sensitivity and specificity for MSAFP detection of Trisomy-21 and assuming a constant threshold risk in opting for amniocentesis, indicates that genetic amniocentesis for Trisomy-21 may be deferred in some women who have a normal MSAFP screening. Sensitivity analysis of varying thresholds for a normal MSAFP demonstrates that a 37 year old woman with a median MSAFP level has the same risk for Trisomy-21 as an unscreened women who is 4.5 years younger. An abnormal MSAFP is useful in screening for neural tube defects and possibly for Trisomy-21. A normal MSAFP may allow for delaying the potentially risky amniocentesis in otherwise low-risk pregnancies. ",9 163,"Invasive migration of epidemic Kaposi's sarcoma cells in vitro. Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier. ",3 3194,"Brachial-jugular polytetrafluoroethylene fistulas for hemodialysis. A retrospective analysis was made of 16 patients who had received a brachial-jugular polytetrafluoroethylene (PTFE) graft for hemodialysis. In four patients, the procedure was used to treat malfunctioning brachio-axillary fistulas due to long venous stenosis in the axillary vein. In 12 other patients, the operation was chosen in cases of exhaustion of the veins in the upper extremity because of previous multiple failed fistulas. Two patients died with a functioning fistula 7 and 10 months after placement of the graft of causes unrelated to the vascular access. The other 14 patients retained functioning fistulas between 8 and 26 months after construction of the shunt. Three patients needed graft thrombectomy to treat occlusive episodes. No venous stenosis was found in a postoperative fistulography made in those patients. One patient needed substitution of a graft segment due to stenosis of the prosthesis crossing over the clavicle. We believe that the brachial-jugular graft is a procedure that can be considered as vascular access for hemodialysis in cases where the use of veins in the upper extremity and the axilla is not possible. ",22 1791,"High-risk reparative surgery. A neglected alternative to heart transplantation. The selection of patients for either high-risk reparative operations on the heart or for transplantation has become increasingly difficult as a result of improved results with both modalities. A retrospective review was done of patients referred for heart transplantation who were not considered candidates for conventional cardiac surgery, yet instead underwent reparative procedures rather than transplantation. Of 23 adult patients referred during a 7-year period, 18 had coronary artery disease, and five had valvular heart disease. All had New York Heart Association class IV symptoms. Preoperative left ventricular ejection fractions were in the range 0.08-0.63 (mean, 0.28). Ten of 18 patients with coronary artery disease required insertion of an intra-aortic balloon pump for hemodynamic support perioperatively. Seven patients had primary coronary artery bypass grafts, and 10 had reoperative coronary bypass procedures. One patient had a left ventricular aneurysmectomy, and one had endocardial stripping in addition to myocardial revascularization procedures. Of the patients with valvular disease, three had aortic valve replacement, of which two were reoperations, and two others had mitral valve replacements with tricuspid annuloplasties. With a mean follow-up of 25 months, 1-, 3-, 12-, and 24-month actuarial survival rates were 91%, 87%, 82%, and 76%, respectively. One patient who underwent aortic valve replacement in this study successfully received heart transplantation 19 months postoperatively. These results compare favorably with the current results for patients undergoing first-graft heart transplantation. All survivors enjoy New York Heart Association class I or II functional capacity. ",13 2661,"Circadian basis of the late asthmatic response. The late asthmatic response (LAR) to an allergen challenge has a marked impact on lung function in the patient with asthma. Virtually all studies on the LAR have been done during the daytime. This study evaluated the LAR as a function of the time of day an inhaled allergen challenge was performed. An allergen challenge given in the morning produced a LAR in 4 of 10 subjects, while the same challenge in the evening caused a LAR in 9 of 10 (p less than 0.05). The time to onset of the LAR following the morning and evening challenges was 9.4 +/- 2.0 h versus 3.1 +/- 0.3 h, respectively (p less than 0.05). The maximal decrease in FEV1 for the LAR was 32.8 +/- 5.6% for the morning challenge versus 43.0 +/- 3.1% in the evening (p less than 0.05). Additionally, the bronchial responsiveness to methacholine was significantly greater at 24 h following evening allergen challenge than after the morning (p less than 0.05) challenge. Thus, it is important to take into account the time of day a patient is exposed to an allergen in regard to the development of the LAR. ",19 436,"Mediastinal hibernoma, a rare tumor. Hibernoma is an uncommon soft tissue tumor that is derived from the remnants of fetal brown fat. Review of the world medical literature revealed 90 cases, 6 of which were intrathoracic. We present the seventh case of intrathoracic hibernoma; in this case, the hibernoma was within the mediastinum without direct invasion of other structures. ",3 1165,"Gilles de la Tourette syndrome is not linked to D2-dopamine receptor. Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29, and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region. ",9 429,"Variations in sensitivity after sectioning the intercostobrachial nerve. The authors present a prospective study of the variations in sensitivity that appear in the armpit and arm after the intercostobrachial nerve has been sectioned in a modified radical mastectomy. Of a total of 208 patients studied between 1978 and 1987, the intercostobrachial nerve was sectioned in 139 patients, whereas in 30 it remained intact; in 39 patients only peripheral branches of the nerve were sectioned. The patients were examined at regular postoperative intervals in order to evaluate their sensitivity both to touch and to pain in the axilla and arm. Four hundred thirty-three examinations were carried out and the 3 operative groups were assessed accordingly. After the nerve was sectioned, there was increasing anesthesia in the armpit and hypoesthesia on the posterointernal face of the arm, while for the patients in whom the intercostobrachial nerve remained intact, these alterations were less intense and long-lasting. Significant statistical differences between the two groups also exist. In the absence of axillary lymphatic ganglia infiltrated by the tumor, the conservation of the intercostobrachial nerve is recommended. ",3 2740,"Foreign body removal through an appendicostomy. The removal of button cell batteries or small coins impacted in the terminal ileum or right colon through an appendicostomy is described. This technique was used effectively in three patients. ",20 1232,"Familial trigeminal neuralgia and Charcot-Marie-Tooth neuropathy. Report of two families and review. Typical trigeminal neuralgia has occasionally occurred in multiple members of the same family over several generations. The clinical features of such cases, including the increased incidence in females, and the absence of other apparent hereditary, neurologic, metabolic, or structural abnormalities were identical to those of sporadic cases. More rarely, familial trigeminal neuralgia has been described in the setting of hereditary peripheral neuropathy, especially Charcot-Marie-Tooth disease. We describe patients from two different families with Charcot-Marie-Tooth disease and medically intractable trigeminal neuralgia. Both patients were successfully treated by percutaneous retrogasserian glycerol rhizolysis. The occurrence of cranial nerve symptoms in patients with demyelinating peripheral neuropathies is discussed in light of the current hypotheses regarding the etiology of trigeminal neuralgia. ",9 2215,"Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa. The microsatellite marker DXS426 maps to the interval Xp21.1-Xp11.21, the chromosomal region which contains two loci for X-linked retinitis pigmentosa (XLRP; RP2 and RP3). We have refined the localization of DXS426 both physically, by mapping it to a deletion which spans the interval Xp21.3-Xp11.23, and genetically, by studying multiply informative crossovers which indicate that DXS426 lies between DXS7 and DXS255 (i.e., Xp11.4-Xp11.22). As this is the region which contains the RP2 gene, RP2 families could be identified on the basis of linkage of XLRP to DXS426. Multiply informative crossovers in two RP2 families indicate that the most likely location of the RP2 gene is between DXS426 and DXS7. DXS426 is therefore an important highly informative marker for the purposes of carrier detection and early diagnosis of RP2 and for the localization of the disease gene. ",15 2198,"Hypoplastic left heart syndrome. Outcome after initial reconstruction and before modified Fontan procedure. The outcome and clinical course before modified Fontan procedure were reviewed for 200 patients with hypoplastic left heart syndrome who underwent initial reconstructive surgery between August 1985 and March 1989. The median age at the time of initial reconstruction was 6 days (range, 1 day to 7.2 months). In 28 patients, a right modified Blalock-Taussig shunt was used; in 172 patients, a central shunt was placed. Additional procedures (n = 41) performed in 38 patients (median age, 5 months; range, 6 days to 17.5 months) were revision of systemic-to-pulmonary shunt (n = 15), arch reconstruction (n = 8), balloon angioplasty of arch obstruction (n = 7), atrial septectomy (n = 4), pulmonary artery angioplasty (n = 2), tricuspid valve annuloplasty or replacement (n = 4), and modified Glenn shunt (n = 1). There was no significant difference in the frequency of additional procedures performed more than 30 postoperative days in the survivors compared with the nonsurvivors. Actuarial survival rates were 0.66 (1 month), 0.48 (12 months), and 0.44 (18 months). Seventy percent of all deaths occurred during the initial admission, with 32% resulting from acute cardiovascular collapse during the first postoperative day. There was no statistical difference in actuarial survival when assessed by the type of shunt used or by anatomical subtype or when the influence of additional interventions was considered. Substantial improvement in outcome may be possible if immediate perioperative mortality can be reduced. We speculate that some of the intermediate mortality (30 days to 1 year) may be related to the effects of chronic exposure of the right ventricle to volume overload at systemic pressure. ",15 1788,"Latissimus dorsi cardiomyoplasty in the treatment of patients with dilated cardiomyopathy. Stimulated skeletal muscle grafts have been proposed as a means to reinforce ventricular wall in the treatment of severe myocardial failure. Latissimus dorsi cardiomyoplasty was performed in 11 patients with advanced heart failure due to cardiomyopathy who were in New York Heart Association (NYHA) class III or IV despite maximal medical therapy. There were no operative deaths. Eight patients were followed for a mean of 10.8 months. Two patients remain in muscle conditioning protocol. One patient died with latissimus dorsi ischemia and congestive heart failure. Four of the eight patients in long-term follow-up are in NYHA class I, three in class II, and one in class III. At 3 months of follow-up, rest radioisotopic left ventricular ejection fraction increased from 20.5 +/- 3.6% to 26.8 +/- 8.1% (p less than 0.01). Doppler-echocardiography demonstrated that left ventricular segmental wall shortening improved from 11.3 +/- 2.5% to 16.5 +/- 3.9% (p less than 0.01) and left ventricular stroke volume from 22.9 +/- 4.6 to 33.1 +/- 10 ml (p less than 0.01). Cardiopulmonary exercise test showed that maximal oxygen consumption during treadmill test increased from 14.8 +/- 3.7 to 18.2 +/- 3.3 ml/kg.min (p less than 0.05). At 6 months of follow-up, all the above values remained essentially unchanged. Furthermore, nonsustained ventricular tachycardia was abolished without specific medical therapy in four patients. Thus, cardiomyoplasty improves left ventricular function, reverses congestive heart failure, and may improve long-term survival in severe cardiomyopathies. ",13 2442,"Daily pattern of %VO2max and heart rates in normal and undernourished school children. The pattern of usage of the VO2max, expressed as %VO2max during ordinary school days, with minute-by-minute heart rate recording, was studied in 106 boys and 83 girls, 6-16 yr of age divided into three age groups (6-8, 10-12, and 14-16 yr), living under economically deprived conditions in Colombia and classified as nutritionally normal or marginally malnourished. In a 12-h period, the 12 groups of children spent, on the average, 7-10 h at less than 30% VO2max, 1.5-4 h at 30-50% VO2max, and an accumulated time of 20-60 min above 50% VO2max. The latter occurred in short bursts rather than during sustained periods. There was a statistically significant but small decrease (approximately -3%) in the average 12 h %VO2max with age but no effects of sex or nutritional status. The overall average was about 25% VO2max in all groups. The data may suggest the existence of the regulation of physical activity to some level easily sustainable for long periods. Expressing the data as 30 min averages during 5 h of school and 5 h of free-time activity allows for the possibility of seeing group differences during shorter periods of time. This may prove useful in exercise training programs and studies of effort in the workplace. ",17 603,"High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Inflammation of neural elements is frequently mentioned clinically in association with lumbar radiculopathy. Mechanical embarrassment of neural elements by definable structural abnormalities is inadequate as a sole explanation of nerve injury in this condition. The purpose of this study was to demonstrate whether an enzymatic marker for inflammation (phospholipase A2) could be identified in human disc samples removed at surgery for radiculopathy due to lumbar disc disease. Samples were assayed for phospholipase A2 activity. The level of activity in the disc samples was compared with values obtained from other human tissues using the same assay. Specific activity (percent hydrolysis radiolabelled substrate) ranged from 238 to 1,014.5 nmol/min/mg. Mean activity for the human disc material was 568.7 nmol/min/mg, compared with 0.006 nmol/min/mg for human PMN, and 12.1 nmol/min/mg for inflammatory human synovial effusion. The pH and cation-related activity were identical to those demonstrated for phospholipase A2 inflammatory conditions. Human lumbar disc phospholipase A2 activity is from 20- to 100,000-fold more active than any other phospholipase A2 that has been described. As the enzyme responsible for the liberation of arachidonic acid from cell membranes, phospholipase A2 is the rate-limiting step in the production of prostaglandins and leukotrienes. These data establish biochemical evidence of inflammation at the site of lumbar disc herniations. ",4 391,"Screening for neuroblastoma at 3 weeks of age: methods and preliminary results from the Quebec Neuroblastoma Screening Project. A large neuroblastoma screening study was recently started in the province of Quebec, Canada. This project, a collaboration between the Quebec Network for Genetic Medicine and the University of Minnesota, is studying the impact of screening infants for the preclinical detection of neuroblastoma on the population-based mortality caused by this tumor. All infants born in Quebec during a 5-year period will be screened twice, at 3 weeks and at 6 months. Urinary homovanillic acid and vanillylmandelic acid determination from dried filter paper samples is used for screening. Initial qualitative screening is done by means of thin-layer chromatography with confirmatory quantitative screening by gas chromatography-mass spectrometry (GC-MS). During the initial 6 months of 3-week screening, 41,673 neonates (92% compliance rate) were screened and 10.6% of them were tested also by GC-MS. Nine of these neonates had positive results on two GC-MS tests and were referred for evaluation to rule out the presence of neuroblastoma. Four had the tumor, 1 had a calcified adrenal gland, and 4 had no tumor detected. Three additional neonates had clinical diagnosis of neuroblastoma before they reached the screening age of 3 weeks. A neuroblastoma that did not secrete homovanillic acid or vanillylmandelic acid was diagnosed clinically in 1 additional patient who tested negative by screening. ",3 965,"Surgical treatment for secondary retracted nose. This surgical technique is presented to correct nasal tip retraction, which is frequently associated with other surgical sequelae that can be corrected simultaneously. It is based on the use of a shield, an anchor, or half an anchor of otocartilage, with one or two posterior supports that are sutured together forming a small L and are fixed to the bed to project the nasal tip and, if necessary, to correct the unilateral or bilateral alar collapse. ",7 2988,"Underlying illness associated with failure to thrive in breastfed infants. Over a four-year period in a suburban pediatric practice, 38 infants aged six months or less were identified with failure to thrive (FTT) while breast-feeding. In seven cases (18.4%), an associated organic illness was diagnosed. Only 2 of 28 breast-fed neonates (8%) were found to have FTT associated with another illness, as compared to 5 of 10 older infants (50%). Breast-fed infants with FTT, particularly those presenting after the first month of life, should be considered high risk for having other disease. Their clinical evaluation should include an appropriate search for organic illnesses. ",22 2232,"Vasa aplasia and cystic fibrosis. Bilateral vasa aplasia is considered an invariable finding in cystic fibrosis, but such patients are rarely seen in male infertility clinics. The improved survival beyond 20 years of age is likely to change this. In a clinical study of a group of male cystics the vasa were absent in 8 of 11 boys and epididymal abnormalities were palpable in the majority. The main cause of infertility appears to be mechanical obstruction. Whether the absence is due to a primary failure of mesonephric duct development or secondary to luminal obstruction and subsequent atrophy is not known. ",15 1674,"Electrocardiographic signal-averaging during atrial pacing and effect of cycle length on the terminal QRS in patients with and without inducible ventricular tachycardia. Electrocardiographic signal-averaging during sinus rhythm (61 to 99 beats/min) and atrial pacing (100 to 171 beats/min) were performed to determine the effect of heart rate on late potentials in 15 patients without (group 1) and 7 patients with (group 2) inducible sustained ventricular tachycardia (VT). In sinus rhythm (79 +/- 12 vs 77 +/- 12 beats/min, difference not significant), the duration of the low-amplitude signal less than 40 microV was longer in group 2 than group 1 (43 +/- 21 vs 26 +/- 8 ms, p = 0.034) and more patients had late potentials (57 vs 7%, p = 0.021), but QRS duration (121 +/- 32 vs 98 +/- 19 ms) and terminal voltage (33 +/- 33 vs 50 +/- 26 ms) were not significantly different. With atrial pacing in group 1 (128 +/- 16 beats/min), 3 patients developed a simultaneous decrease in terminal voltage and an increase in terminal QRS duration consistent with a late potential, but mean total and terminal durations were unchanged. Terminal voltage increased (50 +/- 26 to 59 +/- 40) but not significantly. With atrial pacing in group 2 (119 +/- 12 beats/min) all patients either had a late potential or developed a simultaneous decrease in terminal voltage and an increase in terminal QRS duration (p = 0.001 vs group 1). Root mean square (p = 0.001 vs group 1). Root mean square voltage decreased (33 +/- 23 to 22 +/- 23) and became significantly different from group 1 (p = 0.017). Mean QRS duration, root mean square terminal voltage and low-amplitude terminal QRS duration, however, were unchanged. ",13 1098,"Cognitive function testing in comprehensive geriatric assessment. A comparison of cognitive test performance in residential and clinic settings. Tests of cognitive function are frequently used in geriatric assessment, but the effect of test setting has rarely been explored. To determine the effect of testing site on the performance of elderly patients undergoing a comprehensive geriatric assessment, we administered the Mini-Mental State Exam to 116 geriatric patients in the clinic and at their residence. Their cognitive abilities varied from normal to severely impaired. The patients' scores were 1.5 +/- 3.6 (mean +/- SD) higher at their residence. The clinical importance of a difference in score of 1.5 is not clear. For this reason a second analysis was performed in which a difference in scores of five points or greater between settings was considered clinically meaningful. Twenty-five percent (29 of 116) differed by five points or more. Of these 29 patients, 22 (76%) tested better in the residential setting. These differences were statistically significant (P = .001). We conclude that the testing site may affect test performance and that in-home assessment may reveal the optimal cognitive function of geriatric patients. ",9 316,"Insulin-like growth factor-II: possible local growth factor in pheochromocytoma. Pheochromocytomas, neural crest tumors, express an abundance of insulin-like growth factor-II (IGF-II). To assess further the potential for IGF-II to play an autocrine role for these tumors, we measured 1) IGF-II content by RRA in 7 pheochromocytomas and peripheral blood in these patients, 2) IGF-II receptors by Western analysis, and 3) characterized the tumor binding proteins by ligand blot studies. IGF-II levels in the tumors varied from 2.8-41 micrograms/g. Chromatography revealed that 60% of the peptide eluted as a large mol wt form of IGF-II (8.7-10 kDa); the remainder coeluted with mature peptide (7.5 kDa). This was in contrast to IGF-II levels in normal adrenal tissue (0.225 +/- 0.005 micrograms/g) or another neural crest-derived tumor, medullary carcinoma of the thyroid (0.63 +/- 0.02 micrograms/g). Serum IGF-II levels in the 7 patients with pheochromocytoma (720 +/- 71 ng/mL) were similar to those in 35 normal controls (762 +/- 69 ng/mL). Radiolabeled IGF-II (9 +/- 1%) and IGF-I (20 +/- 2%) bound specifically to pheochromocytoma membranes. Western analysis of these membranes using a specific antiserum directed against the type II receptor demonstrated a band at 210 kDa. Affinity cross-linking studies with [125I]IGF-I demonstrated a specific band at 140 kDa. Ligand blot analysis was performed on the void volume pools from the Sephadex G-75 column and demonstrated bands at about 30 and 25 kDa. In conclusion, these data 1) confirm that pheochromocytomas have increased levels of IGF-II; 2) demonstrate that despite high IGF-II concentrations in the tumors, peripheral levels are not elevated, suggesting that very little tumoral IGF-II is released into the circulation, unlike catecholamines; 3) demonstrate the presence of IGF-II and IGF-I receptors; 4) describe binding protein species similar to those present in other tissues. Thus, the presence of high levels of IGF-II and both type I and type II receptors suggests that IGF II may act through both receptors to alter tumor growth. ",3 3137,"Anatomical relationship between the renal venous arrangement and the kidney collecting system. The anatomical relationships between the renal venous arrangement and the pelviocaliceal system were studied in 52, 3-dimensional polyester resin corrosion endocasts. In 53.8% of the cases, there were 3 large venous trunks and in 28.8% there were 2 venous trunks joining to form the main renal vein. Intrarenal veins demonstrated free anastomoses that were disposed in 3 systems of longitudinal arcades (stellate, arcuate and interlobar veins). There were large venous collars around caliceal necks and also horizontal arches crossing over calices to link anterior and posterior veins. In 84.6% of the cases the upper caliceal group was encircled anteriorly and posteriorly by venous plexuses, which coursed parallel to the infundibulum. In 50.0% of the cases the lower caliceal group also was enriched by 2 venous plexuses. A close relationship existed between a large inferior tributary of the renal vein and the anterior aspect of the ureteropelvic junction in 40.4% of the cases. In 69.2% of the cases there was a posterior (retropelvic) vein: in 48.1% this vein had a close relationship to the junction of the pelvis with the upper calix and in 21.1% it crossed the middle posterior surface of the renal pelvis. ",22 416,"Dietary fat and risk of breast cancer. The relationship between dietary fat and subsequent risk of breast cancer was studied in 3988 initially cancer-free Finnish women aged 20-69 y. During a follow-up period of 20 y, 54 breast-cancer cases were diagnosed. Risk of breast cancer was significantly inversely related to energy intake and nonsignificantly inversely related to absolute fat intake. A positive association between energy-adjusted total fat intake and occurrence of breast cancer was also observed. The relative risk in the highest tertile as compared with the lowest tertile was 1.7 (95% confidence limits 0.6-4.8). The corresponding relative risks were 1.4 (0.5-3.7) for saturated fatty acids, 2.7 (1.0-7.4) for monounsaturated fatty acids, 1.2 (0.6-2.8) for polyunsaturated fatty acids, and 2.2 (1.0-5.0) for cholesterol intake. Adjustment for different potential confounding factors did not alter the results. The present data suggest that breast cancer is associated inversely with energy intake and weakly positively with energy-adjusted fat intake. ",3 301,"Cerebral tumor staging in patients with bronchial carcinoma by computed tomography. Computerized tomographic (CT) scans of 271 patients with histologically proven bronchial carcinoma accomplished for initial tumor staging were retrospectively evaluated for signs of cerebral metastasis. The results for the histologic subtypes were quite different. In 13.8% of patients with small cell carcinoma and limited disease the authors found signs of brain metastasis. However, routine cerebral staging in these patients did not seem to be useful because of lack of therapeutic consequences. On the other hand, no patient with non-small cell carcinoma (N-SCC) and tumor Stage I or II had brain metastases. All patients with brain metastasis from N-SCC had been classified as tumor Stage III before cerebral imaging. Among these patients, however, the authors found brain metastasis in 17.5% of those without known distant metastatic disease (III/M0), especially in large cell carcinoma and in adenocarcinoma. Stage III/M0 patients should undergo routine cerebral imaging if their tumor is surgically resectable and thoracotomy is planned. ",3 938,"Predicting risk for bronchopulmonary dysplasia: selection criteria for clinical trials Early identification of neonates in whom bronchopulmonary dysplasia is most likely to develop permits appropriate enrollment into clinical trials testing early intervention therapies for the prevention or treatment of bronchopulmonary dysplasia. Analysis of 160 neonatal intensive care unit survivors to 28 days revealed that supplemental oxygen requirement at 28 days could be predicted by a logistic regression including (1) birth weight, gestational age, 5-minute Apgar score, and peak inspiratory pressure at 12 hours for 12-hour-old neonates and (2) birth weight, gestational age, peak inspiratory pressure at 12 hours, and mean airway pressure at 10 days for 10-day-old neonates. These two regression analyses were applied prospectively to three new data sets totaling 238 neonates to test their predictive ability. Neonates were classified into low-, moderate-, or high-risk groups on the basis of their predicted probability of requiring oxygen supplementation at 28 days; low = probability of less than 25%, moderate = probability of 25% to 75%, and high = probability greater than 75%. Although these populations were demographically distinct from the original group, the regression analyses performed well. The regression analysis for 12 hours of age classified 125 neonates at low risk of whom 9% required supplemental oxygen at 28 days, and the regression analysis for 10 days classified 141 neonates at low risk of whom 7% required supplemental oxygen. The 12-hour regression analysis classified 80 neonates at moderate risk of whom 33% required supplemental oxygen at 28 days and the 10-day regression analysis classified 49 neonates at moderate risk of whom 24% required supplemental oxygen. ",7 230,"Is DNA ploidy of prognostic significance in stage I cutaneous melanoma? Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide-stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas. ",3 1820,"Effects of heparin versus saline solution on intermittent infusion device irrigation. The purpose of this study was to compare the effectiveness of 1 ml of 0.9% sodium chloride with 10 units of heparin in 1 ml sodium chloride solution, both containing benzyl alcohol, in maintaining patency and reducing the incidence of phlebitis in patients with intermittent infusion devices. The subjects (N = 32) were randomly assigned in a double-blind experimental design. Repeated-measures analysis of variance revealed no significant difference between the groups in phlebitis or patency variables. The results from this controlled study would suggest that 0.9% sodium chloride is as effective as 10 units of heparin in sodium chloride solution in maintaining intermittent infusion device patency and preventing phlebitis. ",13 820,"Extracorporeal shock wave lithotripsy for biliary stones. Extracorporeal shock wave lithotripsy is a noninvasive technique for treatment of patients with gallbladder and bile duct stones. Selected patients with gallbladder stones can be treated on an outpatient basis without general anesthesia and may return to full activity within 1 or 2 days. Stone-free rates of 40% to 60% at 6 months have been achieved in most reported series with minimal morbidity. Bile duct stone lithotripsy has achieved stone clearance in 80% of patients in whom conventional methods were unsuccessful and therefore constitutes a valuable second-line treatment for these patients. ",5 3109,"Two discharge patterns of carotid body chemoreceptors in the goat. Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer. ",22 396,"Transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus: discrimination between homologous and heterologous transfer in intact heterokaryons. To examine aspects of the transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus in situ, heterokaryons were formed between Hep G2 human hepatoma cells and WI-38 human fibroblasts. The cells were appropriately treated with cycloheximide before fusion, which emptied them of their respective secretory proteins, serum albumin for the Hep G2 cells and procollagen I for the WI-38 cells. After fusion was complete, the cycloheximide was washed out, protein synthesis was resumed, and the rates of reappearance of serum albumin and procollagen I in the two separated Golgi apparatuses within each heterokaryon were followed by immunofluorescence microscopy. Serum albumin was found to always reappear first in the Golgi apparatus contributed by the Hep G2 half of the heterokaryon, and procollagen I in the Golgi apparatus of the WI-38 half. These results suggest that the endoplasmic reticulum-to-Golgi apparatus transfer in situ is not simply a stochastic process but is either spatially restricted or exhibits cell-type specificity or both. ",3 3050,"The alien hand sign. Localization, lateralization and recovery. The alien hand sign was first described by Brion and Jedynak as a ""feeling of estrangement between the patient and one of his hands."" The affected hand frequently shows a grasp reflex and an instinctive grasp reaction as well as elements of what Denny-Brown referred to as a ""magnetic apraxia"" associated with frontal lobe damage. Most notably, however, the affected hand is observed to perform apparently purposive behaviors that are perceived as being outside the volitional control of the patient. The patients interpret the behavior of their own affected limb as being controlled by an external agent. They do not feel that they are initiating or controlling the behavior of the hand and often express dismay at the hand's ""extravolitional"" activity. The patients attempt to control behavior of the alien hand with the unimpaired hand by forcibly restraining the affected limb, an act that may be termed ""self-restriction."" In this paper, we report an additional four cases of alien hand sign in right-handed subjects: two involving the right hand and two involving the left hand. In each case, the clinical findings were associated with extensive unilateral damage of the medial frontal cortex of the hemisphere contralateral to the affected hand. Furthermore, the alien movement gradually disappears over the course of 6-12 months after the stroke. These clinical case studies are presented and discussed in the context of the ""dual premotoer systems hypothesis,"" an anatomicophysiological model that proposes that action is organized by two separate but interactive premotor brain systems corresponding to evolutionarily defined medial and lateral cortical moieties. It is hypothesized that the alien mode behavior results from unconstrained activity of the lateral premotor system in the damaged hemisphere. The residual volitional control in the limb occurs through the activity of the intact medial premotor system of the ipsilateral hemisphere. Recovery may occur through extension of these ipsilateral control mechanisms by compensatory changes in subcortical systems controlling hemispheric activation associated with adaptive behavior. This observation may be important in understanding mechanisms involved in motor recovery after stroke. ",22 395,"Human colorectal cancers display abnormal Fourier-transform infrared spectra. Fourier-transform infrared spectroscopy (FT-IR) was applied to the study of tissue sections of human colorectal cancer. Pairs of tissue samples from colorectal cancer and histologically normal mucosa 5-10 cm away from the tumor were obtained from 11 patients who underwent partial colectomy. All cancer specimens displayed abnormal spectra compared with the corresponding normal tissues. These changes involved the phosphate and C-O stretching bands, the CH stretch region, and the pressure dependence of the CH2 bending and C = O stretching modes. Our findings indicate that in colonic malignant tissue, there are changes in the degree of hydrogen-bonding of (i) oxygen atoms of the backbone of nucleic acids (increased); (ii) OH groups of serine, tyrosine, and threonine residues (any or all of them) of cell proteins (decreased); and (iii) the C = O groups of the acyl chains of membrane lipids (increased). In addition, they indicate changes in the structure of proteins and membrane lipids (as judged by the changes in their ratio of methyl to methylene groups) and in the packing and the conformational structure of the methylene chains of membrane lipids. The cell(s) of the malignant colon tissues responsible for these spectral abnormalities is unknown. Cultured colon adenocarcinoma cell lines displayed similarly abnormal FT-IR spectra. The diagnostic potential of the observed changes is discussed. ",3 2524,"Intercellular propagation of individually programmed growth bursts in FRTL-5 cells. Implications for interpreting growth factor actions. Five methods are commonly used to quantify FRTL-5 cells' and other thyrocytes' growth in vitro and the impact of growth inhibiting or stimulating maneuvers: Total cell count, mitotic index, DNA measurement, total [3H]thymidine incorporation, and the fraction of [3H]thymidine labeled cells. All of them assess cell growth as though all cells were homogeneous with an identical response to growth factors. We demonstrate here that this assumption is not valid. Rather, some intrinsically growth-prone cells appear to pass a growth signal to neighboring cells so that variably sized colonies of synchronized cells within each cluster growing from monodispersed cells are formed. This is true for FRTL-5 cells growing in vitro in monolayers and in three-dimensional, collagen embedded spheroids. The pattern is the same when cell suspensions or collagen-embedded spheroids are implanted onto nude mice. Patches with alternating high and low growth become particularly prominent in the large tumor-like organoids grown from monodispersed cells in nude mice. The pattern much reminds of similar observations in growing intact thyroids. Since there is no significant correlation between the fraction of [3H]thymidine labeled cells and the size of two- or three-dimensional clusters in any experiment, growth of signal-spreading cells is assumed to occur in leaps and bounds. Growth velocity in each subclone of a cell population depends on the mean interval between bursts of replications and on the number of cells synchronized by cell-to-cell diffusion of the growth signal emanating from one dividing cell. Thus, growth-promoting and growth-inhibiting factors may not only act on the mean interval between successive growth bursts, but they may also change cell-to-cell spreading of growth signals. ",18 2664,"Rescue of interleukin-1 activity by leucovorin following inhibition by methotrexate in a murine in vitro system. We have recently shown that methotrexate (MTX) inhibits interleukin-1 (IL-1) activity in vitro. This effect may play an important role in the rapid antiinflammatory action of MTX in rheumatoid arthritis. In the present study, we showed that the inhibition of IL-1 activity in vitro by MTX is dependent on folate pathways since, after the addition of leucovorin, the inhibitory effect of MTX was abolished. These findings may shed more light on the mechanism of action of MTX in rheumatoid arthritis. They also point to the fact that some IL-1 activities may be dependent on intracellular folate pathways. ",19 1202,"Glucocorticoid-induced muscle atrophy prevention by exercise in fast-twitch fibers. Exercise has been shown to be effective in preventing glucocorticoid-induced atrophy in muscles containing high proportions of type II or fast-twitch fibers. This investigation was undertaken to further evaluate this response in type IIa and IIb fibers, determined by histochemical staining for myofibrillar adenosinetriphosphatase with alkaline and acid preincubation. Steroid [cortisol acetate (CA), 100 mg/kg body wt] and exercise (running 90 min/day, 29 m/min) treatments were initiated simultaneously for 11 consecutive days in female rats. Fiber distribution and area measurements were performed in a deep and superficial region of plantaris muscle. The exercise regimen spared approximately 40% of the CA-induced plantaris muscle atrophy. In the deep region, the fiber population, which contained approximately 13% type I (slow-twitch), 24% type IIa, and 63% IIb fibers, was not affected by either treatment. In the superficial section, which consisted solely of type II fibers, the proportion of type IIa fibers was higher (27 vs. 9%, P less than 0.01) in the steroid- than in the vehicle-treated groups. Within each region, type IIa fibers were less susceptible to atrophy than type IIb fibers, and within each fiber type, the deep region had less atrophy than the superficial region. Type I fibers were unchanged by steroid treatment. For type IIa fibers, exercise prevented 100% of the atrophy in the deep region and 50% in the superficial region. For type IIb fibers, the activity spared 67 and 40% of the atrophy in these same regions, respectively. These results show that glucocorticoids are capable of changing the myosin phenotype. ",9 1444,"The percutaneous operative gastrostomy for gastric decompression in major urological surgery. When postoperative gastric decompression is necessary a percutaneous gastrostomy tube is an alternative to nasogastric intubation. The percutaneous insertion of a suprapubic bladder catheter is an easy procedure without notable complications that increases the comfort of the patient in the immediate postoperative period. We advocate its use in all major urological abdominal operations. ",11 3079,"The influence of calcium alginate haemostatic swabs upon operative blood loss in adenotonsillectomy. Although adenotonsillectomy is regarded as a minor procedure, it has been shown that 18% of patients may experience an operative blood loss of 10-20% of the total blood volume. The aim of this study was to determine whether calcium alginate haemostatic swabs reduce operative blood loss in adenotonsillectomy. Seventy-two patients (ages 2-12 years) entered a prospective trial in which the operation was performed either with normal gauze swabs or calcium alginate swabs. Thirty-six children were randomized to each group. The mean blood loss was found to be 34.9 ml (2.07% of total blood volume) and 47.8 ml (2.97% of total blood volume) respectively. Although there was no significant reduction in operative blood loss using calcium alginate, in both groups the blood loss was much smaller than that stated by the majority of previous workers. ",22 21,"In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae. Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae. These compounds have been defined as the V-factor growth requirement. We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics. Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs. These compounds and several other nicotinamide riboside analogs were evaluated for their ability to support the growth of H. influenzae and for their ability to block the uptake of [carbonyl-14C]nicotinamide riboside by H. influenzae. 3-Aminopyridine riboside blocked the uptake of [carbonyl-14C]nicotinamide riboside and inhibited the growth of H. influenzae when NAD, nicotinamide mononucleotide, or nicotinamide riboside served as the V factor. The antibacterial activity of 3-aminopyridine riboside was found to be specific for H. influenzae but had no effect on the growth of Staphylococcus aureus or Escherichia coli. In additional experiments by reversed-phase high-performance liquid chromatography, it was determined that whole cells of H. influenzae degrade 3-aminopyridine adenine dinucleotide to 3-aminopyridine riboside, which is then internalized. Inside the cell, 3-aminopyridine riboside has the ability to interfere with the growth of H. influenzae by an undetermined mechanism. ",0 2496,"An efficient method for removing bilirubin. Bilirubin is tightly bound to albumin, making hemoperfusion an ineffective treatment for hyperbilirubinemia. By adding a safe unbinding agent to the blood (solutizer), which itself is adsorbed, hemoperfusion can become efficient and practical. Canines were made hyperbilirubinemic with an intravenous infusion of a 5 mg/ml solution (with Na2CO3) for 1 hour. Peak concentrations of 14-22 mg/dl were reached in adult dogs (25-35 kg). Hemoperfusion was then initiated with or without (control) the solutizer (sodium benzoate). The bilirubin unbinding effect of sodium benzoate was rapid and effective. Because of the simultaneous adsorption of sodium benzoate, a small activated carbon section that was presaturated with the solutizer was located proximal to the main hemoperfusion column, in addition to continuous infusion to reach 20 mM in the blood. Comparison of the normalized bilirubin concentration for benzoate augmented hemoperfusion with the average for control dogs, shows that benzoate results in a threefold decrease in the normalized bilirubin concentration after 1.5 hr of hemoperfusion. Sodium benzoate may also have the advantage of protecting platelets during hemoperfusion. ",17 1330,"Ethical and legal issues in geriatric nephrology. Ethical and legal issues affecting geriatric nephrology are conditioned more by individuals' status as elderly, sick people than by the distinctive characteristics of kidney disease or failure. Key ethical issues are the obligation to respect persons, in particular by recognizing competent persons' autonomy of medical choice and affording due protection to dependent or vulnerable individuals, by beneficence or doing good, and by acting with justice, treating like cases alike and avoiding unjust discrimination. The law reinforces ethical obligations through such legal concepts as informed consent and the duty to maintain appropriate confidentiality, which have special applications concerning medication and management of the elderly. Additional legal issues concern advanced care directives and terminal care decisions. ",11 240,"A diagnostic expert system for colonic lesions. The diagnostic expert system for colonic lesions (DESCL) was designed to discriminate colonic adenoma and adenocarcinoma from normal colonic tissue. Although it was originally developed for use in conjunction with a machine vision analytic system, the DESCL has evolved into a teaching tool and a model for conceptual machine learning. The expert system is table driven and consists of a shell and a knowledge base. The latter comprises a series of architectural and cytologic observations and a quantitative estimate of diagnostic importance relating these observations to diagnostic outcome. In a validation study of 100 colonic lesions, the expert system achieved a success rate of 98%. It has the flexibility to allow individual pathologists to ""customize"" the knowledge base to suit their diagnostic criteria. ",3 214,"Selection of therapy for stage III breast cancer. Locally advanced breast cancer is a heterogenous group including both operable and inoperable lesions. Local surgery or radiation alone produces poor survival rates, indicating micrometastases at diagnosis. Systemic chemotherapy as part of multimodality regimens has increased the length and rate of disease-free survival. ",3 517,"Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies. The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas. ",3 1030,"Effects of cyclophosphamide on the pathogenesis of cytomegalovirus-induced labyrinthitis. Cyclophosphamide was used in this study to define the contribution of the inflammatory response relative to direct cytopathic effects of guinea pig cytomegalovirus (GPCMV) in inducing sensorineural hearing loss in the guinea pig. The eighth nerve compound action potential (CAP) threshold on day 7 after inoculation of GPCMV into the scala tympani was an average of 35 dB greater for control animals than for those that were immunosuppressed with daily intraperitoneal injections of cyclophosphamide (20 mg/kg body weight). The amount of GPCMV antigen in the cochlea, detected immunohistochemically did not correlate with the CAP threshold. However, the greater the inflammatory response to GPCMV in the cochlea, the higher the CAP threshold and thus the greater the hearing loss. This study demonstrates that the inflammatory response to GPCMV may be more important than direct cytopathic effects of the virus in producing sensorineural hearing loss in GPCMV-induced labyrinthitis. ",8 2995,"The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival. ",22 1582,"Effects of differential touch on nervous system arousal of patients recovering from cardiac disease. Previous research suggests that the neural properties of certain types of touch as well as their perceived significance to the disease state may be related to heightened activation of the nervous system. In this study the effects of different types of touch on nervous system arousal were examined in 59 adult patients who were receiving treatment for coronary artery disease. They were exposed to a standardized protocol that systematically varied the neural properties and procedural nature of the touch received. Measures of cardiovascular reactivity (heart rate and rhythm data as well as blood pressure measurements) and state anxiety were used as indexes of arousal. The results indicated that all types of touch evoked heart rate deceleration in contrast to both baseline and verbal conditions. However, there were no differential effects related to either the neural properties or procedural nature of touch. Diastolic blood pressure and state anxiety were also lower as a result of the touch. No changes were observed for systolic blood pressure or heart rhythm. In general, findings suggested that touch served to reduce arousal rather than to produce negative psychophysiologic consequences for recovery. ",13 1078,"Total knee arthroplasty fixation. Comparison of the early results of paired cemented versus uncemented porous coated anatomic knee prostheses. The results of 18 matched pairs of Porous Coated Anatomic knee prostheses were studied to compare the early clinical and functional performance of cemented versus uncemented fixation with an average five-year follow-up period for both. The knee score improved from a preoperative average of 35 points to a postoperative average of 90 points in the cemented group, and from 38 points to 93 points in the uncemented group. In particular, the individual pain scores and the range-of-motion values were well matched at the three-, six-, and 12-month follow-up visits and showed a steady improvement. Subjectively, all patients were pleased with the results of surgery; one-third preferred the cemented side, one-third preferred the uncemented side, and one-third found no difference in the performance of either knee. The clinical and functional performance of knee prostheses in patients who had one cemented knee and one uncemented knee were comparable and possibly unrelated to the type of fixation method. ",9 1206,"Multiple muscle enzyme release with psychiatric illness. Associations (p less than .001) between serum concentrations of lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (SGOT) were observed in physically well patients with mania (N = 100, r = .70), depression (N = 138, r = .51), chronic schizophrenia (N = 85, r = .68), and schizoaffective or atypical psychosis (N = 39, r = .52) discharged from 1978 through 1981. In contrast, there was a negligible association between these enzymes in 90 nonpsychiatric inpatient control subjects. Patients with mania (229.0 +/- 106.1 IU/l) showed significantly (t = 3.16, p less than .002, two-tailed) higher lactate dehydrogenase (LDH) levels than control subjects (191 +/- 41.7 IU/l) and a 14% incidence of abnormally high serum LDH levels vs. 1% among control subjects. Results were unchanged when patients taking neuroleptics were excluded. These results indicate that psychiatric illness, especially mania, induces release of LDH and SGOT, occasionally to unusually high levels. This is similar to previous reports of muscle creatine phosphokinase release in psychiatric patients. Presumably, these enzymes are released from skeletal muscle in association with agitation, with muscle tension, or with blood stasis and local tissue hypoxia consequent to hypoactivity. ",9 756,"Schatzki's ring: long-term results following dilation The purpose of this study is to report long-term results of 61 patients with Schatzki's ring who were dilated for relief of dysphagia. The severity of Schatzki's ring was mild in 28 patients (46%), moderate in 26 (43%), severe in 5 (8%), and indeterminate in 2 (3%). Follow-up information was available in 56 of 61 patients (mean, 75 months). During follow-up, 35 patients (63%) developed recurrent dysphagia and required repeated dilations: 19 patients (34%) had one to two dilations, 9 patients (16%) had three to seven dilations, 6 patients (11%) had more than seven dilations; 1 patient underwent surgery for resection of the Schatzki's ring (2%). The mean (range) dilation-free interval was 50.1 months (11.8 to 100 months) in mild cases, 44.5 months (8.9 to 82 months) in moderate cases, and 28.6 months (9 to 76 months) in severe cases. There was no significant correlation between the severity of Schatzki's ring on initial presentation and the subsequent dilation-free interval. Our data indicate that recurrent dysphagia is common among patients with Schatzki's ring after a successful dilation, and that the severity of Schatzki's ring is not a good prognostic indicator of the need for subsequent dilation. ",5 83,"Botulism among Alaska Natives. The role of changing food preparation and consumption practices. Alaska Natives have one of the highest rates of food-borne botulism worldwide. All outbreaks have been associated with the consumption of native foods, but in recent years outbreaks have occurred in previously unaffected areas and have involved new food items. Five botulism outbreaks occurred between 1975 and 1985 in an area of southwestern Alaska without previous confirmed outbreaks and among one ethnic group, the Yupik Eskimo. Of the 5 outbreaks, 3 were associated with fermented beaver tail, a nontraditional native food recently introduced into the region. Preparation techniques vary widely within villages and among ethnic groups. Traditional fermentation techniques have changed over the past 50 years; current preparation methods used by some families and ethnic groups may be more favorable for Clostridium botulinum growth. Prevention efforts should be targeted at high-risk subgroups of Alaska Natives who appear to have modified traditional practices and increased their risk of food-borne botulism. ",0 2635,"Protection against allergen-induced asthma by salmeterol. The effects of the long-acting beta 2-agonist salmeterol on early and late phase airways events provoked by inhaled allergen were assessed in a group of atopic asthmatic patients. In a placebo-controlled study, salmeterol 50 micrograms inhaled before allergen challenge ablated both the early and late phase of allergen-induced bronchoconstriction over a 34 h time period. Salmeterol also completely inhibited the allergen-induced rise in non-specific bronchial responsiveness over the same time period. These effects were shown to be unrelated to prolonged bronchodilatation or functional antagonism. These data suggest novel actions for topically active long-acting beta 2-agonists in asthma that extend beyond their protective action on airways smooth muscle. ",19 1536,"Preliminary characterization of angiogenic activity in media conditioned by cells from luteinized rat ovaries. Angiogenic activity was detected in media conditioned by ovarian cells from superovulated, pseudopregnant (PMSG/human CG treated) immature Holtzman rats. Media conditioned by cells from luteinized rat ovaries stimulated the directed migration of rabbit endothelial cells or mouse Balb/c3T3 cells, but was not mitogenic to either cell type. That endotheliotropic activity was not associated with a steroid was indicated by the finding that chemoattractant activity was detected in fractions after reversed-phase C18 chromatography, which removes more than 95% of steroids present in the media, and that chemoattractant activity was precipitated by ammonium sulfate and by ethanol. Full chemoattractant activity was recovered after boiling (95 C for 30 min), lyophilization, dialysis, Sephadex G-25 desalting columns, and pH changes from 3-10. After Sephadex G-200 chromatography, chemoattractant activity emerged at elution volumes corresponding to 20,000-30,000 mol wt. Chemoattractant activity was not retained by Concanavalin A-Sepharose or gelatin-Sepharose, and was only partially retained by heparin-agarose. Chemoattractant activity was also partially retained on both cation and anion exchange columns. Our collective findings indicate the presence of a nonsteroidal, heat-stable, pronase-sensitive factor, nominal mol wt of 20,000-30,000, in media conditioned by cells from luteinized rat ovaries; this factor is chemoattractive but not mitogenic to endothelial cells. Ovarian-derived chemoattractant activity appears to be distinct from fibroblast growth factor because it lacked detectable mitogenic activity, and because fibroblast growth factor was not active in our cell migration bioassay. Because stimulation of endothelial cell migration is a key event during angiogenesis, demonstration of an ovarian endotheliotropic chemoattractant is consistent with our hypothesis that angiogenesis factors play a role in the paracrine regulation of ovarian function. ",12 2437,"Conjugated catecholamines in human plasma: where are they coming from? The origins of conjugated catecholamines remain poorly known. The aim of the present study was to see whether a major contribution comes from the sympathetic nervous system. We have assumed some kind of parallelism between the activity of the sympathetic nervous system, the amount of catecholamines released and taken up, and the amount of conjugated catecholamines circulating in plasma. Accordingly, an increase in sympathetic activity should be followed by an increase in the plasma level of conjugated catecholamines. The plasma levels of sulfoconjugated and glucuroconjugated catecholamines were measured in 10 patients with mental disease resistant to drug treatment, before and after electroconvulsive therapy. As expected, blood pressure, norepinephrine concentration, and epinephrine concentration in plasma were transiently increased. Neither sulfoconjugated nor glucuroconjugated catecholamines were significantly changed. Conjugated catecholamines were measured in 10 volunteers before and at the nadir of insulin-induced hypoglycemia. As expected, plasma levels of norepinephrine and epinephrine were drastically increased. Plasma levels of sulfoconjugates were decreased and glucuroconjugates increased; these were narrow but statistically significant variations. Data reported in the present article do not support a major role for the activity of the sympathetic system in fixing the level of conjugated catecholamines in human plasma. This is a negative, but nonetheless important, observation. In human subjects, currently available information suggests an important role for the intestinal wall and renal function in determining the level of circulating sulfoconjugates. ",17 538,"The role of elective lymph node dissection in the management of patients with thick cutaneous melanoma. A retrospective search of patients seen at the Duke Melanoma Clinic from 1970 to 1986 identified 308 clinically Stage I patients, with 4.0 to 10.0 mm cutaneous melanomas. Five-year and ten-year survival was 56% and 43%, respectively. Elective lymph node dissection (ELND) was done in 116 patients (37.7%); there was no difference in disease-free interval (DFI) or survival between these patients versus patients treated with wide excision only (P = 0.9). Thirty-two patients (27.6%) had pathologically positive nodes on ELND. These patients had a shorter DFI (P = 0.05) and survival (P = 0.03) compared with patients with negative node dissections. When further divided by Breslow's thickness, this difference persisted in patients with 4.0 to 6.0 mm lesions (P = 0.01). However, for thicker lesions (greater than 6.0 mm), there was no difference in survival between the node-negative and node-positive groups (P = 0.9). The mean follow-up was 7.1 years. Elective lymph node dissection was not done in 192 patients; 78 of these recurred first in the regional nodes. These 78 patients were compared with the 32 patients who had pathologically positive nodes by ELND to see if patient survival was improved by early removal of nodal disease. There was no difference in DFI (P = 0.5) or survival (P = 0.3) between these two groups. It is concluded that ELND may provide prognostic information for patients with thick cutaneous melanomas. However, there was no change in DFI or ultimate survival when patients were followed, and nodes removed when clinically positive. The authors do not recommend ELND for patients with thick melanomas because the risk of distant metastases outweighs any benefit of regional node dissection. ",3 1501,"Menorrhagia. Excessive vaginal bleeding, or menorrhagia, is one of the most common presenting symptoms for gynecologic patients. Although this disorder has many possible etiologies, it is generally possible to approach its diagnosis and management in an orderly fashion. When evaluating the menorrhagic patient, it important to gear the work-up toward a differential diagnosis that includes pregnancy-related causes, hormonal problems, iatrogenic etiologies, mechanical intrauterine disorders, infections of the lower genital tract, and gynecologic cancers (PHIMIC). This differential approach can guide the types of historical data obtained from the patient, focus the physical examination, and alert the practitioner to the most appropriate laboratory and radiologic evaluation. Therapy can differ widely, depending on the cause of the bleeding. Most types of menorrhagia respond to medical therapy with oral contraceptives, oral synthetic estrogens or progestins, and long-acting intramuscular progestins or GnRH agonists. Surgical approaches, such as dilatation and curettage or hysterectomy, are less and less a first-line therapy; but innovative surgical techniques such as hysteroscopy and laparoscopic surgery are becoming increasingly important. With rapid, goal-directed diagnosis and specific therapy, the medical complications, anxiety, and discomfort suffered by the woman with menorrhagia can be alleviated quickly. ",12 1279,"Whitnall's sling for poor function ptosis. Severe unilateral ptosis with poor levator function has previously been treated with maximal levator muscle resection or bilateral or unilateral frontalis suspension. One of us (R.L.A.) has developed a technique called ""Whitnall's sling,"" where only the levator aponeurosis is resected, preserving Whitnall's ligament and its attachments. Whitnall's ligament and the underlying resected levator muscle are sutured to the superior portion of the tarsal plate. This surgery preserves levator muscle, Muller's muscle, and Whitnall's ligament without altering the structures that produce the three-layer tear film. In 69 eyelids operated on between July 1976 and July 1986, in which a minimum of 1 year of follow-up by one of use was obtained, results have been satisfactory and directly related to levator function. We believe this technique to be anatomically and physiologically superior to ""maximal levator resection"" with similar long-term results. More recent results have shown that the addition of a 5-mm superior tarsectomy provides an additional elevation of 1 to 1.5 mm. Whitnall's sling is best suited for cases where the opposite fissure height is 9 mm or less and levator function of the ptotic eyelid is 3 to 5 mm. ",10 2056,"Role of echocardiography in acute myocardial infarction. Interventional therapies such as thrombolytic agents, angioplasty and surgery have emerged as important options in the management of patients with myocardial infarction. These therapies are aimed at improving myocardial perfusion with the ultimate improvement or restoration of myocardial function. Two-dimensional echocardiography with digital storage and display is an ideal technique for temporally monitoring regional ventricular function and the effectiveness of interventional therapy. By design, 2-dimensional echocardiography is noninvasive and can be performed conveniently at the bedside. For these reasons, echocardiography is the principal imaging technique at Indiana University Hospital for patients with acute myocardial infarction. Computer retrieval of echocardiograms can be achieved in about 10 seconds at the nurses' station in the coronary care unit. With the availability of such an examination, the physician has a better understanding of the site, size and function of the infarct area. The state of the noninfarcted myocardium is also assessed and may be critical to the patient's prognosis. With the digital recordings, serial studies can be displayed side-by-side, making it easier for the physician to follow the natural history or to judge the effect of therapy. Echocardiography also is useful in identifying many complications that can occur with myocardial infarction. For these reasons, and because echocardiography will also show related cardiac problems, it is indispensable in the management of acute myocardial infarction. ",13 390,"The epidemiology of ophthalmic malignancies in New York State. The epidemiologic characteristics of more than 1400 primary eye cancers (ICD-9, site 190) diagnosed among New York State (NYS) residents between 1975 and 1986 are described. Among NYS male residents, the average annual age-adjusted incidence rate was 7.5 per 1,000,000, and among NYS female residents, the rate was 5.4 per 1,000,000 (male:female rate ratio, 1.39). The majority of ophthalmic malignancies were included within three histologic groupings: melanomas (70.4%), retinoblastomas (9.8%), and squamous cell carcinomas (9.2%). The average annual incidence of retinoblastoma among persons in NYS who were less than 5 years of age was 9.5 per 1,000,000 for boys and 8.7 per 1,000,000 for girls (male:female rate ratio, 1.09). The average annual incidence (age-adjusted) of ocular melanomas was 4.9 per 1,000,000 among men and 3.7 per 1,000,000 among women in NYS (male:female rate ratio, 1.32). Expanded knowledge of the epidemiology of ophthalmic cancers can help to develop a foundation on which to monitor disease patterns and can serve to stimulate further etiologic research involving these rare malignancies. ",3 228,"Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast. Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node (""skip"") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor-involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer. ",3 3317,"Transformed and nontransformed cells differ in stability and cell cycle regulation of a binding activity to the murine thymidine kinase promoter. A DNA binding activity to an upstream region of the murine thymidine kinase gene is regulated differently in a transformed and nontransformed cell line pair. Differences in regulation were observed (i) after serum levels were reduced, (ii) when serum levels were returned to initial high levels, and (iii) while protein synthesis was inhibited. After reduction of serum levels, the binding activity was unstable in nontransformed BALB/c 3T3 clone A31 cells but was significantly more stable in benzo[a]pyrene-transformed BALB/c 3T3 cells. After serum concentration was returned to high levels, the kinetic pattern of the binding activity differed between nontransformed and transformed cells. While protein synthesis was inhibited, the binding activity was unstable in nontransformed cells and stable in transformed cells. Partial inhibition of protein synthesis--a more stringent condition to test instability--prevented the induction of the binding activity in nontransformed cells. Previously, the labile protein hypothesis set forth the criterion that a protein regulating the onset of DNA synthesis should be unstable in nontransformed cells and stable in transformed cells. The DNA binding activity described here satisfies this criterion. ",22 1878,"Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage. Early changes in intracranial pressure (ICP), ICP volume index, and resistance to absorption of cerebrospinal fluid induced by experimental subarachnoid hemorrhage were studied in cats. After SAH, the ICP was slightly elevated, and there was a decrease in the buffering capacity of the intracranial space and a sharp rise in outflow resistance. During infusion of blood into the cisterna magna with a constant infusion rate, an extensive increase in ICP could be demonstrated in contrast to the infusion of saline, which caused only slight elevation of ICP. Furthermore, during blood infusion, the ICP level did not reach a plateau phase of pressure, as was demonstrated during infusion of saline. It is suggested that the marked increase in ICP during blood infusion into the subarachnoid space is caused by intracranial volume loading and the simultaneous increase in cerebrospinal fluid outflow resistance. It is concluded that the reported relationship between increased cerebrospinal fluid outflow resistance and increased ICP supports the hypothesis of a strong increase in ICP during subarachnoid hemorrhage in human subjects. ",13 1795,"Right ventricular function and metabolism. Right ventricular protection may be limited with current methods of cardioplegic delivery. Sensitive measurements of right and left ventricular function and metabolism were made in 30 patients undergoing elective coronary artery bypass surgery with cold cardioplegic arrest. Myocardial adenine nucleotide concentrations decreased with cardioplegia and reperfusion in both the right and left ventricles despite adequate levels of precursors, suggesting perioperative mitochondrial dysfunction. Postoperatively, right and left ventricular pressures were measured with micromanometer catheters and volumes were measured by nuclear ventriculography. Right and left ventricular systolic elastance was calculated by the isochronic method and by the end-systolic method. Both methods provided sensitive indexes of end-systolic elastance. This study demonstrated that right ventricular function and metabolism can be evaluated by methods analogous to methods used in the left ventricle. These results suggest that right ventricular functional and metabolic recovery are delayed despite apparently adequate myocardial protection. Sensitive measurements may permit improved assessment of alternative methods of right ventricular protection. ",13 2558,"Medical treatment of juvenile arthritis. The range of medications available to treat juvenile arthritis has markedly expanded over the past 15 years. Multiple new nonsteroidal antiinflammatory drugs (NSAIDs) are available in the United States, although only a few are approved for use in children, and none have been proven to be significantly better than aspirin in suppressing inflammation. The average time before significant improvement is noticed is over 30 days in the 50% of the children who respond to any NSAID within three months. The percentage of responders progressively increases with the length of therapy, so treatment should be continued until one is reasonably certain that improvement will not occur before changing medication. In the more severely involved child, gold and other disease-modifying medications are used. However, it has been difficult to prove the value of these medications in controlled studies because of the high rate of significant improvement in the control group treated with NSAIDs. In preliminary studies, methotrexate appears to have significant benefit in children who have failed other treatments. Other newer therapies, such as intravenous gammaglobulin, have only been used in a small number of patients and have not as yet been proven beneficial. ",19 3086,"An all-polyethylene cementless tibial component. A five- to nine-year follow-up study. An all-polyethylene cementless tibial component was used in 221 total knee arthroplasties. With one exception, failures did not occur before three years. Failure was characterized by medial subsidence of the tibial component. There was abrasion of the polyethylene on the undersurface of all components that failed. Survivorship was seven to nine years (87.1%). This study demonstrated that a flexible cementless component can function well when used with any type of bone. However, abrasion of the polyethylene that occurs from shearing forces is a concern. Polyethylene components need adequate provisions to prevent shearing or need surface treatment to prevent abrasion. ",22 2801,"Whole bowel irrigation and the cocaine body-packer: a new approach to a common problem. Gastrointestinal drug smuggling is a common problem in many major cities. Though the majority of cases never require medical attention, the ""body-packer"" frequently presents with life-threatening symptoms of intoxication, including seizures and cardiorespiratory collapse, as well as mechanical obstruction from the ingested drug packets. The risk to asymptomatic smugglers may vary with packaging materials, and remains unknown. Lack of controlled studies, and variations in packaging materials and clinical outcomes have prevented formulation of a consistent management strategy. Current recommendations for asymptomatic body-packers vary from immediate surgical removal, to use of laxatives, to observation. The authors present the first reported case of an asymptomatic cocaine body-packer treated with whole bowel irrigation with polyethylene glycol electrolyte lavage solution. This strategy was safe, well tolerated, resulted in the rapid elimination of drug packets from the gastrointestinal tract, and facilitated assessment by contrast radiography. The potential benefits and limitations for the use of whole bowel irrigation in this difficult problem are discussed. ",20 1663,"Technetium-99m sestamibi myocardial imaging: same-day rest-stress studies and dipyridamole. Unlike thallium-201, technetium-99m (Tc-99m) sestamibi does not redistribute in the myocardium after injection. Thus, 2 separate injections, 1 at rest and the other at stress (or after dipyridamole), are required to differentiate ischemia from scar. From a physical viewpoint, a 24-hour interval between the 2 injections is preferable for detection of coronary artery disease (CAD) with Tc-99m sestamibi imaging. However, same-day studies are more convenient in clinical practice. Results of studies using different Tc-99m sestamibi injection protocols are presented with emphasis on the advantages of a rest-stress injection sequence with a low dose at rest (7 mCi) followed 2 hours later by a higher dose at stress (25 mCi). A prospective study was conducted in a patient population with proven CAD using same-day studies to compare a rest-stress (7 and 25 mCi, respectively) to a stress-rest (7 and 25 mCi) Tc-99m sestamibi injection sequence. There was an agreement in 87.3% of the analyzed segments between the 2 protocols. However, the largest discordance for type of defect applied to 7.4% of the segments judged ischemic in the rest-stress protocol, which were called scars on stress-rest. This study showed that a rest-stress sequence is preferable when using a same-day protocol with a short time interval (less than 2 hours) between the 2 Tc-99m sestamibi injections because the rest image performed initially represents a ""true"" rest study, which is not necessarily the case with the stress-rest sequence. Preliminary studies were performed to evaluate dipyridamole with Tc-99m sestamibi imaging in normal subjects and in patients with CAD. These studies showed that treadmill and dipyridamole Tc-99m sestamibi imaging are comparable and the results are similar to those obtained with thallium-201. ",13 2380,"The uncoupling of biliary lipid from bile acid secretion by organic anions in the rat. A number of organic anions has been shown to inhibit biliary phospholipid and cholesterol secretion without affecting bile acid secretion. However, the mechanism of this uncoupling phenomenon is still unclear. This study shows a comparison of the effects of ampicillin (18 mumol/100g body wt), sulfated taurolithocholic acid (0.2 and 1.0 mumol/100 g body wt), and indocyanine green (0.6 mumol/100 g body wt) in control and Groningen Yellow-Wistar rats with chronic (8 days) biliary drainage. Groningen Yellow rats have a hereditary defect in hepatobiliary transport of various organic anions. Bile secretion, but not hepatic uptake, of the three organic anions was strongly impaired in Groningen Yellow rats compared with controls. Ampicillin and sulfated taurolithocholic acid caused a strong uncoupling in control rats but had no effect or a much smaller effect on lipid secretion in Groningen Yellow rats. Indocyanine green did not affect lipid secretion, in either control or in Groningen Yellow rats. Gel-filtration chromatography of bile showed a specific coelution of ampicillin and sulfated taurolithocholic acid with the bile acid fraction, whereas indocyanine green coeluted with the phospholipid/cholesterol fraction. This study concludes that the uncoupling by ampicillin and sulfated taurolithocholic acid occurs after their secretion into bile and is caused by interaction of these compounds with bile acids. It is hypothesized that this interaction inhibits the capacity of bile acids to induce secretion of phospholipids and cholesterol into the bile. ",17 3074,"Identification of patients at greatest risk for developing major complications at cardiac surgery [published erratum appears in Circulation 1991 Jul;84(1):446] As part of a prospective program to use risk-adjusted outcome (operative mortality and morbidity) as a measure of quality of care, we have analyzed perioperative complication data in 10,634 patients representing 73% of all patients undergoing cardiac surgery requiring cardiopulmonary bypass at Veterans Administration medical centers between April 1, 1987, and March 31, 1989. One or more complications occurred in 15% of patients undergoing coronary artery bypass grafting, and in 24% of patients undergoing valve and other cardiac surgery. Patients experiencing one or more complications had an eightfold to 10-fold increase in operative mortality compared with patients with no perioperative complications. The most frequent complication was requirement for mechanical ventilation for at least 48 hours occurring in 8% of patients undergoing coronary artery bypass and in 15% of patients undergoing valve and other cardiac surgery; 24-25% of these patients died within 30 days of surgery or as a direct result of a surgical complication. Previous heart surgery was a strong predictor of development of one or more complications in both groups of patients, being associated with an adjusted relative risk of 1.6-2.0. Other important predictors in both surgical groups were surgical priority, older age, peripheral vascular disease, and higher serum creatinine. Although a number of preoperative risk factors could be identified for the development of renal failure, low cardiac output, and requirement for prolonged mechanical support, few risk factors could be identified for the development of mediastinitis and reoperation for bleeding. This observation suggests that mediastinitis and reoperation for bleeding are more likely the result of technical factors rather than patient-related risk factors. ",22 2421,"Contribution of impaired muscle glucose clearance to reduced postabsorptive systemic glucose clearance in NIDDM. The reduced postabsorptive rates of systemic glucose clearance in non-insulin-dependent diabetes mellitus (NIDDM) are thought to be the consequence of insulin resistance in peripheral tissues. Although the peripheral tissues involved have not been identified, it is generally assumed to be primarily muscle, the major site of insulin-mediated glucose disposal. To test this hypothesis, we measured postabsorptive systemic and forearm glucose utilization and clearance in 15 volunteers with NIDDM and 15 age- and weight-matched nondiabetic volunteers. Although systemic glucose utilization was increased in NIDDM subjects (14.5 +/- 0.5 vs. 11.2 +/- 0.2 mumol.kg-1.min-1, P less than 0.001), systemic glucose clearance was reduced 1.40 +/- 0.06 vs. 2.13 +/- 0.05 ml.kg-1.min-1, P less than 0.01). Although forearm glucose utilization was increased in NIDDM subjects (0.663 +/- 0.058 vs. 0.411 +/- 0.019 mumol.dl-1.min-1, P less than 0.001), forearm glucose dl-1 clearance was reduced (0.628 +/- 0.044 vs. 0.774 +/- 0.037 ml.L-1.min-1, P less than 0.01). However, extrapolation of forearm data to total-body muscle indicated that impaired clearance reduced muscle glucose disposal by only 61 +/- 21 mumol/min, whereas impaired systemic clearance reduced systemic glucose disposal by 662 +/- 82 mumol/min. Thus, impaired muscle glucose clearance accounted for less than 10% of the reduced systemic glucose clearance in NIDDM subjects. Therefore, we conclude that muscle insulin resistance plays only a minor role in the reduced systemic glucose clearance found in NIDDM in the postabsorptive state and propose that reduced brain glucose clearance is largely responsible. ",17 1886,"Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain. Acute cerebral ischemia increases the generation of free radicals, causing cell damage, and theoretically may decrease the activity of the scavenging enzyme superoxide dismutase. To investigate the role of superoxide dismutase in cerebral ischemia, we used a model of middle cerebral artery occlusion in rats. In this model an infarct is produced in the pyriform and frontoparietal cortices, extending into the lateral basal ganglia. We measured superoxide dismutase activity by using the xanthine oxidase cytochrome c reduction assay in these areas of rat brains. Tissue samples were analyzed 20 minutes, 2, 6, or 24 hours, or 7 days after middle cerebral artery occlusion and 2 or 24 hours or 7 days after sham operation (n = 8-10 at each time). There was no significant change in superoxide dismutase activity relative to control values in any brain area at any time up to 24 hours after surgery. However, 7 days after middle cerebral artery occlusion a significant decline in superoxide dismutase activity, to 55%-68% (p less than 0.05) of that in unoperated controls, was observed in all brain areas. Our results do not support an important role for changes in the activity of endogenous superoxide dismutase during the acute phase of cerebral ischemia. However, the decrease in superoxide dismutase activity 7 days after ischemia could indicate ongoing additional damage to peri-infarct tissue. ",13 404,"A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. The purpose of this study was to determine the efficacy of autogenous vein grafts as nerve grafts (AVNC) for bridging of small peripheral sensory nerve gaps as compared with direct repair and with conventional nerve grafting techniques (ANG). Patients with painful neuroma or segmental nerve injury of 3 cm were chosen as the test group. Those amenable to direct repair were classified as controls. Between 1982 to 1988, a total of 22 patients were enrolled in this study. A total of 34 nerves were repaired, 15 with a venous nerve conduit, 4 with a sural nerve graft, and 15 with direct repair. Significant symptom relief and satisfactory sensory function return were uniformly observed. The two-point discrimination measurements indicated superiority of direct repair and probably of conventional nerve grafting. However, the universally favorable patient acceptance and the return of measurable two-point discrimination indicates the effectiveness of autogenous vein grafts as nerve conduits when selectively applied to bridge a small nerve gap (less than or equal to 3 cm) on nonessential peripheral sensory nerves. ",3 2346,"Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene. Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs. ",17 2955,"The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues. III. Effects on lung function. The effect of single and fractionated doses of fast neutrons (42 MeVd----Be) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 +/- 0.94 for infinitely small X-ray doses per fraction. ",20 874,"Mapping of epitopes on the La(SS-B) autoantigen of primary Sjogren's syndrome: identification of a cross-reactive epitope. Autoepitopes on the ribonucleoprotein La(SS-B) were identified by using recombinant La(SS-B) polypeptides and sera from 166 patients with the antinuclear autoantibody anti-La(SS-B). The La(SS-B) polypeptides were encoded by polymerase chain reaction-derived overlapping or nonoverlapping fragments of the La(SS-B) gene, which encodes a protein of 408 amino acids (aa). Of the 166 sera tested, 99% reacted with a fusion protein comprising the first 107 N-terminal aa (LaA); 91% reacted with a fusion protein comprising aa 111 to 242 (LaC), and 91% reacted with a fusion protein comprising aa 346 to 408 (LaL2/3) at the C terminus of La(SS-B). The order of immunodominance as assessed by the number of sera reacting with each epitope and the strength of the reactivity was LaA (aa 1 to 107) greater than LaC (aa) 111 to 242) much greater than LaL2/3 (aa 346 to 408). Cross-reactivity was observed between antibodies eluted from LaC (aa 111 to 242) and LaL2/3 (aa 346 to 408), but there was no significant primary sequence homology between the two regions. The LaC region contained at least two epitopes, one encompassing a putative RNA-binding motif (aa 112 to 187) which was recognized by 83% of patient sera. Serial serum samples from three patients showed that the antibody response to La(SS-B) was initially directed to the N terminus (LaA, aa 1 to 107), but over a period of time all three major epitopes, including that encompassing the putative RNA-binding motif, were recognized. This result suggests that the primary immune response to La(SS-B) is restricted to an immunodominant epitope. As the specificity of the autoantibody response broadens, it includes the RNA-binding motif, which may have important implications for the expression of disease. ",6 3135,"Facial muscle reanimation using the trigeminal motor nerve: an experimental study in the rabbit. Surgical repair of facial nerve deficits may be marred by lack of muscle control and donor region paresis. Using New Zealand white rabbits, a study was undertaken to evaluate facial muscle reanimation with a donor source not previously used: the motor division of the trigeminal nerve. The results were compared with the severed facial nerve and hypoglossal-facial coaptation. An atrophy scale was calibrated for facial muscles of the rabbit. Clinical, electromyographic, and histomorphometric findings confirmed that the trigeminal nerve was a suitable donor source. The neurorrhaphy produced an exponential rate of repair. ",22 63,"Quinolone antibiotics in the treatment of Salmonella infections The 4-fluoroquinolones are a new class of antimicrobial agents that possess broad in vitro antibacterial activity, including efficacy against enteric pathogens such as Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio species. These drugs are clinically effective against both drug-sensitive and multiresistant strains of Salmonella typhi and Salmonella paratyphi that cause enteric fever. In salmonella enterocolitis, the quinolones--unlike older antimicrobial agents that may have little impact on the duration of symptomatic illness and can in fact prolong fecal carriage of salmonellae--actually shorten the course of clinical disease and terminate excretion of these organisms in the stool. Similarly, for chronic carriers of both typhoidal and nontyphoidal Salmonella strains, the quinolones are effective in eradicating biliary and fecal reservoirs of infection. Immunosuppressed persons with salmonellosis, such as those with AIDS, may benefit from both short-term treatment and prolonged prophylaxis with a quinolone antibiotic. The optimal agent, dose, and duration of quinolone therapy for all salmonella syndromes remain to be determined by larger controlled trials. ",0 1553,"Multivariate analysis in the prediction of death in hospital after acute myocardial infarction. Prognostic factors in patients with acute myocardial infarction based on clinical and investigative data on admission were evaluated prospectively in 111 consecutive patients. Seventeen patients (15.3%) died during hospital stay. Age, a previous infarct, high Killip class, cardiomegaly, high serum concentrations of cardiac enzymes, a low ejection fraction, and a high wall motion score index correlated significantly with in-hospital mortality; whereas sex, risk factors, and pericardial effusion did not. Multivariate analysis showed that age and the wall motion score index were the best predictors of death in hospital. Wall motion detected by cross sectional echocardiography may reflect the extent of myocardial involvement. Age and wall motion score index predicted in-hospital mortality with a sensitivity of 76.5%, a specificity of 91.5%, and a predictive accuracy of 89.2%. Age and the wall motion score index can be determined on admission and are useful for identifying patients at high risk of cardiac death who might benefit from early intervention. ",13 1657,"Planar imaging techniques used with technetium-99m sestamibi to evaluate chronic myocardial ischemia. The results of published and some unpublished studies comparing planar imaging performed with 2 radionuclides, thallium-201 (T1-201) and technetium-99m (Tc-99m) sestamibi, are reviewed. The average sensitivity for the detection of coronary artery disease (CAD) in studies involving 594 patients was 85% (range 73 to 96%). The average sensitivity for individual vessels was 65% (range 60 to 70%). The average segmental concordance between T1-201 and Tc-99m sestamibi was 89%. End-diastolic gated perfusion images improved the concordance between Tc-99m sestamibi and angiography in 22 patients from 83.4 to 87%. Semiquantitative analysis increased the concordance between T1-201 and Tc-99m sestamibi from 89 to 91%. Ventricular function derived from gated Tc-99m sestamibi perfusion images showed a significant correlation with echocardiography (n = 62, r = 0.85); with angiography (n = 70, r = 0.91); and with equilibrium radionuclide ventriculography (n = 18, r = 0.86). The ratio of lung to left ventricle uptake and the ratio of right ventricle to left ventricle uptake was assessed. Eight of 52 patients had an abnormally elevated lung index (greater than 42%) and these patients had the most severe CAD. Six of the 52 patients had an abnormally elevated right ventricular index (greater than 56%) and these patients had more severe CAD. ",13 528,"Carotid body tumors. The surgical management of carotid body tumors requires identification and preservation of neural and vascular structures without compromising resection of the neoplasm. Fifteen patients were examined and treated for carotid body tumors at the Cleveland (Ohio) Clinic Foundation from 1979 through 1987. The benchmark of diagnosis is bilateral carotid angiography. When neural structures are free of tumor, meticulous dissection facilitates their preservation. Large tumor size increases risk for arterial resection necessitating reconstruction. The use of a vascular shunt minimizes the risk of cerebral ischemia. Postoperative intravenous digital subtraction angiography allows for evaluation of arterial repair. A retrospective review of 15 carotid body tumor resections performed in 14 patients revealed no evidence of tumor recurrence, no mortality associated with surgical intervention, no postoperative cerebrovascular accident, and limited morbidity associated with unavoidable sacrifice of neural elements. ",3 251,"Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. The integrin superfamily represents a major class of receptors mediating cell-substrate adhesion. Our recent study of the tissue distribution of the alpha 2 beta 1 integrin, a cell-surface collagen receptor, revealed that high levels of receptor expression were associated with orderly, regulated epithelial cell proliferation. Those observations prompted the present investigation of alpha 2 beta 1 and other integrins in adenocarcinoma of the breast. The alpha 2 beta 1 integrin was highly expressed on the epithelium of the ducts and ductules of normal breast tissue. Normal or nearly normal levels of the receptor were expressed in fibroadenomas. In contrast, markedly decreased or undetectable alpha 2 beta 1 expression was typical of poorly differentiated adenocarcinomas. Well-differentiated lesions exhibited intermediate levels of expression. Similar, but less extensive, decreases in expression were observed for the alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor). Significant expression of the beta 1 subunit on even poorly differentiated tumors suggests that the expression of other undefined members of the beta 1 family is not reduced to the same low level as alpha 2 beta 1 and alpha 5 beta 1. Expression of the alpha 2 beta 1 integrin was highly correlated with estrogen-receptor expression. Decreased expression of alpha 2 beta 1 and other integrin adhesive protein receptors probably contributes to the altered adhesive properties of tumor cells characteristic of the malignant phenotype. ",3 486,"Comparison of lymphangiography and computed tomography scanning in evaluating abdominal disease in stages III and IV Hodgkin's disease. A Southwest Oncology Group study. The authors reviewed the records of 139 patients who had laparotomy plus computed tomography (CT) and/or lymphangiograms (LAG) as part of a their staging workup for Hodgkin's disease, in accordance with Southwest Oncology Group (SWOG) protocol 7808. They evaluated the relative ability of CT and LAG to detect disease in the abdomen. Two regions of the abdomen were designated, the upper and the lower, to further examine the capabilities of CT and LAG in the lower abdomen and CT in the upper abdomen. A LAG was more sensitive (P less than 0.05) than CT in detecting positive lower abdominal nodes. In the upper abdomen, CT scan had low sensitivity for detecting positive nodes, liver, or spleen. This study suggests that LAG of the lower abdomen provided more information than CT, and therefore should not be abandoned as a valid method for detecting nodal disease. ",3 801,"Feasibility of digital teleradiology for imaging evaluation of patients with acute right upper quadrant abdominal pain. To assess the utility of a commercially available digital teleradiology system in evaluating patients with acute pain in the right upper quadrant, hard-copy images from 100 examinations (50 hepatobiliary scintigrams and 50 sonograms of the right upper quadrant) were digitized, transmitted via standard telephone lines, and viewed remotely on a video monitor. Video and hard-copy interpretations were then compared for degree of concordance. For the scintigraphic studies, hard-copy and video images were equal in demonstrating gallbladder and bile duct activity. Video images failed to depict the presence of bowel activity in one case. Gallstones were depicted equally well on hard-copy and video sonographic images. The video interpreters overestimated the presence of abnormal hepatic parenchyma and overlooked one case of right hydronephrosis. The video interpretations of the scintigrams and sonograms showed an overall error rate of 4%, comparable to the rate obtained when radiographs are interpreted remotely with digital teleradiology systems. ",5 31,"Infection control in the nursing home: the physician's role. Infection control in the nursing home or long-term care facility is an increasingly complex activity. The high rates (approximately 15%) and special risks (group activities, crowding) for nosocomial infection demand special attention by attending physicians. Some specific responsibilities include: recognition of infection; knowledge and use of basic infection control principles; appropriate antibiotic use; review of immunizations; facilitation of communications among office, hospital, and long-term care facility; and involvement with infection control program(s). ",0 2330,"Effect of long-term PUVA treatment of psoriasis on the collagen and elastin gene expression and growth of skin fibroblasts in vitro. The proliferation rate, collagen metabolism and collagen and elastin messenger-RNA levels were studied in fibroblasts derived from patients who had received many courses of either systemic 8-methoxypsoralen or topical trioxsalen PUVA treatment. The proliferation rate of fibroblasts as measured by the incorporation of 3H-thymidine or by cellular division was decreased in those obtained from patients who had PUVA treatment as compared with controls. Collagen synthesis was slightly increased in the cells from PUVA-treated patients, but the relative collagen synthesis and the ratio between types I and III collagen were unchanged. The levels of collagen and elastin mRNAs were increased in fibroblasts derived from the PUVA-treated patients. No significant differences in histology or immunochemistry could be found in the biopsies taken from topical and systemic PUVA-treated patients. ",16 1567,"Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery. Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to-left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period. ",13 154,"Quantitative in vitro drug potency and drug susceptibility evaluation of Leishmania ssp. from patients unresponsive to pentavalent antimony therapy. Quantitative in vitro drug sensitivity of 32 Leishmania isolates (16 from patients failing pentavalent antimony [SbV] therapy) was determined using a radiorespirometric microtechnique (RAM). Of 30 isolates with histories, 22 (73%) RAM tests agreed with patient history; the remaining 8 (27%) did not. There was no difference in RAM drug sensitivity: clinical correlation between 15 isolates tested blindly and 15 with known clinical history (4 did not agree with clinical history in both). Test sensitivity appeared to be limited only by the sensitivity of the Leishmania to SbV and could be detected at 2 micrograms/ml Sb (about 10% of serum drug level). An isolate from a patient with untreated self-healing cutaneous disease was drug resistant. Using RAM, parasite drug sensitivity can be quantified apart from patient physiologic and immunologic variables intrinsic to clinical data. Potency differed a maximum of 100% (weight% Sb:weight% Sb) among drug lots and also between Glucantime and Pentostam. Potency changes between drug lots were not explainable based on Sb content or test-to-test variability. This microtest offers a rapid method for evaluating the drug sensitivity of patient isolates and for determining of the activity of pentavalent antimonials and other candidate anti-leishmanials prior to the initiation of therapy. ",2 2750,"Incidence of lingual nerve trauma and postinjection complications in conventional mandibular block anesthesia. Trauma to the lingual nerve is potential risk factor for patients receiving mandibular block anesthesia. This paper describes the results of a patient survey of 9,587 conventional mandibular blocks received by 2,289 adults. The incidence of lingual nerve trauma and postinjection complications is reported along with an associated analysis of the duration of complications, procedures at the time of incident, the side of occurrence (right or left), and gender ratios. In addition, recommendations for patient evaluation, treatment, and follow-up care are discussed. ",20 879,"Flow and volume dependence of respiratory system mechanics during constant flow ventilation in normal subjects and in adult respiratory distress syndrome. Seven control subjects and seven patients with adult respiratory distress syndrome (ARDS) were artificially ventilated and flow, volume, and tracheal pressure were monitored. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. In both groups Ers did not vary with different inspiratory flows and volumes, but was significantly higher in ARDS. With increasing volume (isoflow maneuvers), Rrs,max and Rrs,u increased but Rrs,min remained unaltered in ARDS. In control patients, however, resistances did not vary but Rrs,max and Rrs,u were smaller and Rrs,min equaled their corresponding values in ARDS. Hence, stress relaxation seems to be increased in ARDS. During isovolume maneuvers Rrs,max and Rrs,u decreased with increasing flows (both groups), although they were significantly higher in ARDS. Rrs,min was not modified by different flows and was similar in both groups. Thus, pendelluft is also increased in ARDS. In conclusion, the mechanical profile of ARDS is characterized by increased Ers and Rrs,max, the latter being secondary to augmented mechanical unevenness within the system. ",7 1761,"Balloon rupture due to lesion morphology during coronary angioplasty. We report a case of coronary angioplasty of a left anterior descending artery lesion that was complicated by the rupture of three successive balloon catheters. Each rupture occurred as a pinhole jet of contrast into a diagonal side branch, causing subintimal staining. This case demonstrates that balloon rupture may result from lesion morphology. ",13 2172,"Newborn screening for sickle cell disease. When is an infant 'lost to follow-up'? Success of programs to screen newborns for sickle cell disease depends on timely follow-up. Education regarding fever and splenic palpation, and initiation of prophylactic penicillin therapy, will reduce morbidity and mortality and should occur prior to 4 months of age. However, contacting parents to permit implementation of care may be difficult, particularly in large urban populations; only nine (36%) of 25 infants recently identified as having sickle cell disease arrived at our institution for initial appointments. Medical providers must be aware of medical and legal obligations related to follow-up of newborns with sickle cell disease to prevent untoward events in ""missed cases."". ",14 1004,"Vestibular recruitment in Meniere's disease. The aim of this study was to search for vestibular recruitment in a sample of patients with Meniere's disease. Recruitment was defined as an abnormal growth of response with increasing stimulus intensity. Twenty-nine patients were tested with sinusoidal rotation of three different magnitudes at four different frequencies. We also searched for auditory recruitment in each patient via tests of auditory brain stem responses, acoustic reflexes, and loudness balance and discomfort level. Analysis of vestibular responses indicated, on average, a linear relationship between stimulus magnitude and response magnitude, ie, doubling the stimulus magnitude resulted in twice the response magnitude. Meniere's patients did not yield results significantly different (although they were more variable) from those of the normal subjects. The vestibular responses of patients with auditory recruitment did not differ systematically from those of patients without auditory recruitment. We conclude that vestibular recruitment, if it exists in patients with Meniere's disease, is not demonstrated by sinusoidal rotational testing. ",8 3034,"Electrocardiographic abnormalities in cerebrovascular accidents. The electrocardiographic abnormalities found in 100 patients with acute cerebrovascular disease and previously normal hearts are described. The abnormalities were more often seen in patients with intracerebral and subarachnoid hemorrhages. The most common changes were Q-Tc Prolongation and ST segment and T wave abnormalities. The mechanisms of these electrocardiographic abnormalities appear to be multiple. ",22 2203,"Comparative value of transthoracic and transesophageal echocardiography in the assessment of congenital abnormalities of the atrioventricular junction. Information obtained from transthoracic and transesophageal echocardiography (two-dimensional echocardiography with spectral Doppler and color flow imaging) was compared in 17 patients with major congenital abnormalities of the atrioventricular (AV) junction (10 discordant AV connections, 1 criss-cross connection, 5 absent right connections and 1 absent left connection). The findings by either technique were correlated with findings at cardiac catheterization (12 patients) and at surgery (5 patients). In two of six patients with an absent AV connection as defined by transthoracic echocardiography, transesophageal imaging demonstrated an imperforate AV valve. In 11 of 11 patients with a discordant or criss-cross connection, assessment of AV valve and ventricular morphology (by defining the chordal attachments of both AV valves) was possible with transesophageal echocardiography (3 of 11 patients by transthoracic echocardiography); chordal straddling was detected in 1 patient and excluded in 3 others with an associated inlet ventricular septal defect. Anomalous pulmonary venous connection (one patient), atrial septal defect (three patients) and subpulmonary stenosis (five patients) were better assessed by transesophageal imaging, and atrial appendage morphology could be demonstrated in all. The transesophageal technique was less useful in demonstrating the anterior subaortic infundibulum or aortopulmonary shunt (two patients). Although systemic ventricular function could be assessed by either method with use of short-axis M-mode scans, transesophageal pulsed Doppler interrogation of AV valve and pulmonary venous flow patterns provided clues to diastolic dysfunction of the systemic ventricle. ",15 1322,"Geriatric pharmacokinetics and the kidney. The general population is aging and, as a result, drugs are increasingly prescribed for a variety of medical conditions in a group of patients with multiple physiologic and pharmacokinetic abnormalities. The present report summarizes principles of prescribing for the elderly, especially those related to the decline in renal function that frequently occurs. ",11 2227,"Magnetic resonance imaging evaluation of congenital dislocation of the hips. Magnetic resonance (MR) images were obtained preoperatively and postoperatively for 12 pediatric patients with congenital dislocation of the hip (CDH). The images were compared with arthrograms and computed tomography scans. The MR images were more accurate in defining soft-tissue anatomy, hip position, and obstructive factors to relocation. MR imaging is an efficient diagnostic tool in CDH. ",15 73,"Tetanus immunization status and immunologic response to a booster in an emergency department geriatric population. STUDY OBJECTIVES: Although effective procedures for the prevention of tetanus have long been available, serosurveys done since 1977 demonstrate that 49% to 66% of the elderly population lacks a protective antitoxin level (more than 0.01 IU/mL). This study was undertaken to assess the tetanus immunization status of patients presenting to an emergency department and to evaluate their immunologic response to a tetanus booster. SETTING: The study was conducted in a tertiary care ED. TYPE OF PARTICIPANTS: The patients enrolled were 65 or more years old and had breaks in their skin barriers. DESIGN: At each patient's initial presentation, pertinent demographic data and tetanus immunization history were recorded. The patient was then followed for 21 days. INTERVENTIONS: Each patient's antitoxin titer was determined on a serum sample by ELISA, and, if required by the Advisory Committee on Immunization Practices criteria, a booster was administered at the first visit. MEASUREMENTS AND MAIN RESULTS: Serum antitoxin assays were repeated on days 7, 14, and 21 after the initial visit until seroconversion (titer more than 0.01 IU/mL). Forty-four patients (55%) had protective levels at initial presentation, and in 36 (45%) the levels were not protective. Age and sex were not predictive of protection. Past military service and a definite history of three or more previous immunizations were good predictors of protection. Of 34 patients who were followed serially for inadequate initial titers, only 19 (56%) seroconverted by day 14. Patients who did not seroconvert were more likely to be older (P less than .05). CONCLUSIONS: This study demonstrated that a significant number of elderly patients lacked an initial protective level of tetanus antitoxin. Of these, 44% failed to seroconvert within 14 days and carried a potential risk of developing tetanus. ",0 420,"Malignant rhabdoid tumor of the liver. A distinct clinicopathologic entity. A malignant rhabdoid tumor occurring as a primary hepatic neoplasm in a six-month-old white infant is reported. It was treated by an attempt at total resection involving right hepatic lobectomy and by chemotherapy with cis-platinum, VP-16, and Adriamycin. Despite this, recurrence of the tumor resulted in the girl's death within three months. The neoplasm showed typical light microscopic features of malignant rhabdoid tumor as well as filamentous cytoplasmic inclusions by electron microscopic examination and staining for both cytokeratin and vimentin by immunohistochemistry. The classic clinicopathologic features of this tumor support the concept that malignant rhabdoid tumors similar to those of the kidney may occur in extrarenal sites. ",3 471,"Biopsy of the breast for mammographically detected lesions. We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001). ",3 2559,"The surgery of juvenile chronic arthritis. An overview. Surgery now has a well-established place in the management of childhood arthritis. However, satisfactory results can only be achieved by a team of medical experts composed of a pediatric rheumatologist, an orthopedic surgeon, an anesthetist, a physiotherapist, and others who are knowledgeable about the particular problems of juvenile chronic arthritis. An aggressive team approach offers the best available help. ",19 1097,"Rat soleus muscle ultrastructure after hindlimb suspension. The aim of the present investigation was to determine, by quantitative electron microscopy, the effects of a 5-wk tail-suspension period on rat soleus muscle ultrastructure. A marked decline (-60%) in muscle mass occurred. The mean fiber cross-sectional area decreased to a greater extent (-75%) than the capillary-to-fiber ratio (-37%), leading to a higher capillary density (+148%) after hypokinesia. The total mitochondrial volume density remained unchanged, whereas the volume density of myofibrils was slightly but significantly reduced (-6%). A shift from subsarcolemmal to interfibrillar mitochondria occurred. Interfibrillar mitochondrial volume density was highest near the fiber border and decreased toward the fiber center. An increase in volume density of satellite cells suggested muscle regenerative events. Soleus atrophy with tail suspension greatly decreases the muscular volume but leaves the ultrastructural composition of muscle fibers relatively unaffected. ",9 2507,"Hyperglycemia-induced B cell toxicity. The fate of pancreatic islets transplanted into diabetic mice is dependent on their genetic background. The role of pancreatic B cell dysfunction in the phase preceding clinical onset of insulin-dependent and non-insulin-dependent diabetes mellitus has been much debated. In this investigation, the impact of a prolonged diabetic environment on pancreatic islet B cells transplanted syngeneically under the kidney capsule of C57BL/6 (B6) and C57BL/Ks (BKs) mice was studied. Alloxan-diabetic mice bearing a subcapsular islet graft insufficient to normalize the blood glucose level were rendered normoglycemic by a second intrasplenic islet graft after various period of hyperglycemia to examine the reversibility of hyperglycemia-induced B cell dysfunction. Using a perfusion technique of the graft-bearing, it was found that both strains of mice exhibited a diminished glucose-induced insulin secretion after 6 wk of hyperglycemia, when compared with normoglycemic mice carrying islet grafts. When normoglycemia was restituted by the splenic graft after 4 or 12 wk, there was a normalization of glucose-stimulated insulin secretion in the renal islet grafts in B6 mice, whereas insulin secretion from the grafted BKs islets remained impaired. Morphometric measurements of the islet grafts demonstrated a 50% reduction in the graft volume in diabetic BKs mice after 12 wk, compared with normoglycemic animals, whereas no such decrease was observed in B6 mice. Islet grafts removed from hyperglycemic mice of both strains exhibited diminished insulin mRNA contents, and in the BKs mice there was also a reduced glucose oxidation rate in the islet grafts in vitro. This metabolic dysfunction can only partly be explained by a reduced graft size. The present findings emphasize the genetic constitution as a decisive factor for the survival and function during a period of sustained stress on a limited B cell mass. ",17 1502,"Abnormal bleeding in the climacteric. In the perimenopausal years, we encounter a situation where the normal diminution in reproductive capacity, with its resulting disruption of the normal menstrual hormonal pattern, coincides with a very real risk of pelvic pathology. Limitation in the ability to diagnose and to treat these patients conservatively has in the past resulted in a high rate of hysterectomy. With increased understanding of the normal physiology of this stage of transition and with improved diagnostic tools, we are now able to come to a definitive diagnosis in most patients. This ability to assure the diagnosis has made it much easier to counsel the patient confidently about the appropriate course of action. We will continue to encounter the problem of hysterectomy for bleeding with no histologic lesion being found. Although reviewers' letters may be considered an unnecessary thorn in the side, the improved practice that has resulted from these efforts gives strong support to their continued activities. We can have confidence that our treatment plan evolved in a logical manner and offers our patients a high probability of benefit at justifiable risk. ",12 2225,"Intraoperative transesophageal versus epicardial ultrasound in surgery for congenital heart disease. Twenty-eight patients (age range, 0.7 to 65 years; median age, 6.1 years) who were undergoing correction for congenital heart disease were entered into a prospective study with both intraoperative transesophageal and epicardial ultrasound to determine the relative values of these techniques before and after bypass surgery. Introduction of the transesophageal probe was successful in 26 patients (93%); children were studied with use of dedicated pediatric transducers. Epicardial studies were performed in all 28 patients. Epicardial studies allowed for higher resolution imaging and a more complete assessment before bypass surgery of the intracardiac morphological condition (ventricular septum and right ventricular outflow tract) than the assessment that was obtained by the transesophageal approach. In the period immediately after bypass surgery, the transesophageal technique allowed a more detailed insight into atrioventricular valve function (valvar regurgitation [five patients] and ventricular inflow patterns) and the continuous monitoring of left ventricular function and volume. Residual interventricular shunting (three patients) or residual outflow tract obstruction (four patients) could not be reliably documented by transesophageal studies. It is concluded that intraoperative transesophageal and epicardial ultrasound in surgery for congenital heart disease are complementary rather than alternative techniques. ",15 2136,"Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia. Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation. ",14 246,"Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, nonobese women. Suppression of serum insulin levels with diazoxide is associated with a decrease in serum testosterone and an increase in serum sex hormone-binding globulin in obese women with the polycystic ovary syndrome. To determine whether physiologic insulin levels play a regulatory role in the androgen status of nonobese women with normal menses, the androgen status of five nonobese normal women was assessed on two occasions: during a control study and after 10 days of oral diazoxide (100 mg, three times daily) administration. Insulin release in response to 100 gm oral glucose administration decreased from 108.0 +/- 28.2 to 49.3 +/- 5.2 nmol.min/L (p = 0.05) after diazoxide administration. However, despite suppression of insulin release, diazoxide administration did not affect serum total testosterone (diazoxide, 0.73 +/- 0.10; control, 0.69 +/- 0.11 nmol/L; p = NS) or sex hormone-binding globulin (diazoxide, 79.7 +/- 16.6; control, 70.2 +/- 12.6 nmol/L; p = NS) concentrations. These observations suggest that physiologic insulin levels in nonobese healthy women do not regulate testosterone metabolism and that diazoxide does not exert a direct or independent effect on serum testosterone or sex hormone-binding globulin levels. ",3 807,"Effects of short-term pancreatic duct obstruction in rats. The short-term effects of rat pancreatic duct obstruction were evaluated and compared with those recently reported to follow obstruction of the rabbit pancreatic duct. In both species pancreatic edema and hyperamylasemia are noted, and the lysosomal hydrolase cathepsin B is redistributed from the lysosome-enriched to the zymogen granule-enriched subcellular fraction. Theoretically, this redistribution phenomenon might lead to digestive enzyme activation because cathepsin B is known to be capable of activating trypsinogen. The hyperamylasemia and pancreatic edema (but not the cathepsin B redistribution) that follow rat pancreatic duct obstruction were increased by infusion of a submaximally stimulating dose of the cholecystokinin analogue cerulein. Administration of the cholecystokinin-receptor antagonist L-364,718 reduced the hyperamylasemia but did not alter the pancreatic edema or cathepsin B redistribution. These observations indicate that cholecystokinin may modulate some but not all of the effects of duct obstruction. Secretin administration increased the degree of pancreatic edema and had no demonstrable protective effect. The rat duct-obstruction model described in this report may prove particularly useful in future studies designed to clarify the early events underlying the development of acute pancreatitis. ",5 963,"Avoiding a wrapped endotracheal tube in laser laryngeal surgery: experiences with apneic anesthesia and metal laser-flex endotracheal tubes. Ninety-one laser laryngeal procedures using the apneic technique of anesthesia were performed in 28 patients between 2 months and 64 years of age. Seventy-two procedures (79%) were performed on children and 19 on adults. There were no complications. Eight laser laryngoscopies were performed using a new metal Laser-Flex endotracheal tube. Obstruction of the endotracheal tube with a mucous plug occurred in one case. The apneic technique described in this paper provides a laser operative field free of an endotracheal tube, virtually eliminating the danger of a laser fire. It is a relatively safe and effective means of performing laser laryngeal surgery. In addition, the Laser-Flex endotracheal tube appears to be an acceptable alternative to a metallic tape-wrapped endotracheal tube. ",7 358,"Squamous cell carcinoma-antigen for detection of squamous cell and mucoepidermoid carcinoma after primary treatment: a preliminary report. This study evaluated the efficacy of using the periodic measurement of the serum level of squamous cell carcinoma antigen (SCC-antigen) for determining the local recurrence and/or metastasis of squamous cell and mucoepidermoid carcinomas after primary treatment. It was found that at the time of clinical recognition of recurrence, the SCC-antigen level was normal, but metastasis to regional lymph nodes or to remote organs generally was accompanied by an increase of SCC-antigen. Changes in the SCC-antigen level with mucoepidermoid carcinoma seemed to be less sensitive than with squamous cell carcinoma. ",3 1428,"Pressure effects on roller pump blood flow during hemodialysis. Accurate measurement of blood flow during hemodialysis is essential to avoid underdialysis. When blood roller pumps are pushed to the high-flow rates demanded by high performance dialyzers, flow may be overestimated. This study examined the effect of inflow (Pa) and outflow (Pv) pressures induced by hemodialysis roller pumps on flow in vitro and in vivo. Blood flow was measured volumetrically, and with an ultrasonic flow probe, whereas Pa was adjusted from -50 to -400 torr and Pv from 50 to 300 torr. Only Pa influenced flow. At -200 torr, true flow measured volumetrically averaged 8.5% +/- 1.3% less than the blood pump revolutions per minute (RPM) meter reading. At -400 torr, the difference was 33.0% +/- 1.9%. There was no visible indication that flow was reduced to less than pump meter readings. Pv, hematocrit, and the source of pump tubing had no significant effect. Flow measured with an ultrasonic transit-time probe during routine hemodialysis in 64 patients was 9.0% +/- 2.7% less than pump meter readings when Pa varied from -180 to -220 torr. Blood pump meter readings greater than 400 ml/min were usually inaccurate because of low Pa. Prepump monitoring of arterial inflow pressure can prevent hidden reductions in blood flow that decrease dialysis efficiency. ",11 3261,"Delta sleep ratio. A biological correlate of early recurrence in unipolar affective disorder. Slow wave sleep abnormalities have long been described in depression but were considered to be nonspecific indicators of psychopathology. Computerized techniques, including amplitude frequency measures and spectral analyses, are permitting new approaches to the examination of delta sleep. Early studies suggested that many depressed patients demonstrate lower delta wave intensity during the first non-rapid eye movement period than the second one. This finding, prominent in middle-aged depressed patients, has led to an examination of the ratio between the first and second non-rapid eye movement periods. This delta sleep measure seems to be a more robust predictor of recurrence than rapid eye movement latency. Analysis of data on 74 patients in a long-term maintenance treatment study for a minimum of 24 months demonstrates that the delta sleep ratio can predict survival time following discontinuation of drug treatment. Individuals with a high delta sleep ratio remain clinically remitted five times longer than those with a low delta sleep ratio. ",22 2067,"Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension. 1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy. 2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye. 3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise. 4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality. ",13 890,"Changes in self-concept during pulmonary rehabilitation, Part 2. This two-part study describes changes in self-concept during pulmonary rehabilitation. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future self-concepts on program admission, on program discharge, and 2 to 6 months after home discharge. In this part of the study item-level quantitative data as well as qualitative data from the counseling session at program discharge are reported. The quantitative data documented detailed changes in self-concept at various stages of pulmonary rehabilitation. Counseling session results indicated that patient involvement in item-level analysis greatly facilitates psychosocial intervention. Findings from this study establish clinical indications for use of the Self-concept Evaluation tool in adult patients with chronic obstructive pulmonary disease. Use of this tool is recommended early in the rehabilitation process. ",7 247,"Autologous antibodies eluted from membrane fragments in human ovarian epithelial neoplastic effusions. III. Cytotoxic potential in vitro and characterization of antigen(s). Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d. ",3 1662,"Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability. This report reviews the applications of tomographic imaging with current and new tracers in assessing myocardial perfusion and viability. Multiple studies with thallium-201 (TI-201) single photon emission computed tomography (SPECT) imaging for the detection of coronary artery disease (CAD) have demonstrated high sensitivity, high rates of normalcy and high reproducibility. In assessing viability, fixed defects are frequently detected in viable zones in 4-hour studies with TI-201 imaging. Redistribution imaging performed 18 to 72 hours after injection or reinjection of TI-201 before 4-hour redistribution imaging has been shown to improve accuracy of viability assessment. TI-201 SPECT studies are limited by the suboptimal physical properties of TI-201, which result in variable image quality. The 2 new technetium-99m (Tc-99m) - labeled myocardial perfusion tracers offer the ability to inject much higher amounts of radioactivity, making it possible to assess ventricular function as well as myocardial perfusion from the same injection of radiotracer. Tc-99m sestamibi has very slow myocardial clearance, which allows for prolonged imaging time and results in image quality superior to that obtained with TI-201 and Tc-99m teboroxime. The combination of minimal redistribution of Tc-99m sestamibi and high count rates makes gated SPECT imaging feasible, and also permits assessment of patients with acute ischemic syndromes by uncoupling the time of injection from the time of imaging. The combination of high image quality and first-pass exercise capabilities may lead to a choice of this agent over TI-201 for assessment of chronic CAD. ",13 128,"American blood donors seropositive for human T-lymphotropic virus types I/II exhibit normal lymphocyte subsets. Recent reports have demonstrated that some lymphocyte subsets are abnormal in Japanese blood donors who are seropositive for human T-lymphotropic virus type I (HTLV-I). To determine if similar changes characterize American blood donors who are seropositive for HTLV-I/II, lymphocyte subsets were measured in 42 HTLV-seropositive and 42 HTLV-seronegative blood donors. The seronegative individuals were matched by age, race, and gender to the seropositive individuals. Peripheral blood mononuclear cells were treated with a panel of 12 monoclonal antibody pairs and then analyzed by two-color flow cytometry. No significant differences were observed between the seropositive and seronegative groups with respect to the absolute number of circulating lymphocytes or the percentages of lymphocytes belonging to the subsets assessed. These subsets included B, T, CD4, and CD8 cells and subpopulations of CD4 and CD8 cells defined by the coexpression of markers that appear (CD25, HLA-DR, CD38) or disappear (Leu 8, CD45RA) after activation. These findings indicate that HTLV-seropositive persons in the American blood donor pool do not exhibit the lymphocyte subset alterations reported for HTLV-I-seropositive blood donors in Japan. ",1 1091,"Platelet monoamine oxidase activity in female migraine patients. Platelet monoamine oxidase activity (MAO) in a group (n = 17) of white, female migraineurs during an acute migraine attack was similar to both the values obtained for the same group of patients two to three weeks after the headache episode (pain-free period) and to the results obtained for a group (n = 18) of sex and race-matched, age-comparable, drug-free healthy volunteers (blind study; substrate p-tyramine, 38.7 +/- 5.7, 41.9 +/- 8.8 and 43.0 +/- 3.4 or p-methoxybenzylamine, 178.9 +/- 11.3, 177.2 +/- 6.9 and 181.0 +/- 9.7 nmole/hr/10(9) platelets +/- SD respectively). With each patient serving as its own control, MAO activity during the migraine episode and when pain-free failed to show a significant trend. Neither a number of other medical conditions nor the use of several medications appeared to significantly influence our results. The present work, while dealing only with a small but well defined patient population, argues against the possible usefulness of platelet MAO activity as a biological marker for migraine headaches. ",9 1295,"Visual results and complications of transsclerally sutured intraocular lenses in penetrating keratoplasty. We retrospectively reviewed the charts of 56 consecutive patients who had undergone penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens. Follow-up ranged from 3 to 28 months (mean, 11.1 months). Postoperative visual acuity improved in 46 patients (82%), remained the same in eight (14%), and worsened in two (3.6%). In 32 patients with at least 10 months' follow-up, best corrected visual acuity as measured with a pinhole or hard contact lens was 20/40 or better in 12 (38%), 20/50 to 20/10 in 10 (31%), and 20/200 or worse in 10 (31%). Problems with lens decentration, tilt, or scleral suture-related infections were minimal. Glaucoma was the msot common cause of decreased vision in patients with 10 or more months' follow-up. Three patients (5.4%) developed rhegmatogenous retinal detachments early in the postoperative course. ",10 1589,"Right coronary artery injury during tricuspid valve annuloplasty. An unusual complication after tricuspid valve annuloplasty is described where a ring suture ligated right coronary artery and precipitated myocardial infarct and patient death. The need for caution to prevent this complication with such surgery is emphasized. ",13 1637,"Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion. Thrombolysis and Angioplasty Study Group. Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population. ",13 2312,"What to do about pruritus scroti. Pruritus scroti is a common clinical disorder that is caused by various inflammatory disorders, infections, infestations, and neoplasms. Laboratory evaluation, including bacterial and fungal cultures, microscopic examination, skin biopsies, and measurement of blood glucose levels, is useful in establishing the diagnosis. Management of pruritus scroti includes avoidance of irritants, allergens, and restrictive clothing and use of topical and systemic agents that provide both symptomatic relief and specific treatment of the underlying cause. ",16 3221,"Tracheotomy in the first year of life. Much has been written concerning complications of pediatric tracheotomies, but few studies have reviewed the complication rates of tracheotomies performed in the first 12 months of life. We reviewed the records of 60 patients who underwent tracheotomy in the first year of life between 1976 and 1988. This study includes 30 full-term infants and 30 premature infants, 16 of whom were very low birth weight preterm infants (less than or equal to 32 weeks' gestation and less than 1,500 g birth weight). Overall complication rates were 3% intraoperative, 13% early postoperative, and 38% late postoperative. The early postoperative complication rate in preterm infants was nearly double that of full-term infants. The late postoperative complication rate of patients undergoing tracheotomy for airway obstruction was more than double that of patients requiring tracheotomy for pulmonary indications. Duration of tracheotomy, however, was felt to be the most important factor in the development of a late postoperative complication. ",22 479,"Immunocytochemical profile of benign and carcinomatous effusions. A practical approach to difficult diagnosis. One of the great challenges in the cytodiagnosis of effusions is the distinction between reactive mesothelium/histiocytes and cancer cells. This is notably true in patients having undergone radiation and/or chemotherapy. To establish whether monoclonal antibodies (MoAbs) could be used as reliable diagnostic adjuvants, the authors retrospectively and blindly studied 60 cases diagnosed by standard cytologic criteria (malignant, benign, and equivocal), with a panel of seven readily available MoAbs (cytokeratins, vimentin, EMA, B72.3, alpha-CEA, HMFG-2, and Leu-M1) and the lectin Ulex europaeus I. All 18 (100%) malignant cases showed reactivity with EMA and HMFG, whereas 17 (95%) and 11 (61%) reacted with B72.3 and alpha-CEA, respectively. Combinations of (1) EMA + B72.3, (2) EMA + alpha-CEA, and (3) EMA + alpha-CEA + B72.3 displayed positivity in 17 (95%), 11 (61%), and 10 (56%) malignant cases, respectively. Of the 18 benign cases, 7 reacted with HMFG and 2 each with EMA and B72.3. Only one case (5.5%) reacted with both EMA and B72.3. Based on these results, the 24 equivocal cases were regrouped into 14 malignant and 10 benign cases. Follow-up effusions obtained within the ensuing three months in all these patients allowed the authors to unequivocally confirm the diagnosis in all but five. The combination of EMA and B72.3 MoAbs detected malignant cells in 95% of the cases, with a 3.5% incidence of false positive cases in this study. A panel of EMA, B72.3, and alpha-CEA MoAbs should prove the most useful and simple approach to the correct diagnosis in most questionable effusions. Some of the potential pitfalls are discussed. ",3 1965,"Inotropic effects of angiotensin II on human cardiac muscle in vitro. The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure. ",13 1956,"Postinfarction ventricular septal defect repair: retrospective thoughts and historical perspectives. Evolution of surgical techniques for repair of postinfarction ventricular septal rupture initially involved differentiation of these lesions from prior experience with surgical approaches to congenital ventricular septal defects, which were in the main not applicable. Second, understanding of the differing anatomical locations of postinfarction ventricular septal defects required innovation in terms of the location of the cardiotomy and type of repair necessary to achieve a successful result in any given patient. The gradual appreciation of different clinical courses pursued by patients after postinfarction ventricular septal rupture both in terms of location of the defect and the degree of right ventricular functional impairment has led to increased urgency relative to the timing of surgical repair. The incorporation of specific anatomical concepts of surgical repair and better understanding of the time course of physiological deterioration of patients can ultimately lead to an integrated approach aimed toward improved salvage of patients suffering this catastrophic complication of acute myocardial infarction. ",13 1992,"Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease. To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Women's Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis. ",13 2309,"The natural history of Peyronie's disease. The natural history of Peyronie's disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronie's disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression. We found no statistically significant association between disease duration and spontaneous improvement in penile bending. A similar lack of statistical significance was found when improvement in a variety of categories was compared in patients who received no therapy versus those who received a variety of conventional medical therapies. ",16 608,"The effect of local deep microwave hyperthermia on experimental zymosan-induced arthritis in rabbits. The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis. ",4 1967,"Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy. To investigate the incidence of abnormal exercise blood pressure responses in hypertrophic cardiomyopathy (HCM) and the potential role of hemodynamic instability as a mechanism of sudden death, 129 consecutive patients with HCM underwent maximal symptom-limited treadmill exercise testing with blood pressure recording. Four patterns of blood pressure response were observed. Forty-three patients had significant exercise hypotension, with either a continuous fall in systolic blood pressure (n = 5) from the start of exercise or a sudden fall in systolic blood pressure (20-100 mm Hg; mean, 40 mm Hg) from the peak value (n = 38), 23 patients had a normal response during exercise but an abnormal blood pressure response in the recovery period, and the remaining 62 patients demonstrated a normal blood pressure response. Patients with exercise hypotension were younger (33 +/- 14 versus 46 +/- 14 years) and more of them had a family history of HCM and sudden death compared with those with a normal blood pressure response (15 of 43 versus 6 of 62 patients). Similarly, the 23 patients with abnormal recovery blood pressure responses were younger (43 +/- 16 versus 46 +/- 14 years) and had a higher incidence of a family history of sudden death (10 of 24 versus 6 of 62 patients). Left ventricular cavity dimensions were smaller in those with exercise hypotension, but 11 other clinical, echocardiographic, and arrhythmic variables were similar. To assess the mechanism of exercise hypotension, 14 patients who demonstrated exercise hypotension and 14 symptomatic patients with a normal exercise blood pressure response underwent invasive hemodynamic exercise testing. ",13 2461,"The NT 1311 polymorphism of G6PD: G6PD Mediterranean mutation may have originated independently in Europe and Asia. A polymorphic site exists in exon 11 of G6PD: in the wild-type enzyme, nucleotide (NT) 1311 is a C, but is some individuals from diverse populations a T is present instead. Nine of 54 X chromosomes from Europeans of mixed origins, nine of 41 X chromosomes of Ashkenazi Jewish subjects, three of 18 X chromosomes of Sicilians, five of 20 African X chromosomes, and nine of 20 Asian Indian X chromosomes had the mutant genotype. In contrast, the mutation was found in only three of 59 Oriental X chromosomes and in three of 30 Central/South American X chromosomes. The mutation was absent from four samples of chimpanzee DNA. Twenty-one of 22 male subjects from Mediterranean countries who had the G6PD Mediterranean 563T genotype investigated in the present study or reported previously had a T at NT 1311. Only one had the normal C at NT 1311. In contrast, both G6PD Mediterranean563T males from the Indian subcontinent had the normal C at NT 1311. These findings suggest that the same mutation at nucleotide 563 giving rise to G6PD Mediterranean may have arisen independently in Europe and in Asia. ",17 1054,"Resistance to d-tubocurarine in lower motor neuron injury is related to increased acetylcholine receptors at the neuromuscular junction The hypothesis that lower motor neuron injury, with its associated proliferation of acetylcholine receptors (AChR), induces resistance to the neuromuscular effects of d-tubocurarine (dTC) was tested in the rat. The left gastrocnemius was denervated by a 75-80% lesion of the sciatic nerve. The effective dose for 95% twitch depression (ED95) was studied in the denervated gastrocnemius and compared to the contralateral undenervated and sham-injured (control) gastrocnemius muscles approximately 2 weeks after injury. The AChR number was quantitated by the specific ligand 125I-alpha-bungarotoxin (125I-alpha-BT). Plasma dTC concentrations, measured by high-performance liquid chromatography (HPLC), were correlated to twitch tension during spontaneous recovery from neuromuscular blockade in the denervated animal. The ED95 (mean +/- SE) of dTC for the denervated leg was significantly (P less than 0.05) higher (0.26 +/- 0.06 mg.kg-1) than contralateral (0.16 +/- 0.03) and sham-operated left (0.13 +/- 0.03) legs. The twitch tension recovered to 50% of control twitch height at significantly (P less than 0.05) higher plasma dTC concentrations in the denervated (0.78 micrograms.ml-1) compared to contralateral (0.24 micrograms.ml-1) limb. The AChR number was significantly increased in the denervated limb (1041 +/- 96 fmol.mg protein-1) compared to contralateral right (109 +/- 4) and control left limb (113 +/- 11). There was a significant (P less than 0.05) positive correlation (R2 = 0.73) between ED95 and AChR number; that is, 73% of the variability in ED95 could be explained by changes in AChR. This study, therefore, confirms the hypothesis that proliferation of AChR after nerve denervation results in resistance to the neuromuscular effects of dTC. ",9 1187,"Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography. We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset. ",9 3184,"Possible mechanisms limiting N-methyl-D-aspartate receptor overactivation and the therapeutic efficacy of N-methyl-D-aspartate antagonists. Cytotoxic overactivation of neuronal N-methyl-D-aspartate receptors is postulated to contribute to the pathogenesis of neuronal loss in hypoxia-ischemia. However, several events associated with hypoxia-ischemia may limit N-methyl-D-aspartate receptor-mediated injury. Perhaps the most important of these events is the development of extracellular acidosis. These limiting events may help explain why N-methyl-D-aspartate receptors contribute to injury more in focal ischemia or hypoxia in vitro than in global ischemia. ",22 2567,"Amyloidosis in saphenous vein aortocoronary bypass grafts. A patient in whom idiopathic amyloidosis of aortocoronary saphenous vein grafts was found at autopsy two years after myocardial revascularization due to coronary atherosclerosis is reported. Idiopathic generalized immunocyte derived amyloidosis extensively studied at autopsy was obviously present at the time of surgery although it remained unnoticed macroscopically in the inserted graft. It appears that simultaneously with arterialization further deposition and also significant redistribution of amyloid within the walls of the vein grafts additionally took place after their insertion. It seems interesting that in spite of the amyloidosis the grafts functioned well and were found patent two years after surgery. ",19 1345,"Validity of creatinine clearance estimates in the assessment of renal function. In clinical practice, estimations of renal function are commonly used to calculate the appropriate dose for drugs that are renally cleared. Continuous-infusion inulin clearance (CLIN), 4-hour creatinine clearance (CLCR,m), and 24-hour creatinine clearance (CLCR,a) were measured in 109 subjects (86 men and 23 women) with varying degrees of stable renal function (CLIN, 6 to 209 ml/min) and compared with CLCR values as predicted by five equations on the basis of plasma creatinine concentrations, age, weight, and/or height. The CLCR,m was positively correlated with CLIN (r = 0.92; p less than 0.0001) but exceeded CLIN by 15% between the range of 30 and 209 ml/min (CLIN). Similarly, CLCR,a correlated well with both CLCR,m (r = 0.84; p less than 0.0005) and CLIN (r = 0.84; p less than 0.0001). The relative role of tubular secretion in the overall clearance of creatinine increased with declining CLIN and exceeded 40% when CLIN was below 30 ml/min. CLCR estimated by the Cockcroft-Gault and Mawer methods did not significantly differ from either CLCR,m or CLCR,m, whereas the other equations generally underestimated CLCR. Among the numerous mathematical equations, CLCR as estimated by the method proposed either by Mawer or Cockcroft and Gault was the best predictor of CLIN (CLIN = 1.05CLRCR - 18.38 or CLIN = 1.12CLCR - 20.60, respectively; r = 0.81; p less than 0.0001). The present data support the use of estimator equations proposed by Cockcroft and Gault or Mawer for rapid estimation of renal function in the clinical setting. ",11 1494,"Frequency and costs of diagnostic imaging in office practice--a comparison of self-referring and radiologist-referring physicians BACKGROUND. To assess possible differences in physicians' practices with respect to diagnostic imaging, we compared the frequency and costs of imaging examinations as performed by primary physicians who used imaging equipment in their offices (self-referring) and as ordered by physicians who always referred patients to radiologists (radiologist-referring). METHODS. Using a large, private insurance-claims data base, we analyzed 65,517 episodes of outpatient care by 6419 physicians for acute upper respiratory symptoms, pregnancy, low back pain, or (in men) difficulty urinating. The respective imaging procedures studied were chest radiography, obstetrical ultrasonography, radiography of the lumbar spine, and excretory urography, cystography, or ultrasonography. RESULTS. For all four clinical presentations, the self-referring physicians obtained imaging examinations 4.0 to 4.5 times more often than the radiologist-referring physicians (P less than 0.0001 for all four). For chest radiography, obstetrical ultrasonography, and lumbar spine radiography, the self-referring physicians charged significantly more than the radiologists for imaging examinations of similar complexity (P less than 0.0001 for all three). The combination of more frequent imaging and higher charges resulted in mean imaging charges per episode of care that were 4.4 to 7.5 times higher for the self-referring physicians (P less than 0.0001). These results were confirmed in a separate analysis that controlled for the specialty of the physician. CONCLUSIONS. Physicians who do not refer their patients to radiologists for medical imaging use imaging examinations more frequently than do physicians who refer their patients to radiologists, and the charges are usually higher when the imaging is done by the self-referring physician. From our results it is not possible to determine which group of physicians uses imaging more appropriately. ",12 959,"Systems architecture for quantification of dynamic myoelectric and kinematic activity of the human vocal tract. This paper describes a systems architecture useful for scientific investigations that require the acquisition and analysis of multiple, time-synchronous signals in large volume. The architecture has recently been developed by this group to enhance our capability to research and quantify central nervous system function in the production of normal and pathologic speech. The architecture utilizes modern advances in desktop microcomputers and has been designed so that vocal motor control laboratories (or similar settings) with modest funding can more fully participate in comprehensive investigations of speech production. Research experiments organized with this architecture may involve many more subjects and measures than previously possible without significant increases in time and personnel resources. This paper will demonstrate the technique and practicality of this architecture as it is being used to successfully guide research to map hierarchic central nervous system regions of involvement in two speech disorders: spasmodic dysphonia and stuttering. The architecture has broad usefulness to many areas of otolaryngology and health science. ",7 2268,"Autoantibodies from patients with localized and generalized bullous pemphigoid immunoprecipitate the same 230-kd keratinocyte antigen. Two patients demonstrating the typical clinical, histologic, and immunopathologic features of nonscarring localized bullous pemphigoid are described. These patients possess circulating IgG autoantibodies that bind the epidermal side of 1.0-mol/L sodium chloride-split human skin in indirect immunofluorescence microscopy. Immunnoprecipitation studies demonstrate that these patients have circulating autoantibodies that immunoprecipitate the same 230-kd bullous pemphigoid antigen that is precipitated by autoantibodies from patients with generalized bullous pemphigoid. These findings indicate that localized bullous pemphigoid is a true clinical variant of generalized pemphigoid rather than a separate nosologic entity. ",16 2443,"The accuracy of self-reports of physical activity. This investigation determined the accuracy of self-reports of physical activity compared to observations obtained surreptitiously. Subjects were 44 adults engaged in 1 h of their preferred physical activity while actual activity levels were surreptitiously obtained and compared to immediate self-reported estimates of physical activity. Results indicated that subjects were moderately accurate in recalling their physical activity levels (R = 0.62) but underestimated sedentary activities and overestimated aerobic activities by over 300%. Males overestimated their activity relative to females, and obese subjects underestimated their activity levels compared to normal-weight subjects. Finally, a number of two-way interactions that moderated the accuracy of those subjects engaging in high chronic levels of physical activity were observed. ",17 1634,"Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II) The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled multicenter trial. Eight hundred seventy-eight patients started treatment with verapamil, 360 mg/day, and 897 patients with placebo. Treatment started in the second week after admission and continued for up to 18 months (mean 16 months). Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group. The 18-month mortality rates were 11.1 and 13.8% (p = 0.11, hazard ratio, 0.80; 95% confidence limits, 0.61 to 1.05), and major event rates 18.0 and 21.6% (p = 0.03, hazard ratio, 0.80; 95% confidence limits, 0.64 to 0.99) in the verapamil and placebo groups, respectively. In patients without heart failure in the coronary care unit the mortality rates were 7.7% in the verapamil group and 11.8% in the placebo group (p = 0.02, hazard ratio, 0.64; 95% confidence limits, 0.44 to 0.94), and major event rates 14.6 and 19.7% (p = 0.01, hazard ratio 0.70; 95% confidence limits (0.52 to 0.93). In patients with heart failure the mortality rates were 17.9 and 17.5% (p = 0.79, hazard ratio, 1.05; 95% confidence limits, 0.72 to 1.54), and major event rates 24.9 and 24.9% (p = 1.0, hazard ratio 0.98; 95% confidence limits 0.72 to 1.39). Long-term treatment with verapamil after an acute myocardial infarction caused a significant reduction in major events, and the positive effect was found in patients without heart failure. ",13 157,"B cell responses to paramyosin. Isotypic analysis and epitope mapping of filarial paramyosin in patients with onchocerciasis. To examine the fine specificity of the human immune response to filarial paramyosin, the antigenicity of an expressed rcDNA (2.55 kb) of Dirofilaria immitis paramyosin was detailed by ELISA. Using sera from patients infected with Onchocerca volvulus, we analyzed both the entire paramyosin molecule and six subcloned fragments for their IgG, IgG subclasses, and IgE responses. Patients from both Guatemala (64% positive) and Ghana (100% positive) reacted to paramyosin with specific IgG levels above normal controls. Although there was no anti-paramyosin subclass restriction common to all patients, the IgG3 response in the Ghananians was significantly greater than that of Guatemalans (p less than 0.001). IgE anti-paramyosin responses showed positive correlations with IgG2 (p less than 0.001), IgG4 (p less than 0.002), and IgG1 (p less than 0.04) responses. Epitope mapping using the IgG response to the six subclones demonstrated preferential recognition of the amino terminal end of the molecule (nucleotides 1 to 360). IgG2 reactivity was clearly localized to the most amino-terminal 120 amino acids, and the IgG4 antibodies recognized amino acids immediately adjacent to this fragment. These studies examining the fine specificity of anti-filarial immune reactions should provide a method for understanding how parasites either evade or induce host immune responses. ",2 666,"Biomechanics of mammalian terrestrial locomotion. Mammalian skeletons experience peak locomotor stresses (force per area) that are 25 to 50% of their failure strength, indicating a safety factor of between two and four. The mechanism by which animals achieve a constant safety factor varies depending on the size of the animal. Over much of their size (0.1 to 300 kilograms), larger mammals maintain uniform skeletal stress primarily by having a more upright posture, which decreases mass-specific muscle force by increasing muscle mechanical advantage. At greater sizes, increased skeletal allometry and decreased locomotor performance likely maintain stresses constant. At smaller sizes, skeletal stiffness may be more critical than strength. The decrease in mass-specific muscle force in mammals weighing 0.1 to 300 kilogram indicates that peak muscle stresses are also constant and correlates with a decrease in mass-specific energy cost of locomotion. The consistent pattern of locomotor stresses developed in long bones at different speeds and gaits within a species may have important implications for how bones adaptively remodel to changes in stress. ",4 26,"Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization. We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment. ",0 1321,"Confronting cisternae presenting as intracytoplasmic inclusions in monocytes. Small gray-blue intracytoplasmic inclusions were noted in the peripheral monocytes and neutrophils from a patient with renal failure. Ultrastructural analysis revealed confronting cisternae within the cytoplasm. The authors submit a case report to introduce a previously undescribed morphologic feature of leukocytes that may be mistaken at the light microscopic level for Dohle bodies or other inclusions. ",11 1356,"Diagnostic use of angiotensin converting enzyme (ACE)-inhibited renal scintigraphy in the identification of selective renal artery stenosis in the presence of multiple renal arteries: a case report. In patients with renovascular hypertension, it is unknown whether the angiotensin converting enzyme-(ACE) inhibited renal scan will identify stenosis of a segmental branch of a single renal artery or of an accessory artery where multiple renal arteries are present. Since multiple renal arteries may be present in approximately 25% of all individuals, it will be important to establish whether the ACE-inhibited renal scan is useful in this population. We report a case of stenosis involving a renal artery in a patient with multiple renal arteries, successfully identified by ACE-inhibited renal scintigraphy. ",11 1656,"Detection and assessment of unstable angina using myocardial perfusion imaging: comparison between technetium-99m sestamibi SPECT and 12-lead electrocardiogram. Forty-five studies using technetium-99m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) were performed on patients hospitalized for spontaneous chest pain suggestive of myocardial ischemia. The studies were done after an injection during an episode of chest pain and a repeated injection when the patients were free of pain. All patients were hospitalized with a presumed diagnosis of unstable angina, and none had evidence of a previous myocardial infarction. The presence of a perfusion defect observed with Tc-99m sestamibi injected during chest pain had a 96% sensitivity and a 79% specificity for the detection of significant coronary artery disease (stenosis greater than or equal to 50%) on subsequent angiography. When the criterion of a larger perfusion defect during pain compared to absence of pain was used, the sensitivity was 81% and the specificity was 84%. In contrast, transient electrocardiographic ischemic changes during pain had a sensitivity of 35% and a specificity of 68%; electrocardiographic changes during or outside episodes of chest pain had a sensitivity of 65% and a specificity of 63% for the diagnosis. Tc-99m sestamibi SPECT represents a reliable noninvasive diagnostic tool that could aid in the diagnosis of myocardial ischemia in patients with spontaneous chest pain and provide additional information to that provided by the electrocardiogram. ",13 2110,"Clinical use of the Berlin Biventricular Assist Device as a bridge to transplantation. The Berlin Artificial Heart System/Biventricular Assist Device (BVAD) was used in 38 patients. 1) Twenty-eight patients were awaiting cardiac transplantation (Tx) (age 23-56 yrs). All patients had contraindications not allowing immediate Tx. 2) Five patients were emergency cases not on our Tx list (postcardiotomy cardiac failure, acute myocarditis) (age 28-59). 3) Five patients were post Tx patients with graft failure (age 22-52). Extracorporal circulation was used for implantation of the BVAD. In group 1, 21 of 28 patients (pts) recovered, and all were subsequently transplanted after 6 hours to 39 days, when all organ function was restored. In 7 pts, mechanical circulation was terminated after 1-40 days because of further deterioration. Five of the transplanted pts died, 14 pts survived (greater than 30 days), and 2 pts were just transplanted with satisfactory postoperative courses. Of group 2 and 3 pts, two were successfully weaned. In one patient the allograft recovered after 11 days of support. ",13 2263,"Marfan syndrome in China: a collective review of 564 cases among 98 families. This is a collective review of 564 patients with Marfan syndrome among 98 pedigrees reported from 18 provinces and cities in China over a 37-year period from 1951 to 1987. A positive family history of Marfan syndrome was found in 74.3% of the patients: the mode of inheritance was dominant in 73.8% and recessive in 0.5%. Sporadic cases occurred in 25.7%. A screening of 29,067 children found five children with Marfan syndrome, giving a prevalence of 17.2 per 100,000 of the population, a gene frequency of 8.61 per 100,000 genes, and a penetrance of 71.69%. Pleiotropy was clear in these cases: arachnodactyly in 77%, ectopia lentis in 86.8%, and dilated aortic root in 80.1%. Chromosome examination showed no regular aberrations except in a family of five in whom a giant-satellited chromosome 14 was found in three afflicted members but not in the two unaffected relatives. The high prevalence of aortic root dilation in Marfan syndrome makes echocardiography the most useful and practical means of diagnosis. Close follow-up and regular echocardiographic evaluation are indicated not only in patients with Marfan syndrome but also in their families, for both diagnostic and therapeutic purposes. ",16 131,"Are stressful life events risk factors for herpes zoster? To determine if psychologically stressful life events are risk factors for herpes zoster, we conducted a case-control study of zoster and self-reported recent negative life events and major changes in spousal relationships. The subjects were 101 healthy community-dwelling cases of zoster and 101 healthy controls matched for age, sex, and race and generated by random digit dialing. The Geriatric Scale of Recent Life Events was administered to case and control subjects, and additional questions were asked regarding the perception of the life event. The results showed that case subjects experienced negative life events significantly more often than subjects in the control groups in the 2 months before zoster onset by analysis of discordant pairs (26 versus 10, odds ratio 2.60, 95% confidence interval [CI] 1.13, 6.27, P = .012), 3 months before (29 versus 11, odds ratio 2.64, 95% CI 1.20, 6.04, P = .007), or 6 months before (35 versus 16, odds ratio 2.00, 95% CI 1.04, 3.93, P = .012). The mean number of total life events was significantly higher in cases at 6 months before zoster (case means = 2.64, control means = 1.82, P = .008), but there were no significant differences at 2, 3, or 12 months before. There were no significant differences between case subjects and control subjects for spousal events, or any given single life event. In conclusion, we found that whereas patients with herpes zoster experienced the same kinds of life events in the year preceding the illness as did control subjects, recent events perceived as stressful were significantly more common among patients with zoster. ",1 438,"Needle-localized mammographic lesions. Results and evolving treatment strategy. From January 1981 to December 1987, 932 needle-localization breast biopsies were performed at our institution for mammographically detected abnormalities. We reviewed 531 needle-localization breast biopsy procedures performed during two periods (January 1981 to June 1984, n = 311; and January to August 1987, n = 220) to compare results and treatment patterns, and to determine the prevalence of the missed lesions. Mammographic abnormalities detected on routine screening accounted for a larger proportion of needle-localization breast biopsies in the later series (94 [30%] of 311 vs 94 [43%] of 220). However, the rate at which carcinoma was identified remained constant at 29% as did the percentage of cancers that were invasive (46% vs 51%). Overall, the rate of malignant diagnoses after needle-localization breast biopsy was lowest in asymptomatic women undergoing routine screening mammography (44 [24%] of 188) and significantly higher in women undergoing mammographic follow-up of the contralateral breast after treatment for breast cancer (28 [43%] of 65). There were seven missed lesions in 531 needle-localization breast biopsies, necessitating a second procedure in six and interval mammograms in one. ",3 2501,"Developmental adaptations in cytosolic phosphate content and pH regulation in the sheep heart in vivo. This study examines adaptations in myocardial cytosolic phosphate content and buffering capacity that occur in vivo as a function of development. Phosphate metabolites were monitored in an open chest sheep preparation using a 31P magnetic resonance surface coil over the left ventricle. Newborn lambs (aged 4-9 d, n = 5) underwent exchange transfusion with adult blood to reduce blood-borne 2,3-diphosphoglycerate contamination of the heart monophosphate and phosphomonoester resonances, thus allowing determination of these phosphate concentrations. The blood-exchanged newborns and mature controls (aged 30-60 d, n = 5) were infused with 0.4 N hydrochloric acid to decrease pH from greater than 7.35 to less than 7.00. Simultaneously, intracellular and extracellular pH were determined from the chemical shifts of the respective phosphate peaks and compared to arterial blood pH. Findings were as follows: (a) diphosphoglycerate contribution to the cardiac spectrum was found to be negligible, (b) significant decreases in cytosolic phosphate (P less than 0.03) and phosphomonoester (P less than 0.01) content occurred with maturation, and (c) large decreases in extracellular pH (greater than 0.5 U) in both groups were similarly associated with only small changes in intracellular pH (less than 0.1 U). Change in cytosolic phosphate content implies that alterations occur in the phosphorylation potential with resulting effects on regulation of myocardial respiration, and cardiac energetics. ",17 2166,"Cytokine production (IL-1 alpha, IL-1 beta, and TNF alpha) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin's disease, and in non-Hodgkin's lymphomas. An immunocytochemical study. Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1 alpha, and with monoclonal antibodies directed to IL-1 alpha (Vmp18), IL-1 beta (Vhp20 and BRhC3), and tumor necrosis factor alpha (TNF alpha) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1) by endothelial cells. Cells containing IL-1 and/or TNF alpha were detected mainly in pathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease, in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1 alpha was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 beta were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1 beta even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor alpha (TNF alpha) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLA-DR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNF alpha production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells. ",14 964,"Trends in lung cancer incidence and mortality--United States, 1980-1987 [published erratum appears in MMWR Morb Mortal Wkly Rep 1990 Dec 14;39(49):906] Lung cancer is the most common fatal malignant neoplasm in the United States. Based on current smoking patterns, the substantial public health burden of smoking-related lung cancer will continue during the next several decades. This report describes trends in lung cancer incidence from 1980 through 1986 and lung cancer mortality from 1980 through 1987. ",7 2885,"Coding external causes of injury (E-codes) in Maryland hospital discharges 1979-88: a statewide study to explore the uncoded population. We examined the trends in hospital discharge E-coding in Maryland over a 10-year period. The overall proportion of E-coded discharges has increased from 40 percent in 1979 to 55 percent in 1988. E-coding was lower in the severely injured, the elderly, and patients with long hospital stays. Our findings demonstrate that E-code reporting varies because of the limited number of data fields available for coding of discharge diagnoses. Universal, systematic reporting of E-codes in hospital discharge data is essential if these data are to provide critically needed information about nonfatal injuries. Hospital discharge data formats should contain separate fields for E-codes and the use of these codes, we believe, should be mandated. ",20 126,"Measles in Israel, the West Bank, and Gaza: continuing incidence and the case for a new eradication strategy. Measles continues to occur in epidemic waves in Israel, Gaza, and the West Bank, causing morbidity and mortality. In Israel, immunization of infants against measles began in 1967, and 90% had been immunized by the mid-1980s. In Gaza and the West Bank, where immunization of infants against measles began in 1973 and 1976, respectively, the immunization rate reached 75% in the late 1970s and increased to greater than 90% in the 1980s. Measles epidemics, which previously had occurred in 5- to 7-year cycles, occurred every 2-4 years in the 1980s and affected individuals who were older than those affected in previous years. Israel's commitment to eradicating measles by 1992 will require a substantially expanded immunization program in comparison with the traditional program that requires immunization of infants alone. The benefits of several alternative immunization strategies considerably exceed their costs. A new, two-dose immunization will be needed as a minimal strategy, and a campaign for administering booster doses to school-aged children may be required as well to achieve control and eradication of measles. Measles is a serious but preventable public health problem; appropriate strategies must be devised by national and international public health officials to control the disease in developing and developed countries. ",1 912,"Heterogenous amplification of myc family oncogenes in small cell lung carcinoma. One hundred forty-two foci of small cell lung carcinoma (SCLC) from 47 patients were examined for amplification of myc family oncogenes (c-myc, N-myc, and L-myc), by dot blot hybridization using formalin-fixed and paraffin-embedded materials which were resected surgically or obtained at autopsy. Some selected patients were also examined by in situ hybridization. Amplification of myc family genes was detected in 11 patients (23.4%) (c-myc in one, N-myc in five, and L-myc in five). Two of the 11 patients (one with N-myc and one with L-myc) had heterogenously amplified clones. In the patient with N-myc amplification, amplification was detected in metastatic tumors in the pancreas, lung, and pleura, but not in the liver and lymph node metastases. In the primary tumor, areas with and without N-myc amplification were seen. In the patient with L-myc amplification, although amplification was not detected in the surgically resected primary lesion, mediastinal lymph node metastatic lesions obtained at autopsy showed L-myc gene amplification. These two cases, together with previously reported evidence, suggest that myc gene amplification plays an important role in malignant progression, rather than development, of SCLC. In Stage III and IV groups, patients with over ten-fold myc gene amplification were suggested to survive for a shorter time than patients without such amplification (P = 0.06). ",7 943,"Virologic and pathogenetic aspects of cytomegalovirus infection. Cytomegalovirus (CMV) is a ubiquitous agent that rarely causes disease in immunocompetent humans but is an important cause of morbidity and mortality in the immunocompromised. A number of host and viral factors are associated with pathology following CMV infection. CMV can be found at many sites in the body but only causes disease at some of these and then only in certain patient populations. In some situations the mechanism underlying disease is direct viral replication, but in others, particularly CMV pneumonitis in allogeneic transplant recipients, an immunopathologic basis is strongly implicated. An important factor in the pathogenesis of infection and the expression of symptomatic disease is the source of CMV infection-whether it arises from an exogenous source or is due to reactivation of latent endogenous virus. Exogenous infection can occur in previously seronegative individuals or in those with prior exposure to the virus. In renal transplant recipients both types of exogenous infection have been associated with disease. Another factor that affects the interaction between CMV and its host is the modulating effect of the virus on the host immune response, the mechanism of which remains unknown. ",7 1693,"Immunohistochemical study of fibronectin in experimental myocardial infarction. Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing. ",13 939,"Dyspnea. A multidimensional model of dyspnea that includes sensation, perception, distress, response, and reporting components is presented. Assessment tools currently available are evaluated as are recent research findings for pharmacologic, oxygen, physical, and psychologic treatments. This article concludes by suggesting a role for the nurse in dyspnea amelioration. ",7 1026,"Chondrogenic potential of tragal perichondrium: a cause of hearing loss following stapedectomy. Tragal perichondrium is a widely used tissue seal in the oval window following stapes surgery. Autogenous and easily accessible, it is a suitable substance to cover the vestibule in total stapedectomy, and to seal around the prosthesis in small-fenestra stapedotomy. The incidence of complications from the use of perichondrium in this manner is exceedingly low. We report a case where tragal perichondrium in the oval window resulted in the proliferation of cartilage. The cartilage displaced the stapes prosthesis, resulting in a conductive loss. Although the chondrogenic potential of perichondrium is known, we are not aware of other reports implicating this as a cause of failure in stapes surgery. The pertinent clinical and experimental literature regarding chondrogenesis is reviewed. This information suggests that the formation of cartilage from perichondrium in the oval window might be influenced by mechanical trauma and tissue orientation. ",8 2327,"IL-1 regulation of transin/stromelysin transcription in rheumatoid synovial fibroblasts appears to involve two antagonistic transduction pathways, an inhibitory, prostaglandin-dependent pathway mediated by cAMP, and a stimulatory, protein kinase C-dependent pathway. IL-1, like other agents that have been shown a capacity to induce protein kinase C, is a potent transcriptional activator of the metalloproteinase, stromelysin, in synovial and other fibroblasts. cAMP has been shown to inhibit stromelysin transcription in fibroblasts of nonsynovial origin, and is regarded as an important second messenger for IL-1. In addition to stimulating metalloproteinase transcription, IL-1 also induces PGE2 production in synoviocytes. We determined that rIL-1 alpha led to the time-dependent accumulation of intracellular cAMP in serum-starved rheumatoid synovial fibroblasts, and that the effect was blocked by indomethacin. The cAMP agonists forskolin, 3-isobutyl-1-methylxanthine, and PGE2 suppressed the IL-1 induction of stromelysin; conversely, indomethacin superinduced IL-1-elicited stromelysin mRNA. These results were recapitulated on the transcriptional level in cells transfected with the rat transin/stromelysin promoter in a reporter (CAT) construct. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, also augmented the IL-1 induction of stromeylsin mRNA, as did H-8, a specific inhibitor of the cAMP-dependent protein kinase A. Staurosporine and H-7, inhibitors of protein kinase C, blocked the IL-1 induction of stromelysin mRNA. We conclude that IL-1 appears to stimulate at least two transduction pathways in synovial fibroblasts from patients with rheumatoid arthritis, and that these have antagonistic effects on the regulation of stromelysin transcription. ",16 236,"Apocrine mammary carcinoma. A clinicopathologic study of 72 cases. Apocrine carcinoma (AC) is an uncommon, poorly characterized type of breast tumor. In this review, 55 patients with intraductal (ID) AC and 17 patients with infiltrating (IF) AC were analyzed retrospectively to define the histologic features and clinical course of this neoplasm. Recurrences in the breast occurred in 3 of 20 ID-AC patients treated by biopsy alone, but not in the 2 patients who received local radiation therapy after biopsy. One patient with ID-AC had axillary metastases at the time of treatment by mastectomy and died of disease five years later. The remaining patients with ID-AC treated by mastectomy have remained disease free. One of the three patients with IF-AC treated by biopsy alone died of disease, and one of two patients with IF-AC treated by biopsy and radiotherapy was alive with carcinoma. Twelve patients with IF-AC were treated by mastectomy. Ten of them were recurrence free at the time of last observation. More than one-third of the cases of ID-AC and IF-AC were detected by mammography alone. Survival analysis of IF-AC cases compared with nonapocrine duct carcinoma cases matched for stage revealed no statistical difference in estimated recurrence-free survival or estimated survival probability. AC is a distinct morphologic entity with a natural history similar to that of nonapocrine ductal carcinoma. ",3 2471,"The importance of context in choosing nutritional indicators. Nutritional indicators are used to screen, diagnose, and evaluate interventions in individuals. They are also used in populations to ascertain and place under surveillance the magnitude of nutritional problems, their location and causes, and to evaluate the impact of programs and policies. Nutritional indicators are also used for research to make inferences about biological and social mechanisms affecting or being affected by nutrition. All these activities include measurements of nutritional indicators, but the choice of indicators, their measurements, analyses, and the need for other data can be very different for inferences from research, for patient management, for making public policy, or for planning or evaluating programs. There is no best indicator, best measure of an indicator, or best analysis of an indicator in a generic sense. The definition of ""best"" depends ultimately on what is most appropriate for the decision that must be made. This paper gives examples. ",17 3231,"Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up. Thirty patients with restless legs syndrome, who initially had all responded well to treatment with levodopa and benserazide, were studied as to the long-term effect of the drugs (at least 2 years). During the 2-year period, two patients were switched from levodopa to bromocriptine. Two patients no longer needed levodopa; one of them had developed paraplegia and in the other the symptoms of restless legs syndrome had disappeared completely. The remaining 26 patients continued to use levodopa. Eight patients maintained the original dose, nine had to use an increased dose, and nine found a decreased dose to be sufficient. The only side effect was transient nausea reported by two of the 30 patients. The study showed that the relief of symptoms of restless legs syndrome by dopaminergic drugs does not wear off with the passage of time, that side effects are minimal even with long-term use, and that the dose needed to obtain relief may increase as well as decrease. ",22 314,"Liver fatty acid-binding protein: a marker for studying cellular differentiation in gut epithelial neoplasms. Human liver fatty acid binding protein is a 127 residue cytoplasmic protein synthesized in liver and in the intestinal epithelium. Previous studies of normal and transgenic mice indicated that the liver fatty acid-binding protein gene is a sensitive marker of enterocytic differentiation. This study shows the use of immunohistochemical methods to examine liver fatty acid-binding protein gene expression in normal human colonic epithelium, colonic villoglandular adenomas, nonmucinous and mucinous adenocarcinomas, and several types of noncolonic epithelial neoplasms. Cells containing liver fatty acid-binding protein were found in normal colonic epithelium, in two thirds of colorectal villoglandular adenomas and nonmucinous adenocarcinomas, and in one third of mucinous adenocarcinomas but not in noncolonic, nonhepatic carcinomas. All liver fatty acid-binding protein-positive colonic adenomas and adenocarcinomas contained patches of immunoreactive cells distributed among histologically identical patches of cells without liver fatty acid-binding protein immunoreactivity. This ""mosaicism"" was also found in metastases from liver fatty acid-binding protein-positive colonic adenocarcinomas. Immunostaining of these liver fatty acid-binding protein-positive tissues for carcinoembryonic antigen did not show a mosaic cellular pattern in its expression. These data suggest that within a given neoplasm, differences exist in the differentiation programs of monoclonally-derived, malignant colonic epithelial cells and that liver fatty acid-binding protein is a useful marker for operationally defining these subpopulations. Liver fatty acid-binding protein is also a potentially useful diagnostic marker for colorectal and hepatic carcinomas. ",3 1419,"Morbidity and mortality in hemodialysis patients. Increase in mortality in hemodialysis patients in the United States is a rising concern. In this study, the annual mortality rate from 1981 to 1989 was determined and the morbidity and mortality of 136 patients dialyzed during 1988 was analyzed. All patients were followed with urea kinetics (UK). Patients were divided according to NCDS mapping of BUN and protein catabolic rate (pcr): Group 1, inadequate protein intake (n = 28); Group 2, adequate dialysis (n = 51); Group 3, excessive dialysis (n = 28); Group 4, undefined domain (n = 13); and Group 5, transitional domain (n = 16). The UK parameters measured were midweek predialysis BUN, pcr, and Kt/V. Group 1 by definition had the lowest pcr (0.7 g/kg/day vs. greater than 1.0 in the other groups). Patients in Group 1 had significantly lower BUN, creatinine, hematocrit, and serum albumin. Results of all other laboratory tests were not significantly different. Numbers of hospitalizations and days in the hospital were higher in Group 1. Causes of hospitalization were similar in all groups. Mortality rate was 8% in Group 1 vs. 4.4% in Group 2. Dialysis prescription using UK has maintained the annual mortality rate at about 14% for the past nine years. ",11 1353,"Anti-5 alpha-reductase autoantibodies in the serum of patients with prostatic cancer. Human sera were tested for their ability to inhibit 5 alpha-reductase binding of a potent inhibitor of the enzyme. Thirty one of 227 serum samples from patients diagnosed or suspected of prostatic cancer had a significant inhibitory activity, whereas 128 serum samples from other patients were inactive. The majority of the inhibitory activity was in the IgG fraction purified by chromatography on a protein A-Sepharose affinity column and an anti-human IgG-agarose column. IgG fractions from non-inhibitory sera were inactive. Inhibitory IgG also inhibited the enzymatic activity of microsomal 5 alpha-reductase from liver, ventral prostate and preputial gland of rat, and liver, prostate, and facial skin of human. The inhibitory IgG had no effect on NADH-menadione reductase or 17 beta-hydroxysteroid dehydrogenase. These results suggest that 5 alpha-reductase autoantibodies are present in the blood of some prostatic cancer patients. ",11 3241,"Chronic illness and depressive symptoms in the elderly: a population-based study. A cross-sectional study of the distribution of depressive symptoms and association between depressed mood and chronic illness was conducted in a geographically defined population in southern California of 1617 men and women aged 65 years and older. The prevalence of depressed mood for the total population was 5.2%. Women exhibited a significantly higher mean depressive symptom score and a prevalence rate almost twice that of men. Depressive symptoms were associated with several risk factors in both sexes, including age, self-perception of current health status, number of reported chronic diseases and medications and amount of exercise. However, the relationship between physical illness and depressive symptoms appeared to differ by sex with respect to the nature of the disease or disability and the type of medication currently used. These findings indicate that the risk of depression does not diminish with age among the elderly as other studies have suggested. ",22 2626,"Analysis of lymphocytes, monocytes, and neutrophils from human immunodeficiency virus (HIV)-infected persons for HIV DNA. The human immunodeficiency virus (HIV) infects and depletes or alters the function of cells involved in immune responsiveness. While both T helper lymphocytes and monocyte/macrophages can be infected via cell-surface CD4 in vitro, previous studies showed that few blood cells express HIV RNA in vivo. This study used DNA amplification to determine the levels of HIV DNA in purified lymphocytes, monocytes, and neutrophils from HIV-infected asymptomatic individuals and persons with AIDS. The average numbers of HIV DNA copies in lymphocytes from AIDS patients and asymptomatic individuals were similar (approximately 100-140 copies/150,000 cells). However, when expressed on the basis of numbers of CD4+ T cells, AIDS patients' cells contained approximately 2.5 times more HIV DNA. While HIV DNA was present in lymphocytes from all 27 subjects, little or no HIV DNA was observed in monocytes or neutrophils. Only 1 asymptomatic person contained levels of HIV DNA in monocytes (125 proviral copies/150,000 cells) that were comparable to levels expressed in lymphocytes (160/150,000). While expression of monocyte HIV DNA in this person was persistent over at least 8 months, it was not observed in neutrophils, suggesting that monocyte HIV DNA did not originate in myeloid precursors. This study shows that in AIDS or asymptomatic HIV infection, lymphocytes are the predominant infected cell found in blood. ",19 529,"Oncogene amplification in squamous cell carcinoma of the head and neck. Cellular oncogenes appear to be involved in the control of normal cell growth and differentiation. The abnormal activation of these genes in naturally occurring and experimentally induced cancers may have an important role in the expression of the malignant phenotype in cancer cells. Mechanisms for the activation of these genes include chromosomal translocation, point mutation, and DNA amplification. The amplification of specific oncogenes correlates with clinical prognosis in several human malignancies, including breast cancer and neuroblastoma. We examined 21 fresh-frozen human squamous cell carcinomas of the aerodigestive tract for amplification of 10 known cellular oncogenes (c-myc, N-myc, L-myc, N-ras, H-ras, K-ras, erb-B, erb-B2, raf, and int-2), using Southern blotting techniques. Eleven of 21 tumors demonstrated a two-fold to 11-fold amplification of the int-2 oncogene, one member of a family of genes related to basic fibroblast growth factor. Amplification of c-myc, a gene that codes for a DNA-binding protein involved in the regulation of cell growth, was seen in two tumors. None of the other eight genes studied were amplified in any of the tumor specimens. ",3 1385,"Whole bladder photodynamic therapy: critical review of present-day technology and rationale for development of intravesical laser catheter and monitoring system. Present-day whole bladder photodynamic therapy (WBPDT) is cumbersome and time consuming because cystoscopic and ultrasonic manipulations are necessary to position the light emitter within the bladder. More important, WBPDT is inherently unsafe and often ineffective since neither uniform photoirradiation nor accurate light dosimetry can be achieved with the techniques employed to photoirradiate the bladder wall. The intravesical laser catheter (IVLC) eliminates the need for cystoscopy and ultrasonography because passage of the treatment fiber into the catheter's central lumen automatically positions its light-diffusing tip within the center of the bladder. Use of the IVLC delivery system also assures accurate photoirradiation of the bladder wall since inflation of the catheter's balloon transforms the asymmetric bladder into a sphere of known diameter. The light sensor incorporated in the balloon wall provides a method to monitor light fluence and measure total light dose. When provided the parameters of bladder volume, laser energy output, and desired light dose, the computerized control system calculates treatment time and automatically adjusts the period of photoirradiation to compensate for variations in laser light production, energy losses during transmission, and for variations in light intensity resulting from the integrating sphere effect of the bladder wall. This delivery system also increases the safety of WBPDT since the monitor automatically discontinues treatment if any unsafe situation, with respect to light fluence, develops during photoirradiation. ",11 623,"Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background. The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements. ",4 2212,"Macular dystrophy of the cornea. A systemic disorder of keratan sulfate metabolism. The serum of most patients with type 1 macular corneal dystrophy (MCD), the most prevalent subtype, lacks detectable antigenic keratan sulfate (KS), and it has been postulated that such individuals may lack antigenic KS in their cartilage as well. To test this hypothesis, we studied the cornea, serum, and nasal cartilage from an MCD patient using light and electron microscopy, immunohistochemistry, and a quantitative enzyme-linked immunosorbent assay (ELISA) which uses a monoclonal antibody against a sulfated epitope on the KS chain to measure KS content. Histologically, corneal deposits seen were characteristic of MCD. No abnormal deposits were noted in the cartilage. The lack of immunoreactivity in corneal sections with antibodies against sulfated epitope on KS and the absence of this epitope in serum showed that the patient had type 1 MCD. The cartilage specimen showed no immunoreactivity in the chondrocytes or extracellular matrix. Quantitative analysis by ELISA demonstrated that the antigenic KS content of the cornea and cartilage was at least 800 times lower than that in normal controls. This provided direct evidence that the abnormality in the sulfation of keratan in type 1 MCD involves the cornea and cartilage. ",15 606,"A multicenter analysis of percutaneous discectomy. This study was performed to evaluate a group of patients undergoing percutaneous discectomy. All patients had a single level unilateral L4-5 or L5-S1 disc herniation documented on either computer tomographic (CT) scan, myelogram, and/or magnetic resonance imaging (MRI). Average follow-up after percutaneous discectomy was 16.8 months (range, 2-46 months). The average hospitalization time was 1.7 days (range, 1-5 days). Only 21 patients (55%) were able to return to work after the procedure. Thirteen patients ultimately underwent surgical discectomy for continued symptoms after the procedure. The additional 4 patients did not undergo surgical discectomy and never returned to work. Of those 25 percutaneous discectomy patients who did not undergo surgical discectomy, there was significantly more pain, residual weakness, and numbness compared with the patients undergoing surgical discectomy. The results of this study clearly indicate that percutaneous discectomy does not appear to be as predictable or successful a treatment modality as surgical discectomy. ",4 2413,"Characteristics of learning and memory in streptozocin-induced diabetic mice. We demonstrated that mice with streptozocin-induced diabetes mellitus have normal acquisition for relatively simple tasks but show problems in learning more complex tasks such as shuttle box avoidance. Enhanced learning previously reported in simple passive avoidance tasks appears to be due to increased foot shock sensitivity. Diabetic mice show a marked memory retention deficit after learning an active avoidance T-maze task. This retention deficit was reversed by a single injection of insulin, suggesting that it may be related to hyperglycemia per se. Diabetic mice have a shift to the left in the inverted U-shaped dose-response curve for memory retention produced by the acetylcholine agonist arecoline. Based on a preliminary screening, responses to several other pharmacological memory enhancers are probably altered in diabetic mice. These studies suggest that this mouse model of diabetes mellitus demonstrates a deficit in memory retention and retrieval similar to that seen in humans with diabetes mellitus. ",17 2260,"Piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. A photocontact dermatitis developed in three patients after the application of gel containing 0.5% piroxicam. Patch tests were positive to thiomersal and thiosalicylic acid. Photopatch tests with piroxicam at several concentrations were positive in the three patients but negative in 62 normal volunteer subjects. Patch tests performed on 14 patients with proved systemic photosensitivity to piroxicam were positive for thiomersal and thiosalicylic acid. Nine of 12 patients previously sensitized to thiosalicylic acid and with no history of exposure to piroxicam showed positive photopatch test reactions to this chemical. These results support a relation between piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. Contact allergic sensitivity to the latter is a marker for patients with a high risk of developing photosensitivity reactions to piroxicam. These reactions may be due to photoproducts of the drug rather than metabolites. ",16 2407,"Insulin administration via liposomes. Liposomes have been used in insulin therapy as a means to selectively target insulin to the liver, enhance oral absorption of insulin, and prolong insulin action. Liposomes are an effective means of delivering insulin specifically to hepatocytes. The usefulness of hepatically targeted liposomes in the treatment of diabetes is restricted due to the requirement that they be given intravenously, the dilute concentration of insulin present in liposomal preparations, and the cost associated with liposome production. Encapsulating insulin in liposomes results in enhanced oral absorption of insulin. The high doses of liposome-entrapped insulin required perorally, coupled with extreme variability in the glycemic response to peroral liposomes, limits the value of peroral liposomal insulin as a viable diabetic therapy. Insulin action can be sustained via encapsulation of insulin in liposomes given subcutaneously. Most insulin appears to remain at the injection site, and the presence of a lipid matrix for subcutaneous insulin delivery raises concerns over enhanced antigenicity of liposomal insulin given subcutaneously. Viewed in the light of the limitations outlined above, the contribution of liposomal insulin to understanding and treatment of diabetes mellitus will probably be via use of hepatically targeted liposomes as a pharmacological probe to decipher the role of the liver in the metabolic complications associated with diabetes mellitus. ",17 2025,"Thromboxane A2 and development of genetic hypertension in the Lyon rat strain. To determine whether the increased renal biosynthesis of thromboxane A2 observed in young genetically hypertensive rats of the Lyon strain could be involved in the development of their hypertension, Lyon hypertensive female rats received either thromboxane synthetase inhibitors (Dazmegrel or OKY 046) or a thromboxane A2 receptor antagonist (AH 23848) during their prehypertensive stage. Treatment from 5 to 9 weeks of age with Dazmegrel failed to reduce systolic blood pressure. When given from 3 to 9 weeks of age, Dazmegrel and OKY 046 induced a similar progressive and specific reduction (60%) in the urinary excretion of thromboxane B2 that was associated with a transient decrease in blood pressure level with Dazmegrel and a longer lasting blood pressure-lowering effect with OKY 046. AH 23848, given according to the same schedule, normalized the blood pressure level. This effect persisted 1 week after the cessation of the treatment. Interestingly, active doses of thromboxane synthetase inhibitors or of thromboxane A2 receptor blocker required a 3-week delay to exhibit their antihypertensive properties. It is concluded that 1) the elevated production of thromboxane A2 observed in young Lyon hypertensive rats is likely to participate actively in their blood pressure regulation and 2) this effect may be independent of its direct vasoconstrictor properties. ",13 898,"Prostaglandin F2 alpha enhancement of capsaicin induced cough in man: modulation by beta 2 adrenergic and anticholinergic drugs. The effect of inhaled prostaglandin (PG) F2 alpha on the response to the inhaled tussive agent capsaicin was investigated in normal subjects. Seven subjects inhaled three breaths of four doses of capsaicin (0.3, 0.6, 1.2, and 2.4 nmol) before and immediately after inhaling PGF2 alpha (0.1 mumol) or placebo (0.15M NaCl) on separate days. The numbers of capsaicin induced coughs were greater after PGF2 alpha (mean 42.3 coughs) than after 0.15M sodium chloride (30.1). Visual analogue scores (0-10 on a 10 cm continuous scale) showed that capsaicin was more irritant after PGF2 alpha than after saline. Total respiratory resistance (Rrs), measured by the forced oscillation technique, was unaltered throughout the study. A double blind, placebo controlled study of the effects of inhaled salbutamol (200 micrograms, 0.6 mumol) and ipratropium bromide (40 micrograms, 0.1 mumol) on cough induced by capsaicin (2.4 nmol) and by PGF2 alpha (0.1 mumol) and on PGF2 alpha augmented, capsaicin induced coughing was performed in seven subjects. Neither drug had any effect on capsaicin induced coughing. Salbutamol reduced coughing due to PGF2 alpha (mean 7.7 coughs after salbutamol, 9.3 after placebo) but ipratropium bromide did not (mean 6.9 coughs after ipratropium bromide, 6.6 after placebo). Salbutamol also inhibited the augmentation of the capsaicin induced cough that followed inhalation of PGF2 alpha (mean augmentation 1.9 coughs after salbutamol, 4.1 after placebo), whereas ipratropium bromide did not (augmentation 1.7 coughs after ipratropium bromide, 2.7 after placebo). No changes in Rrs were seen after PGF2 alpha or either drug. Thus salbutamol reduces PGF2 alpha induced cough and the augmentation of capsaicin induced cough that follows PGF2 alpha. ",7 104,"Drug therapy for Helicobacter pylori infection: problems and pitfalls. Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer. Whereas there is presently no ""optimal"" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone. Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients. Recently, it has appeared from several clinical trials that H. pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure. A critical review of the literature on H. pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome. Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H. pylori and negatively affect the ecology of the gastric microflora. Likewise, an accurate definition of a subset of patients with H. pylori who really will require treatment needs to be rapidly established. ",0 826,"Reproducibility of 24 hour oesophageal pH studies in infants. Thirteen infants who had undergone 24 hour oesophageal pH monitoring to diagnose gastro-oesophageal reflux had a second study carried out to see if the results were reproducible. The studies were done without restricting the babies' activities. Appreciable differences were found, the percentage of the total time during which the pH was less than 4 varying by up to 3.7-fold between the two tests. The differences were largely the result of biological rather than technical variability. From these results estimates were made of the reliability of a single diagnostic study and the size of changes that would be necessary to show the effect of treatment. These findings have a considerable impact on the diagnosis of abnormal gastro-oesophageal reflux and its response to treatment whether using 24 hour pH monitoring or any other method of measurement. ",5 125,"Use of single fiber EMG and macro EMG in study of reinnervation. The use of single fiber EMG and macro EMG in studies of reinnervation is discussed. SFEMG gives information about changes in the topography of the motor unit and in function of transmission in terminal nerve, motor endplate and muscle fiber. Dynamics of reinnervation may be studied with this technique. The amount of reinnervation is obtained from macro EMG studies. The capacity for reinnervation is discussed for a few conditions as well as factors that limit the reinnervation process. ",1 2048,"Regional blood flow supply and demand in heart failure. Heart failure results not only in a fall in cardiac output but also in a redistribution of blood flow favoring some regional beds (the brain and the heart) at the expense of others (the kidney and working skeletal muscle). The chronic resting hypoperfusion of striated muscle is further compromised with exercise. Maladaptive vasoconstrictor control mechanisms prevent the redirection of blood flow from nonworking muscle and liver to working muscle. This inappropriate preservation of nonworking organ perfusion further compromises the functional capacity of working muscle and is associated with evidence for metabolic deconditioning with reduced oxygen extraction and impaired oxidative phosphorylation. It is becoming increasingly clear that the clinical response to the inotropic and vasodilator therapy used in heart failure is in part dependent on the differing regional blood flow profiles of the various agents studied. The ability of the angiotensin-converting enzyme inhibitors to redirect blood flow away from nonworking regional beds to exercising muscle, and thereby to reestablish an appropriate physiologic response to changing metabolic needs, may be the overriding reason for their long-term efficacy. Certainly in the future the comprehensive therapy of heart failure will have to take into consideration not only central hemodynamic but also regional blood flow/supply and demand issues. ",13 507,"IgE receptor-mediated phosphatidylinositol hydrolysis and exocytosis from rat basophilic leukemia cells are independent of extracellular Ca2+ in a hypotonic buffer containing a high concentration of K+. In isotonic buffer, IgE receptor-mediated exocytosis from rat basophilic leukemia cells is dependent on extracellular Ca2+, with half-maximal degranulation requiring 0.4 mM Ca2+. No significant exocytosis occurs in the absence of extracellular Ca2+. This absolute requirement for Ca2+ is eliminated by suspending the cells in a hypotonic buffer containing 60 to 80 mM K+; Na+ cannot substitute for K+. Optimal Ca2(+)-independent exocytosis occurs in a buffer containing 20 mM dipotassium Pipes, pH 7.1, 40 mM KCl, 5 mM glucose, 7 mM Mg acetate, 0.1% BSA, and 1 mM EGTA. The cells maintain this Ca2(+)-independent exocytosis even if they are preincubated with 1 mM EGTA for 40 min at 37 degrees C before triggering. Exocytosis is eliminated as isotonicity is approached by adding sucrose, NaCl, KCl, or potassium glutamate to the buffer. Quin 2 fluorescence measurements reveal only a very small rise in [Ca2+]i when the cells are triggered in hypotonic buffer in the absence of extracellular Ca2+ and the presence of 1 mM EGTA. In isotonic buffer, degranulation does not occur under conditions that lead to such a small rise in [Ca2+]i. Sustained IgE receptor-mediated phosphatidylinositol hydrolysis, which is also Ca2+ dependent in isotonic buffer, becomes independent of Ca2+ in the hypotonic buffer. In fact, the rate of phosphatidylinositol hydrolysis in hypotonic buffer in the absence of Ca2+ (and presence of 1 mM EGTA) is twice that observed in isotonic buffer in the presence of 1 mM Ca2+. These data show that in hypotonic buffer, the requirement of IgE receptor-mediated PI hydrolysis for extracellular Ca2+ is eliminated, and degranulation proceeds with a [Ca2+]i of 0.1 microM, the baseline level of [Ca2+]i found in resting cells. These results are consistent with the hypothesis that, in isotonic buffer, the Ca2+ requirement for mast cell degranulation is for the generation of second messengers via hydrolysis of membrane phosphatidylinositols. ",3 115,"Treatment of adult chickenpox with oral acyclovir. Thirty-one late adolescents and adults with varicella were studied. Patients identified within 72 hours of varicella exanthem were offered open treatment with acyclovir (4 g/d), and those patients identified after 72 hours of exanthem were followed up but not treated. Twenty-two patients were treated with acyclovir. Nine patients were not treated. No severe complications occurred in any of the 31 patients. Minor complications, including prolonged fever, localized secondary infections, persistent cough, and prolonged fatigue were more frequent in the untreated group. If the acyclovir therapy was begun within the first 24 hours of varicella exanthem, then the rash and clinical illness were dramatically lessened. Treatment with oral acyclovir should be considered for varicella in adults who are identified within the first 24 hours of exanthem. ",1 1635,"Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction. To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit ECGs to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field ECG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 +/- 9.7 minutes for the ECG group versus 16.1 +/- 7.0 minutes for the non ECG group (difference not significant). Time of transport averaged 18.2 +/- 9.9 and 17.6 +/- 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 48 +/- 12 minutes after hospital arrival (range 30 to 60) compared with 103 +/- 44 minutes (p less than 0.01) for 51 historical control patients and 68 +/- 29 minutes for 6 concurrent control patients without in-field ECG. Thus, in-field ECG causes negligible delays in paramedic time, leads to significant decreases in time to in-hospital thrombolysis and may make in-field therapy feasible. In-field ECG may be an important addition to reperfusion strategies. ",13 559,"Multisurface method of pattern separation for medical diagnosis applied to breast cytology. Multisurface pattern separation is a mathematical method for distinguishing between elements of two pattern sets. Each element of the pattern sets is comprised of various scalar observations. In this paper, we use the diagnosis of breast cytology to demonstrate the applicability of this method to medical diagnosis and decision making. Each of 11 cytological characteristics of breast fine-needle aspirates reported to differ between benign and malignant samples was graded 1 to 10 at the time of sample collection. Nine characteristics were found to differ significantly between benign and malignant samples. Mathematically, these values for each sample were represented by a point in a nine-dimensional space of real variables. Benign points were separated from malignant ones by planes determined by linear programming. Correct separation was accomplished in 369 of 370 samples (201 benign and 169 malignant). In the one misclassified malignant case, the fine-needle aspirate cytology was so definitely benign and the cytology of the excised cancer so definitely malignant that we believe the tumor was missed on aspiration. Our mathematical method is applicable to other medical diagnostic and decision-making problems. ",3 2797,"Ethanol-inducible cytochrome P-450 activity and increase in acetaldehyde bound to microsomes after chronic administration of acetaldehyde or ethanol. Chronic ethanol consumption results in acetaldehyde adduct formation with proteins such as haemoglobin and liver proteins in vivo. Our purpose was to study the binding of acetaldehyde to liver microsomal proteins, a site of ethanol oxidation via cytochrome P-450 (especially P-450 II E1), after chronic administration of ethanol or acetaldehyde for 21 days to rats. The liver microsomal oxidation of 1-butanol by the ethanol-inducible P-450 also was examined. Acetaldehyde bound to liver microsomal proteins was higher in ethanol-fed rats compared with acetaldehyde-treated rats (0.735 vs 0.413 nmol/mg of protein respectively). The biotransformation of n-butanol to butyraldehyde by liver microsomes was increased (by 136%) in ethanol-fed rats vs controls, whereas in acetaldehyde-treated rats this increase was much lower (only 27%). However, in this last group, a significant negative relationship between the quantity of acetaldehyde bound to microsomal proteins and the monooxygenase-catalyzed transformation of butanol by liver microsomes was demonstrated (r = -0.79, P less than 0.01). These results suggest that proteins of liver microsomes are a target for acetaldehyde binding during ethanol oxidation and such adduct formation could impair the oxidative properties of the alcohol-inducible cytochrome P-450. ",20 198,"Activation and inducer subset phenotype of the lymphocytic infiltrate around epidermally derived tumors. An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response. ",3 69,"Epidemiologic differences between chlamydia and gonorrhea. To assess the prevalence, demographics, and transmission patterns of genital chlamydia infection, we screened 3,078 patients, and compared identified cases (N = 511) to gonorrhea cases (N = 291) diagnosed in the same setting. Chlamydia cases were younger and more likely to be White than their gonorrhea counterparts. Chlamydia cases were distributed diffusely; geographic overlap between the two diseases was only about 40 percent. Gonococcal coinfection was noted in less than 10 percent of patients with chlamydia. Nearly half of men with chlamydia and four-fifths of women were asymptomatic and most cases were identified through screening or contact tracing. Populations at high risk for chlamydia are seemingly different from those for gonorrhea. Differences may be due to control interventions (active for gonorrhea, passive for chlamydia). Chlamydia case reporting and control initiatives are recommended. ",0 2976,"Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin. Elevated free Ca2+ concentrations found in adult dystrophic muscle fibers result in enhanced protein degradation. Since the difference in concentrations may reflect differences in entry, Ca2+ leak channels in cultures of normal and Duchenne human myotubes, and normal and mdx murine myotubes, have been identified and characterized. The open probability of leak channels is markedly increased in dystrophic myotubes. Other channel properties, such as mean open times, single channel conductance, ion selectivity, and behavior in the presence of pharmacological agents, were similar among myotube types. Compared to the Ca2+ concentrations in normal human and normal mouse myotubes, intracellular resting free Ca2+ concentrations ([Ca2+]i) in myotubes of Duchenne and mdx origin were significantly higher at a time when dystrophin is first expressed in normal tissue. Taken together, these findings suggest that the increased open probability of Ca2+ leak channels contributes to the elevated free intracellular Ca2+ concentration in Duchenne human and mdx mouse myotubes. ",21 2409,"Devices for insulin administration. There is a significant need for revised, safe, and more effective insulin-delivery methods than subcutaneous injections in the treatment of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. The aim of this review is to describe the rationale and methods for better use of injection and infusion devices for intensive insulin therapy and to describe results of animal and human research that will lead to an implantable artificial pancreas. Injection devices, e.g., jet injectors, insulin pens, and access ports, cannot be considered as a major breakthrough in the quest for improved control, although they may improve the patient's comfort. External pumps have benefits over multiple injections and conventional insulin therapy only in specific subgroups of patients, e.g., those with recurrent severe hypoglycemia, but only when used by experienced personnel. The external artificial pancreas (Biostator) is also to be used by experienced personnel for limited clinical and research applications, e.g., surgery of the diabetic patient. The development of an implantable version of the artificial pancreas is linked to progress in the field of reliable long-duration glucose sensors. Finally, programmable implantable insulin pumps, used as an open-loop delivery system, are the most promising alternative to intensive subcutaneous insulin strategies in the short term, although clear evidence of improved safety and efficacy remains to be documented. ",17 329,"Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft. Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature. Cultured human PBL distributed in moderate concentrations to intraperitoneal tumor when administered i.p., but not when administered i.v. The poor localization of i.v. injected PBL to tumor may reflect species disparity in homing receptors and/or endothelial ligands, a problem which may be overcome with a syngeneic model. These results suggest that regional therapy with HA antibodies and PBL may offer advantages over systemic therapy for initial clinical trials. ",3 460,"Mammographic measurements before and after augmentation mammaplasty. Thirty-five augmented women underwent mammography using both the standard implant-compression technique and, when possible, the implant-displacement technique; all had preaugmentation film-screen mammography available for evaluation. The area of mammographically visualized breast tissue before and after augmentation mammaplasty was measured using a transparent grid. Patients with subglandular implants had a mean decrease of 49 percent of measurable tissue area with compression mammography and a 39 percent decrease with displacement mammography. Patients with submuscular implants had a 28 percent decrease in measurable tissue area with compression mammography and a 9 percent decrease with displacement mammography. Anterior breast tissue was seen better with displacement mammography; posterior breast tissue, with compression mammography. Most patients had some degree of parenchymal scarring and lower image quality after augmentation. State-of-the-art mammography was not possible in most patients augmented with silicone-gel-filled implants. ",3 1833,"Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct-related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis. ",13 2503,"Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new inborn error of metabolism. Cultured fibroblasts were shown to be capable of catalyzing the conversion of 7 alpha-hydroxy-cholesterol to 7 alpha-hydroxy-4-cholesten-3-one, an important reaction in bile acid synthesis. The apparent Km was approximately 7 mumol/liter and Vmax varied between 3 and 9 nmol/mg protein per h under the assay conditions used. The assay was used to investigate fibroblasts from a patient who presented with a familial giant cell hepatitis and who was found to excrete the monosulfates of 3 beta, 7 alpha-dihydroxy-5-cholenoic acid and 3 beta, 7 alpha, 12 alpha-trihydroxy-5-cholenoic acid in urine (Clayton, P. T., J. V. Leonard, A. M. Lawson, K. D. R. Setchell, S. Andersson, B. Egestad, and J. Sjovall. 1987. J. Clin. Invest. 79:1031-1038). In addition 7 alpha-hydroxy-cholesterol was found to accumulate in the circulation. Cultured fibroblasts from this boy were completely devoid of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity. Fibroblasts from his parents had reduced activity, compatible with a heterozygous genotype. The results provide strong evidence for the suggestion that this patient's liver disease was caused by a primary defect in the 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase involved in bile acid biosynthesis. ",17 1823,"Muscle oxidative capacity and work performance after training under local leg ischemia. Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg. ",13 341,"The unique aspects of acute promyelocytic leukemia. Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML. ",3 305,"Leiomyoma of a digital artery. Benign, soft-tissue masses of the hand are common. A vascular leiomyoma is an unusual tumor of smooth-muscle origin. In a 62-year-old man, the tumor arose from within a digital artery. Persistent symptoms prompted an excisional biopsy, requiring resection of a portion of the artery. Adequate collateral circulation preempted the need for a vascular graft. Vascular repair or grafting may be necessary if collateral circulation is not adequate. ",3 758,"Selective intestinal decontamination increases serum and ascitic fluid C3 levels in cirrhosis. Selective intestinal decontamination for 7 days with norfloxacin was performed in 14 cirrhotic patients with ascites and low ascitic fluid total protein. Variations in serum and ascitic fluid of C3 and C4 and ascitic fluid total protein after therapy were compared with those of a control group of 14 untreated patients with similar characteristics. After oral norfloxacin administration, we saw a significant increase of C3 in serum (p less than 0.05) and ascitic fluid (p = 0.01). A significant increase was also observed in ascitic fluid total protein (p less than 0.05) but not in serum and ascitic fluid C4. There were no changes in serum C3, ascitic fluid C3, ascitic fluid C4 or in ascitic fluid total protein in group 2. These data demonstrate that selective intestinal decontamination increases serum and ascitic fluid C3 levels and, therefore, might be useful in preventing spontaneous infections in cirrhotic patients at high risk of infection. ",5 1441,"Activity of type 1 erythrocyte complement receptors in uremia and after renal transplantation. The effect of uremia on the activity of the erythrocyte complement receptors type 1 (CR1), and the changes occurring after renal transplantation, were studied. The complement receptor activity was measured by immune adherence utilizing a rosette technique. Patients with terminal kidney failure on the hemodialysis program exhibited significantly lower values of the erythrocyte CR1 activity in comparison with healthy controls. The circulating immune complexes did not affect erythrocyte CR1 activity. After successful renal transplantation, irrespective of the immunosuppressive program used, a significant increase in erythrocyte CR1 activity appeared, similar to control group values. However, the activity of erythrocyte CR1, in the graft recipients under cyclosporin A treatment, was significantly higher than in the patients receiving azathioprine with prednisone. Therefore, it is possible that cyclosporin A, transported in the erythrocytes, modifies the complement receptor function. ",11 1227,"Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Descending influences on the spinal nociceptive tail-flick (TF) reflex produced by focal electrical stimulation and glutamate microinjection in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) were examined and characterized in rats lightly anesthetized with pentobarbital. Both inhibition and facilitation of the TF reflex were produced by electrical stimulation at identical sites in the NGC/NGC alpha; glutamate microinjection only inhibited the TF reflex. The chronaxie of stimulation for inhibition of the TF reflex was 169 +/- 28 microseconds. Inhibition of the TF reflex by stimulation was produced throughout the NGC and NGC alpha; intensities of stimulation for inhibition were least in the ventral NGC and in the NGC alpha. At threshold intensities of stimulation, inhibition of the TF reflex did not outlast the period of stimulation. Facilitation of the TF reflex was produced at many of the same sites at which stimulation inhibited the TF reflex, but always at lesser intensities of stimulation (mean, 10 microA vs. 43 microA for inhibition, n = 25). Stimulation in the NGC/NGC alpha at threshold intensities for facilitation or inhibition of the TF reflex did not significantly affect blood pressure. Strength-duration characterization of electrical stimulation and microinjection of glutamate into identical sites in the NGC and NGC alpha suggest that descending inhibition of the TF reflex results from activation of cell bodies in the NGC and NGC alpha. ",9 1166,"Quantitative evaluation of sway as an indicator of functional balance in post-traumatic brain injury. The test of sway, using different conditions of stance with measurements of the average radial deviation of the center of pressure and its path length of sway per unit of time, has been shown to be a useful clinical tool in determining balance problems in traumatic brain injury (TBI) patients. Normative values were established to determine if an individual patient's sway values fell within the normal range (mean +/- 2SD). The tests have shown good test-retest reliability for TBI patients. In addition, it has been shown that the sensitivity of the test is sufficient to identify changes in patients' performances as their clinical conditions change. It has been demonstrated that the different stance conditions of the battery of tests become progressively more difficult to perform (from comfortable stance, eyes open and eyes closed, through narrow stance, eyes open and eyes closed, to tandem stance with right or left foot forward, eyes open and eyes closed). By using these subtests, it is easy to distinguish between the performances of able-bodied patients and TBI patients with very mild balance problems. The validity of the measure has been documented by correlating the sway performance with clinical functional performance tests. The test performance also correlates with the patient's own assessment of his or her gait difficulties. The limited data available suggest that the test of sway relates difficulties in static balance to the frequency of falls. Finally, subtests permit identification of specific problems in maintaining balance as a basis for therapeutic intervention. ",9 1331,"Rationing of health care and the end-stage renal disease program. The potential impact of rationing health care on the end-stage renal disease (ESRD) program is considered. The possible implications of the recommendations emanating from the study being conducted by the Institute of Medicine of the National Academy of Sciences are also mentioned. Particular emphasis is given to the potential consequences of rationing health care on the elderly and on certain socioeconomic groups with ESRD. ",11 463,"Chemical shift imaging of human brain: axial, sagittal, and coronal P-31 metabolite images. Multivoxel magnetic resonance (MR) spectroscopy and novel data analysis techniques were developed to obtain high-quality phosphorus-31 metabolite images from the human brain and to overlay each metabolite distribution directly onto corresponding hydrogen-1 MR images. The P-31 MR spectroscopic data were acquired by means of three-dimensional chemical shift imaging (phase encoding in three spatial dimensions) on a 1.5-T clinical instrument equipped with a specially designed quadrature P-31 birdcage coil constructed in the authors' laboratory. Axial, sagittal, and coronal metabolite images based on the area for any one of five peak regions (phosphodiester; phosphocreatine; gamma, alpha, and beta adenosine triphosphate) were generated from 8 X 8 X 8 or 12 X 12 X 8 CSI arrays with voxel sizes of 27 cm3 and 12 cm3, respectively. The positions of these images were aligned with anatomic features by means of the voxel-shifting capability of the Fourier transform. Direct overlays of these metabolite images on corresponding proton images demonstrated excellent correlation with anatomy, factors indicating the utility of this technique for viewing P-31 metabolite levels in all areas of the brain simultaneously. ",3 2679,"A random double-blind trial of the combination of nebulized atropine methylnitrate and albuterol in nocturnal asthma. The combination of nebulized atropine methylnitrate (AMN) and a beta-agonist has been shown to produce greater and longer lasting bronchodilation than either drug alone. We examined the efficacy of the combination in diminishing the ""morning dipping"" in PEFR in eight hospitalized but stable asthmatics. The patients received nebulized albuterol along with either AMN (AMN + ALB) or placebo (ALB) in a random double-blind cross-over fashion at 10 PM on four nights. PEFR and FEV1 were recorded at 6 PM, 10 PM, and 6 AM before the administration of bronchodilators. There was no statistically significant difference between ALB and AMN + ALB in reducing the morning dipping in these patients. ",19 846,"Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment. ",5 35,"Efficacy and tolerability of topical terbinafine in the treatment of tinea cruris. Thirty men with clinical and mycologic evidence of tinea cruris were enrolled in a controlled, randomized, double-blind trial comparing terbinafine 1% cream and its cream vehicle as placebo. Patients applied the test medications to the affected area twice daily for 2 weeks. Therapeutic response was evaluable in 18 patients after each week of treatment and at a follow-up visit 2 weeks after therapy ended. At each visit, terbinafine was found to be more effective than the cream vehicle in the reduction of the signs and symptoms of infection and in the conversion of culture and microscopy findings to negative or normal. At the end of treatment, therapy was effective in 67% of the nine terbinafine-treated patients compared with only 11% of the nine placebo-treated patients. At the follow-up examination, efficacy rates were 78% in the terbinafine treatment group and 33% in the placebo group--a difference of borderline statistical significance (p = 0.077). Possible reasons for this result may include the higher incidence of chronic disease in the terbinafine group and the large number of patients who were classified as delayed exclusions because of negative initial culture for dermatophytes. No side effects or significant alterations in laboratory or hematologic tests were observed in either treatment group. ",0 883,"Acute pulmonary effects of aerosolized pentamidine. A randomized controlled study. Toronto Aerosolized Pentamidine Study (TAPS) Group. From June 1988 to February 1989, we enrolled 36 patients with human immunodeficiency virus into a randomized double-blind placebo-controlled trial assessing the efficacy and toxicity of aerosolized pentamidine (AP) as secondary prophylaxis for Pneumocystis carinii pneumonia. Each patient underwent spirometric evaluations before and after aerosolized treatment. There was no significant difference in the results of baseline pulmonary function tests between the two groups. Eleven patients (65 percent) in the AP group developed cough but only four demonstrated significant reduction in the forced expiratory flow rates after AP; four patients (21 percent) in the placebo group developed cough, but no significant change in the expiratory flow rates was noted. All bronchospastic episodes were self-limited and symptomatically responded to remedial inhaled albuterol (salbutamol) treatment. We conclude that AP treatment is frequently associated with coughing attacks (65 percent), but the actual incidence of bronchospasm on spirometry is much lower (24 percent) and is generally quite mild. ",7 3096,"Morphological and biochemical changes in gastric mucosa of aging rats. Although previous data from this laboratory have indicated that aging is associated with increased gastric mucosal proliferative activity, no direct assessment of proliferative potential of the tissue has been made during aging. In order to assess this, and to determine whether changes in mucosal proliferative potential would be reflected in growth of the tissue, we have examined the labeling index (LI), height and morphology of the gastric mucosa in young (4-month-old) and aged (24-month-old) Fischer-344 rats. In addition, tyrosine kinase (Tyr-k) activity and the levels of phosphotyrosine proteins were determined to evaluate their relationship to mucosal proliferative activity. Histologic evaluation revealed a marked atrophy of the mucosal glandular component with 32% reduction in height in aged rats when compared with young animals. In aged rats, there was also a decrease in gland density, resulting in a reduction in the number of epithelial cells of all types with evidence of decreased secretory activity. Despite the occurrence of mucosal atrophy in aged rats, LI in these animals was significantly increased by 28%. This was associated with a parallel rise in mucosal Tyr-k activity, and a two- to threefold increase in the relative concentrations of seven phosphotyrosine membrane proteins with Mr of 120, 105, 90, 60, 55, 48 and 32 kDa. We conclude that (1) although aging is associated with increased gastric mucosal proliferative activity, this does not result in mucosal growth and that (2) Tyr-k and tyrosine phosphorylation of certain proteins play a role in the regulation of gastric mucosal cell proliferation during aging. ",22 955,"Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia. Although the muscarinic antagonist Ipratropium bromide is used clinically as a bronchodilator in infants ventilated because of bronchopulmonary dysplasia (BPD), no studies have compared the response or efficacy of different dosages or its effectiveness in combination with beta-adrenergic agonists. We measured the response of respiratory system mechanics in 10 ventilated infants (25 +/- 2 days of age) to 75, 125, and 175 micrograms ipratropium bromide (IB), 125 micrograms IB plus 0.04 mg salbutamol (SAL), 175 micrograms IB plus 0.04 mg SAL, and saline vehicle, delivered via nebulizer into the ventilator circuit. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive flow-volume technique. Rrs and Crs were measured before and at 1 to 2 h and at 4 h after delivery of the five drug dosages or saline. All six studies were completed within a 72-h period. Saline had no significant effect on mechanics. Significant responses to ipratropium alone were seen only after 175 micrograms where Rrs decreased 20 +/- 3% (SEM) (p less than 0.05) at 1 to 2 h and 16 +/- 5% (p less than 0.05) at 4 h. After 125 micrograms IB + SAL and 175 micrograms IB + SAL, Rrs was significantly decreased both at 1 to 2 h and at 4 h, and Crs was significantly increased 20 +/- 6% and 20 +/- 4%, respectively, at 1 to 2 h. The greatest decrease in Rrs (26 +/- 6%) was seen 1 to 2 h after 175 micrograms IB + salbutamol. ",7 1372,"Extracorporeal shock wave lithotripsy in patients with bleeding diatheses. Five patients with known bleeding diatheses were treated with extracorporeal shock wave lithotripsy. Specific therapy was administered before extracorporeal shock wave lithotripsy to reverse the bleeding disorder. After treatment each patient was monitored with serial hemoglobin determinations and renal ultrasonography. The course during and after lithotripsy was uneventful in all patients. We conclude that extracorporeal shock wave lithotripsy is a viable option for patients with significant bleeding diatheses provided that specific therapy to reverse the coagulopathic condition is available and used before treatment. ",11 899,"Use of a fenestrated silicone drain to stent a malignant tracheobronchial stenosis. An innovative use of a fenestrated silicone drainage tube as an endobronchial stent is reported. The patient had respiratory obstruction due to a carinal tumour and laser photoresection had failed to restore airway patency. ",7 1215,"Infantile CNS spongy degeneration--14 cases: clinical update. We studied 14 Arab infants with infantile spongy degeneration, 13 of whom were products of consanguineous marriages. They presented in infancy with macrocephaly, poor visual behavior or blindness, and axial hypotonia with appendicular spasticity. Brain CT and MRI showed diffuse symmetric leukoencephalopathy, even before neurologic symptoms. There were relatively normal EEGs. The visual evoked responses (P100) were either absent or delayed early in the course. The brainstem auditory evoked responses showed milder abnormalities, with loss of later components before the earlier ones. Deficient aspartoacylase activity in cultured fibroblasts or brain biopsy confirmed the diagnosis in all patients. ",9 577,"Shear stress induces not only platelet aggregation but also platelet-tumor cell interaction. To investigate the interaction between platelets and tumor cells under well-defined flow conditions, the effect of tumor cells on platelet aggregation induced by shear stress was studied using a cone and plate viscometer adapted for measuring transmitted light intensity. Aggregation was markedly enhanced by HMV-1 cells in a cell number-dependent fashion under shear stress of 12 dyne/cm2. Enhancement was not observed at a high shear stress of 108 dyne/cm2. A monoclonal antibody against GPIIb/IIIa, 7E3 completely abolished enhancement of aggregation by HMV-1. Apyrase had similar inhibitory effects. Scanning electronmicroscopy showed that direct contacts of platelets with HMV-1 cells could be demonstrated when platelet-platelet interaction was inhibited by 7E3 or apyrase. These results may indicate that, at a shear stress of 12 dyne/cm2, direct contacts of platelets and HMV-1 cells may trigger enhancement of platelet aggregation. ",3 751,"Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. Primary biliary cirrhosis is characterized by the presence of antimitochondrial antibodies. Recently, six of the autoantigens have been identified as components of the 2-oxo acid dehydrogenase multienzyme complexes located within mammalian mitochondria. Immunoblotting studies have shown that two of these components, namely E2 and protein X of pyruvate dehydrogenase complex, are the major antigenic polypeptides recognized by autoantibodies. This study shows the development of an enzyme-linked immunosorbent assay to detect and quantitate antibodies to these two purified antigens. Coded serum samples from 166 patients with primary biliary cirrhosis, 140 patients with other liver and/or autoimmune disease, and 52 normal women were analyzed for reactivity using this immunoassay. These results indicate that this rapid, simple method has a 93% sensitivity and 96% specificity in the diagnosis of primary biliary cirrhosis. The titer of immunoglobulin G autoantibodies correlated not only with antimitochondrial antibody titer measured by indirect immunofluorescence (P less than 0.0001) but also with histological stage of disease (P less than 0.04) and prognostic biochemical variables such as higher serum bilirubin and lower serum albumin levels (P = 0.038 and 0.028, respectively). There was no significant correlation between titer of autoantibodies and serum globulin or immunoglobulin G levels, indicating that the positive correlation with disease progression was not secondary to hypergammaglobulinemia. ",5 2622,"Ultraviolet cross-linking of helical oligonucleotides to two monoclonal MRL-1pr/1pr anti-DNA autoantibodies. Variations in H and L chain binding to DNA. Experiments were performed to determine whether both H and L chains of different anti-native DNA autoantibodies are uniformly involved in binding to DNA. Two purified monoclonal mouse (MRL-1pr/1pr) IgG autoantibodies, H241 and 2C10, were tested. They both bound synthetic helical oligonucleotides of 10 to 20 base pairs in a gel electrophoresis retardation assay but differed in their preferences for given base sequences. Exposure of antibody-radiolabeled oligonucleotide mixtures to UV light (254 nm) for 10 min led to specific covalent cross-linking of oligonucleotide to both the H and the L chains of H241 but only to the H chain of 2C10. Single labeling events were detected without higher aggregation. The oligonucleotides were not cross-linked to unrelated IgG, even after 2 h of irradiation. Cross-linked (radioactively labeled) H and L chains of H241 and 2C10 were isolated from denaturing electrophoresis gels and digested with lysyl endopeptidase and/or staphylococcal V8 protease. H241 and 2C10 H chains each yielded a major labeled peptide fragment, but the peptides from the two antibodies were different. These experiments measured only some of the antibody-DNA interactions, probably with bases in the major groove of the DNA. They indicated that two MRL-1pr/1pr IgG anti-native DNA antibodies differ in their H and L chain contacts with DNA and provide an approach to identifying affinity-labeled binding sites in the antibodies. ",19 200,"Cutaneous surgery and the pregnant patient. Cutaneous surgery in 34 pregnant women is described. The main indication for surgery was the diagnosis and/or treatment of malignancy. Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible. Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome. Monitoring of the fetal heartbeat is desirable. Local anesthetics, penicillin, and erythromycin are safe if used carefully. Acetaminophen is the analgesic of choice. Exposure to the sun should be avoided during the perioperative period. ",3 1016,"Vocal cord paralysis in children. Bilateral vocal cord paralysis is a common cause of stridor in infants and children. There are significant differences in this entity between children and adults with regard to etiology, diagnosis, management, and outcome. A review of 10 years' experience at Children's Hospital of Philadelphia identified 51 children seen with the diagnosis of vocal cord paralysis. These cases were evaluated with respect to etiology of paralysis, whether unilateral or bilateral, delay in diagnosis, need for tracheotomy, abnormality of voice, surgical treatment, and outcome. Guidelines for management for a child with vocal cord paralysis are presented with emphasis on flexible endoscopic evaluation and conservative management. ",8 3322,"Hypoxic events in the surgical intensive care unit. An oxygen-monitoring protocol was established in the surgical intensive care unit (SICU) at the Denver General Hospital in July 1988. A 3-month surveillance audit ending March 1989 prospectively documented 100 consecutive hypoxic events in 51 of 241 (21%) SICU patients. These episodes occurred during mechanical ventilation in 46 patients, during spontaneous ventilation in 15 patients with artificial airways, and the remaining 39 occurred in nonintubated patients. Hypoxemia was recognized by pulse oximetry in 59, arterial blood gas analysis in 24, mixed venous oximetry in 15, and transcutaneous oxygen monitoring in 2. These events were due to problems with the ventilator or airway in 42, recent interventions in 21, new pulmonary process in 19, progression of underlying disease in 11, and unknown causes in 7. Two thirds resulted from mechanical problems amenable to simple intervention; there were two adverse outcomes. In conclusion, acute hypoxia is a frequent potentially morbid SICU event. Advances in continuous oxygen monitoring permit early identification and thereby may limit adverse outcomes, but should not prompt an expensive diagnostic work-up. ",22 2139,"Autoimmune hemolytic anemia in Kawasaki disease: a case report A 3-year-old boy presented with the fever, conjunctivitis, rash, and lymphadenopathy diagnostic of Kawasaki disease. Treatment with antibiotics, aspirin, and intravenous immunoglobulin was instituted. The hematocrit decreased from 35 percent on admission to 11 percent by hospital Day 10, and the white cell count had increased from 13.7 to 42 x 10(3) per microL, and the patient had a leukoerythroblastic blood smear. The direct antiglobulin test demonstrated IgG but not complement on the red cell (RBC) surface. An acid eluate reacted (titer of 4) with all panel cells in the antiglobulin phase. Intravenous immunoglobulin from the same lot used for treatment did not contain antibody that reacted with the patient's group O RBCs or a panel of group O RBCs, but did contain IgG anti-A and -B (titer of 4). The patient received a transfusion and was given methylprednisone. The direct antiglobulin test and acid eluate were negative 4 days later. The patient had an uneventful recovery. The distinction between antibody-mediated hemolytic anemia and autoimmune hemolytic anemia is important in the treatment of this disease. ",14 2530,"Cold follicles in a multinodular human goiter arise partly from a failing iodide pump and partly from deficient iodine organification. To investigate whether the common cold follicles in human multinodular goiters are the consequence of a functional defect of the apical membrane peroxidase, a failure of the iodide transport system, or both deficiencies, we studied iodide accumulation and iodine organification in 30 fragments of a large multinodular goiter transplanted to nude mice and labeled with 125I. Transplants were frozen to -80 C immediately after removal to avoid diffusion of inorganic iodide. Autoradiographic assessment of over 1000 cryosections (exposed either at -20 C or after thawing and washing out unbound iodide) showed two types of cold follicles, namely those that failed to accumulate iodide and, therefore, did not organify iodine, and those that readily accumulated iodide but failed to bind it, suggesting a failure of apical membrane peroxidase. The two types of pathogenetically different cold follicles coexisted in an apparently randomly intermingled fashion throughout the whole goiter. ",18 37,"Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis. The safety and effectiveness of oral terbinafine, 125 mg twice daily, and griseofulvin, 250 mg twice daily, in patients with moccasin-type tinea pedis were examined in a double-blind randomized trial. At the end of the 6-week treatment period, both a clinical and mycologic cure or a mycologic cure with minimal signs of infection was noted in 12 (75%) of the 16 terbinafine-treated patients compared with only 3 (27%) of the 12 patients treated with griseofulvin. The overall response rate 2 weeks after the completion of treatment was 88% in the terbinafine-treated group and 45% in the griseofulvin-treated group. When contacted again 6 to 15 months after completion of the study, 94% of the terbinafine-treated patients reported sustained clearing of tinea pedis, and 88% of those with nail involvement at the time of treatment reported improvement. In contrast, tinea pedis remained cured in only 30% of the patients who had received griseofulvin, and onychomycosis improved in only 14%. ",0 505,"Antigen-induced cross-linking of the IgE receptor leads to an association with the detergent-insoluble membrane skeleton of rat basophilic leukemia (RBL-2H3) cells. Cross-linking of the IgE receptor on the surface of rat basophilic leukemia cells by multivalent Ag (DNP-BSA) causes a rapid conversion to a detergent-insoluble form. There is a concurrent increase in the amount of filamentous actin associated with the plasma membrane. Both the degree of receptor detergent insolubility and the rise in F-actin content are rapid with a half-maximal response of less than 1 min and can be rapidly reversed by the addition of monovalent Ag (DNP-lysine). These two early steps in the triggering of rat basophilic leukemia cells can be dissociated from each other by pretreatment of the cells with either cytochalasin or sodium azide. These reagents block the increase in F-actin but have no effect on receptor detergent insolubility. This indicates that microfilaments are not responsible for detergent insolubility of the receptor and that it may be the membrane skeleton that is interacting with the complex. This was further confirmed by the finding that cross-linking of the IgE receptors on the surface of purified plasma membranes also leads to detergent insolubility of the receptor. Therefore, all of the components necessary for detergent insolubility of the receptor are present in the plasma membrane, and cytoplasmic components are not needed. These results suggest that detergent insolubility and immobility of the cross-linked receptors are caused by multivalent interaction with the membrane skeleton. Actin filaments may then interact with these receptor-membrane skeletal complexes in order to produce large scale clustering and capping. The membrane skeleton may therefore be acting as an intermediate structure between the cell-surface receptors and microfilaments. ",3 2621,"A small proportion of cationic antibodies in immune complexes is sufficient to mediate their deposition in glomeruli. Positively charged antibodies mediate enhanced deposition of circulating immune complexes at the glomerular basement membrane. The presented experiments demonstrate that when soluble immune complexes were prepared with a mixture of antibodies containing 10 to 25% cationic antibodies, then noncationic antibodies in the complexes were deposited in mouse glomeruli. One or two cationic antibodies in each immune complex sufficed for deposition of the complexes. Proof for this was obtained by two kinds of experiments. First, the injected immune complexes were prepared in Ag excess from mixtures of radiolabeled noncationic rabbit antibodies to human serum albumin (HSA) and unlabeled cationized rabbit antibodies to HSA, thus permitting the specific quantitation of the deposition of noncationic antibodies in glomeruli because of the presence of cationized antibodies within the same complexes. As a control experiment, immune complexes prepared only with noncationic antibodies resulted in very little deposition in kidneys over the same time period. Second, detection of the localization of the noncationic antibody in deposits in glomeruli by immunofluorescence microscopy was accomplished using immune complexes prepared with mixtures of noncationic goat antibodies to HSA and cationized rabbit antibodies to HSA. Thus, the synthesis of a small population of cationic antibodies during the immune response may lead to the formation of circulating immune complexes with enhanced propensity for deposition in glomeruli in patients with SLE or other immune complex diseases. ",19 3204,"Effects of spermatic vascular division for correction of the high undescended testis on testicular function. Orchiopexy with division of the spermatic artery and veins is a commonly used technique for correcting the high undescended testis, although the longterm results have not been clearly defined. The left spermatic artery and veins of 22 adult Wistar albino rats were divided while preserving the vessels associated with the vas and cremaster muscle (DT). A sham operation was performed on the left testicle of six additional rats (ST). At 3 weeks postoperatively, both testes from all rats were removed. All testes were viable and bled when incised, although bleeding was considerably reduced in testes with DT. Mean testicular weights after DT were 1,061 +/- 423 mg compared with 1,634 +/- 125 mg for ST rats (p less than 0.02) and 1,508 +/- 119 mg for contralateral testes. The mean tubular diameter after DT was 220 +/- 37 mu compared with 303.1 +/- 10.7 mu for ST testes (p less than 0.02). The testicular biopsy score based upon the morphology of the spermatic tubules was 4.46 +/- 3.32 for DT testes and 8.65 +/- 0.23 for ST testes (p less than 0.02) compared with 8.38 +/- 0.18 for contralateral testes and an absolute normal value of 10. No morphologic abnormalities were observed in the contralateral unoperated testes from any of the rats. The contralateral testes in 12 additional rats were removed before DT. The mean testosterone values in these rats with one testicle was 1.43 +/- 0.75 ng/mL. Three weeks after DT, testosterone values were 0.19 +/- 0.31 ng/mL (p less than 0.01). It is concluded that division of the main spermatic artery and vein in rats produces testicular atrophy with spermatogenic arrest and interstitial cell dysfunction. Although collateral blood flow to the testis may be demonstrated, tissue perfusion is inadequate for normal spermatogenesis and endocrine function. ",22 524,"Prognostic significance of nondiploid DNA determined by flow cytometry in sporadic and familial medullary thyroid carcinoma. To clarify the role of DNA measurements in predicting outcome after surgical treatment of medullary thyroid carcinoma (MTC), we performed flow cytometric analysis in nuclear suspensions of 119 MTC tumors. Of the 119 patients, 63 (53%) patients had sporadic tumors and 56 (47%) patients had familial tumors; survivors were followed for a mean of 13 years. DNA content was normal in 92 (77%) patients and abnormal (nondiploid) in 27 (23%) patients. Ten-year cause-specific mortality rates were 12%, 42%, and 49% with diploid, tetraploid/polyploid, or aneuploid tumors (p = 0.0009) and were greater with nondiploid tumors both in the sporadic (p = 0.012) and multiple endocrine neoplasia (familial) cases (p = 0.114). None of 27 patients with TNM stage I disease died of MTC. In patients with TNM stages II, III, and IV disease, DNA nondiploid tumors were associated with increased deaths from MTC. In a Cox proportional hazards model involving all 119 patients and adjusted for disease stage and inheritance pattern, nondiploid DNA was independently associated with increased deaths from MTC (p = 0.008). In an identical Cox model restricted to the 92 DNA diploid tumors, an S-phase fraction of 15.0% or more remained a significant variable (p = 0.034) after adjustment for stage and inheritance pattern. We therefore conclude that DNA measurements do have a role to play in predicting outcome after surgical treatment of MTC. ",3 1626,"Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction. We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole (300 mg) to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days (range 3 to 11) in 50 patients. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct-related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients (53%) with open infarct vessels and in 10 of 14 patients (71%) with occluded infarct vessels. In conclusion, thallium-201 single photon emission computed tomography using oral dipyridamole was safely performed in patients with recent myocardial infarctions who receive thrombolytic therapy. ",13 197,"Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients. Multiple gastric and duodenal biopsy specimens from 102 asymptomatic patients with familial adenomatous polyposis, taken during a prospective endoscopic screening programme were examined. One hundred patients had microscopic gastroduodenal pathology, often in the absence of macroscopic lesions. Adenomas were found in 94 patients in the duodenum, in the second and third parts. Hyperplasia of villous and crypt epithelium was also seen, sometimes in the absence of adenomas: this may be a precursor of neoplastic change. In the stomach fundic gland polyps were the commonest abnormality, seen microscopically in 44 patients. Chronic antral gastritis was common in patients without fundic polyps. Gastric adenomas were present in six patients, all of whom also had duodenal adenomas. If duodenal adenomas in familial adenomatous polyposis have a similar malignant potential to those in the colorectum sequential endoscopy and biopsy are necessary to detect cancer in these patients. ",3 1266,"Assessing acquired ocular diseases. When assessing a patient's ocular complaint, one must listen carefully to the description of the symptoms. A decrease in vision is most frequently the symptom that prompts a person to seek attention. Pain in and around the eye is the next most frequent symptom complained about. Discomfort is often tolerated for long periods before professional attention is obtained. Visual acuity must be checked, for this is the vital sign by which exacerbation or improvement of many conditions is measured. We all take our eyes for granted until we suddenly cannot see, then the world takes on a completely different complexity, for loss of vision may mean loss of livelihood and independence. ",10 1920,"Videodensitometry versus digital calipers for quantitative coronary angiography. Single-plane left coronary angiograms in 18 patients were prospectively analyzed using videodensitometry (XR-70 system) and handheld digital calipers to compare arterial dimensions, stenosis dimensions, intraobserver variability and interobserver variability for the methods. A total of 648 arterial segments were measured, yielding a highly significant correlation between videodensitometry and caliper-determined cross-sectional area (r = 0.96, p = 0.0001). Similarly, a highly significant linear relation was observed between videodensitometry and caliper-determined diameter (r = 0.95, p = 0.0001). When data subsets for small, medium and large arterial segments were examined, higher variability in the correlation between videodensitometry and caliper-determined area was observed in the large segments (greater than 10 mm2). In addition, caliper-estimated areas tended to be slightly smaller than videodensitometry-estimated areas in these segments. For diameter estimations, correlations between caliper and videodensitometry data were similar for the entire range of arterial segment sizes. Intra- and interobserver variability was low for both caliper and videodensitometry determination of diameter or area. Thus, over a wide range of arterial dimensions, results obtained with caliper estimates of luminal area and diameter are comparable to those obtained with videodensitometry using the XR-70 system. ",13 3146,"Indications of the carbon dioxide laser in tracheobronchial pathology of the infant and young child: 14 cases. Fourteen children aged between 6 months and 7 years (mean age = 3.5 years) were treated by CO2 broncholaser in the ENT Department of Trousseau Hospital. Three groups of diagnostic indication were identified: 1. Granulomas treated after mucosal trauma (tracheotomy, foreign body). 2. Granulomas due to pulmonary and/or lymph node tuberculosis. 3. Adhesions and stenosis secondary to neonatal ventilation. The operative and anesthetic technique is described in detail, together with any possible adverse events. The CO2 broncholaser appears to be a technique of choice in this age group, in which the narrowness of the airways makes any endoscopic procedure difficult. The broncholaser allows the early treatment of obstructive tracheobronchial pathology with its risks of severe ventilatory sequelae. ",22 1751,"Transoesophageal echocardiography in the longitudinal axis: correlation between anatomy and images and its clinical implications. Transoesophageal echocardiographic imaging in the longitudinal axis is a recent addition to the non-invasive evaluation of congenital and acquired heart disease. The technique provides unique images of intracardiac anatomy but their interpretation remains difficult. A heart specimen was therefore cut according to the echocardiographic imaging planes to elucidate the morphological details. The results suggested that longitudinal transoesophageal imaging complements the transverse axis approach. It gave new imaging information on the right ventricular outflow tract and the pulmonary trunk, the atrioventricular valves, the interventricular septum, the cardiac apex, and the thoracic aorta. In particular, it showed the entire length of the right ventricular outflow tract. When longitudinal imaging was used in combination with transverse imaging almost all the thoracic aorta could be examined. Imaging in the longitudinal axis may also allow better assessment of the mechanisms of atrioventricular valve regurgitation. ",13 2814,"Medical education for alcohol and other drug abuse in the United States. Initiatives by individuals, private foundations and government have led to improvements in the United States in medical education dealing with alcohol and drug-related problems. Progress has been made, particularly in the past 5 years, in developing new medical school curricula and in faculty development. Greater activity by national professional organizations has helped raise the priority of training in alcohol- and drug-related areas for undergraduate and postgraduate medical education. As an example, Project ADEPT (Alcohol and Drug Education for Physician Training in primary care) at Brown University in Providence, Rhode Island, is described. The importance of positive and motivated faculty role models and of skills training is emphasized. ",20 1131,"Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. In experiment 1, quantitative regional comparisons of the antinociceptive and cardiovascular responses produced by electrical stimulation in the caudal medulla, including regions such as the nucleus tractus solitarius (NTS), nucleus reticularis ventralis (NRV), nucleus reticularis gigantocellularis (NRGC), nucleus reticularis paragigantocellularis (NRPGC), nucleus raphe obscurus (NRO), and medial portions of the lateral reticular nucleus (LRN), were made in the rat. Electrical stimulation in all of these regions resulted in inhibition of the nociceptive tail-flick reflex, although the threshold intensity for inhibition was greater for sites in NTS compared to many sites ventral to the NTS. Antinociception was generally accompanied by an increase in mean arterial blood pressure, with the exception of sites in the NRO, where depressor responses were evoked by stimulation. Detailed comparisons between the NTS and NRV revealed that greater intensities of electrical stimulation were required to produce antinociception for sites in the NTS as compared to the NRV. There were no significant differences in threshold intensities for antinociception as a function of rostrocaudal subdivisions of the NTS, but the lateral subdivision of the NTS was significantly more efficacious than the medial subdivision. This mediolateral difference within NTS was primarily due to stimulation in medial sites producing overt movements in some animals, probably due to stimulation of adjacent midline nuclei or pathways. Within the NRV, thresholds for inhibition of the tail-flick reflex were greater for sites in the dorsal subdivision as compared to the ventral subdivision, which contains spinopetal projections from the NRM. The slopes of the lines of recruitment for inhibition of the tail-flick reflex at stimulation sites in either the NTS or NRV were both very steep, similar to other forms of antinociception. In experiment 2, the pulse duration of electrical stimulation was varied for sites of stimulation in the lateral NTS and NRV to generate strength-duration curves. This experiment confirmed that stimulation sites in the lateral NTS required greater current intensities to inhibit the tail-flick reflex than sites in the NRV. However, the chronaxies derived from the strength-duration functions for the NTS or NRV were both approximately 170 microseconds, indicating that the antinociceptive effects in these regions may not be exclusively due to the stimulation of fibers of passage. These results are discussed in terms of the role of the NTS, NRV, and caudal medulla in the modulation of nociceptive responses and cardiovascular function. ",9 433,"Localization and peptide content of endocrine pancreatic tumors. Endocrine pancreatic tumors contain and frequently secret neurohormonal peptides. This phenomenon can be used as a diagnostic and classifying tool. This study analyzes 31 patients operated on because of an endocrine pancreatic tumor, including the diagnostic procedures and the localization methods. In 15 insulinoma cases only 6 patients had a positive arteriography, while all 11 selective pancreatic vein samplings were positive. The immunoreactivity showed that, besides insulin, most tumors also contained other peptides. Of four gastrinoma cases the arteriography was positive in three, but the selective vein sampling localized the tumor in all. The tumor's content of peptides showed mixed patterns. In the four glucagonomas, the arteriography was positive in all and the venous sampling performed in three of the cases also was positive. In five pancreatic polypeptide-containing tumors (PP-omas) the arteriography was positive in four and sampling performed in two was positive in both. In the PP-omas the peptide pattern showed that these tumors frequently contain several peptides. We used selective pancreatic vein sampling in 21 cases with positive result in all. In the cases in which arteriography was negative, the sampling results helped the surgeon to find the tumor. The peptide pattern in the tumors varied greatly and most tumors were multihormonal. ",3 523,"Intraoperative decision making during thyroid surgery based on the results of preoperative needle biopsy and frozen section. Prognostic factors in well-differentiated thyroid cancer are age of the patient and grade, size, distant metastasis, and extracapsular spread of the disease. However, the surgeon is often not sure about the pathologic diagnosis of thyroid nodules. The accuracy of preoperative studies, such as ultrasonography and thyroid scanning, is limited. The most cost-effective test is fine-needle aspiration, the accuracy of which exceeds 80% in most series. However, a large group of nodules exist for which aspiration cytologic studies are considered to be either suspicious or indeterminate. The decision about the extent of thyroidectomy may be difficult in these patients. Intraoperative frozen section may help the surgeon to distinguish benign from malignant lesions, but as in fine-needle aspiration, the major problem is the distinction between follicular adenoma and follicular carcinoma. The frozen section diagnosis of follicular adenoma was changed to follicular carcinoma in one third of the cases (13 of 38 cases). The decision about the extent of thyroidectomy in patients with follicular adenomas was based on other prognostic factors, such as age and sex of the patient and the size of the nodule. The accuracy of frozen section diagnosis was 95%. Our experience suggests that decisions regarding the extent of thyroidectomy can best be made by preoperative fine-needle aspiration with confirmation by frozen section diagnosis in equivocal cases. ",3 2650,"The prevalence of antibody to HTLV-I/II in United States plasma donors and in United States and French hemophiliacs. Antibody to HTLV-I/II was detected in 19 (0.3%) of 6286 plasma donors from five regions of the United States (US). This seroprevalence rate is approximately 10 times that in whole blood donors. The regional distribution of infection was as follows: Southwest, 0.68 percent; Southeast, 0.45 percent; Midwest, 0.28 percent; Northwest, 0.1 percent; and Northeast, 0.0 percent. Rates of HTLV-I/II infection in blacks (0.74%) and Hispanics (0.66%) were higher (both, p less than 0.001) than those in whites (0.08%). All 19 infected units were donated by subjects aged 30 or older, even though 52.9 percent of the donations came from persons less than 30 years old. Equal rates of HTLV-I/II infection were found in men (0.31%) and women (0.29%). No HTLV-I/II antibody was detected in 154 French and 25 US hemophiliacs who were transfused regularly with noninactivated plasma or its derivatives. This suggests that the transfusion of HTLV-I/II-seropositive plasma products does not transmit the viral infection. ",19 2862,"Portrayals of alcohol on prime-time television. Alcohol portrayals were analyzed for a 3-week composite sample of prime-time fictional television programs aired in the fall of 1986. Approximately 64% of the 195 episodes contained one or more appearances of alcohol. Alcohol was ingested on 50% of all programs. Overall, there were 8.1 alcohol drinking acts per hour. Movies made-for-television had the highest rate of drinking acts per hour (10.0) followed by situation comedies (9.2) and then theatrical movies (7.4) and dramas (7.4). Within the category of dramas, evening soap operas stand out with 13.3 acts per hour. Drinking and nondrinking characters were compared on a number of attributes relevant to role modeling. Regularly appearing characters were more likely to drink than nonregular characters. Drinking characters also tended to be of high status, largely being white, upper-class professionals. A time trend analysis showed a regular increase in alcohol on television from 1976 to 1984, reaching 10.2 acts in 1984. After 1984 the trend appears to reverse. ",20 2112,"Socioeconomic conditions in childhood and ischaemic heart disease during middle age OBJECTIVE--To examine the association between socioeconomic conditions in childhood and ischaemic heart disease in middle aged men, including the role of physiological and behavioural risk factors. DESIGN--Prevalence study with extensive examination and testing and with recall of childhood conditions. SETTING--Population based study in Kuopio, Finland. SUBJECTS--Representative sample of 2679 men aged 42, 48, 54, and 60. MAIN OUTCOME MEASURES--Ischaemic findings on progressive maximal exercise test. RESULTS--Low socioeconomic style in childhood was associated with significantly higher prevalence of findings indicating ischaemias. Compared with those in the highest tertile of childhood socioeconomic conditions, the age adjusted odds ratio for subjects in the lowest tertile was 1.44 and for those in the middle tertile 1.35. Adjustment for years of cigarette smoking times the average number of cigarettes smoked, ratio of high density lipoprotein to low density lipoprotein cholesterol, fibrinogen and serum selenium concentrations, and adult height did not appreciably weaken the association. Adjustment for adult socioeconomic state resulted in a 16% decline in the association. The association was reduced to non-significance by adjustment for measures of prevalent cardiovascular illness. CONCLUSIONS--Socioeconomic state in childhood was significantly associated with ischaemic heart disease in middle aged men. Levels of risk factors measured at middle age did not account for this association, nor did adult height. Because childhood socioeconomic conditions precede the development of ischaemic heart disease the substantial impact of prevalent illness on the observed association suggests that ischaemic heart disease develops earlier in those with lower socioeconomic state during childhood. ",13 611,"A sequential three-step lateral release for correcting fixed valgus knee deformities during total knee arthroplasty. An approach to mild, moderate, and severe fixed valgus deformities of the knee is described. The sequential approach to soft-tissue releases in the fixed valgus knee allows the surgeon to regain a neutral alignment in valgus deformities of up to 90 degrees. An additional benefit of the approach is spontaneous correction of fixed external tibial rotation deformities. Using this approach, early and late stability allows the use of unconstrained knee implants, including those with mobile-bearing elements. ",4 2738,"Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep. Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI. ",20 1609,"Lower extremity venography with iohexol: results and complications. The frequency of side effects of a nonionic contrast agent (iohexol) was studied in 463 consecutive patients who underwent venography for clinically suspected deep-vein thrombosis (DVT) and compared with the frequency of adverse reactions of another series in which patients received either the same contrast material or a high-osmolar ionic compound. Minor side effects, including local pain and discomfort, nausea and vomiting, dizziness, skin reactions, superficial phlebitis, and edema, occurred in 83 patients (17.9%; 95% confidence interval [CI], 15%-22%). The only serious adverse reaction (bronchospasm) was seen in two patients (0.4%; 95% CI, 0.1%-1.4%). Postvenographic thrombosis confirmed by means of repeat venography occurred in one of 41 consecutive patients with a previous normal venogram (incidence, 2%; 95% CI, 0%-13%). The frequency of side effects appears to be significantly less than when conventional high-osmolar contrast agents are used. Use of iohexol for venography is associated with minor side effects in approximately one-fifth of patients, and serious adverse reactions necessitating therapy are rare. ",13 3254,"Effects of 1.32-micron Nd-YAG laser on brain thermal and histological experimental data. Considering that the 1.32-microns Nd-YAG laser should have physicothermal properties close to those of the CO2 laser, a series of experiments were conducted on rat cortex (N = 51). Three laser wavelengths were compared: CO2 laser (10.6 microns), 1.06-microns Nd-YAG, and 1.32-microns Nd-YAG lasers. For each shot, temperature measurements were recorded with an infrared thermographic videocamera. The digitized signals were figured as thermal profiles and temperature developments. Ninety-five shots were correctly studied and analyzed: CO2, N = 29; 1.06-microns Nd-YAG, N = 20; 1.32-microns Nd-YAG, N = 46. The histological lesions produced by these three lasers were compared on animals killed 24 hours (N = 20), 8 days (N = 20), and 30 days (N = 5) after the laser impacts. For equivalent densities of energy, the depth of cortical necrosis was comparable for the CO2 laser (200-250 microns) and the 1.32-microns Nd-YAG laser (210-260 microns) whatever the date of death; the 1.06-microns Nd-YAG laser shots were responsible for much more important damage (400-550 microns). Because of its important absorption in water and nervous tissue, the authors consider the 1.32-microns Nd-YAG laser most suitable for neurosurgery, particularly because it is conducted through optic fibers, and therefore is easy to handle during neurosurgical procedures. ",22 1212,"Phenotypic heterogeneity of spinal muscular atrophy mapping to chromosome 5q11.2-13.3 (SMA 5q). We made phenotypic analysis of 14 families with spinal muscular atrophy (SMA) linking to chromosome 5q11.2-13.3 (SMA 5q), and 2 that may not map to this locus, to assess clinical symptoms among SMA families known to result from mutation at the identical gene/locus. Although the current number of families is still small, the correlation of clinical phenotype and molecular genotype supports 2 observations. First, SMA mutations at the 5q locus present with a broad continuum of clinical abnormalities, and 2nd, the single clearly unlinked family presents with an unusual phenotype characterized by relatively late onset and early death. Thus, there are as yet no unambiguous cases of typical SMA families that are clearly unlinked to the locus at 5q-ie, no clear cases of nonallelic heterogeneity. Analysis of SMA 5q families supports the view that, with certain exceptions, there is little phenotypic intrafamilial variability. When families were ranked by severity of disease there was a strong correlation with age of onset. Onset within the 1st few months was associated with early death, but not in all cases. With rare exception, onset after 1 year of age was associated with less severe disease and greater longevity. ",9 3245,"The use of gadolinium-enhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. Gadolinium-enhanced magnetic resonance imaging has been used to evaluate 20 patients with surgically confirmed facial nerve lesions. When the nerve could be seen, gadolinium-enhanced magnetic resonance imaging accurately revealed the lesion site as well as the known extent, which in some cases was not predicted by topognostic testing. This technique appears to provide accurate lesion-site testing and may have importance in surgical planning. Currently used topognostic tests of facial nerve function are frequently inaccurate and can only determine the most proximal lesion site when there are multiple or extensive lesions. The focal nerve enhancement seen in nerve injury, globally increased signal intensity within the temporal bone after trauma, and increased signal intensity within the dura after surgery can occasionally mask nerve lesions and may be confused with tumors. ",22 3290,"Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study. This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05). ",22 351,"The potential of 2-deoxy-2[18F]fluoro-D-glucose (FDG) for the detection of tumor involvement in lymph nodes. To assess the potential of FDG for PET imaging of nodal tumor metastases, we evaluated its uptake into normal lymph nodes, tumor-involved lymph nodes, and subcutaneous tumor xenografts in rodents. Normal lymph nodes in mice and rats accumulate FDG moderately, developing node/blood ratios of 1.3-11.9/1 at 2 hr following i.v. injection. By contrast, FDG given subcutaneously to healthy Sprague Dawley rats developed very high normal draining lymph node/blood ratios (272/1) versus 7.7/1 by i.v. injection. In nude mice, subcutaneous human ovarian cancer xenografts had 1.27-fold more uptake relative to blood than did normal popliteal lymph nodes. Subcutaneous tumor xenografts of rat breast cancer developed tumor/normal node uptake ratios of 4.91 +/- 0.43/1 and tumor/blood ratios of 6.6 +/- 0.9 at 2 hr postinjection. Mouse nodes involved with 38C13 murine B-cell lymphoma had mean node/blood ratios of 42.9 +/- 6.7/1 and tumored node/normal lymph node uptake of 6.3/1. Thus, FDG given intravenously but not subcutaneusly (due to high normal nodal uptake) has potential as an agent for the detection of metastatic tumors in regional lymph nodes using PET scanning. ",3 2514,"Total serum glycosylated proteins in detection and monitoring of gestational diabetes. The goal of this study was to determine whether serum glycosylated protein levels (i.e., fructosamine) can reliably screen for gestational diabetes and whether these levels are valid markers of short-term glycemic control in the third trimester of pregnancy. Ninety-seven pregnant women at 26-28 wk gestation were evaluated over 9 mo. HbA1c and serum glycosylated protein (serum fructosamine) were determined at the baseline venipuncture of the 100-g oral glucose tolerance test performed to detect gestational diabetes. Of the 97 women studied, 13 tested positive for gestational diabetes (National Diabetes Data Group criteria). There were significant differences in the fasting and 1-, 2-, and 3-h glucose values between nondiabetic and diabetic patients (P less than 0.005 at each time point). No difference was noted in the baseline serum glycosylated protein level (2.02 +/- 0.08 vs. 1.98 +/- 0.02 mM, NS) or HbA1c level (4.42 +/- 0.2 vs. 4.6 +/- 0.3%, NS) between gestational and nondiabetic patients. Diabetic patients were followed at 2-wk intervals, with serum glycosylated protein analysis, HbA1c, fasting glucose, and mean glucose determined by outpatient monitoring. Serum glycosylated protein correlated significantly to fasting blood glucose (r = 0.81, P less than 0.001) and mean outpatient glucose (r = 0.62, P less than 0.001) at the 2-wk follow-up visits. No correlation was found between HbA1c and fasting blood glucose (r = 0.11, NS) or mean outpatient glucose (r = -0.12, NS) during the follow-up period. The serum glycosylated protein level (serum fructosamine) is not a useful screening test for gestational diabetes. However, this assay shows potential as an objective marker of short-term control in evaluating the maternal glycemic state. ",18 266,"Persistence of mucosal gastric carcinomas for 8 and 6 years in two patients. A small gastric carcinoma was detected in a man, but he refused surgery. Eight years later, he was readmitted for a check-up, and a partial gastrectomy was performed. Pathologic examination revealed a well-differentiated adenocarcinoma restricted within the mucosa. In another man, an irregularly shaped, grossly depressed lesion indicating a malignancy was present at the gastric angle, and 6 years later he agreed to a partial gastrectomy. The lesion proved to be a well-differentiated adenocarcinoma confined to the mucosa. Retrospective examination of the original biopsy specimen revealed a small area of adenocarcinoma, presumably overlooked at the initial examination. Thus, some gastric carcinomas of the well-differentiated type can grow at an extremely slow rate, without extensive spread or invasion. Findings in these cases contribute to knowledge of the biological behavior of gastric carcinomas. ",3 2271,"Use of molecular cloning methods to map the distribution of epitopes on topoisomerase I (Scl-70) recognized by sera of scleroderma patients. We report the initial molecular characterization of the autoimmune response against DNA topoisomerase I (topo I; Scl-70). Sera from 36 patients with scleroderma and 4 healthy control subjects were studied using 6 subcloned portions of topo I. Twenty-three sera recognized at least 2 independent epitopes on the molecule. Therefore, anti-topo I, like other non-organ-specific autoantibodies characterized to date, is polyclonal and multifocal. The cloned protein should prove suitable for sensitive early detection of anti-topo I in the clinical setting. ",16 222,"Clinical problems in follow-up of patients after conservative surgery and radiotherapy. Patients treated with conservative surgery and radiotherapy for early-stage breast carcinoma are at risk of developing an ipsilateral breast recurrence for a long period. Fortunately, few such patients present with an inoperable recurrence or simultaneous distant metastases. Salvage rates are high and may be improved by early detection. Although usually unambiguous, physical examination of the treated breast may reveal changes attributable to surgery and radiotherapy that can mimic a recurrent cancer. There also is substantial overlap in radiologic appearance between benign and malignant lesions. It may be necessary to perform a biopsy when there is a question of recurrence. Careful life-long follow-up of patients thus is a critical part of their care. ",3 2943,"Arterial abnormalities of the shoulder in athletes. Vascular lesions of the shoulder may be misinterpreted as one of the more familiar shoulder abnormalities by a treating physician. We are reporting on 13 athletes who were found to have symptoms related to compression of the subclavian or axillary artery or their tributaries. Nine were amateur or professional baseball pitchers. Severe arm fatigue or finger ischemia, secondary to embolization, were presenting symptoms. Arm fatigue was noted in all pitchers. After complete history and physical examination, including auscultation for bruits in functional positions, all athletes were evaluated by noninvasive tests (Doppler and Duplex scanning). Arteriography was performed with positional testing, recreating overhead activity, and complete radiographic visualization of the dye to the digital arteries. Two patients were found to have subclavian artery aneurysm. The remaining athletes were found to have compression of the subclavian artery beneath the anterior scalene muscle (five patients), the axillary artery beneath the pectoralis minor (two patients), both arterial segments (two patients), and one was found to have arterial compromise at the level of the humeral head. Branch artery compression was also noted. One pitcher occluded the posterior circumflex humeral artery with embolization to the digit. The two patients with subclavian aneurysms underwent saphenous vein bypass with cervical rib resection. All of the other athletes except one underwent resection of a 2 to 3 cm segment of the anterior scalene muscle or pectoralis minor muscles. All returned to their previous level of activity except one patient who developed impingement type symptoms and required acromioplasty. He is currently undergoing rehabilitation. Proper recognition of vascular compromise in the upper extremity of athletes is essential to avoid the catastropic complications of arterial thrombosis. ",20 1375,"The kinetics of cellular proliferation in rat urinary bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. The cellular proliferation of the bladder epithelium was determined sequentially in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in vitro labeling technique. The percentage of labeled cells was expressed as the labeling index (LI). The average LI values in normal subjects and cancer-bearing subjects were 5.1(%) and 24.2(%) respectively. With the transition of the bladder epithelium from simple hyperplasia to cancer, the LI values of the bladder epithelium were increased. Cases of papillary or nodular (PN) hyperplasia were divided into two types according to the localization of the BrdUrd-labeled cells. The LI in PN hyperplasia was 12.4(%); the difference from cancer was significant. In another experiment, the effect of partial cystectomy on bladder tumors was examined. The group with partial cystectomy showed increases in grade and stage of cancer, and the LI of cancer was more than that in the group without partial cystectomy. The results indicate that partial cystectomy may play a role as promotor for bladder tumors. The current study may be of more practical value than is the conventional one for investigating the histogenesis and progression of human bladder cancer. ",11 864,"Periodontics in general practice: professional plaque control Traditionally the primary emphasis of preventive periodontics was daily patient performed plaque control. Recent studies indicate that frequent professional subgingival toothcleaning is a mandatory treatment for prevention of recurrent periodontitis. Pathogenic subgingival bacterial complexes are disrupted by frequent cleaning and require time to reestablish. Disease progression is prevented if the recall interval does not exceed the time required for reestablishment of a pathogenic plaque. Legally, patients have acquired the duty to comply with the prescribed recall interval. Both the patient and the practitioner will benefit from a preventive program that includes frequent professional subgingival toothcleaning. ",6 752,"Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years. To define long-term prognosis of children who underwent surgery for biliary atresia, a retrospective study was undertaken in 122 children who underwent one of the Kasai procedures between 1968 and 1977. Forty of the 122 children (32.7%) were alive after 10 years. Firm hepatomegaly was present in 31 and splenomegaly in 29 children. Serum bilirubin or all liver function tests were normal in 21 and 11 children, respectively; survival rate decreased with the age at operation, but no significant difference was observed in the rate of children surviving with normal serum bilirubin whether they underwent surgery before age 2 months or between 2 and 3 months. Twenty-four had esophageal varices and 15 experienced gastrointestinal bleeding. Normal liver-function tests and absence of portal hypertension were observed in 11 of 122 children. These results indicate that Kasai's procedures were helpful in a significant proportion of children with biliary atresia who underwent surgery during this period. However, 80% of children who initially underwent surgery with Kasai's procedures should eventually undergo liver transplantation. ",5 2991,"Rapid admixture blood warming: technical advances. The technique of rapid admixture blood warming of cold erythrocyte units is designed to warm erythrocyte units rapidly (less than 30 sec) while simultaneously providing saline for dilution. However, questions have been raised about the recommended use of a standard 250-ml bolus of 70 degrees C admixture saline, the uniformity and speed of blood unit warming, the difficulties inherent in keeping saline bags at 70 degrees C, and the safety of the methodology. To answer these questions, a series of tests were performed and modifications of the technique were introduced. The mean weight of 1000 successive units of erythrocytes for adult infusion was 305 g (range 220 to 410). The maximum temperature was 44 degrees C, using an internal temperature probe (1-cm temperature gradations; 2-sec recording intervals) when the smallest unit was admixed with a 250 ml 70 degrees C saline bolus; the largest unit had a minimum temperature of 30 degrees C. Plasma Hgb, osmotic fragility, and K of the minimum size erythrocyte unit showed no significant deviation from its control. Both thermographic photographs and the internal temperature recordings of the erythrocyte units demonstrated that solely due to fluid turbulence, uniform mixing occurs within approximately 30 sec of beginning the admixture process. Inverting the blood units caused a thermal layering of fluids and an unacceptable maximum blood temperature of 50 degrees C. There was no difference between the mixing time or efficacy in the presence of standard or large-bore iv tubing or additional in-line filters. Volumes of the 250-ml saline bags for admixture decreased markedly with deviations in electrolyte composition after greater than 2 wk at 70 degrees C. ",22 1511,"Screening for trisomy 21 with ultrasonographic determination of biparietal diameter/femur length ratio. Ultrasonographic determination of biparietal diameter/femur length ratios performed at 16 or 17 weeks' gestation in fetuses with trisomy 21 were not statistically different from those of 155 normal fetuses. It appears that this test could not be used for screening for trisomy 21. ",12 1005,"Identification and characterization of middle ear vascular leakage sites in experimental otitis media. The site of leakage in middle ear vessels was determined and characterized in experimental otitis media in rats. Middle ear effusion was induced by intravenous administration or local application in the tympanic bulla of substance P (SP), acetylcholine, and histamine. In another experiment, a 14 degrees C airstream was blown into the external auditory canal. Colloidal carbon was used to trace leakage sites at the light and electron microscopic levels. All mediators tested and the 14 degrees C airstream resulted in an increased number of leaking vessels in the pars flaccida and the middle ear mucosa. The leakage sites were restricted to capillaries and postcapillary venules. Increased numbers of degranulated pars flaccida mast cells were observed for SP only. Interendothelial gaps formed in leakage vessels after administration of mediators and stimulation of the external auditory canal with a 14 degrees C airstream. Also, cytoplasmic vesicle-like structures within the endothelial cells increased in number following SP and histamine treatment, suggesting that an increased permeability in experimental otitis media does not occur exclusively through interendothelial gaps. ",8 1261,"Increase of neuroretinal rim area after surgical intraocular pressure reduction. The Optic Nerve Head Analyzer was used to measure the optic disc structure of 18 eyes (13 adult glaucoma patients) before and after surgical intraocular pressure reduction. Neuroretinal rim area markedly increased (from +0.15 mm2 to +0.45 mm2) in eight eyes, but changed either very little (less than +/- 0.1 mm2) or not at all in the remaining 10 eyes. The mean increase was from 0.75 +/- 0.26 mm2 to 0.92 +/- 0.36 mm2. The increased neuroretinal rim area found at this time remained in all eyes reexamined 1 to 3 years after surgery. Our data support previous findings that glaucomatous disc cupping may be reversed even in adult eyes, perhaps as the result of adequate pressure reduction. ",10 1457,"Heterologous transplantation of activated murine peritoneal macrophages inhibits gamete interaction in vivo: a paradigm for endometriosis-associated subfertility. Macrophage hyperactivation has been postulated to be the pathologic aberration in patients suffering from endometriosis-associated subfertility. In this report an in vivo model for macrophage-mediated infertility is described. Populations of macrophages were obtained from an inbred strain of mice (Balb/C) as follows: (1) in vivo hyperactivated macrophages (harvested from donor mice treated with intraperitoneal thioglycolate); (2) hyperactivated macrophages deactivated ex vivo with the protein synthesis inhibitor emetine; and (3) basal state (nonactivated) macrophages obtained from untreated mice. Recipient mice underwent ovarian hyperstimulation with pregnant mare serum gonadotropins; 2 x 10(6) macrophages were transferred on the afternoon of stimulation day 3 before injection of human chorionic gonadotropin (hCG) and mating. Unfertilized oocytes and 4-cell embryos were counted on day hCG +2 as a reflection of reproductive performance. Heterologous transfer of in vivo hyperactivated macrophages, but not basal state macrophages, significantly inhibited fertilization. This effect was largely reversed by pretreatment with emetine. These experiments confirm the relevance of macrophage-mediated interference with early reproductive performance and provide a model for the development of alternative therapies (e.g., immunomodulation of the peritoneal fluid environment) for endometriosis-associated subfertility. ",12 1999,"Bronchiolar morphology after systemic arterial interruption. To assess ischemic lesions as a factor in obliterative bronchiolitis after lung transplantation, the authors severed the left bronchial arteries of 15 dogs, together with the left stem bronchus, the latter being immediately reanostomosed. They examined the bronchioles at weekly interfals up to three and a half months. On the week chosen each dog was anesthetized, totally heparinized, and exsanguino-perfused with saline. Just after heart arrest, the thoracic aorta was injected with a barium solution until this white medium appeared in the bronchial arteries. The heart-lung blocs were excised en bloc, submitted to soft-tissue x ray, fixed, and then sliced to 1 cm. Corresponding right and left 5-mm-thick samples of these slices were prepared for contact microradiography followed by histologic 5-to-20-micron-thick, stained, correlated specimens. For two weeks the left bronchial arteries remained empty, but there was no necrosis or edema. Between two and four weeks barium solution appeared in the bronchial arteries, and the bronchiolar epithelium had become multistratified. Later the left bronchiangiogram became similar to the right, but there were more folds of the mucosa and a little submucosal fibrosis. These studies provide proof that no significant ischemic lesions occurred during repermeation of the bronchiolar vascular bed. Ischemia, if existent, is not a significant factor in obliterative bronchiolitis. ",13 2747,"Long-term prognosis of soft-tissue injuries of the neck. We reviewed 43 patients who had sustained soft-tissue injuries of the neck after a mean 10.8 years. Of these, only 12% had recovered completely. Residual symptoms were intrusive in 28% and severe in 12%. Pain in the neck and lower back was the commonest complaint and older patients had a worse prognosis. After two years, symptoms did not alter with further passage of time. ",20 1910,"Transient myocardial ischemia and its relation to determinants of myocardial oxygen demand. Because of conflicting data and a clear need to establish the relative role of increase in myocardial oxygen demand versus reduction in coronary blood flow in the causation of transient ischemia, the role of heart rate and blood pressure changes immediately preceding and during the transient ischemic events observed during daily life were evaluated in 25 patients with coronary artery disease. Elevations in heart rate before onset of ischemia were observed in 61% of the episodes. Similarly, 73% of the ischemic events were preceded by an increase in arterial pressure. These data provide evidence for a significant role of increased myocardial oxygen demand in the genesis of transient myocardial ischemia. ",13 605,"Lumbar discography followed by computed tomography. Refining the diagnosis of low-back pain. Two hundred fifty patients with low-back pain who underwent lumbar discography followed by computed tomography (CT) are the subject of this prospective study. In 93% of the patients, these combined imaging techniques provided additional useful diagnostic information that affected patient management and the selection of treatment alternatives. Lumbar discography followed by CT proved valuable in determining the significance of equivocal or multiple level abnormalities, determining the type of disc herniation, defining surgical options, and evaluating the previously operated spine. In 94% of patients who had surgery, CT-discography correctly predicted the type of disc herniation as protruded, extruded, sequestrated, or internally disrupted. Computed tomography-discography may be more sensitive that magnetic resonance imaging (MRI) in the early stages of disc degeneration because 18 of 177 discs with a normal T2-weighted image were discographically abnormal and the CT-discogram revealed annular tears or radial fissuring. The radiographic morphology of the normal herniated and degenerative lumbar discs shown by CT-discography gives unique insight into the pathogenesis of disc degeneration. The complications that followed the 750 discograms were one case of urticaria and one disc space infection. Even with the availability of high resolution CT and MRI, lumbar discography remains the only pain provocation challenge to the lumbar disc. ",4 1973,"Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis. Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction. ",13 2984,"Is fibrillation chaos? Ventricular fibrillation is examined to determine whether it is an instance of deterministic chaos. Surface ECGs from dogs in fibrillation were used to generate a state space representation of fibrillation. Our analysis failed to identify a low-dimensional attractor that could be associated with fibrillation. The results suggest that fibrillation is similar to a nonchaotic random signal. We note, however, that such random-looking but nonchaotic behavior can also be generated by a nonlinear deterministic system. ",22 40,"Monoclonal antibody to mouse lipopolysaccharide receptor protects mice against the lethal effects of endotoxin. Specific endotoxic lipopolysaccharide (LPS) binding sites on the cell membranes of murine lymphocytes and macrophages that may serve as functional receptors for LPS have recently been identified using photoactivatable cross-linking LPS derivatives. A monoclonal antibody (Mab 5D3) with specificity for this 80-kDa protein has also been generated and characterized. The capacity of MAb 5D3 to protect mice against the lethal effects of endotoxin was investigated. Pretreatment of CF1 mice with as little as 15 micrograms of MAb 5D3 provided virtually complete protection against a dose of endotoxin 10-fold greater than that required to kill all mice in an untreated control group using the galactosamine sensitization model. Significant protection was also afforded normal mice given MAb 5D3 relative to saline. Several lines of evidence suggest that MAb 5D3-mediated protection is due to the agonist properties of this antibody rather than a receptor blockade mechanism. ",0 3115,"Balloon dilatation versus surgical revision of infra-inguinal autogenous vein graft stenoses: long-term follow-up. Although infra-inguinal autogenous vein graft stenoses may be treated by balloon dilatation (PTA) or surgical revision, the optimal approach is undefined. Over the last 7 years 24 PTA procedures were performed on 37 vein graft stenoses in 19 grafts. Graft stenoses were diagnosed from 2 to 72 (mean = 17.3) months after implantation. PTA was successfully completed in 23 (96%) of the 24 procedures including 18 (95%) of the primary, and 5 (100%) of the secondary procedures. Recurrent vein graft stenosis or graft thrombosis developed in 12 (67%) grafts from 3 to 47 (mean = 12.5) months after primary PTA. Long-term patency after primary PTA was 69% at 6, 29% at 12, and 22% at 36 months; secondary patency was 81% at 6, 45% at 12, and 27% at 36 months. During the same period vein graft stenosis in 7 fem-pop and 2 fem-tib grafts were surgically revised with an initial success rate of 100%, and 2 (22%) complications. Four (44%) of these grafts occluded from 1-17 (mean 6.2) months after repair, yielding a primary 5-year patency of 62%. Although vein graft stenosis may be safely, effectively, and repeatedly treated with PTA, long-term durability appears to be superior after surgical revision. ",22 726,"From Leningrad to the day-care center. The ubiquitous Giardia lamblia. Giardiasis is recognized as a worldwide public health problem. Seroprevalence data from both the developing and developed world show high rates of carriage in populations at risk for fecal-oral transmission, such as children in day-care centers. Outbreak investigation has expanded our understanding of reservoirs for Giardia lamblia and of the routes of transmission. Various host factors have been associated with infection. The pathogenesis of giardial infections is being elucidated, in particular the role of lectin activation in producing disease. Three standard chemotherapeutic agents are available in the United States. The institution of community-wide prevention measures is equally important. Current areas of investigation including antigenic composition and enzymatic variants should result in effective forms of immunotherapy, while more effective forms of chemoprophylaxis could assist in eradicating the pathogen from institutional settings. ",5 2248,"Prevalence and sources of sensitization to emulsifiers: a clinical study. 737 patients with suspected cosmetic- or medicament-related contact dermatitis were patch tested with 6 emulsifier agents: triethanolamine, cetyl stearyl alcohol, sorbitan sesquioleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monooleate, and Amerchol L 101. 39 patients (5.3%) gave 1 or more positive patch tests to emulsifiers. A total of 54 positive reactions were found, 23 of which were clinically relevant, triethanolamine being the most frequent sensitizer. Patients with emulsifier sensitivity generally give a high prevalence of positive patch tests to other common ingredients of topical preparations, such as preservatives or active ingredients. Cosmetics and topical medicaments were detected as the source of sensitization in an equal number of patients. Patch tests with patients' own causative preparations were frequently negative. To avoid overlooking emulsifier sensitivity, it is advisable to test these compounds in patients with contact dermatitis that is possibly due to topical preparations, regardless of whether they have other clinically relevant positive reactions or whether patch tests with their own products are negative. ",16 1598,"Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. To precisely define the incidence, type and consequences of cardiac arrhythmias early after heart transplantation, 25 cardiac transplant recipients were monitored continuously for 728 days from the day of surgery to discharge or death. A subset of 15 patients had sinus node function studies with overdrive suppression performed weekly at the time of endomyocardial biopsy. Results revealed sinus bradycardia in 10 patients (40%) and junctional bradycardia in 6 (24%). Supraventricular tachycardia in the form of atrial tachycardia, atrial fibrillation and atrial flutter occurred in 11 patients (44%). Ventricular tachycardia occurred in 15 patients (60%) and was nonsustained in all. Cardiac pacing for 1,403 h was used in nine patients with a pulse rate less than 50 beats/min; seven recovered and permanent pacing was instituted in two. In the subgroup that had sinus node function studies, seven patients were identified with clinical bradyarrhythmia; each had abnormal sinus node recovery time (greater than 1,400 ms) and abnormal corrected sinus node recovery time (greater than 525 ms) in at least one study. These seven patients also had a significantly prolonged ischemic time (236 +/- 26 versus 159 +/- 68 min, p less than 0.01). In conclusion, cardiac arrhythmias, particularly ventricular tachycardia and bradyarrhythmia, occur more commonly early after orthotopic heart transplantation than has previously been reported. Sinus node dysfunction due to prolonged organ ischemic time, antiarrhythmic drug use or surgical trauma, alone or in combination, may contribute to these arrhythmias. ",13 742,"Effect of race upon organ donation and recipient survival in liver transplantation. The effect of the race of the donor on organ donation and on the outcome of clinical liver transplantation has not been addressed previously. The aims of this study were to determine: (1) the number of organs donated by each of the major racial groups of the United States, (2) the outcome of transplantation of these organs across racial groups, and (3) the pattern of liver disease that required transplantation in each of these racial groups. A significantly higher proportion of organs were donated by white non-Hispanic Americans than either black or Hispanic Americans. There was no significant difference in survival when an organ was transplanted between black and white Americans and vice versa. Postnecrotic cirrhosis from a variety of causes was the most common indicator affecting black and white recipients, while primary biliary cirrhosis and primary sclerosing cholangitis were uncommon in the black population. While the number of organs donated by blacks was low, it was, however, proportional to the number of black recipients in this study. Reasons for the low rate of donation by the black and white Hispanic population are discussed. It is concluded that race is not a criteria to be used in selection of donors for liver transplantation. Educational programs addressing issues of organ donation and transplantation directed towards the black and Hispanic populations are recommended. ",5 2605,"SLE nephritis: an ultrastructural immunogold study to evaluate the relationship between immune complexes and the basement membrane components type IV collagen, fibronectin and heparan sulphate proteoglycans. The nature of immune complexes and their relationship to the normal glomerular basement membrane (GBM) components type IV collagen, fibronectin, and heparan sulphate proteoglycans (HSPG) have been examined in the glomeruli of 7 cases of systemic lupus erythematosus (SLE) glomerulonephritis using an ultrastructural immunogold technique. In paraformaldehyde-fixed, Lowicryl resin-embedded tissue, the electron-dense deposits contained IgG, IgM, IgA, and C3 whether they were subepithelial, intramembranous, subendothelial, or mesangial and there was no particular relationship between the class of immunoglobulin and site of immune complex localization within the glomerulus. The normal GBM components type IV collagen, fibronectin, and HSPG were found within all the glomeruli, but did not have the same distribution. Type IV collagen and fibronectin were found predominantly on the inner aspect of the GBM and diffusely throughout the more central regions of the mesangial matrix. By contrast the HSPG was seen mainly on the outer aspect of the GBM and at the periphery of the mesangial matrix. In none of the cases were GBM antigens localized within the electron-dense deposits, results which suggest that autoantibodies to these GBM components may not play a role in the development of the glomerulonephritis. ",19 38,"Leprotic involvement of peripheral nerves in the absence of skin lesions. Case report and literature review. In the absence of clinically apparent cutaneous lesions, primarily neural leprosy is uncommon. Primarily neural leprosy presents clinically as a peripheral neuropathy that most frequently affects motor nerves and that occasionally involves sensory nerves as well. The long incubation period for leprosy and its occurrence outside endemic areas often lead to delayed diagnosis. We present a case of glove and stocking hypoesthesia, weakness of the flexor muscle of the right great toe, palpable thickening of the right popliteal nerve, and hypoesthetic but normal-appearing areas on the back, which developed in a Trinidadian immigrant who lived in Canada for 16 years. A skin biopsy specimen obtained from a visibly normal but hypoesthetic area on the back demonstrated a few acid-fast bacteria in small dermal nerves, in arrector pili smooth muscle, and in rare perivascular histiocytes, associated with a sparse mixed inflammatory cell infiltrate. The patient responded well to therapy with dapsone, rifampin, and clofazamine. A classification and review of primarily neural leprosy is presented. Our patient represents the first reported case of primarily neural borderline lepromatous leprosy in Canada. ",0 976,"Bilious pleural effusion following liver biopsy. Pleural effusions in patients with chronic liver disease are common and usually are of little consequence. Bilious pleural effusion can occur following percutaneous biopsy or cholangiography procedures if the pleura is traversed. This report emphasizes the role of biliary tract obstruction in the development of a bilious effusion and the importance of biliary tract decompression in treatment. We discuss the laboratory evidence supporting the diagnosis of bilious effusion and review the reported experience with this complication. ",7 1259,"Multifocal posterior uveitis: clinical and pathological findings. A pathological study was performed on the necropsy eyes of a 59-year old-woman who had suffered for nine years from multifocal posterior uveitis. The disease had been controlled by steroid therapy with good preservation of visual function. Extensive investigation did not reveal the aetiology. On macroscopic examination numerous focal lesions with various degrees of pigmentation were observed scattered across the fundi. These lesions were studied by light and electron microscopy and immunohistochemistry. There was ongoing chorioretinal inflammation in the foci, producing destruction of Bruch's membrane, the retinal pigment epithelium (RPE), and the outer retina. The focal scars showed migration of RPE and glial cells and neovascularisation. Capillary and venule endothelial cells were swollen at the inflammatory sites. Attempts to establish a cause for this condition were unsuccessful. ",10 2930,"The corneoscleral limbus in human corneal epithelial wound healing. We studied re-epithelialization of the ocular surface in 17 human eyes (14 patients) with large corneal and conjunctival abrasions. We focused on the healing of the limbal region. During re-epithelialization, cell movement was found to occur circumferentially along the corneoscleral limbus and centripetally from the corneoscleral limbus. In no patient did the central corneal defect close before the corneoscleral limbus had first re-epithelialized completely. Normal limbal healing was observed to occur by circumferentially migrating tongue-shaped corneal limbal epithelium. These tongue-shaped projections developed from either side of the remaining intact epithelium and advanced along the corneoscleral limbus until they met. A centripetal movement of cells from the corneoscleral limbus then completed the healing process. In three patients, however, the advancing conjunctival epithelium extended across the corneoscleral limbus before the tongue-shaped projections of corneal limbal epithelium had met. The surface of the cornea covered by conjunctival epithelium was thin and irregular, and later showed peripheral scarring, vascularization, and recurrent erosions. ",20 1925,"Atenolol therapy for exercise-induced hypertension after aortic coarctation repair. After successful repair of coarctation of the aorta in childhood, exercise-induced upper body systolic hypertension is well documented. Beta blockade has been shown to reduce the arm/leg gradient in untreated coarctation of the aorta; treatment before coarctation repair has decreased paradoxical hypertension after repair. Ten patients with successful surgical repair of coarctation, defined as a resting arm/leg gradient of less than or equal to 18 mm Hg, were evaluated by treadmill exercise before and after beta blockade with atenolol. Mean age was 5.5 years at repair and 18 at study. At baseline evaluation, systolic blood pressures at termination of exercise ranged from 201 to 270 mm Hg (mean 229 mm Hg). Arm/leg gradients at exercise termination ranged from 30 to 143 mm Hg (mean 84). Follow-up treadmill exercise studies were performed after beta blockade. Upper extremity systolic pressures at exercise termination were normalized in 9 of 10 patients. Maximal systolic blood pressure recorded at exercise termination ranged from 163 to 223 mm Hg (mean 196 mm Hg, p less than or equal to 0.005). Arm/leg gradient at termination of exercise also decreased significantly to a mean of 51 mm Hg (p less than 0.05). No patient had symptoms on atenolol and exercise endurance times were unchanged. The study results in this small series suggest that cardioselective beta blockade can be used to treat exercise-induced upper body hypertension effectively after surgical repair of coarctation. Because a high incidence of premature cardiovascular disease has been well documented after satisfactory surgical repair, the findings are of importance for this group of postoperative patients. ",13 2130,"Effects of recombinant human interleukin-3 in aplastic anemia. In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained. ",14 455,"Chondrosarcoma of the head and neck. Chondrosarcoma is a malignancy rarely encountered in the head and neck. In an attempt to define this tumor's characteristics and response to therapy, all cases of chondrosarcoma treated at the University of Michigan over the past 25 years were retrospectively studied. Fourteen cases originating in the nose and paranasal sinuses, mandible, temporal bone, and larynx were reviewed. Aggressive surgical resection was the mainstay of treatment, and resulted in an overall survival of 70%, with an average follow-up of 3.5 years. Survival was highest in primary temporal bone lesions, and lowest in paranasal sinus lesions. Unresectable lesions were not cured by other modalities. This study, therefore, continued to support the crucial role of wide surgical resection in the treatment of head and neck chondrosarcoma, but conservative resection, when needed to preserve important structures, has resulted in long-term survival. ",3 720,"Further study of mucosal repair by sofalcone in experimental gastritis. The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis. ",5 2760,"Effort rupture of the diaphragm. Effort rupture of the diaphragm is rare and accounts for only 1% of all diaphragmatic injuries. A 23 year old patient with bilateral rupture that followed sudden movement is described. ",20 1127,"Spatiotemporal contrast sensitivity differs in normal aging and Parkinson's disease. We measured contrast sensitivity for static and laterally drifting vertical gratings in 12 young adults, 7 normal elderly adults, and 8 patients with Parkinson's disease (PD). We compared static and motion contrast sensitivity for spatial frequencies of 0.25, 1, and 4 cycles per degree (cpd), and temporal frequencies of 1, 3, and 9 Hz. Results show that normal aging leads to a reduction of motion sensitivity for the spatial frequency of 0.25 cpd. Compared with elderly controls, PD patients do not present specific abnormalities in this domain. However, for spatial frequencies of 1 and 4 cpd and temporal frequencies of 1 and 3 Hz, motion sensitivity is worse than static sensitivity in PD patients and not in elderly controls. These findings suggest a specific deficit of motion perception in PD, and possible dopaminergic involvement in the control of visuospatial behavior. ",9 3159,"Management of postoperative inflammation: dexamethasone versus flurbiprofen, a quantitative study using the new Flare Cell Meter. A consecutive, random, prospective study was conducted to compare the effect of topical dexamethasone and flurbiprofen drops on postoperative inflammation in patients undergoing extracapsular cataract extraction with lens implantation. Objective, quantitative measurements were made postoperatively, using the Kowa FC-1000 Flare Cell Meter. The two treatments were equally effective. ",22 731,"Update on the epidemiology of anorexia nervosa in a defined region of Switzerland. In this follow-up investigation, the authors studied all Swiss women in the canton of Zurich who developed anorexia nervosa between ages 12 and 25 years and who were hospitalized for the first time with this diagnosis between 1983 and 1985. Data were compared with those from an earlier study, which focused on the periods 1956-1958, 1963-1965, and 1973-1975. The incidence of anorexia nervosa did not increase significantly during 1983-1985 compared to 1973-1975, in contrast to the constant increase found between 1956 and 1975. However, the more frequent use of vomiting and abuse of laxatives in 1983-1985 may indicate an increase in cases with mixed features of anorexia nervosa and bulimia. ",5 255,"Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck. Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months. ",3 2990,"Inflammatory nodular reactions after hepatitis B vaccination due to aluminium sensitization. In 2 patients, pruritic nodules appeared after revaccination against hepatitis B. Aluminium was found to be responsible for this side effect: contact allergy to aluminium was present in both patients, whereas controls were negative. ",22 3229,"Circadian variation in onset of acute ischemic stroke. A circadian pattern for the onset of myocardial and cerebral infarction has been identified. To evaluate this phenomenon further, we analyzed prospectively collected data from 151 patients with acute ischemic stroke. The number of strokes per 6-hour period were the following: midnight to 6 AM, 20 (13%); 6 AM to noon, 86 (57%); noon to 6 PM, 21 (14%); and 6 PM to midnight, 24 (16%). This pattern was not affected by previous use of aspirin. The most frequent time of onset was 6 AM to noon for all subgroups of ischemic stroke: small artery, 71%; cardioembolic, 62%; large artery atherothrombotic, 57%; large artery atheroembolic, 46%; and ""other"" or unknown cause, 40%. We also investigated the time between awakening and stroke onset in 145 patients and found that 24% of ischemic strokes occurred within the first hour after awakening. Our data demonstrate that an early morning peak exists for all subtypes of stroke. Our data also suggest that the most critical period is the first hour after awakening. ",22 2259,"Transdermal viprostol in the treatment of male pattern baldness. Fifty-seven men were randomly assigned for treatment of androgenetic alopecia with viprostol, vehicle, or placebo twice daily for 24 weeks. Nonvellus hair growth was assessed subjectively by both patient and investigator and objectively through hair counts from macrophotographs of the target area. Nonvellus target area hair counts declined in all three treatment groups at the end of the 6-month study. Viprostol is not an effective hair growth promoter in androgenetic alopecia. ",16 584,"Role of ultrasound guided fine needle aspiration biopsy in the diagnosis of hepatocellular carcinoma. In 170 cases of hepatocellular carcinoma, ultrasound showed a high sensitivity in identifying focal liver lesions. Fine needle aspiration biopsy guided by ultrasound yielded a pathological diagnosis in the majority of cases. The advantages of this technique, its high diagnostic yield and low cost, render the older technique of blind percutaneous biopsy using a coarse needle obsolete. Laparoscopy retains its essential role in selected cases. Complementary use of fine needle aspiration biopsy under ultrasound guidance and laparoscopy assures the highest rate of diagnostic accuracy in hepatocellular carcinoma. We confirm the poor sensitivity of alpha fetoprotein. ",3 2527,"Thyroid hormones influences sex steroid binding protein levels in infancy: study in congenital hypothyroidism. In order to test the hypothesis of a role of thyroid hormones on the circulating levels of sex steroid binding protein (SHBG) in children, SHBG levels were determined in 15 infants with congenital hypothyroidism at diagnosis and during the first 18 months of T4 therapy and in a separate group of 13 children with congenital hypothyroidism (7.1 +/- 0.5 yr, mean +/- SD), treated before 1 month of age, both during adequate L-T4 therapy and 4 weeks after withdrawing therapy. SHBG levels were significantly lower in hypothyroid infants than in controls (48.2 +/- 6.5 vs. 77.8 +/- 7.9 nmol/L; P less than 0.01), and significantly lower in infants with athyreosis compared to those with ectopic or eutopic glands (P less than 0.05). In patients with low values at diagnosis, SHBG increased rapidly and remained normal during LT4 therapy. After 1.5-18 months of treatment, a positive correlation (P less than 0.01) was found between SHBG, FT4, and FT3 levels. In older hypothyroid children, 4 weeks after withdrawal of therapy a significant (P less than 0.05) decrease in SHBG concentrations was observed. Analysis of these results as well as previous reports in adults, indicates that thyroid hormones influence SHBG concentrations in infants and children. This study also indicates that thyroid hormones may play a role in the physiological postnatal increase of SHBG. ",18 1505,"The effect of physical activity during pregnancy on preterm delivery and birth weight. The relationship between physical activity during pregnancy, preterm birth, and gestational age-adjusted birth weight was investigated prospectively in a cohort of 7101 women. This study is one of few to evaluate both employment- and non-employment-related physical activity. Prolonged periods of standing were associated with a modestly increased risk of preterm delivery (adjusted odds ratio for greater than or equal to 8 hours/day of standing = 1.31). Heavy work or exercise was not associated with preterm delivery (adjusted odds ratio for greater than or equal to 4 hours per day of heavy work = 1.04). The proportion of infants born preterm did not differ among women working in predominantly standing, active, and sedentary occupations. Physical activity was not associated with gestational age-adjusted birth weight after controlling for confounding variables. These data suggest that unmeasured socioeconomic differences among women reporting different levels of activity may account for previously described associations between physical activity and pregnancy outcome. Most pregnant women who report increased levels of physical activity are not at increased risk of preterm delivery or reduced intrauterine growth. However, these data do not address the role of activity restriction in the management of selected women at high risk for adverse pregnancy outcome. ",12 2736,"Toxic psychosis due to chloroquine--not uncommon in children. Toxic psychosis due to Chloroquine is a relatively uncommon occurrence in childhood. This entity must be kept in differential diagnosis in a case of unexplained psychosis, before resorting to a sophisticated array of detailed investigations. The purpose of this is to familiarize pediatricians with this relatively uncommon entity. The authors encountered four cases of psychosis with a wide variety of symptomatology over a period of the past 18 months. ",20 1822,"Left ventricular asynchrony in patients with pulmonary hypertension. Left ventricular regional wall motion was evaluated in 11 patients with pulmonary hypertension and 18 control subjects. All 11 patients had secondary pulmonary hypertension and less than 20% measured diameter stenosis in any vessel. This study utilizes a video-intensity-based frame-by-frame computerized technique. All pulmonary hypertensive patients showed early diastolic asynchrony in the anterior or apical regions that lasted 100-200 ms. The size of the abnormal area varied from 2 to 20% of the ventricular silhouette. Four patients also showed systolic abnormalities. No abnormalities were detected in the control group. The cause of the asynchrony detected in pulmonary hypertension is probably due to interventricular interaction caused by pressure gradients across the septum. ",13 1623,"Time delays in the diagnosis and treatment of acute myocardial infarction: a tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project. To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy. ",13 1469,"Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol A double blind, controlled study was performed to see whether the use of prophylactic oral salbutamol would reduce the incidence of preterm labour in twin pregnancy. Of the 144 women studied, 74 took salbutamol and 70 placebo. No difference was found in the length of gestation, birthweight or fetal outcome, although fewer babies suffered from respiratory distress syndrome in the salbutamol group. Women did not experience troublesome side-effects from salbutamol. ",12 841,"Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity. Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24-hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitro of antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivo pH-metry studies, because we found that the greatest absolute difference between raw fast acquired (4-6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1-A2; glass-glass, G1-G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland-Altman technique for assessing measurement agreement, the differences between the 24-hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P = .903 and P = 0.824, respectively) and their 95% confidence limits are comprised within the range (+/-) of the reading error of the measuring systems (namely, +/- 0.3 pH units and +/- 12 mmol/liter in terms of [H+]). ",5 2395,"Pseudohypophosphatasia: aberrant localization and substrate specificity of alkaline phosphatase in cultured skin fibroblasts. We explored the biochemical basis for the disorder pseudohypophosphatasia (PsHYPT) in one patient by examining the substrate specificity and localization of alkaline phosphatase (ALP) in cultured dermal fibroblasts. Despite substantial ALP activity, in cell homogenates, toward the artificial substrate 4-methyl-umbelliferyl phosphate (4-MUP), there was a marked deficiency in ALP activity toward the natural substrates pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA), indicating altered substrate specificity. Furthermore, although 4-MUP phosphatase (4-MUP-P'tase) activity was predominantly localized as an ecto-enzyme, the small amount of PLP phosphatase (PLP-P'tase) activity was intracellular. This differential localization was apparent in intact cells, since (1) brief acidification of the medium at 4 degrees C inactivated a majority of the 4-MUP-P'tase activity but only 15% of the PLP-P'tase activity (in contrast to greater than 85% inactivation of both in homogenates), (2) greater than 70% of the 4-MUP-P'tase activity but only 30% of the PLP-P'tase activity was released by phosphatidylinositol-specific phospholipase C (PI-PLC) digestion, and (3) degradation of extracellular PLP was less than 35% of that of disrupted cells. Both 4-MUP- and PLP-P'tase activities were predominantly in a lipid-anchored form that could be converted to a soluble, lipid-free form by PI-PLC digestion. Our findings suggest that the clinical and biochemical presentation of this PSHPT patient results from the production of two aberrant ALP species. One form of ALP has appropriate ectoorientation but is preferentially deficient in activity toward natural substrates; the other ALP species has appropriate substrate specificity but is sequestered from substrates by its intracellular location. ",17 861,"Repair of salivary fistulae after laryngectomy. A new surgical technique is described for the repair of salivary fistulae. It has been used in three patients. The fistulae occurred after laryngectomy and had been unsuccessfully treated with local and regional flaps. The principle of the technique is to use a bipedicled jejunal patch as a free microvascular transfer. One patch is used for reconstruction of the pharynx and after excising the mucosa the skin defect is closed with the other patch. The mucosa is excised to expose the muscle and to create a recipient site for a split skin graft. ",6 2993,"Lung sound nomenclature survey. We report the terms used by 223 pulmonary physicians and 54 physicians in other specialties to describe eight recorded examples of lung sounds. The participants listened to the lung sounds at the 1988 American College of Chest Physicians annual convention and wrote ""free form"" answers. Pulmonary physicians used the terms ""crackles"" and ""rales"" with equal frequency to describe discontinuous adventitious lung sounds (ALS) and not at all to describe continuous ALS. Other physicians preferred the term ""rales"" in describing discontinuous ALS. The terms ""wheeze"" and ""stridor"" were used only in describing continuous ALS; however, the term ""rhonchi"" was frequently used to describe continuous and discontinuous ALS. The majority of participants recognized the normal breath sounds but not the pleural friction rub. Most did not use a qualifying adjective to describe ALS, and there was little agreement among those who did. The lung sound terminology used by physicians is not well standardized and the recommendations of the ATS/ACCP nomenclature subcommittee are not widely accepted. ",22 2678,"Low level atmospheric sulfur dioxide pollution and childhood asthma. Quarterly analysis (1983-1987) of childhood asthma in Hong Kong from 13,620 hospitalization episodes in relation to levels of pollutants (SO2, NO2, NO, O3, TSP, and RSP) revealed a seasonal pattern of attack rates that correlates inversely with exposure to sulfur dioxide (r = -.52, P less than .05). The same cannot be found with other pollutants. Many factors may contribute to the seasonal variation of asthma attacks. We speculate that prolonged exposure (in terms of months) to low level SO2 is one factor that might induce airway inflammation and bronchial hyperreactivity and predispose to episodes of asthma. ",19 1045,"Dementia: what to do. Dementia is a syndrome of acquired intellectual deterioration that interferes with personal or social functioning. Diagnosis requires historical information from the family and the mental status evaluation of orientation, recent memory, comprehension, calculation, and abstraction. Most dementias create permanent, even progressive cognitive deterioration, yet there are some presentations for which remission exists. Common reversible conditions include depression, drug toxicity, normal-pressure hydrocephalus, hypothyroidism, subdural hematoma, and neoplasm. Screening laboratory studies consist of urinalysis, chemistry profile, blood count, thyroid survey, vitamin B12 and folate measurements, serology, chest roentgenogram, computerized tomographic scan of the head, electroencephalogram, and electrocardiogram. Treatment focuses on potential reversibility, psychosocial issues, restoring deficits, and specific symptoms. ",9 3305,"Profound digital collagen atrophy: a new cutaneous presentation of adrenal-dependent Cushing's syndrome. A 59-year-old Caucasian housewife presented with a 2-year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome. ",22 1686,"Systolic hypertension in the elderly: reasons not to treat. Isolated systolic hypertension in the elderly is associated with increased morbidity and mortality. Accurate measurement of blood pressure in older patients is difficult. Therapy can be associated with various complications, and the special problems of the elderly, such as orthostatic hypotension and hyperkalemia, should be carefully considered. Drugs should be used in low doses and changes in dosage should be made infrequently. Patients should be monitored frequently for untoward effects of therapy. The benefits of blood pressure reduction and the optimal degree of blood pressure reduction remain unknown. ",13 2674,"Seroprevalence of HIV infection in the general population of the Cote d'Ivoire, West Africa. A seroepidemiological survey to determine the prevalence of human immunodeficiency virus (HIV) infection in the general population of the Ivory Coast was carried out in February 1989. Sera were collected from subjects between 15 and 65 years old in urban areas (not including Abidjan) and rural areas using the cluster sample technique. A total of 1,700 people were tested in urban areas, and 125 (7.3%) were HIV positive. This rate varied significantly with age and sex; a maximum rate of 16.3% was observed among men between 35 and 44 years old. In rural areas, a total of 3,199 people were tested, and 159 (4.9%) were positive for HIV; the highest rate (10.7%) was noted in the men aged 25-34 years. The high seroprevalence recorded in the general population in urban and rural areas is compatible with the incidences of acquired immune deficiency syndrome (AIDS) cases reported in hospitals all over the country. ",19 561,"Glucocorticoids locally disrupt an array of positioned nucleosomes on the rat tyrosine aminotransferase promoter in hepatoma cells. Transcriptional activation by steroid hormones is often associated with the appearance of a DNase I hypersensitive site resulting from a local alteration of the nucleoprotein structure of the promoter. For the mouse mammary tumor virus long terminal repeat, a viral promoter under glucocorticoid control, a model has been proposed: the appearance of the hormonodependent DNase I hypersensitive site reflects the displacement of a single precisely positioned nucleosome associated with the glucocorticoid responsive elements. To determine if such a mechanism is of general relevance in transcriptional activation by steroid hormones, we have investigated the nucleosomal organization of the rat tyrosine aminotransferase promoter over a 1-kilobase region that contains the glucocorticoid regulatory target. This region displays a hormonodependent DNase I hypersensitive site. In the absence of hormone, micrococcal nuclease digestion of nuclei demonstrates the presence of positioned nucleosomes, with cutting sites centered around positions -3080, -2900, -2700, -2800, -2255, and -2040. Treatment of the cells with dexamethasone induces a disruption of the chromatin structure over a relatively short stretch of DNA (approximately positions -2400 to -2650) that overlaps two nucleosomes. These observations suggest a strong similarity in the role of chromatin structure in glucocorticoid-dependent transcriptional activation of mouse mammary tumor virus and tyrosine aminotransferase promoters. ",3 2162,"Total and differential leukocyte counts in clinically well children. Information or misinformation? To determine whether the total and differential leukocyte count is of value as a case-finding test, we applied the evaluation criteria developed by the US Preventive Services Task Force. The criteria comprise review of the current burden of suffering of the disease to be prevented, the attributes of the intervention to be used, and the quality of the evidence available. A literature search revealed no evidence in the form of data from patients, so a chart review of all complete blood cell counts ordered during a 1-year period by one group of pediatricians was undertaken. At least one value outside of published normal ranges was found on 74.7% of the tests performed on clinically well children. No unsuspected illness was discovered as a result of an abnormal total and differential leukocyte count. ",14 2446,"Molecular mapping of the mouse db mutation. Diabetes (db) is an autosomal recessive mutation located in the midportion of mouse chromosome 4 that results in profound obesity with hyperphagia, increased metabolic efficiency, and insulin resistance. To clone this gene and generate a molecular map of the region around this mutation, two genetic crosses were established: an intraspecific backcross between C57BL/6J db/db females and C57BL/6J db/db x DBA/2J +/+ F1 (B6D2 db/+ F1) male mice and an interspecific intercross between B6D2 db/+ F1 males and C57BL/6J db/db x Mus spretus F1 (B6spretus db/+ F1) females. The progeny of both crosses were characterized for genotype at the db locus to map a series of restriction fragment length polymorphisms relative to the db locus. Measurements of body weight, body length, and plasma concentrations of glucose and insulin in the animals allowed the assignment of genotype (db/db vs. db/+ or +/+). A total of 132 progeny of the intraspecific cross and 48 db/db progeny of the interspecific cross were typed for individual restriction fragment length polymorphisms to generate a gene order of: centromere-brown (Mt4)-P lambda Mm3(2)-Ifa (Inta)-Cjun-db-D4Rp1-Glut1-Mtv-13-Lck. Several of the genes that are linked to db [Cjun, glucose transporter (Glut1) and Lck] map to human chromosome 1p, suggesting that db may be part of a syntenic group between human 1p and the distal portion of mouse chromosome 4. In addition, phenotyping of the progeny of these crosses revealed a wide range in plasma concentrations of glucose and insulin among the obese progeny, with some animals developing overt diabetes and other remaining euglycemic. Distributions of age-controlled plasma [glucose] and [insulin] among the intraspecific-cross obese progeny were not bimodal, suggesting a role for polygenic differences between the progenitor strains (C57BL/6J and DBA/2J) in the development of overt diabetes. ",17 453,"A phosphatase activity present in peripheral blood myeloid cells of chronic myelogenous leukemia patients but not normal individuals alters nuclear protein binding to transcriptional enhancers of interferon-inducible genes. Cytoplasmic protein from peripheral blood myeloid cells of chronic myelogenous leukemia (CML) patients altered the electrophoretic mobility of complexes formed between nuclear proteins and interferon-inducible transcriptional enhancers. Immature myeloid marrow cells (blasts and promyelocytes) have a higher level of this activity than do mature myeloid marrow cells (bands and polys). This activity, which is not detectable in the peripheral blood cells of normal individuals, is at least 50-fold higher in CML marrow blasts and promyelocytes than that found in marrow blasts and promyelocytes of normal individuals. This activity was inhibited by in vivo incubation of immature myeloid cells with the phosphatase inhibitor, sodium orthovanadate (0.2 mM), and by adding orthovanadate (20 mM) directly to cytoplasmic proteins of myeloid cells. Interferon-alpha (1,000 U/ml) reduced the effects of the CML myeloid cell cytoplasmic protein on the electrophoretic mobility of nuclear protein-DNA complexes. These data suggest that a unique phosphatase may be involved in the abnormalities in CML which are modulated by interferon-alpha. ",3 1725,"Effect of captopril injection in patients with moderate to severe hypertension. The effect of intravenous captopril was studied in 24 white patients who had moderate to severe hypertension. Patients received incremental doses of 1 to 10 mg delivered at 10 min intervals over 50 to 80 min. Blood pressure (BP) was lowered within 5 to 10 min after the initial dose was administered and continued to decline, reaching a maximum response after 20 min (2 to 4 mg). At this time group mean BP fell from 175 +/- 3/111 +/- 1 to 166 +/- 3/97 +/- 2 mm Hg (P less than 0.01). Additional dose increments to an average cumulative dose of 40 mg did not increase the initial effect. No adverse side effects or symptomatic hypotension occurred in any subject. There was a significant correlation between diastolic BP decreases observed in response to intravenous captopril and subsequent long-term oral captopril therapy. The addition of hydrochlorothiazide increased the proportion of patients reaching normotension. We conclude that small intravenous bolus injections of captopril appear to be effective rapidly and are well tolerated in moderate to severe essential hypertension. Short-term intravenous administration seems to predict the response to chronic oral captopril therapy. ",13 646,"A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined. PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment. RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups. CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder. ",4 1479,"Effect of serum from patients with minimal to mild endometriosis on mouse embryo development in vitro. Two-cell mouse embryos were cultured at 37 degrees C in 5% CO2, 95% air with a 7.5% serum supplement from patients with minimal to mild endometriosis, (group I, n = 31), tubal factor (group II, n = 33), male factor (group III, n = 17), fetal cord samples (group IV, n = 37), and Ham's F-10 medium (Gibco, Grand Island, NY) without a serum supplement (group V, n = 30). The progression to blastocyst stage (mean percent +/- SE) at 96 hours in groups I, II, III, IV, and V was 29.9% +/- 3.7%, 60.6% +/- 4.9%, 56.2% +/- 5.2%, 61.7% +/- 5.8%, and 63.2% +/- 6.9%, respectively. Serum factors appear to be associated with an inhibition of early embryogenesis, which may explain the decreased fertility rates observed in patients with minimal to mild endometriosis. ",12 2543,"A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. The primary decision about male or female sexual development of the human embryo depends on the presence of the Y chromosome, more specifically on a gene on the Y chromosome encoding a testis-determining factor, TDF. The human sex-determining region has been delimited to a 35-kilobase interval near the Y pseudoautosomal boundary. In this region there is a candidate gene for TDF, termed SRY, which is conserved and specific to the Y chromosome in all mammals tested. The corresponding gene from the mouse Y chromosome is deleted in a line of XY female mutant mice, and is expressed at the expected stage during male gonadal development. We have now identified a mutation in SRY in one out of 12 sex-inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome. The four-nucleotide deletion occurs in a sequence of SRY encoding a conserved DNA-binding motif and results in a frame shift presumably leading to a non-functional protein. The mutation occurred de novo, because the father of the sporadic XY female that bears it has the normal sequence at the corresponding position. These results provide strong evidence for SRY being TDF. ",18 1815,"Early 24-hour blood pressure elevation in normotensive subjects with parental hypertension Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH++), 15 normotensive subjects with one hypertensive parent (FH(+)-), and 15 normotensive subjects whose parents are not hypertensive (FH--); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH-- group (p less than 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the FH-- group; the difference was always significant (p less than 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH-- group (p less than 0.01). The blood pressure values and echocardiographic values of the FH(+)- group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation. ",13 1178,"Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery in hydrocephalus before and after treatment. We studied Pourcelot's index (PI), which shows cerebral vascular resistance, in the anterior cerebral arteries and basilar artery, and the PI ratio (Pourcelot's index in the anterior cerebral artery/Pourcelot's index in the basilar artery) in 11 measurements of hydrocephalus. The mean values of PI in the anterior cerebral artery, basilar artery, and the PI ratio before treatment were significantly higher than those after treatment and those in normal infants. Before treatment, the mean PI in the anterior cerebral arteries was significantly higher than the mean PI in the basilar artery. All PI ratios increased to 1.00 or more. After treatment and in normal infants, the mean PI in the anterior cerebral arteries was significantly lower than the mean PI in the basilar artery. All PI ratios decreased to less than 1.00. We believe that the PI ratio is useful to evaluate the need or effect of treatment in hydrocephalus. ",9 2980,"Tissue expansion of the head and neck. Indications, technique, and complications. Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local, regional, or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept, it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck, particularly in the cheek and neck area. Despite the frequency of complications, in the vast majority of cases the intended reconstruction is successful. ",22 3121,"Comparison of ventricular arrhythmia induction with use of an indwelling electrode catheter and a newly inserted catheter. Two methods of serial electrophysiologic testing are in widespread use. Most commonly, the electrode catheter is removed after each study and a new catheter reinserted through the femoral vein for every subsequent test. An alternative method employs an electrode catheter that remains in place during several days of serial testing. Little is known about differences between these two methods with respect to the likelihood of induction of arrhythmia or the frequency of complications. To determine whether inducibility of sustained arrhythmia is altered or if the frequency of complications is unacceptably high with use of an indwelling catheter, a prospective randomized study was conducted in 78 patients. Each patient underwent baseline testing, several days of electropharmacologic testing with an indwelling catheter, a 24 h drug elimination period and placement of a new electrode catheter. Ventricular stimulation studies were then performed in each patient with both the indwelling and new electrode catheters. No differences were found between the indwelling and new catheter tests with respect to induction of arrhythmia, number of extrastimuli required to induce arrhythmia, rate of arrhythmia or requirement for cardioversion. Ventricular pacing thresholds were higher and effective refractory periods were slightly longer when measured with the indwelling catheter. Complications related to the 156 catheter insertions included two that may have been related to the indwelling catheter (one episode of staphylococcal sepsis and one presumed pulmonary embolism) and four that were related to invasive procedures (pneumothorax in all). There were no long-term adverse sequelae of these complications. ",22 2840,"Poly(L-lactide) implants in repair of defects of the orbital floor: an animal study. Because of the life-long presence of alloplastic, nonresorbable orbital floor implants and the complications of their use mentioned in literature, the use of a resorbable material appears to be preferable in the repair of orbital floor defects. A high-molecular-weight, as-polymerized poly(L-lactide) (PLLA) was used for repair of orbital floor defects of the blowout type in goats. An artificial defect was created in the bony floor of both orbits. Reconstruction of the orbital floor was then carried out using a concave PLLA implant of 0.4-mm thickness. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed. Microscopic examination showed full encapsulation of the implant by connective tissue after 3 weeks. After 6 weeks, resorption and remodeling of the bone at the points of support of the implant could be detected. A differentiation between the sinus and orbital sides of the connective tissue capsule was observed. The orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. At 19 weeks, a bony plate was progressively being formed, and at 78 weeks, new bone had fully covered the plate on the antral and orbital side. No inflammation or rejection of the PLLA implant was seen. ",20 2157,"Viral infections in transfusion-dependent patients with beta-thalassemia major: the predominant role of cytomegalovirus. For 9 months, 38 transfusion-dependent patients with beta-thalassemia, ranging in age from 3.4 to 19.1 years, were observed for serologic evidence of viral infections, by the collection of serial serum samples. Seventy-six age-matched healthy subjects, two for each patient, were followed as controls. Samples taken at the beginning, middle, and end of the study were tested against 18 viral antigens by complement fixation (CF). In addition, tests for antibodies to HIV, Epstein-Barr virus, hepatitis A virus, and markers for hepatitis B virus were performed. When changes in the antibody titer on CF tests (greater than or equal to 2-fold increase or decrease) or persistently high titers (greater than or equal to 64) were revealed, specific enzyme immunoassays (EIAs) for IgM and IgA antibodies were performed concomitant with CF tests in all sera. When symptomatic infections occurred, viral cultures and/or direct detection of antigens were carried out by immunofluorescence methods, EIA, or latex agglutination tests. Thalassemic patients and controls had similar (p greater than 0.05) overall rates of serologically confirmed viral infections (53 versus 132), but the former group had a higher (p less than 0.01) incidence of cytomegalovirus (CMV) infections (9 versus 4). CMV infections were associated in the thalassemic patients with hepatitis (2 cases), lymphadenitis (2 cases), and upper respiratory tract infection (1 case), while the remaining cases of CMV had a subclinical course. Moreover, the thalassemic patients had a lower (p less than 0.01) incidence of symptomatic infections (27 versus 110) than controls. Therefore, this study showed that both symptomatic and subclinical CMV infections may occur often in thalassemic patients, who otherwise have subclinical viral infections at an overall rate similar to that in healthy subjects. ",14 2592,"Cytotoxic activity against HIV-infected monocytes by recombinant interleukin 2-activated natural killer cells. Natural killer (NK) cells have long been known to aid in the control of viral infections by killing virus-infected cells, including those infected with human immunodeficiency virus (HIV). Among the possible NK-susceptible target cells in an infected individual, the monocyte/macrophages are of special significance since they may serve as both a reservoir of HIV and aid in dissemination of the virus throughout the body. A new technique for the enrichment and cultivation of large numbers of recombinant interleukin 2 (rIL-2)-stimulated NK cells has been developed which provides cells with high cytotoxic activity. These IL-2-activated NK cells, adherent lymphokine-activated killer cells (A-LAK), can kill monocytes infected with HIV for 24 h to 7 days, with optimal target sensitivity between 3 and 7 days. Recognition and killing of the infected monocytes did not appear to be restricted by the major histocompatibility complex (MHC) antigens and could be cold-target inhibited by tumor cell lines. A-LAK cells may be useful in newer therapeutic approaches to treatment of HIV infection. ",19 1927,"Erythrocyte fatty acids, plasma lipids, and cardiovascular disease in rural China. Cardiovascular disease (CVD) mortality (coronary heart disease, hypertensive heart disease, and stroke), plasma lipids, and red blood cell fatty acid composition were examined in an ecologic study in 65 rural counties in the People's Republic of China. Means of plasma total cholesterol, triglyceride, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations were substantially lower and the ratio of HDL cholesterol to total cholesterol was higher in this Chinese population than in Western populations. Mortality rates for CVD in China were well below Western values. Within China neither plasma total cholesterol nor LDL cholesterol was associated with CVD. A strong inverse correlation between red blood cell oleate concentrations and CVD was observed. However, red blood cell oleate concentrations were not associated with plasma cholesterol but were strongly negatively associated with arachidonate concentrations, suggesting potential diminution of CVD by oleate through reduced platelet aggregability. The results indicate that geographical differences in CVD mortality within China are caused primarily by factors other than dietary or plasma cholesterol. ",13 2919,"Biomechanical strength of non-vascularised and vascularised diaphyseal bone transplants. An experimental study. We studied the healing and torsional strength of non-vascularised (28) and vascularised (28) sections of tibial diaphyses in 56 cats. Both types of graft achieved fracture union in the same period of time, and at 12 and 16 weeks the non-vascularised grafts were as strong as the vascularised grafts. ",20 2632,"Evaluation of active control trials in AIDS. In settings in which effective standard treatment exists, active control trials provide an ethically appealing approach to evaluating experimental therapies by allowing all patients to be randomized either to a promising new regimen or to the standard as it would be routinely delivered in clinical practice. This paper describes an appropriate statistical approach for analyzing the clinical efficacy of new treatments in such studies. Confidence intervals for the relative efficacy of the new treatment vis-a-vis standard therapy are used to provide information required to determine whether the experimental treatment has an improved therapeutic index. Desirable properties of this approach include the ability to implement standard group sequential guidelines for early trial termination, the ability to use valid surrogates for hard clinical outcomes, and the availability of straightforward formulas for sample size calculations. ",19 784,"Technical aspects of biliary extracorporeal shock wave lithotripsy. Radiologic imaging procedures play a major role in the evaluation of the potential patient for biliary extracorporeal shock wave lithotripsy, both during the procedure and in follow-up evaluation. The treating physician must have a thorough knowledge of ultrasonography techniques. Lithotripsy requires continual monitoring and frequent reassessment to optimize targeting and fragmentation of the gallstones while maintaining patient comfort. ",5 1877,"The frequency-dependent behavior of cerebral autoregulation. Cerebral autoregulation is a complex physiological process composed of both fast and slow components that may respond differently to different rates and patterns of blood pressure variation. To assess the temporal nature of autoregulation, transcranial Doppler velocity recordings of the middle cerebral artery obtained over prolonged periods were compared with blood pressure recordings in 5 patients without cerebral disease and in 13 patients with intracranial pathological changes. Correlations between the velocity and pressure wave forms at various frequencies of variation were measured with systems analysis techniques. Patients with aneurysmal subarachnoid hemorrhage had high correlations indicating pressure-dependent flow and impaired autoregulation. Patients without cerebral disease had significantly lower correlations (P less than 0.01), indicating intact autoregulation. Examples of increasing correlations and correlations at new frequencies emerging as the clinical condition worsened are given. These preliminary examples suggest that the application of systems analysis techniques to velocity and pressure data allow measurement of the temporal nature of cerebral autoregulation. ",13 1156,"Neurologic complications of cocaine abuse. The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures. ",9 2072,"Changes in myocardial ischemic threshold during daily activities. This study assesses the variations in myocardial ischemic threshold (heart rate at the onset of ischemia) during daily activities in patients with ischemic episodes on Holter monitoring. Eighty patients with known coronary artery disease, positive treadmill stress test results and greater than or equal to 2 ischemic episodes during a 24-hour period of Holter monitoring were studied. The lowest and the highest ischemic thresholds were determined for each patient. The mean lowest ischemic threshold was 85 beats/min, and the mean highest ischemic threshold was 109 beats/min. The highest ischemic threshold was identical to ischemic threshold values noted during exercise. Of the 895 ischemic episodes, 654 (74%) were preceded by a moderate (greater than 10%) increase in heart rate. The variability of ischemic threshold (difference in percentage between the highest and lowest ischemic thresholds) increased with the number of ischemic episodes (range 2 to 60%). However, in different patients with a similar number of ischemic episodes, different variability was observed. These differences in ischemic thresholds are probably indirect indicators of the vasomotor activity of the coronary arteries in different patients. ",13 2269,"The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P less than 0.0001), DP (P less than 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large. For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P less than 0.05) and higher total dropout rates (P less than 0.01) than any other drug; 30% of gold-treated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs.(ABSTRACT TRUNCATED AT 400 WORDS). ",16 690,"The role of ERCP in children and adolescents. The diagnostic and therapeutic role of ERCP in 42 patients ranging from 1 to 19 years of age is discussed. ERCP provided useful additional information in 15 patients with biliary tract disease, 15 patients with pancreatic disease, and 9 patients with abdominal pain. The appropriate duct was cannulated in 95% of cases. Mild pancreatitis occurred in two patients after ERCP. Endoscopic papillotomy was successful in five patients. ERCP plays an important part in the investigation of unexplained biliary tract and pancreatic disease. It rarely demonstrates abnormal pathology in patients with otherwise unexplained abdominal pain. ",5 3232,"Hemifacial spasm in Rochester and Olmsted County, Minnesota, 1960 to 1984. The incidence of hemifacial spasm in residents of Olmsted County, Minnesota, was studied by reviewing the medical records of patients residing in the community between 1960 and 1984. The average annual incidence rate was 0.74 per 100,000 in men and 0.81 per 100,000 in women, age-adjusted to the 1970 US white population. The average prevalence rate was 7.4 per 100,000 population in men and 14.5 per 100,000 in women. The incidence and prevalence rates were highest in those from 40 to 79 years of age. ",22 1071,"Epidural hematoma: an unusual presentation. The authors present a patient with a traumatic epidural hematoma who complained only of headache and presented to the emergency department 48 hours after a fall. Mental status and neurological examination were normal. This delayed presentation is more commonly seen when a subdural hematoma is present but may result from epidural bleeding. Delayed formation of a traumatic epidural hematoma may occur when the following are present: elevated intracranial pressure, hypovolemic shock, a concomitant mass lesion, coagulopathy, bleeding from dural or diploic veins, a dural sinus laceration, a traumatic pseudoaneurysm, or an arteriovenous fistula. Although criteria for computed tomography of patients with head injuries remain variable in the literature, delayed presentation of epidural bleeding must be considered in the differential diagnosis of posttraumatic headache irregardless of the time interval or neurological presentation. ",9 2644,"Therapeutic approaches to neoplasms in AIDS. The multifactorial etiology of Kaposi's sarcoma (KS), which is seen primarily in men, includes genetic predisposition and immunosuppression. Recently, the KS seen in association with human immunodeficiency virus (HIV) infection has been shown to be mediated by the production of certain growth factors. HIV per se may also play an etiologic role via its tat gene. Therapeutic options include irradiation for local or cosmetic control, interferon-alpha, combinations of antiretroviral agents and interferon-alpha, and chemotherapy. The use of antineoplastic agents, either individually or in combination, in cases of advanced disease has been somewhat successful, but resultant immunosuppression and neutropenia may predispose patients to further infection, thereby adversely affecting survival. AIDS-related lymphoma, a late manifestation of HIV infection, often presents with widespread extranodal disease; the median survival time in all series has been approximately 6 months. Two-thirds of patients may have central nervous system involvement at some time in the course of illness. Intensive chemotherapeutic regimens are associated with an increased likelihood of opportunistic infection and do not prolong survival. Combinations of antineoplastic agents given at low doses for short periods may be associated with long-term remissions. ",19 661,"Bipolar versus total hip arthroplasty for avascular necrosis of the femoral head. A comparison. In a relatively small series of cases the results of bipolar prostheses in avascular necrosis were inferior to those of total hip arthroplasty (THA). Femoral loosening rates were not reduced by using bipolar prostheses. THA produced more inferior results in avascular necrosis than in degenerative joint disease. Early results of noncemented THA for avascular necrosis were good but also must withstand the test of time. A fixed noncemented acetabular component was preferable over a bipolar prosthesis for avascular necrosis of the femoral head. ",4 2473,"Increased testosterone in type I diabetic subjects with severe retinopathy. Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured serum testosterone, estradiol, DHEA-S, and sex hormone binding globulin levels in 26 men and 22 women with type I diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic complications. The mean age was 23 years and the mean duration of diabetes was 14 years. Subjects with proliferative or preproliferative retinopathy (greater than or equal to retinopathy level 51-80) were matched by duration of diabetes (+/- 2 years) and sex to subjects with minimal or no retinopathy (less than or equal to retinopathy level 21). Seven stereoscopic retinal photographs of each eye were obtained and photographs were read by the University of Wisconsin Reading Center. Serum testosterone concentrations were significantly higher in male diabetic subjects with proliferative retinopathy (648 +/- 36 ng/dl) than in male diabetic subjects with minimal or no retinopathy (512 +/- 43 ng/dl) (P = 0.017). No other statistically significant differences in sex hormones between subjects with and without proliferative retinopathy were observed. Although these results should be regarded as preliminary because of the small number of subjects, they support the hypothesis that testosterone concentrations may be associated with the development of retinopathy in type I diabetic patients. ",17 2099,"Additional salutary hemodynamic effects of the combined use of the paraaortic counterpulsation device and intraaortic balloon pump versus a paraaortic counterpulsation device alone. The hemodynamic effects of the combined use of the paraaortic counterpulsation device (PACD) (stroke volume 65 ml) implanted on the ascending aorta, and a 20 ml intraaortic balloon pump (IABP) placed in the descending aorta, were compared with the PACD working alone in 12 dogs after the induction of heart failure. Heart failure was characterized by left ventricular end-diastolic pressure (LVEDP) greater than 18 mmHg and systolic aortic pressure (SAP) in stage A: 116 mmHg greater than or equal to SAP greater than 70 mmHg; in stage B: 70 mmHg greater than or equal to SAP greater than 30 mmHg; and in stage C: SAP less than or equal to 30 mmHg. Both modalities of mechanical assistance produced significant salutary hemodynamic effects in stages A and B. No difference was observed in stage C. In conclusion, the combined use of PACD and IABP is more effective than the use of either of these devices alone. This modality of mechanical assistance may easily be applied in patients that cannot be weaned from extracorporeal circulation, and in whom IABP was unsuccessfully applied. ",13 1117,"A review of techniques employed to estimate the number of motor units in a muscle. Being the smallest functional units under neural control, motor units play an integral role in muscle physiology. However, at the present time, there does not exist any widely accepted technique for quantifying or estimating the number of motor units in a muscle. Specifically, the existing techniques are the increment-counting technique, a technique based on spike-triggered averaging, and a macro-EMG based technique which vary in invasiveness from noninvasive to highly invasive, respectively. We discuss each of these techniques, along with their associated shortcomings, in detail. ",9 809,"Intrahepatic cholesterol stones: a rationale for dissolution therapy. A case of primary cholesterol hepatolithiasis is reported. Stone composition was documented by infrared spectroscopy, and the presence of cholesterol saturated bile was demonstrated using standard biochemical techniques. The patient was treated with operative stone extraction, choledochoscopy, biliary enteric anastomosis, and oral dissolution therapy. The administration of oral dissolution agents has altered the composition of the patient's bile and may prevent further stone formation. We advocate the use of both stone and biliary biochemical analysis for patients with primary hepatolithiasis to facilitate optimal therapy. ",5 1647,"Pharmacology of angiotensin-converting enzyme inhibitors as a guide to their use in congestive heart failure. The pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitors are difficult to assess for several reasons. First, these compounds exert their influence by inhibiting an intermediary enzyme of a cascade of enzymatic events, whose rate-limiting enzyme (renin) is not directly affected by ACE inhibition. Second, renin and angiotensin I accumulate during ACE inhibition and a change in the dose of an ACE inhibitor could produce sudden shifts of angiotensin I to angiotensin II. Third, components of the circulating renin system require the interaction of several organ systems and effector sites. Fourth, the kinetics of ACE inhibitors can be influenced by the organ systems responsible for drug absorption, metabolism and excretion, and the functional status of these systems can be affected by the heart failure process. Fifth, at least some portion of the cardiovascular effects of ACE inhibitors is influenced by the contributions of other systems whose physiologic effects may be of importance in some patients with congestive heart failure. Sixth, the potential impact of tissue-bound ACE is not yet fully understood. Finally, for appropriate drug dosing, the effects of aging on the heart failure process, the extent of renin system activity, and the disposition of ACE inhibitors need to be considered. Because of their complex pharmacokinetics, treatment with ACE inhibitors has been guided by their pharmacodynamic and clinical characteristics. ",13 3272,"Muscle blood flow and muscle metabolism during exercise and heat stress. The effect of heat stress on blood flow and metabolism in an exercising leg was studied in seven subjects walking uphill (12-17%) at 5 km/h on a treadmill for 90 min or until exhaustion. The first 30 min of exercise were performed in a cool environment (18-21 degrees C); then subjects moved to an adjacent room at 40 degrees C and continued to exercise at the same speed and inclination for a further 60 min or to exhaustion, whichever occurred first. The rate of O2 consumption, 2.6 l/min (1.8-3.3) (average from cool and hot conditions), corresponded to 55-77% of their individual maximums. In the cool environment a steady state was reached at 30 min. When the subjects were shifted to the hot room, the core temperature and heart rate started to rise and reached values greater than 39 degrees C and near-maximal values, respectively, at the termination of the exercise. The leg blood flow (thermodilution method), femoral arteriovenous O2 difference, and consequently leg O2 consumption were unchanged in the hot compared with the cool condition. There was no increase in release of lactate and no reduction in glucose and free net fatty acid uptake in the exercising leg in the heat. Furthermore, the rate of glycogen utilization in the gastrocnemius muscle was not elevated in the hot environment. There was a tendency for cardiac output to increase in the heat (mean 15.2 to 18.4 l/min), which may have contributed to the increase in skin circulation, together with a possible further reduction in flow to other vascular beds, because muscle blood flow was not reduced. ",22 2265,"Abnormal essential fatty acid metabolism in Darier's disease. Fatty acid levels in plasma and erythrocyte cell membranes were determined in 13 Danish patients with Darier's disease and 21 Danish controls. Concentrations of the main dietary essential fatty acids, linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), were consistently modestly above normal; concentrations of the delta 6-desaturase metabolites of both linoleic and alpha-linolenic acids, however, were consistently and often significantly below normal. These results suggest that the capacity of the enzyme delta 6-desaturase activity is inadequate in patients with Darier's disease. ",16 3278,"Aggressive granulomatous lesions in cementless total hip arthroplasty. We describe six patients with aggressive granulomatous lesions around cementless total hip prostheses. Two patients previously had a cemented prosthesis in the same hip. The Lord prosthesis was used in five patients, the PCA in one. Both prostheses were made of chrome-cobalt alloy. Pain on weight-bearing occurred on average 3.2 years after the cementless arthroplasty, and at that time radiography revealed aggressive granulomatosis around the proximal femoral stem and the acetabular component in five of the patients; one had a large solitary granuloma in the proximal femur. Revision was performed on average 4.8 years after the cementless arthroplasty. At that time all granulomas had grown large in size; while waiting for revision operation, two femoral stem components fractured. All the granulomas showed a uniform histopathology, which included histiocytosis; the cause for these lesions was thought to be plastic debris from the acetabular socket. ",22 146,"In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice. The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T. gondii in infected mice. At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads. Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection. Untreated control mice died within 9 days and showed early and predominant lung involvement. All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy. When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy. When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy. All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable. ",2 1410,"X linked hypophosphataemia: treatment, height gain, and nephrocalcinosis. The clinical data of 18 patients with X linked hypophosphataemia were analysed retrospectively. The height data were expressed as SD scores. There was no difference in the final height of patients treated with vitamin D (or 1,25-dihydroxyvitamin D) and phosphate for at least two years (n = 12) and that of 16 hypophosphataemic family members who had never been treated. The mean final SD score (-2.07) of treated patients, however, was significantly higher than the value before treatment (-2.79), which indicated an average absolute height gain of 4-4.5 cm compared with the expected height values. Six of the treated patients developed ultrasonographically detectable nephrocalcinosis with normal renal function. The daily phosphate intake and excretion of patients with nephrocalcinosis was significantly higher than that of patients with normal renal morphology. There was no difference in the doses of vitamin D between the two groups. The average urinary calcium:creatinine ratio of the two groups was similar to and below the hypercalciuric 0.6 mmol:mmol limit. The group with nephrocalcinosis, however, had a higher incidence of hypercalciuric episodes than the group without nephrocalcinosis (12 in 130 observations compared with six in 334 observations, respectively). The benefits and risks of treatment of patients with X linked hypophosphataemia must be further evaluated. The high dose of phosphate seems to be an important factor in the development of nephrocalcinosis in this group of patients. ",11 2937,"Two cases of fatal atlantoaxial distraction injury without fracture or rotation. Atlantoaxial injuries, regardless of mechanism, typically result in bony injury. We present two unusual cases of fatal traumatic C-1-C-2 distraction without associated fracture or rotation. The ligamentous anatomy, common underlying structural/medical predispositions, and the possible mechanism of injury are discussed. ",20 2220,"Cardiac transplantation for hypoplastic left heart syndrome: a modified technique [see comment] A modified technique of infant orthotopic cardiac transplantation with arch reconstruction using bicaval cannulation is described, and the results in 4 infants with hypoplastic left heart syndrome are presented. This technique minimizes donor myocardial ischemic time and recipient circulatory arrest time. ",15 1790,"The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Between 1970 and 1987, 112 patients were diagnosed as having thromboangiitis obliterans (TAO). The age was 42 +/- 11 years (mean +/- SD; range, 20-75 years); 23% were women, and 7% were more than 60 years old when they were first diagnosed. Ischemic ulcerations were present in 85 (76%) patients: 24 (28%) patients with upper-extremity, 39 (46%) patients with lower-extremity, and 22 (26%) patients with both upper- and lower-extremity lesions. Ninety-one (81%) patients had rest pain, 49 (44%) patients had Raynaud's phenomenon, and 43 (38%) patients had superficial thrombophlebitis. We were able to follow up 89 of the 112 (79%) patients for 1-460 months (mean follow-up time, 91.6 +/- 84 months). Sixty-five (73%) patients had no amputations, while 24 (27%) had one or more of the following amputations: finger, six (15%) patients; toe, 13 (33%) patients; transmetatarsal, four (10%) patients; below knee, 14 (36%) patients; and above knee, two (5%) patients. Forty-three (48%) patients stopped smoking for a mean of 80 +/- 105 months (median, 46.5 months; range, 1-420 months), and only two (5%) patients had amputations after they stopped smoking, while 22 (42%) patients had amputations while continuing to smoke (p less than 0.0001). The spectrum of patients with TAO is changing in that the male-to-female ratio is decreasing (3:1), more older patients are being diagnosed, and upper-extremity involvement is commonly present. In the 48% of patients who stopped smoking, amputations and continued disease activity were uncommon. ",13 1804,"Depression and recovery of right ventricular function after cardiopulmonary bypass. Transient left ventricular dysfunction is commonly described in association with cardiopulmonary bypass (CPB). We evaluated changes in right ventricular (RV) function after elective cardiac surgery in 24 patients with normal preoperative cardiac function. In all, irrespective of distribution of coronary artery disease or use of pharmacologic support, a transient depression of RV systolic function with respect to both preinduction and initial postoperative (Postop) values occurred 262 +/- 116 min post-CPB as represented by a decrease in RV stroke volume index (25.0 +/- 1.7 vs. 33.4 +/- 1.9 ml/m2 Postop) and RV ejection fraction (31.0 +/- 2.2 vs. 45.6 +/- 2.5% Postop), and an increase in RV end-systolic and end-diastolic volume indices. This depression responded readily to pharmacologic therapy within 2 h, resolved within 24 h, and had no adverse consequences in these otherwise healthy patients. Further studies are needed to identify the cause of this phenomenon and its importance in patients with preexisting cardiac dysfunction. ",13 275,"Autologous bone marrow transplantation in multiple myeloma: identification of prognostic factors. Multiple myeloma remains a universally fatal malignancy with a median survival time not exceeding 3 years. A clinical trial was undertaken to determine feasibility and efficacy of marrow-ablative chemoradiotherapy supported by unpurged autologous bone marrow (ABMT) and to define prognostic variables. Total body irradiation and either melphalan or thiotepa were administered to 55 patients (median age 53 years; range 20 to 66 years). The group of 21 patients with resistance to standard melphalan-prednisone and to continuous infusions of vincristine and Adriamycin with high dose dexamethasone (VAD) included 7 with primary unresponsive disease and 14 with resistant relapse; among the 34 patients achieving remission with the VAD regimen, 14 were in first and 20 in a subsequent remission. Marked cytoreduction by greater than or equal to 75% was observed among all 21 patients with refractory myeloma, whereas further cytoreduction of this magnitude was noted in only 56% of the 34 patients already in remission after VAD. Five of the 6 early deaths among all 55 patients occurred in the 14 patients with resistant relapse, none of whom achieved complete remission and who, as a group, had median durations of relapse-free and overall survival of only 8 and 7 months, respectively. Among the 41 remaining patients, there was only one early death, and 27% achieved complete remission including a 36% incidence among the 14 patients treated in first remission; their projected 4-year survival rate was 82% regardless of their disease status (first or later remission or primary resistance). When information about sensitivity to prior therapy is unavailable, the presence before ABMT of both high beta-2-microglobulin levels (greater than 3 mg/L) and non-IgG isotype helped identify 9 among the 55 patients with a very poor prognosis: all 8 responders relapsed within 9 months, and 8 patients died within 15 months. By contrast, a 4-year projected survival rate of over 70% for the other patients (about 80% of this series) justifies further investigation of this novel treatment approach in comparison with standard dose regimens. Our results indicate that marrow-ablative therapy cannot be recommended for myeloma patients with resistant relapse or those with a combination of risk factors (advanced tumor burden, absence of IgG isotype). The apparent lack of an adverse effect of even marked plasmacytosis in autografts (up to 30%) emphasizes the need for better cytoreduction rather than bone marrow purging. ",3 896,"Plasma cross linked fibrin degradation products in pulmonary embolism. Plasma concentrations of cross linked fibrin degradation products, a marker of intravascular thrombosis and fibrinolysis, were measured in 495 patients with suspected pulmonary embolism referred for ventilation-perfusion lung scanning to determine whether concentrations are increased in pulmonary embolism and their potential use in diagnosis. Lung scans were described as normal (n = 66) or as showing a low (n = 292), indeterminate (n = 58), or high probability (n = 79) of pulmonary embolism. There was a difference between the mean levels of cross linked fibrin degradation products in each scan category: normal scans, 142 ng/ml; low probability scans, 295 ng/ml; indeterminate probability scans, 510 ng/ml; high probability scans, 952 ng/ml (p less than 0.001). Of the patients with high probability scans, 96% had raised concentrations. Explanations for discrepant low results include incorrect scan diagnosis, delay in blood sampling, and anticoagulation. Of the patients with a low or indeterminate probability of pulmonary embolism, 43% had increased concentrations of cross linked fibrin degradation products that could be attributed in most cases to another illness. Owing to the wide range of values in each lung scan diagnostic category, raised concentrations of these fibrin degradation products cannot be used without reference to the patient's clinical state as a discriminatory test for pulmonary embolism. Further evaluation of the significance of normal concentrations in excluding a diagnosis of pulmonary embolism appears to be warranted. ",7 999,"Transtympanic endoscopic findings in patients with otitis media with effusion. Using a fine, rigid endoscope (Olympus, SES-1711K), we examined the middle ear, including the tympanic orifice of the eustachian tube, of children with otitis media with effusion (OME) in its active stage (26 ears), in the convalescent stage (13 ears), and during treatment with ventilation tubes for 10 days to 6 months (five ears) through myringotomy with the patients under general anesthesia. Several color photographs of representative ears are shown. In the active stage of OME, edema (73.1%) and hyperemia (23.1%) were characteristic features of the middle ear mucosa, and normal mucosa was seen in only one ear (3.1%). The tympanic orifice of the eustachian tube, which could be examined in 12 ears, were stenosed with edema in four ears (33.3%) or plugged with effusion in three ears (25.0%) in this group. In the convalescent stage of OME, dilated vessels were most often seen (69.2%), but the rest of the patients had normal mucosa (30.8%) in the middle ear, and none of them had edema nor hyperemia. The tympanic orifice of the eustachian tube, which could be examined in five ears, was clearly patent in all the patients in this group. One ear that was treated with a ventilation tube for 1 month showed dilated vessels and less severe inflammation than did ears that were in the active stage of OME, and three ears that were treated for more than 3 months showed almost normal middle ear mucosa. ",8 207,"Effect of somatostatin analogue (octreotide) on blood flow to endocrine tumors metastatic to the liver: angiographic evaluation. The effect of an octapeptide analogue of somatostatin, octreotide, on tumor blood flow was evaluated with angiography in eight patients with hepatic endocrine tumors; one patient had primary intrahepatic gastrinoma, two patients had hepatic metastases from gastrinomas, two patients had VIPomas (vasoactive intestinal polypeptide-secreting tumor), and three patients had carcinoid tumors. Octreotide caused a marked decrease in tumor blood flow in two patients with gastrinomas and two with VIPomas. One patient could not be evaluated due to the lack of a tumor blush on a control angiogram. In patients with carcinoid tumors, octreotide caused a slight reduction in blood flow through the tumors in two patients, while there was no change in one patient. Octreotide markedly decreased gastrin and gastric acid secretion in two of three patients with gastrinomas, lowered VIP and stopped the diarrhea in patients with VIPomas, and controlled symptoms in two of three patients with carcinoid tumors. The vasoactive effect of octreotide on hepatic endocrine tumors may be a direct action on tumor blood supply or secondary to inhibition of the endocrine tumor cell secretion and consequent decreased blood flow. ",3 2257,"A method for the determination of UVA protection for normal skin. Although the UVB portion of the electromagnetic spectrum (290 to 320 nm) is responsible for most of the harmful effects of sunlight on the skin, wavelengths in the UVA region also contribute to photodamage. A simple and rapid clinical test, the sun protection factor determination, is available to assess the sunburn protective effect of a sunscreen, primarily a UVB effect. However, no practical test has been proposed to measure a sunscreen's UVA protection. We described a method for the calculation of UVA protection in normal subjects. The determination of UVA protection involves three steps: (1) the UV absorbance spectrum of the sunscreen on skin is determined spectrophotometrically; (2) a convolution spectrum is calculated by multiplying the solar spectrum with the Commission Internationale de l'Eclairage UV Hazard Spectrum; and (3) the sunscreen transmission spectrum is then incorporated into the convolution spectrum to obtain the UVA effectiveness ratio, which can be expressed as the UVA protection percentage. Because the UVA protection percentage value is based both on normal erythemic risk and on standard sunlight, the protection for any product can be easily measured. The procedure is simple, and values generated can be reproduced in other laboratories. ",16 1028,"Asymptomatic congenital cytomegalovirus infection. Audiologic, neuroradiologic, and neurodevelopmental abnormalities during the first year. Twenty-eight infants with asymptomatic congenital cytomegalovirus infection and 13 control infants were followed up prospectively. Congenital sensorineural hearing loss was documented by auditory brain-stem responses in four infected infants (two had mild bilateral loss, one had mild unilateral loss, and one had extreme unilateral loss) but in no controls. Four infected infants had diffuse periventricular radiolucencies on computed tomographic scan; none had calcifications or ventriculomegaly. No differences between groups were noted on neurologic examination results or on the Bayley Mental Developmental Index; however, one infected infant had a severely delayed Bayley Psychomotor Developmental Index score. In addition, the mean Mental Developmental Index score of the four infected infants with diffuse periventricular radiolucencies was significantly below that of the remaining infected infants (93 +/- 8 vs 109 +/- 13). These data suggest that asymptomatic congenital cytomegalovirus infection may be associated with a broad range of audiologic, subtle neuroradiologic, and neurodevelopmental differences in early infancy. ",8 3293,"Pilot study of nicardipine for acute ischemic stroke. The author performed a pilot study of nicardipine (NC), a Ca(+)+ channel blocker, to study its dosing, toxicity, and possible efficacy for hemispheric cerebral infarction within 12 hours (mean 6.9 hr) of onset to determine the advisability of proceeding with a multi-centered controlled trial. NC was administered IV (3 to 7 mg/hr) X 72 hours by titrating dose to mean arterial blood pressure (MABP not less than 10% of baseline), then orally X 30 days. Forty-three patients have been entered; mean age 63 (range 34-89), 25 male and 18 female. Only 3 had CT evidence of infarct on entry. Results have shown improvement in a 100-point (pt) graded exam (40 pts at entry, 68 pts at 3 months). Of 20 patients completing 3 months' evaluation, 17 improved and none worsened. Sixteen out of 20 were at home and 8 had minimal or no impairment. Mean Barthel's index was 72. Mean maximal serum NC level was 75 ng/mL. MABP decreased from 103 (entry) to 83 (72 hours). A larger controlled study is warranted to determine the efficacy of NC for acute cerebral infarct. ",22 2417,"Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo. The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver. ",17 1069,"Brain imaging abnormalities in mental disorders of late life. Psychiatric inpatients with dementia (N = 61) or depression (N = 67) in late life were 2.6 times more likely to manifest magnetic resonance imaging abnormalities of the brain than were elderly controls (N = 44). Controlling for the effects of age and gender, demented patients were distinguishable from controls by an increased prevalence of cortical atrophy and infarction, while depressed patients exhibited an increased prevalence of cortical infarctions and leukoencephalopathy. Patients with dementia were distinguishable from those with major depression by an increased prevalence of cortical atrophy. These results indicate that major depression in late life, like dementia, is associated with a remarkable increase in overt pathologic changes in the brain. ",9 3270,"Premenstrual syndromes defined by symptom-sets. An analysis is made of the pattern of presenting premenstrual symptoms in randomly selected general practice patients from the Wellington region, New Zealand. Participants, 1826 healthy women 16-54 years old whose characteristics were reasonably representative of the adult female population, were asked about their general, obstetrical and gynaecological health. For the 1456 women who had menstruated within the last month or so, detailed questions were asked about the last menstrual cycle. Each woman was assigned to one of seven premenstrual symptom sets. Three groups had 'pure' symptoms, ie a predominant single symptom (breast tenderness, bloating or irritability). Three groups had 'mixed' symptom-sets. The largest of the 'mixed' groups was formed by the women who reported breast tenderness, bloating and irritability together with tension and depression. Women in this group were most likely to rate their symptomatology as severe. The last group contains a large number of women with miscellaneous symptoms. Characteristics of these groups are outlined. The study highlights the importance of distinguishing among premenstrual syndromes as this can foster more effective clinical management. ",22 2907,"Frostbite. Methods to minimize tissue loss. If frostbite is to be treated successfully, direct and indirect effects of injury must be understood. Rapid rewarming helps to preserve tissue by limiting the amount of direct cellular injury. Selective management of blisters helps protect the subdermal plexus, and application of Aloe vera cream (eg, Dermaide Aloe Cream) combats the local vasoconstrictive effects of thromboxane. Oral administration of ibuprofen decreases systemic levels of thromboxane. ",20 2454,"Cholesterol-lowering effects of soluble-fiber cereals as part of a prudent diet for patients with mild to moderate hypercholesterolemia. Soluble-fiber breakfast cereals were examined for their cholesterol-lowering ability in 58 male patients with mild to moderate hypercholesterolemia in a randomized, double-blind, placebo-controlled study. Patients followed a step 1 diet for a minimum of 6 wk, then were randomly assigned to groups incorporating either corn flakes or one of two soluble-fiber cereals (pectin enriched or psyllium enriched) in the diet for an additional 6 wk. During the diet-only phase, total cholesterol dropped 3.8%. During the cereal-plus-diet phase, total and LDL cholesterol values of the pectin-enriched cereal group dropped an additional 2.1% (P = 0.243) and 3.9% (P = 0.16), respectively, and they dropped 5.9% (P = 0.005) and 5.7% (P = 0.034), respectively, in the psyllium-enriched cereal group. During the cereal-plus-diet phase, no significant effects on HDL cholesterol, triglyceride, or body weight were found within or between any cereal groups. These results support use of soluble-fiber cereals as an effective and well-tolerated part of a prudent diet in the treatment of mild to moderate hypercholesterolemia. ",17 2856,"Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study The prevalence of comorbid alcohol, other drug, and mental disorders in the US total community and institutional population was determined from 20,291 persons interviewed in the National Institute of Mental Health Epidemiologic Catchment Area Program. Estimated US population lifetime prevalence rates were 22.5% for any non-substance abuse mental disorder, 13.5% for alcohol dependence-abuse, and 6.1% for other drug dependence-abuse. Among those with a mental disorder, the odds ratio of having some addictive disorder was 2.7, with a lifetime prevalence of about 29% (including an overlapping 22% with an alcohol and 15% with another drug disorder). For those with either an alcohol or other drug disorder, the odds of having the other addictive disorder were seven times greater than in the rest of the population. Among those with an alcohol disorder, 37% had a comorbid mental disorder. The highest mental-addictive disorder comorbidity rate was found for those with drug (other than alcohol) disorders, among whom more than half (53%) were found to have a mental disorder with an odds ratio of 4.5. Individuals treated in specialty mental health and addictive disorder clinical settings have significantly higher odds of having comorbid disorders. Among the institutional settings, comorbidity of addictive and severe mental disorders was highest in the prison population, most notably with antisocial personality, schizophrenia, and bipolar disorders. ",20 2400,"Biometry of the crystalline lens in early-onset diabetes Lenticular biometry on non-cataractous lenses has been studied by means of Scheimpflug photography and digital image analysis in 153 patients with early-onset insulin-dependent diabetes and 153 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior and posterior lenticular curvatures, and anterior chamber depth were assessed. Highly significant differences between the lenses of the diabetic subjects and non-diabetic controls were found. After the effect of age had been accounted for within the diabetic subgroup, diabetic duration was found to be a highly significant determinant of lens dimensions, such that age-related dimensional changes for various biometric parameters were accelerated by between 52% and 121% after the onset of diabetes. Because the diabetic duration of the early-onset diabetic subjects studied in this work was accurately known, this report is the first in which a precise assessment of the effect of 'true' diabetic duration on lens biometry has been possible. ",17 1639,"Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia. This study examined the implications of left ventricular (LV) dilatation and increased pulmonary thallium uptake during adenosine-induced coronary hyperemia. The lung-to-heart thallium ratio in the initial images was significantly higher in patients with coronary artery disease (CAD) than normal subjects; 0.48 +/- 0.16 in 3-vessel disease (n = 16), 0.43 +/- 0.10 in 2-vessel disease (n = 20), 0.43 +/- 0.08 in 1-vessel disease (n = 16) and 0.36 +/- 0.05 in normal subjects (n = 7) (p less than 0.001, 0.09 and 0.06, respectively). There was a significant correlation between the severity and the extent of the perfusion abnormality (determined from the polar maps) and the lung-to-heart thallium ratio (r = 0.51 and 0.52, respectively, p less than 0.0002). There was also a significant correlation between lung thallium washout and lung-to-heart thallium ratio (r = 0.42, p = 0.0009) and peak heart rate (r = -0.49, p less than 0.0001). The LV dilatation was mostly due to an increase in cavity dimension (30% increase) and to a lesser extent (6% increase) due to increase in LV size. (The cavity dimensions were measured from the short-axis slices at the midventricular level in the initial and delayed images). The dilation was seen in patients with CAD but not in the normal subjects. These changes correlated with the extent and severity of the thallium perfusion abnormality. Thus, adenosine-induced coronary hyperemia may cause LV dilation and increased lung thallium uptake on the basis of subendocardial ischemia. ",13 2986,"The effect of screws and pegs on the initial fixation stability of an uncemented unicondylar knee replacement. Two uncemented unicompartmental tibial components were examined for initial fixation stability. A conventional design that employed a single posteriorly angled peg was compared with a new design that was held in place by cancellous bone screws. The components were implanted into the medial condyles of 12 preserved human tibiae, and a cyclic load was first applied anteromedially and then posteromedially. The screwed implants failed at significantly higher loads (1634.8 +/- 121.6 N, mean +/- standard error of the mean) than the pegged implants (1103.3 +/- 152.0 N). On application of a 19.6-N preload, the screwed implants moved significantly less than the pegged implants. Although the differences in micromotion and subsidence were not always significant, there were definite trends. The screwed implants had much lower levels of temporary and permanent displacement compared with the pegged implants for all load levels from the initial load of 245.2 N up to and including the failure load. When the motion that resulted from moving the load from the anterior position to the posterior position was examined, the screwed implant's average total motion was less than 10 microns compared with almost 135 microns for the pegged implant after the 245.2-N load cycle. For the cycle before failure, the screwed implant's average motion increased to less than 29 microns, whereas the pegged implant's average total motion was almost 354 microns. From this information it appears clear that screws provide better initial fixation stability than angled pegs for uncemented unicondylar tibial components. ",22 1963,"An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8-9% to be effective in lowering total mortality. ",13 3173,"Percutaneous balloon dilatation of benign biliary strictures. Percutaneous biliary dilatation is an effective alternative to surgical management of benign biliary strictures that has low morbidity and no reported mortality. Reported success rates for this procedure range from 40% to 90% depending on the size of the series, the type of patient being treated, and the length of follow-up period. The procedure is done in the fluoroscopy suite with an angioplasty balloon catheter. Transhepatic access is most common, but the procedure may be done via existing T-tube tracts or specially created jejunal loops. As the frequency of radical liver surgery such as liver transplant and radical trisegmentectomy rises, so too, the rate of biliary stricture is likely to rise, making percutaneous balloon dilatation an increasingly important tool in the interventional radiologist's armamentarium. ",22 654,"Focal fibrocartilaginous dysplasia associated with tibia vara. Focal fibrocartilaginous dysplasia of the tibia at the insertion of the pes anserinus (the expanded tendinous insertion of the gracilis, sartorius, and semitendinous muscles) is a rare unilateral lesion with a characteristic deformity of the proximal tibial metadiaphysis. It is associated with unilateral tibia vara in toddlers. Three cases of this entity are described, and the radiologic features are presented. Recognition of this disease is important because the response to conservative therapy is excellent. ",4 449,"Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses. A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF. The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by 50% at a 10-fold excess of TNF-BP. The binding of TNF to the receptor was partially reversed after the addition of TNF-BP. Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed. A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP. Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor. Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters. TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications. ",3 2722,"Differences in knowledge of and risk factors for AIDS between Hispanic and non-Hispanic women attending an urban family planning clinic. Risk factors for AIDS, contraceptive use, seroprevalence of HIV, and level of knowledge before and after an AIDS education session were assessed for 657 clients attending a family planning clinic in Los Angeles, USA. History of a partner who was bisexual, an intravenous drug user, or a blood transfusion recipient were the most common risk factors. Spanish speakers reported fewer traditional risk factors than English speakers. They were also less likely to report a history of drug or alcohol use or sexually transmitted diseases, and to have had fewer sexual partners. Less than one-third of the women identified as being at risk of exposure were using condoms. None of 351 consecutive patients tested for HIV antibodies was positive. English speakers scored higher on both pre- and post-tests of knowledge about AIDS. Cultural factors may lower the personal risk of HIV exposure for Spanish-speaking women, but lack of knowledge about AIDS and partner behavior may increase risk. ",19 2105,"Early and late tamponade with the Novacor left ventricular assist system. Cardiac tamponade can be a major complication after implantation of the Novacor left ventricular assist system (LVAS). Between 1987 and 1989, 14 patients received an LVAS as a bridge to cardiac transplantation: 3 developed early tamponade (33 +/- 12 hr postoperatively) and 5 were diagnosed with a late tamponade (9.4 +/- 3.2 days postoperatively). One patient had both early and late tamponade. Early tamponade was more common in those with increased perioperative blood loss (5,270 +/- 1,942 ml vs. 1,420 +/- 1,160 ml in other patients, p less than 0.05). Early tamponade was suggested by reduction in mean arterial pressure (74 +/- 1 to 64 +/- 3 mmHg), LVAS output (5 +/- 0.5 to 2.7 +/- 0.7 L/min), LVAS stroke volume (55 +/- 4 to 23 +/- 5 ml), and an increase in central venous pressure (13 +/- 1 to 21 +/- 1 mmHg, p less than 0.05 for all values). Late tamponade was associated with a marked rise in central venous pressure (14 +/- 1 to 22 +/- 2 mmHg, p less than 0.05), with only a mild decrease in LVAS output (4.9 +/- 1 to 3.8 +/- 0.9 L/min) and stroke volume (49 +/- 8 to 36 +/- 3 ml), without a significant change in mean arterial pressure. Two of these five late episodes occurred in patients who were anticoagulated with heparin (PTT 52 and 100 sec), and in one other with warfarin (PT 27 sec, PTT 55 sec); two patients were not on any anticoagulants. Surgical drainage of pericardial effusions, and especially of clotted blood found frequently posterior to the left ventricle in the space created by the LVAS decompressed left ventricle, resulted in an immediate return of all hemodynamic measurements to normal in both early and late tamponade. ",13 3313,"Current trends in suture fixation of posterior chamber intraocular lenses. Corneal surgeons were surveyed with regard to their technique of suture fixation of posterior chamber intraocular lenses in the absence of posterior capsular support. Fifty-nine percent of the 260 respondents stated they perform the procedure almost exclusively during penetrating keratoplasty. Scleral fixation was marginally favored over iris fixation by these surgeons. Most intraoperative problems reported were related to the relative technical difficulty of the procedure, although transient hemorrhage from the ciliary body was also mentioned. Postoperative complications cited included mechanical problems involving the lens and iris, cystoid macular edema, glaucoma, and endophthalmitis. ",22 3152,"Hemiparkinsonism-hemiatrophy syndrome: clinical and neuroradiologic features. We evaluated 11 patients with hemiparkinson-hemiatrophy syndrome, 6 with body and contralateral cerebral hemispheric hemiatrophy, 4 with only body hemiatrophy, and 1 with just brain hemiatrophy. The mean age of symptom onset was 38.1 years (range, 18 to 54) with 5.2 +/- 3.1 (mean +/- SD) years of illness until the last follow-up visit. The presenting symptom was unilateral tremor in 6 patients, hand dystonia in 2, bradykinesia in 2, and abnormal gait in 1 patient. Three patients had a good response to levodopa, 4 had moderate response, and 2 patients had a poor response. During a mean follow-up period of 1.7 years (range, 4 months to 5 years), the Hoehn and Yahr score changed in only 3 patients: 2 gained 1.5 points and 1 gained 3 points over 2.5 years. We discuss the association between hemiparkinsonism-body hemiatrophy and contralateral hemispheric hemiatrophy, and raise the possibility of early childhood brain insult with delayed-onset parkinsonism. ",22 2314,"Cicatricial pemphigoid. Identification of two distinct sets of epidermal antigens by IgA and IgG class circulating autoantibodies. A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3 (C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient's serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90 kd, the patient's IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed. ",16 1618,"Lower extremity percutaneous transluminal angioplasty: multifactorial analysis of morbidity and mortality. We analyzed the outcome of 202 percutaneous transluminal angioplasty (PTA) procedures performed between 1983 and 1989 to quantitate procedural risks and define factors associated with suboptimal results or immediate clinical failure. Premorbid factors studied included age, sex, treatment of single versus multiple lesions, stenoses versus occlusions, premorbid status of the limb (claudication vs limb threat), and most distal level of PTA. Adverse outcomes included complications (hematoma, acute occlusion, or thrombosis of PTA site, distal embolization, failure to dilate or cross, arterial dissection, rupture, and significant systemic derangement), major amputations (below knee and above knee), and deaths. There were 66 complications (32.7%), 22 amputations (10.9%), and 12 deaths (5.9%) in our series. Logistic regression analysis revealed that the major predictive variable for the occurrence of a complication (p = 0.002), and the only predictive variable for the outcomes of amputation and death (p = 0.0001 and p = 0.0139, respectively), was the premorbid clinical status of the limb. Lower extremity PTA is not an intrinsically benign procedure and is associated with a significant risk of complication, amputation, and procedure-associated death. These adverse outcomes cluster in patients with limb threat. Therefore it may be reasonable to restrict the use of PTA to patients with claudication and strictly selected cases of limb threat. ",13 1851,"Dissociation of changes in cardiovascular mass and performance with angiotensin-converting enzyme inhibitors in Wistar-Kyoto and spontaneously hypertensive rats. The effects of angiotensin-converting enzyme inhibitors on cardiovascular mass and function were measured in three groups of 22 week old male Wistar-Kyoto normotensive and spontaneously hypertensive rats treated with CGS-16617, cilazapril or quinapril. Left ventricular performance was assessed by electromagnetic flow meter during rapid whole blood infusion before and after arterial pressure and increased abruptly with aortic snare; aortic distensibility also was assessed in vitro. The systemic hemodynamic effects of these three agents were similar, yet their structural effects varied. Although left ventricular and aortic masses diminished and right ventricular mass remained unchanged (with all three agents) in the spontaneously hypertensive rats, CGS-11617 and cilazapril also reduced left ventricular mass in the normotensive Wistar-Kyoto rats without changing aortic mass. All three agents improved aortic distensibility whether or not mass was decreased. Left ventricular structural changes were associated with variable changes in pumping ability. These data show that reduced mass associated with angiotensin-converting enzyme inhibitor treatment was not consistent in ventricles and aorta, that a dissociation exists between structural and functional changes and that reduction of cardiac mass alone does not relate to changes in chamber mass or in function. Thus, biologic and pharmacodynamic differences exist among angiotensin-converting enzyme inhibitors as well as between classes of antihypertensive agents. ",13 2164,"Disseminated intravascular coagulation due to intravenous administration of hetastarch. Disseminated intravascular coagulation occurred in a patient after intravenous administration of hetastarch. The onset was acute within 3 hours after exposure to the agent and the course was fulminating. The patient died in 48 hours. Clinical, hematologic, and pathologic features are presented and possible pathophysiologic mechanism is discussed. In view of this experience and documented effects of hetastarch on coagulation, the use of hetastarch should be avoided if the patient has a history of coagulation disorder, and the patient receiving the agent should be closely monitored with appropriate coagulation tests. ",14 1993,"Coronary artery disease in the octogenarian: angiographic spectrum and suitability for revascularization. The angiographic findings of 84 consecutive octogenarians presenting with symptoms of coronary artery disease (CAD) were examined to determine the extent of CAD as well as suitability for both coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). The frequency of 0-, 1-, 2-, and 3-vessel and left main CAD was 7, 14, 21, 57 and 13%, respectively. Based on angiographic criteria, 69 of 78 patients (88%) with significant CAD had suitable coronary anatomy for CABG. Only 24 patients (31%) had coronary anatomy amenable to PTCA. CABG was performed in 19 patients with an operative mortality of 16% and major complication rate of 37%. PTCA was performed in 12 patients with a clinical success rate of 83%, mortality of 8% and major complication rate of 8%. It is concluded that in octogenarians with CAD, cardiac catheterization will often reveal coronary anatomy that is suitable for CABG but less suitable for PTCA. The morbidity and mortality associated with these interventions are high. ",13 372,"Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma. The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection. ",3 2929,"Familial values as factors influencing long-term psychological adjustment of children after severe burn injury. This study replicates earlier findings that children who survive severe burn injury do make positive psychological adjustment. Family support and a family value of autonomy were predicted to be critical variables in promotion of psychological adjustment. In addition, the study presents the hypothesis that length of time after burn injury and level of intelligence are contributing factors in psychological adjustment. Forty-four adolescents with a mean of 60% total body surface area (TBSA) full-thickness burns were studied. Half of the subjects scored within the normal range on a measure of psychological adjustment. Familial value patterns were critical in the prediction of psychological adjustment. Positive psychological adjustment was predicted by greater family cohesion, independence, and more open expressiveness within the family. Level of intelligence did not contribute to adjustment. Length of time after injury, if it is important to psychological healing, appears to be a factor only during the initial 2 years after burn injury. ",20 2058,"Bone mineral density in spontaneous hypertension: differential effects of dietary calcium and sodium. Dietary calcium and sodium have been postulated to modify both bone mineral status and blood pressure regulation in humans and animals. The spontaneously hypertensive rat (SHR) manifests several defects in calcium metabolism that may contribute to its hypertension. Blood pressure and bone mineral status were measured in SHR and normotensive Wistar-Kyoto rats (WKY) as a marker of whole animal calcium metabolism. In addition, the effect of alterations in dietary calcium and sodium on bone status were examined. At 6 weeks of age, seven male SHR and seven male WKY were placed on a control diet. At the same age, 28 SHR and 28 WKY were randomized to four diets containing either 2.0% or 0.1% calcium and 1.0% or 0.25% sodium. Four markers of bone mineral status were analyzed: bone density measured by direct photon absorptiometry, and total bone calcium, phosphorus, and magnesium content measured by atomic absorption spectrophotometry. The SHR exhibited significantly lower levels (p less than 0.001) of bone density and bone magnesium content than the WKY, whereas bone phosphorus and calcium did not differ between the two strains. The 2.0% calcium diets resulted in increased bone density and bone calcium content, and lower bone magnesium in both strains. The 1.0% sodium diets were associated with decreased bone density in the SHR, but not in the WKY. These findings identify another indicator of disturbed calcium metabolism in the SHR that may be related to impaired renal calcium handling. They are consistent with previously reported reductions in renal calcium reabsorption and decreased intestinal calcium transport in older SHR. ",13 1170,"Neurodevelopmental outcome of children with evidence of periventricular leukomalacia on late MRI. Fifteen children, 8 months of age or older, from a neonatal follow-up program underwent magnetic resonance imaging and neurologic, cognitive, and language evaluations. Magnetic resonance imaging findings in all children included increased white matter signal on T2-weighted images and ventricular enlargement adjacent to regions of abnormal white matter. The extent of degree of abnormal white matter signal and the degree of sulcal prominence were variable. Twelve children had cerebral palsy; 5 children, 4 of whom had cerebral palsy, manifested significant sensory impairments. The median score on cognitive testing was 89; only 2 children exhibited severe-to-profound cognitive disability. Cognitive scores were stable on retesting. The degree of motor disability was correlated with the extent of white matter signal abnormality; however, cognitive outcome was not related to the extent and degree of white matter signal abnormality or to the degree of sulcal prominence. Despite the association of a major handicapping condition and periventricular leukomalacia, cognitive and language functioning may be relatively spared. ",9 946,"Ultrastructural localization of proteinase 3, the target antigen of anti-cytoplasmic antibodies circulating in Wegener's granulomatosis. To investigate the distribution of proteinase 3, the target antigen of anti-cytoplasmic antibodies (ACPA or C-ANCA), within the organelles of resting normal human polymorphonuclear leukocytes and monocytes, the authors used immunocytochemical techniques on thin frozen sections. To obtain valuable tools for immunolabeling, two murine monoclonal antibodies (MAbs) directed against the ACPA antigen were produced. In neutrophils, the authors observed immunogold label for the ACPA antigen, predominantly in myeloperoxidase-positive azurophil granules, and in smaller amounts on the plasma membrane. In monocytes, the ACPA antigen could be detected in small granules, which occasionally also contained myeloperoxidase, and rare labeling was found on the monocyte membrane. The finding that the ACPA antigen is expressed on the plasma membrane of neutrophils and monocytes, thereby becoming accessible to circulating autoantibodies, supports the supposition that ACPA are not only markers of disease activity, but also are involved in the pathogenesis of Wegener's granulomatosis. ",7 2115,"Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +/- 1.3%, P less than 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls. ",13 641,"An analysis of the effect of the Zielke operation on S-shaped curves in idiopathic scoliosis. A follow-up study revealing some skeletal and soft tissue factors involved in curve progression. This article analyzes the fate of S-shaped idiopathic spinal curves during follow-up in 18 patients having the Zielke VDS operation. The spinal radiographs were evaluated by Cobb angle, end-vertebra angles (EVAs), vertebral rotation, and by a new method using the tilt of the surgically fused spinal block in the frontal plane. Spinal growth was measured. Using the conventional criterion for Cobb angle progression, 83% of the lower curves and 50% of the upper curves progress. The use of EVAs shows that progression occurs mainly in the middle (thoracolumbar) segment of the spine. Curve progression occurs in the frontal plane without any significant change in vertebral rotation. The progression of the upper curve Cobb angle is not related to the progression of the Cobb angle of the lower curve; but it is related to 1) tilt of the spinal block, 2) growth of the spine below the block and 3) overall linear spinal growth (T1-S1). Progression of the upper EVA of the upper curve is associated with skeletal immaturity. The key features leading to curve progression after the Zielke operation appear to be spinal asymmetry in the frontal plane, linear spinal growth, and concave lumbar muscle tether (myostatic contracture). The surgical implications of the findings are outlined. ",4 622,"Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. Eicosanoids are important mediators of the inflammatory response to monosodium urate crystals (MSUC) that results in gout. Phospholipase enzymes cleave fatty acids from membrane phospholipids, and this is thought to be the rate-limiting step in eicosanoid production. To understand better the mechanism of eicosanoid production in this disease, we stimulated human peripheral blood neutrophils and monocytes with MSUC and measured phospholipase enzyme activities. MSUC stimulated both intracellular and secretory phospholipase A2 enzyme activities in a time and concentration-dependent manner. Specificity was observed, as phospholipase C activities were not affected. Pretreatment with colchicine, but not aspirin, indomethacin, allopurinol, or islet activating protein, abrogated the enhanced phospholipase A2 activities. We have recently isolated and characterized a phospholipase A2 activating protein termed PLAP from synovial fluid from patients with rheumatoid arthritis, and from murine and bovine cell lines. PLAP was detected in gouty synovial fluid by immunodot blotting and ELISA assays and expressed the same characteristics as PLAP identified from other sources. To examine the role of PLAP in MSUC-induced phospholipase A2 stimulation, we treated cells with MSUC and observed an increase in immunoreactive PLAP. This response also could be blunted by colchicine, but not other drugs. Both phospholipase A2 and PLAP induced production by human monocytes of PGE2 and leukotriene B4 by neutrophils. These findings suggest that phospholipase A2 activation in response to MSUC requires an intact microtubule structure, and that phospholipase A2 and PLAP may be important modulators of at least a portion of the gouty inflammatory response. ",4 3266,"The case for porous-coated hip implants. The femoral side. A series of 1163 total hip arthroplasties (THAs) using porous-coated femoral components were roentgenographically assessed for implant fixation. For 959 primary THAs followed from two to 12 years, the femoral revision rate was 1% and the ten-year survivorship rate was 96.4%; 150 young patients had a fixation failure incidence of only 1.3% at a mean follow-up period of 6.4 years; in 204 revision THAs, the femoral re-revision rate was 4% at a mean follow-up period of 53.4 months. Failures were largely related to inadequate femoral canal filling. Because of refinements in implant design and surgical techniques, a press fit of the implant is currently achieved in 94% of cases compared to 36% during the first five years. Porous-coated femoral components have yielded results equivalent to those with cement in primary THAs. Excellent results were observed in relatively young patients and patients with revisions. ",22 3280,"Endoscopic control of upper gastrointestinal bleeding. It has been estimated that gastrointestinal (GI) bleeding occurs in more than 100,000 patients with peptic ulcer disease each year. In 75-80% of the cases, bleeding will be self-limited. A major predictor of persistent or recurrent bleeding is the magnitude of blood loss before the initial evaluation. Endoscopy has an important role in the evaluation of the patient with suspected or presumed upper GI bleeding. Active bleeding at the time of the endoscopy correlates with the more likely probability of persistent bleeding, which carries a higher morbidity and mortality. In addition, there has been continued interest in the finding of a visible vessel. Although there is some controversy as to what a visible vessel actually is and how closely observations will agree about its recognition, there is general agreement that it is an important endoscopic finding and that it carries a high likelihood of rebleeding. In addition to the finding of a visible vessel, many endoscopists feel that ulcers found in the posterior-inferior wall of the duodenal bulb and high on the lesser curve of the stomach should be considered in a separate category. Owing to their proximity to large vessels, some feel that endoscopic management carries a greater risk because of the possibility of inducing bleeding. A wide variety of endoscopic approaches are available for the therapy of upper GI bleeding. It is convenient to divide these therapies into four categories: (a) topical, (b) injection, (c) mechanical, and (d) thermal. Endoscopic therapy for bleeding ulcers has generally been performed with a high degree of safety. ",22 335,"Head and neck cancer and ageing: a retrospective study in 438 patients. To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non-elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post-operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor. ",3 2820,"Alcohol withdrawal syndromes. Current studies have begun to elucidate the pathophysiology of alcoholism and its withdrawal syndrome. Newer benzodiazepines, beta-blockers, alpha-agonists, butyrophenones and calcium channel blocking agents, alone and in combination, have been studied recently in alcohol withdrawal. This article discusses evaluation and therapy for delirium tremens, major alcohol withdrawal, mild alcohol withdrawal, adjunct therapy, and admission criteria. ",20 900,"Inhaler and spacer use in obstructive airway diseases. The role of inhaled aerosols in the treatment of obstructive airway diseases is increasing for both immediate bronchodilation and prophylactic anti-inflammatory effects. Inhaled aerosol agents are available in metered-dose inhaler and nebulizer forms. Maximum therapeutic benefit from metered-dose inhalers is assured when the correct inhaler technique is used. Spacer devices may be helpful in some patients. ",7 767,"Gallstone disease in north India: clinical and ultrasound profile in a referral hospital. We studied the prevalence of gallstones in patients with upper abdominal pain, heaviness, or discomfort by ultrasound examination of the gallbladder. The actual ultrasound examination was performed by a clinical gastroenterologist blinded to the symptoms. Of 1,680 consecutive dyspeptic patients, 500 (29.8%) had gallstones. The gallbladder was contracted in 450 (91.2%), normal-size in 36 (7.2%), and distended in 8 (1.6%). Biliary colic was more frequently the presenting complaint in patients with a contracted gallbladder than in those with normal size gallbladder (p less than 0.001). Dyspepsia was more frequent in the presence of a normal size gallbladder than a contracted one (p less than 0.001). We conclude that ultrasonography of the gallbladder by the clinician has a high diagnostic yield, and the symptom complex has an excellent correlation with the sonographic appearance. ",5 284,"Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor. Expression of pancreatic secretory trypsin inhibitor (PSTI) gene was examined by Northern blotting analyses in 31 human colorectal tumors that included two benign adenomas and 26 adenocarcinomas. Among the total of 28 cases which proved to be adequate for mRNA analyses, all but one showed the expression of PSTI at various levels. In contrast, PSTI expression was not detected in two malignant lymphomas of the rectum. The level of PSTI expression was not correlated with the patient's age, sex, tumor location or size, stage of differentiation, lymph node metastasis, or progression stage. Some colorectal adenocarcinomas were also shown to express genes that can hybridize with human trypsinogen cDNA probe. It looks as though in these tumors, a protease(s) and its inhibitor are produced simultaneously as part of a cellular self-defense mechanism. ",3 25,"Comparison of cilofungin and amphotericin B for therapy of murine candidiasis. We compared the efficacies of cilofungin and amphotericin B treatment in a murine model of disseminated candidiasis. Three different dosages of each drug plus controls were evaluated. Statistically improved survival was noted only among mice treated with 1 mg of amphotericin B per kg of body weight (P less than 0.05). While all amphotericin B regimens and the two lower-dosage cilofungin regimens significantly reduced yeast cell counts in kidneys compared with the controls, the amphotericin B-treated mice had a significantly higher percentage of sterile kidneys following therapy compared with those treated with cilofungin (P = 0.0001). ",0 337,"Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics. We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of ""trapped"" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions. ",3 3140,"The effects of an iron chelator on cellular injury induced by vascular stasis caused by hypothermia. Rewarming of a cooled rabbit leg was associated with the generation of oxygen-derived free radicals, shown to be instrumental for tissue injury occurring during rewarming. The present study used a compound that, by its ability to bind with free iron, can remove hydroxyl radical (OH.) from tissue. Deferoxamine reduced tissue injury during cooling and rewarming, as evidenced by its ability to decrease tissue release of lactic acid dehydrogenase and creatine kinase. Deferoxamine also reduced the formation of OH. and lipid peroxidation during the rewarming phase. This compound did not have any effect on the arterial blood flow pattern, which uniformly decreased during cooling and was restored during rewarming. The results of this study indicate the efficacy of deferoxamine in reducing cellular injury associated with cold and rewarming and further suggest a role for oxygen-derived free radicals in the pathophysiology of cold-rewarming injury. ",22 65,"Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Lyme borreliosis is a tick-borne illness caused by Borrelia burgdorferi. The gene for outer surface protein A (OspA) from B. burgdorferi strain N40 was cloned into an expression vector and expressed in Escherichia coli. C3H/HeJ mice actively immunized with live transformed E. coli or purified recombinant OspA protein produced antibodies to OspA and were protected from challenge with several strains of B. burgdorferi. Recombinant OspA is a candidate for a vaccine for Lyme borreliosis. ",0 1890,"Silent myocardial ischemia: dilemma or blessing? Developing an optimal strategy for the evaluation and management of patients with silent myocardial ischemia is extremely difficult. Although otherwise healthy, asymptomatic individuals may be at risk of dying suddenly during exercise, neither exercise testing nor Holter monitoring reliably identifies those at greatest risk. In patients with underlying coronary artery disease, silent ischemia increases the risk of an adverse outcome. ",13 3133,"Biologically inert synthetic dural substitutes. Appraisal of a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer. Two types of artificial membranes, a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer, were tested as substitutes for dura in 24 and 12 rabbits, respectively. The films were placed either epidurally, subdurally, or as dural grafts in equal subgroups of animals. The postoperative course was uneventful with no manifestations of convulsive disorder or cerebrospinal fluid leak. The animals were sacrificed 3, 6, or 9 months after implantation of the artificial membranes. Both types of artificial membranes were easily removed from the underlying nervous and the other surrounding tissues. The histological examination failed to reveal adhesions, neomembrane formations, or any type of foreign body reactions to the polyurethane film. The implantation of the polysiloxane-carbonate film caused no reaction when it was applied epidurally. As a dural graft, the polysiloxane-carbonate copolymer induced the formation of a thin neomembrane of one to two layers of fibroblasts which formed a watertight seal of the dural defect. A similar thin neomembrane was found to encase this artificial membrane in the group of animals in which it was implanted subdurally. There was no foreign body reaction to the polysiloxane-carbonate film. The authors conclude that these materials hold promise as dural substitutes or in the prevention of spinal dural scarring, and should be evaluated clinically. ",22 3044,"Upper GI bleeding in an urban hospital. Etiology, recurrence, and prognosis. Acute upper gastrointestinal bleeding (UGIB) continues to be a common cause of hospital admission and morbidity and mortality. This study reviews 469 patients admitted to a surgical service of an urban hospital. There were 562 total admissions because 53 patients were readmitted 93 times (recurrence rate, 20%). The most common causes of bleeding, all endoscopically diagnosed, included acute gastric mucosal lesion (AGML) (135 patients, 24%), esophageal varices (EV) (121 patients, 22%), gastric ulcer (108 patients, 19%), duodenal ulcer (78 patients, 14%), Mallory-Weiss tear (61 patients, 11%), and esophagitis (15 patients, 3%). Nonoperative therapy was sufficient in 504 cases (89.5%). Endoscopic treatment was used in 144 cases. Operations were performed in 58 cases (10.5%), including 29% of ulcers. Emergency operations to control hemorrhage were required in only 2.5% of all cases. The rate of major surgical complications was 11% and the mortality rate was 5.2%. There were 58 deaths (12.6%), with 36 deaths directly attributable to UGIB. Factors correlating with death include shock at admission (systolic blood pressure less than 80), transfusion requirement of more than five units, and presence of EV (all p less than 0.001). Most cases of UGIB can be treated without operation, including endoscopic treatment, when diagnostic endoscopy establishes the source. Subsequent operation in selected patients can be done with low morbidity and mortality rates. ",22 1328,"Strategies for enhancing compliance in the dialysis elderly. Noncompliance must be viewed as a symptom of another problem or problems. Treatment plans should be developed based on an individualized assessment of the patient's physiologic functioning and psychosocial situation. It must be determined whether the patient is intentionally or unintentionally not complying. Staff must also be aware of how they impact compliance. While staff have a responsibility to maximize the individual's efforts to comply, it must be realized that the ultimate decision and responsibility rests with the patient. ",11 2536,"Treating diabetes in the elderly. What are the special considerations? Management of diabetes in elderly patients generally follows the same lines as in younger patients; that is, improvement of blood glucose status with diet, oral hypoglycemic, and insulin therapy as required. Older patients are more fragile, however, and more caution must be used with therapeutic interventions. ",18 1334,"Spontaneous resolution of congenital nephrotic syndrome in a neonate An infant with congenital nephrotic syndrome recovered spontaneously and completely by the age of 11 days and had remained well at the age of 1 year. This reinforces the view that reversible congenital nephrotic syndrome does occur and that it is not a single disease with a universally dismal prognosis. ",11 711,"Unconjugated bilirubin and cholesterol gallstone formation. Cholesterol gallstones usually have small amounts of pigment at their centers and often have diffuse pigmentation or pigmented layers alternating with cholesterol layers and/or pigmented rims associated with calcium carbonate (eggshell calcification). The pigments are primarily monomeric calcium salts of unconjugated bilirubin anions and/or an insoluble, black, network polymer of tetrapyrroles. Bilirubin presumably can precipitate only if bile is supersaturated with calcium bilirubinates. Among various in vitro model systems, the aqueous solubilities and pK'a values for unconjugated bilirubin differ greatly. It is therefore not known whether normal bile is saturated with unconjugated bilirubin. However, all systems indicate that unconjugated bilirubin is solubilized by binding to bile salt monomers and oligomers, as well as micelles; marked metastable supersaturation of unconjugated bilirubin can occur in the presence of bile salt micelles, and both pK'a values of unconjugated bilirubin are greater than 6.0, probably because of internal hydrogen-bonding of the--COOH groups. Lecithin decreases equilibrium solubilization of unconjugated bilirubin crystals but enhances metastable supersaturation of unconjugated bilirubin. Calcium ions form insoluble salts with unconjugated bilirubin monoanions and dianions but soluble complexes with bilirubin conjugates. The solubility products of the calcium bilirubinate salts suggest that normal hepatic bile is not saturated with CaB or Ca(HB)2 but that gallbladder bile may be supersaturated with Ca(HB)2. ",5 1770,"Time course of cellular enzyme release in dog heart injury. The transport time of enzyme from heart to plasma was studied in two experimental models. First, the enzyme alanine aminotransferase was slowly infused into the left ventricular wall in open-chest dogs. The half-life for the washout of alanine aminotransferase activity into plasma was 20 +/- 4 minutes (mean +/- SEM, n = 8) and was not different in ischemic and normally perfused tissue. From measurements of arteriovenous differences in alanine aminotransferase activity and left ventricular blood flow, it was concluded that 77 +/- 14% of total enzyme washout from ischemic tissue occurred by direct entry into the bloodstream. The corresponding value for the vascular permeability-surface area product was 264 +/- 55 ml.kg-1.hr-1. For a second model, we studied myocardial enzyme release into plasma after abrupt heart injury induced by 10 minutes of calcium-free coronary perfusion followed by reintroduction of calcium (calcium-paradox mechanism). The half-life for the release into plasma was 1.9 +/- 0.2 hours (mean +/- SEM, n = 6) and was again not influenced by sustained ischemia. Slower washout, as observed for this second model, is consistent with increased interstitial protein space and corresponds to a permeability--surface area product between 135 and 285 ml.kg-1.hr-1. These results were used to calculate the time course of cellular enzyme leakage from the rate of enzyme release into plasma in various forms of heart injury. Significant shifts between the time curves of evolving cellular injury and enzyme release into plasma are observed after 2 hours of ischemia followed by coronary reperfusion, but not after permanent ischemia. ",13 370,"Total pelvic exenteration with simultaneous bowel and urinary reconstruction. The technique of total pelvic exenteration with simultaneous bowel and urinary reconstruction is described as a surgical option for the management of pelvic sarcoma in adults and for highly selected patients with other types of advanced pelvic malignancy. The surgical technique is presented in detail as performed in a 43-year-old man who presented with extensive primitive pelvic sarcoma. We believe that this approach may provide the benefits of an exenterative operation without the undesirable psychosocial sequelae of a permanent colostomy and external urinary diversion. ",3 152,"Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptide antigens. A mixture of 3 synthetic peptides (35.1, 55.1, and 83.1) corresponding to portions of the 35 kDa, 55 kDa, and 83 kDa proteins from the asexual blood stages of Plasmodium falciparum and a polymer of a syntheic peptide incorporating the 3 individual peptides (SPf66) were tested as candidate malaria vaccine antigens in Aotus nancymai. Monkeys were immunized with combinations of the 3 peptides from 2 separate sources (Centers for Disease Control [CDC], Atlanta, GA or Colombia) or with the synthetic polymer. Animals immunized with a combination of the 3 peptides from CDC had higher antibody titers to the 35.1 and 55.1 peptides than to the 83.1 peptide. Monkeys immunized with a combination of the 3 peptides produced in Colombia developed higher levels of antibody to the 55.1 than to the 83.1 and 35.1 peptides. Animals immunized with the polymer produced detectable antibodies to the 55.1 peptide alone. Following challenge with P. falciparum, no differences were observed between the 3 vaccine groups and 2 control groups with respect to the number of animals with parasitemias greater than or equal to 10%. The inconsistency of serologic response to all 3 peptides in these animals contrasted with previous trials performed in Colombia where the monkeys developed high antibody titers against the 3 peptides and were protected against the experimental infection. ",2 2070,"Apical hypertrophic cardiomyopathy in a non-Oriental man. Japanese investigators first described apical HCM in 2.9% of patients who had diagnostic left ventricular catheterization for suspected ischemic heart disease or cardiomyopathy. This entity was initially thought to be limited to individuals of Asian origin and has been uncommonly described in patients of Western origin. Patients of Western origin differ in several ways from those in the original description of Yamaguchi et al, but they both share the same classic criterion of hypertrophy of the left ventricular apex. The major differences probably relate to the anatomic variation in the distribution of the left ventricular hypertrophy as described by Maron et al. It is not known whether racial, genetic, or environmental factors account for the variation of disease expression in Asian and Western patients. Our case illustrates that this diagnosis should be considered in patients who have chest pain (anginal or atypical) and markedly abnormal findings on electrocardiograms in the absence of hypertension or significant coronary artery disease. ",13 87,"Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome. HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain of endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody. Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment. HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay. A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99). The mean +/- SEM apparent volume of distribution of HA-1A was 48.5 +/- 4.5 ml/kg, and the mean serum clearance was 2.8 +/- 0.4 ml/kg.h. The mean serum half-life of HA-1A was 15.9 +/- 1.5 h. The mean serum level one hour after a 100-mg dose was 33.2 +/- 2.4 micrograms/ml, and the mean concentration 24 h later was 9.1 +/- 1.6 micrograms/ml. The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance. No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient. These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis. ",0 632,"Cross-sectional radiography for implant site assessment. An accurate tomographic technique is described for acquisition of optimal cross-sectional images of implant sites before implant surgery. The described technique is applicable to tomographic systems equipped with a cephalometric head positioner. This cross-sectional tomographic technique was performed on a series of patients and the images of the first 20 patients subsequently evaluated. The cross-sectional images allowed for the characterization of the alveolar crest and visualization of anatomic structures in a buccolingual dimension while providing an accurate estimation of available vertical space from the crest. ",4 2221,"Osmiophilic deposits in cytosomes in Hallervorden-Spatz syndrome. A young child with Hallervorden-Spatz syndrome is presented. She was well until 8 years of age when she lost interest in activities and her school performance declined. At age 11 years, she began having episodes of blepharospasm, accompanied by bilateral ptosis and occasional episodes of oculogyric crisis. By age 12 years, her motor coordination had declined and she began to exhibit evidence of dementia, dystonia, dysarthria, and tremor. Motor incoordination, dystonia, and tremor progressed until the patient was wheel-chair-bound. Multiple tests were performed, including metabolic studies, magnetic resonance imaging, bone marrow biopsy, and electron microscopy of the buffy coat. Both bone marrow and buffy coat revealed inclusions in the cytosomes which were granular and osmiophilic. To our knowledge, this is the third case report of inclusion bodies found in patients with manifestations of Hallervorden-Spatz syndrome. These findings suggest that obtaining a buffy coat and bone marrow biopsy may aid in the diagnosis of Hallervorden-Spatz syndrome and ultimately provide information regarding etiology. ",15 3008,"Different tumor-derived p53 mutants exhibit distinct biological activities. In its wild-type form, the protein p53 can interfere with neoplastic processes. Tumor-derived cells often express mutant p53. Full-length mutant forms of p53 isolated so far from transformed mouse cells exhibit three common properties in vitro: loss of transformation-suppressing activity, gain of pronounced transforming potential, and ability to bind the heat shock protein cognate hsc70. A tumor-derived mouse p53 variant is now described, whose site of mutation corresponds to a hot spot for p53 in human tumors. While absolutely nonsuppressing, it is only weakly transforming and exhibits no detectable hsc70 binding. The data suggest that the ability of a p53 mutant to bind endogenous p53 is not the sole determinant of its oncogenic potential. The data also support the existence of gain-of-function p53 mutants. ",22 2138,"Incubation of platelet concentrates before transfusion does not improve posttransfusion recovery. Incubation of stored platelet concentrates (PCs) at 37 degrees C for 1 hour has been reported to result in a better morphology score and improved platelet recovery. A study was conducted in adult patients with leukemia to determine whether incubation of stored PCs results in an improved platelet recovery as measured by 10-minute posttransfusion corrected count increments (CCI). Eligible patients had platelet counts of less than 30,000 per microL and were clinically stable. Patients were transfused with 6 to 10 units of PC stored for 3 days (15 studies) or 4 days (5 studies). Platelets were pooled and then split in two equal volumes so that each patient received two sequential half-transfusions, one incubated at 37 degrees C for 1 hour and the other kept at 22 degrees C for 1 hour. Patients were randomized as to which half-transfusion was received first. The mean CCI of the incubated half-transfusions was 13.6 x 10(3) when they were given first and 14.5 x 10(3) when given second; this was not significantly different from the mean CCI of the nonincubated half-transfusions: 13.8 x 10(3) when they were given first and 13.8 x 10(3) when given second. In contrast to earlier reports, it can be concluded that incubation of pooled PCs does not improve platelet recovery. ",14 1744,"Responses of cytosolic free calcium to ADP in platelets of spontaneously hypertensive rats. Abnormalities of Ca2+ handling have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, responses of cytosolic Ca2+ to ADP in platelets of SHR were examined. Four- and seven-week-old male SHR and age- and sex-matched Wistar-Kyoto rats (WKY) were used. Basal levels of the intracellular Ca2+ concentration in platelets and responses to ADP were estimated using fluorescent indicator fura-2 in the medium containing 1 mmol/L CaCl2 and Ca2(+)-free buffer with 1 mmol/L EGTA. Basal levels of platelet cytosolic Ca2+ of SHR were significantly higher than those of WKY at 4 and 7 weeks of age in the presence of external Ca2+. However, no significant difference was observed in basal levels of platelet cytosolic Ca2+ in the Ca2(+)-free EGTA-containing buffer between SHR and WKY. The peak cytosolic Ca2+ concentration evoked by ADP was significantly diminished in SHR compared with WKY in the absence of external Ca2+, whereas the responses of platelet cytosolic Ca2+ to ADP were similar in SHR and WKY in the presence of external Ca2+. These results suggest that release from intracellular Ca2+ store is reduced in SHR and that the regulation of cytosolic Ca2+ in SHR is more dependent on extracellular Ca2+ compared with WKY. ",13 828,"Xipamide disposition in liver cirrhosis. The pharmacokinetics of the sulfonamide-type diuretic xipamide was studied in patients with liver cirrhosis and ascites and compared with healthy control subjects. After oral administration of 40 mg xipamide, the diuretic was rapidly distributed in the blood and the ascites. The ratio of the area under the concentration-time curve (AUC) of plasma and ascitic fluid was 7:2, as was the protein content in the respective compartments. The AUC in plasma of cirrhotic patients was significantly greater than in control subjects (p less than 0.001). The most striking finding was the increase of the amount (Ae) of parent drug and main metabolite excreted into the urine (p less than 0.001). The renal clearance of xipamide was only moderately reduced in patients with liver cirrhosis. Both AUC and Ae were positively correlated to the plasma concentration of direct bilirubin of the patients (p less than 0.05). We concluded that nonrenal drug clearance in patients with liver cirrhosis was reduced as a result of the blockade of hepatobiliary excretion during cholestatic conditions. ",5 1622,"Prostaglandins, the kidney, and hypertension Prostaglandins are part of the family of oxygenated metabolites of arachidonic acid known collectively as eicosanoids. While they are formed, act, and are inactivated locally and rarely circulate in plasma, they can affect blood flow in some tissues and so might contribute to the control of peripheral vascular resistance. Few studies have shown any derangement of total body prostaglandin synthesis or metabolism in hypertension, but increased renal synthesis of one prostanoid, thromboxane A2, has been noted in spontaneously hypertensive rats and some hypertensive humans. This potent vasoconstrictor may account for the increased renal vascular resistance and suppressed plasma renin activity seen in many patients with hypertension. Increased renal vascular resistance could increase the blood pressure directly as a component of total peripheral resistance or indirectly by increasing glomerular filtration fraction and tubular sodium reabsorption. Specific thromboxane synthesis inhibitors not only decrease renal thromboxane production but also increase renal vasodilator prostaglandin synthesis when prostaglandin synthesis is stimulated. This redirection of renal prostaglandin synthesis toward prostacyclin might be of benefit in correcting a fundamental renal defect in patients with hypertension. ",13 3237,"Vitamin B6 in the treatment of the premenstrual syndrome--a review [published erratum appears in Br J Obstet Gynaecol 1991 Mar;98(3):329-30] A search of the literature yielded 12 controlled trials on vitamin B6 in the treatment of the premenstrual syndrome. These are discussed with emphasis on methodological aspects. A major drawback of the trials is the limited number of patients included. The existing evidence of positive effects of vitamin B6 is weak, and some well-designed trials with positive results would be needed to change this view. ",22 2243,"DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 analogue MC903 and betamethasone. Twenty patients with psoriasis were treated with the vitamin D3 analogue MC903 and betamethasone ointment in a double-blind trial with a left-right comparison. In addition to the clinical severity scores, Ks8.12 binding which detects keratin 16 expression and the DNA synthesis were quantified using flow cytometry. Both markers decreased significantly with treatment, but remained above the normal range even in those who had total clearance of the lesions. Treatment with MC903 with regard to Ks8.12 binding was significantly better than with betamethasone. ",16 735,"CT diagnosis of acquired small bowel volvulus. Small-bowel volvulus is an uncommon but important cause of small-bowel obstruction and often results in ischemia or infarction. Clinical examination and plain film radiography may be nondiagnostic, leading to delay in surgical intervention with subsequent increase in morbidity and mortality. We present two patients in whom the diagnosis of strangulating small-bowel volvulus was made by computed tomography (CT), allowing rapid surgical correction of this potentially life-threatening condition. ",5 2338,"Digital imaging techniques in dermatology. Digital imaging is a versatile technique that has been infrequently used in dermatology to record visual images. We have used this technology for 10 patients to follow cutaneous lesions, including alopecia mucinosa, psoriasis, and dysplastic nevi. The setup included a personal computer, digitizer board, monitor, video camera, and lights. An introduction to electronic (digital) imaging is given and some of the many possible applications in dermatology are discussed. ",16 242,"Clinical significance of colonic fermentation. Recent evidence of the potential benefits of short chain fatty acids has prompted renewed interest in the area of human colonic fermentation. This paper reviews the clinical and metabolic consequences of colonic fermentation. ",3 1354,"Treatment of testicular cancer: a new and improved model. Testicular cancer has become a model for a curable neoplasm. Prior to the advent of cisplatin combination chemotherapy, standard chemotherapy consisted of dactinomycin, alone or in combination with chlorambucil and methotrexate. Disseminated germ cell tumors were chemosensitive to these older regimens, with a 50% objective response rate and a 10% to 20% complete remission rate; however, the cure rate was only 5% to 10%. In 1974, we began our initial cisplatin plus vinblastine plus bleomycin (PVB) chemotherapy. Thirty-three of 47 patients with disseminated germ cell tumors treated from 1974 to 1976 achieved a complete remission (CR), and an additional five (11%) were rendered disease-free with post-PVB resection of teratoma or carcinoma. Twenty-seven (57%) of these patients are continuously disease-free with a minimal follow-up of 13 + years. Thus, cisplatin-based chemotherapy produced a one-log increase in the cure rate compared with dactinomycin. A subsequent phase III study performed from 1976 to 1978 demonstrated that the vinblastine dosage could be reduced 25% from 0.4 mg/kg to 0.3 mg/kg with a reduction in toxicity but without any decrement in therapeutic efficacy. A third-generation PVB study from 1978 to 1981 documented that optimal cure rates were achieved with 12 weeks of induction therapy with PVB and that long-term maintenance therapy with vinblastine was unnecessary. In 1978, we initiated salvage therapy with cisplatin plus etoposide (VP-16) in patients not cured with PVB, and 25% of these patients were subsequently cured with this regimen. This represented the first time an adult solid tumor had been cured with a second-line regimen. In 1983, we began studies with third-line therapy with cisplatin plus ifosfamide combination chemotherapy, and even in this refractory setting, approximately 20% of patients are curable. From 1981 to 1984, we compared cisplatin plus VP-16 plus bleomycin (PVP16B) with PVB as first-line chemotherapy. There was a significant reduction in neuromuscular toxicity favoring the VP-16 arm, and furthermore, 78% of these patients were continuously disease-free compared with 66% with PVB. Approximately 75% of patients with disseminated germ cell tumors will be cured with PVP16B, and an additional 10% are curable with salvage chemotherapy. This represents the highest cure rate in any adult malignancy. ",11 1110,"Facial bone fracture associated with carotid-cavernous sinus fistula. Out of 989 cases of facial bone fracture, ten patients had carotid-cavernous sinus fistulas (1.01%). Their ages ranged from 25 to 48 years. Seven were male and three female. Two of the ten patients had lower third, three patients had middle third, three patients had upper third, and two patients had combined middle and lower third facial bone fractures. The signs and symptoms of a fistula appeared from the first postinjury day up to 50 days after the injury (mean, 21 days). Four patients had symptoms after operation for facial bone fracture. Most fistulae were identified by arteriography before treatment. Followup ranged from 1 year, 8 months, to 5 years, 9 months (mean, 2 years, 9 months). One patient had a malocclusion. Nine patients had complete resolution of their bruits. Complications included unilateral complete visual loss (two), CSF rhinorrhea (two), and stroke in one of the two CSF rhinorrhea patients. One patient expired due to a severe head injury, and there was one death from an unrelated cause. ",9 394,"The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site-specific mutagenesis of a biologically active HIV-2 proviral clone (HIV-2sbl/isy), which is infectious in both human T cells and macrophages. Viral progeny carrying mutations of nef, vpr, or of both nef and vpr genes replicated more efficiently than the parental virus in primary human peripheral blood cells and in the human Hut 78 T-cell line. In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages. Thus, some lack of nef in HIV-2 enhances viral replication in T cells and does not interfere with viral replication in primary macrophages, whereas vpr is essential for replication of HIV-2 in human macrophages. Because the parental HIV-2sbl/isy cloned virus also infects rhesus macaques, the use in animal studies of these HIV-2 mutants with differences in cell tropism and rates of replication will be highly useful in understanding the mechanism of viral infectivity and possibly pathogenicity in vivo. ",3 2202,"Use of a palatal stabilizing device in prevention of palatal grooves in premature infants. A prospective, randomized study using an acrylic palatal stabilizing device (PSD) was conducted to evaluate the effectiveness of this device in preventing disruptions in palatal architecture. A total of 26 premature infants with birth weights of 540 to 1740 g, and intubated orally for a period varying from 7 to 109 days were randomized to control and experimental groups. All neonates in the control group developed palatal grooving ranging from 2 to 5 mm in depth, whereas those in the experimental group (with a PSD) showed no evidence of palatal grooving. We conclude that a PSD is an effective preventive device in premature orally intubated infants. ",15 3166,"Fatigue. Fatigue is a pervasive, protective phenomenon affecting the totality of the individual. Assessment and management involve a wide range of activities to address the total human being's physical, psychological, cognitive, and spiritual dimensions. When elimination or neutralization of the effect of an antecedent condition is not an option, redesigning one's life-style may be the primary avenue of fatigue management. This protective mechanism, fatigue, may in fact herald the return of quality and purpose to one's life. ",22 509,"Late development of a squamous carcinoma in a reconstructed pharynx. We report a case in which a squamous cell carcinoma was found to have arisen from a delto-pectoral skin flap used in pharyngeal reconstruction. The flap had been forming a neo-pharynx for 24 years. No other signs of recurrent disease had developed in this period. This raises the possibility of tumour induction in heterotopic skin used for oropharyngeal reconstruction. ",3 1265,"Unilateral mydriasis caused by transdermal scopolamine. Contamination of the eye after handling of a transdermal scopolamine patch may cause accidental mydriasis. A simple office test is discussed to identify this pharmacologic blockade and thereby avoid an extensive neurologic workup. ",10 2715,"HTLV-I sequences are not detected in peripheral blood genomic DNA or in brain cDNA of multiple sclerosis patients. Human T-cell lymphotropic virus (HTLV-I) was recently reported to be etiologically associated with multiple sclerosis (MS). Genomic DNA from peripheral blood lymphocytes and brain plaques of patients with MS was analyzed for the presence of sequences homologous to the HTLV-I pol gene using the polymerase chain reaction and dot blot techniques. Comparison of DNA amplification patterns between patients with MS, and with control subjects who have other autoimmune conditions, with those in healthy control subjects and with an HTLV-I-infected cell line indicates that HTLV-I pol sequence is not present in the peripheral blood of patients with MS, and that the virus is not active in MS brain plaques. ",19 3143,"Mitral valve replacement in the first year of life. From 1973 through 1987 25 patients underwent mitral valve replacement in the first year of life for mitral stenosis and mitral regurgitation. The patients with mitral stenosis included two with mitral arcade, two with supravalvular mitral stenosis with hypoplastic mitral valve, and one with parachute mitral valve. Included in the group of patients with mitral regurgitation were 12 with atrioventricular canal defect, six with chordal and leaflet defects, one with Marfan's syndrome, and one with bacterial endocarditis. Prostheses included 12 Bjork-Shiley (17 mm), seven St. Jude Medical (19 mm in four, 21 mm in three), five stent-mounted dura mater valves (12 mm to 16 mm), and one porcine xenograft (19 mm). In four patients the valves were placed in the left atrium in a supraannular location. There were nine operative (atrioventricular canal defect seven, mitral regurgitation two) and five late (atrioventricular canal defect four, mitral stenosis one) deaths, giving actuarial 1- and 5-year survival rates of 52% and 43%, respectively. All 6 patients with tissue valves died; the four with supraannular mitral valve replacement survived. Since 1983 operative mortality has been reduced to 0% (70% confidence limits 0% to 24%). Nine patients required a second mitral valve replacement for prosthetic stenosis 5 to 69 (mean 30) months after the original mitral valve replacement (one operative death). Because of improvements in repair of atrioventricular canal defect in infancy, the need for mitral valve replacement at atrioventricular canal defect repair has decreased. Although valvuloplasty has been advocated for repair of congenital mitral valve disease and is applicable in some infants with mitral regurgitation, mitral valve replacement is frequently unavoidable for congenital mitral disease and can now be accomplished at a low operative risk, even when the prosthesis has to be positioned supraannularly. ",22 2741,"Secondary total hip replacement after fractures of the femoral neck. We studied the rate of revision in 84 consecutive total hip replacements performed for failed osteosynthesis of femoral neck fractures and compared it with that for primary arthroplasty for osteoarthritis. The age and sex adjusted risk of prosthetic failure was 2.5 times higher after failure of fixation, but all the excess risk was in patients over 70 years of age. There were radiographic signs of loosening of the femoral component at five to 12 years after secondary arthroplasty in six of 33 survivors. In general, the results of secondary replacement were no worse than those obtained after primary arthroplasty for femoral neck fracture. We consider that internal fixation should be the primary procedure: total hip replacement is a safe secondary procedure when osteosynthesis fails. ",20 345,"Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial. Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up. ",3 3126,"Isolation of a novel tumor protein that induces resistance to natural killer cell lysis. The human metastatic tumor cell line CAP-2, produces a soluble factor that induces resistance to NK lysis of K-562 susceptible leukemia cell line, and does not inhibit the cytotoxic capacity of effector cells. The use of sequential HPLC, hydrophobic interaction chromatography, and reverse phase chromatography, coupled with cytotoxic assays, resulted in the isolation and separation to homogeneity of a novel protein responsible for this biologic activity. Size estimation studies based on TSK HPLC columns showed that this protein has a mass of 8 to 12 kDa. The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids. Subsequent gas phase sequence analysis, however, was hampered because the N terminus of this protein was blocked and therefore unsuitable for sequencing by Edman degradation. The functional studies showed that the NK lysis-resistance activity of the CAP-2 protein is mediated by interaction with and nonspecific binding to NK target cells. The lymphokine-activated killer and macrophage-mediated cytotoxicity and mitogen-induced proliferation is not affected. Unexpectedly, the CAP-2 protein appears to be mitogenic to its own cell line. Thus, the induction of NK lysis-resistance and the mitogenic activity showed by CAP-2 protein could contribute to the tumor growth and metastatic establishment. ",22 9,"Itraconazole in common dermatophyte infections of the skin: fixed treatment schedules. Itraconazole is an effective medication against the most common dermatophytoses. It has been shown to be more active than griseofulvin and ketoconazole. Ease of use, affinity for keratinized tissues, lack of toxicity, continued activity after discontinuation, and the possibility of using fixed schedules are advantages of itraconazole. The fixed schedules indicated by pharmacokinetics and clinical studies are one 100 mg capsule daily for 15 days in cases of tinea corporis and tinea cruris and the same dosage for 30 days in cases of tinea pedis and tinea manuum. These fixed treatments have some limitations, and they are not recommended for treating tinea capitis and tinea unguium. The drug is well tolerated. ",0 434,"Localization and surgical treatment of occult insulinomas. Management of patients with biochemical evidence of insulinoma and negative preoperative imaging studies (occult) tumors is controversial, varying from primarily medical management to aggressive, blind nearly total pancreatectomy to extirpate the tumor. Since 1982, 12 consecutive patients with occult insulinoma underwent preoperative portal venous sampling (PVS) for insulin followed by surgical exploration with intraoperative ultrasound (IOUS). Eleven of twelve patients (92%) had insulinoma removed and were cured. Portal venous sampling correctly predicted the location of the insulinoma in 9 patients (75%) and that no tumor would be found in another patient. A fourfold insulin gradient in the pancreatic tail of one patient correctly predicted that a distal pancreatectomy would remove the insulinoma despite the fact that neither palpation nor IOUS identified any tumor. Intraoperative ultrasound was the single best method to identify occult tumors because it correctly identified 10 of 11 insulinomas that were found, including five pancreatic head tumors that were not palpable. Palpation identified five insulinomas. Of the 10 tumors that were identified during operation by palpation or ultrasound, IOUS identified significantly more (100% versus 50%, p = 0.03) and guided the successful enucleation of each. The results support the strategy of preoperative PVS and operation with IOUS to localize and remove insulinoma in patients with occult tumors. Most tumors (75%) will be correctly localized to a specific pancreatic region by preoperative PVS and identified by IOUS (83%), allowing simple enucleation and biochemical correction of hypoglycemia. Morbid blind pancreatic resections are no longer indicated and long-term medical management of hypoglycemia should be reserved for the occasional patient (8%) who fails preoperative PVS and operation guided by IOUS. ",3 2286,"Persistent melanocytic lesions associated with cosmetic tanning bed use: ""sunbed lentigines"". A patient with persistent melanocytic lesions after tanning bed use is described. A review of the literature provides two additional examples of similar clinical and histologic presentations after UVA exposure without psoralen. To our knowledge, this is the first reported case of ""sunbed lentigines"" in the United States. ",16 1532,"Aggressive evaluation for atypical squamous cells in Papanicolaou smears. A retrospective study was done on women who had atypical Papanicolaou smears and were referred for immediate colposcopy. The smears were obtained during January 1985 to March 1989 at Edwards Air Force Base, California. Excluded from the evaluation were abnormal Papanicolaou smears with hyperkeratosis, parakeratosis and koilocytotic atypia suggestive of human papillomavirus (HPV) infection. The evaluation included colposcopy, colposcopically directed biopsies, endocervical curettage and repeat Papanicolaou smears. A total of 101 patients were included in the study. Cervical intraepithelial neoplasia (CIN) was seen in 29.7% (30 patients): 12.9% (13) CIN I, 12.9% (13) CIN II and 3.9% (4) CIN III. Carcinoma was seen in 3.9% (4) of the patients: 2.9% (3) was carcinoma in situ, and 0.99% (1) was invasive squamous cell carcinoma, stage IIb. HPV and dysplastic lesions were seen together in 19.8% (20) of the patients. HPV was seen alone in 45% (46). Twenty-one patients (20.8%) had no apparent lesions on colposcopy, although one developed microinvasive keratinizing squamous cell carcinoma within 36 months of colposcopy. Many significant lesions can go undetected for extended periods of time in women with atypical Papanicolaou smears, resulting in delayed management. Referral for immediate colposcopy is advocated strongly. ",12 201,"Comparison of methods for checking surgical margins. Surgical margins of a cutaneous neoplasm can be evaluated by various combinations of three major types of sections: vertical (perpendicular), horizontal (parallel), and oblique (Mohs method). Vertical sections may run transversely through tumor (breadloaf method), longitudinally through tumor (breadloaf-cross method), or peripheral to the tumor. The peripheral (perimeter) sectioning methods are the only methods that can evaluate almost 100% of the margin, but they have the disadvantage of not showing the relationship of the tumor to its margin, which can be seen clearly with the vertical transverse sections. Seven methods of checking surgical margins are compared and contrasted. None of these is judged to be perfect or best. ",3 833,"Incidence and prevalence of ulcerative colitis in the upper Galilee, Northern Israel, 1967-1986. An epidemiological study of ulcerative colitis was performed in the Upper Galilee, Israel, over a 20-yr period (1967-1986). The average annual incidence of ulcerative colitis was 2.23 per 100,000 population, and the prevalence on December 31, 1986, was 44.58 per 100,000. Considering the fact that strict steps were taken to include only definite cases, these figures are probably an underestimation. An increase of the average annual incidence from 0.88 in the period 1967-1976 to 3.79 in 1977-1986 was found. When the data were stratified according to ethnic groups, the highest average annual incidence and the highest point prevalence was found in Israeli-born Jews (6.9 and 138.2 per 100,000 population, respectively). When Jewish residence patterns were compared, the highest average annual incidence and point prevalence were found among Kibbutz members (5.52 and 110.39, respectively), and the lowest (1.94 and 38.76) among Moshav inhabitants. There were 10 Arab patients with an average annual incidence of 0.96 and a point prevalence of 19.27. There were 25 women and 28 men (female:male ratio of 0.89). Among the Jews, the female:male ratio was 1.04. Peak incidence was found in the 25- to 34-yr-old range. No second peak was noticed. Anemia was demonstrated in 66.6% of the women and 27.5% of the men in our study. We suggest that the increase in UC incidence and prevalence in Israeli and Asia/africa-born Jew and in Arabs in the Upper Galilee points toward environmental factors in the etiology of this disease. ",5 2451,"Obesity and iron status in menstruating women. The relationship between iron stores and obesity in menstruating women was studied in 20 obese and 20 nonobese women matched for age and contraception. Although no difference was observed in serum iron or total-iron-binding capacity, the obese group showed significantly higher hemoglobin (137 +/- 9 vs 10 g/L, mean +/- SD; P less than 0.01), hematocrit (0.41 +/- 0.02 vs 0.39 +/- 0.03, P less than 0.05), and serum ferritin concentrations (48.0 +/- 44.3 vs 25.8 +/- 19.5 micrograms/L, P less than 0.05). There was no difference between obese and nonobese women in either the menstrual-cycle interval or the duration of the menstrual flow. Iron intake was significantly higher in the obese group (15.9 +/- 2.9 vs 14.1 +/- 2.9 mg/d, P less than 0.05). These results suggest that obese menstruating women are at low risk of depleting iron stores, possibly because of high iron intake. Iron-fortification programs might thus be undesirable in such subjects. ",17 1602,"Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product. ",13 1364,"Burkitt's lymphoma of the testicle: report of 2 cases occurring in elderly patients. Burkitt's lymphoma is rare in patients older than 50 years and almost never presents as a testicular tumor. We report 2 cases of primary Burkitt's lymphoma of the testicle in men 68 and 79 years old. In 1 man the extragonadal tumor had a rapid and lasting response to combination chemotherapy. The cases are of interest for the unusual presentation of the disease and for the possibility to control Burkitt's lymphoma in older patients without undue toxicity. The management of testicular lymphoma requires radical orchiectomy and prophylactic irradiation of the contralateral testis. Chemotherapy is indicated for advanced disease and may prevent relapses in patients with early disease. The role of central nervous system prophylaxis is controversial. ",11 3026,"Thyroid antibodies as a risk factor for Down syndrome and other trisomies. To test whether the presence of thyroid antibodies in a parent is a risk factor for meiotic nondisjunction, we measured the levels of thyroid antibodies in serum samples drawn during early pregnancy from 101 gravidas who delivered a child with a trisomy, from 11 gravidas who had had a trisomic child in a previous pregnancy, and from 44 of their husbands. For each case mother, three controls were randomly selected from the same population and matched for age, race, sex of the child, and hospital of birth. Cases and controls came from two longitudinal populations, the Child Health and Development Studies (CHDS) and the national Collaborative Perinatal Project (CPP), together comprising more than 70,000 live births. All cases with both a definite diagnosis of trisomy-Down syndrome (DS) or other-and available serum were included. Overall, there was no association between the presence of thyroid antibodies in a mother and a trisomy in her offspring (odds ratio [OR] = .98, confidence interval [CI] = .54-1.85). The lack of association was seen in all three subgroups (DS only, other trisomies, and DS in a previous pregnancy), in all ethnic groups, and in the age groups of white mothers either less than 30 years of age (OR = .80, CI = .40-1.6) or greater than or equal to 30 years of age (OR = 1.26, CI = .82-1.9). In the CHDS population, case fathers, as compared with control fathers, did not have a higher prevalence of thyroid antibodies. ",22 178,"Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia. Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia. Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia. Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial. The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells). This difference was also evident in the immunologic subclass common ALL. Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration. In addition to the independent factor, initial age, this interaction was also prognostic for survival. ",3 2306,"Experimental models for psoriasis. Evidence suggests that inherent in skin of psoriatic subjects are cells, architectural structures, and/or mediators, which are, at a minimum, responsible for its hyperproliferative epidermis. An objective of our laboratory has been to establish an in vitro definition of this inherent aberration. Fibroblasts are important to epidermal proliferation/differentiation. This, and an unconfirmed report that fibroblasts from psoriatic subjects might drive the abnormal epidermal proliferation in psoriasis, have caused further focus on the fibroblast. Data show that fibroblasts from patients with psoriasis, both involved and uninvolved, in the presence of human serum, either normal or psoriatic, have an increased rate of proliferation. Fibroblasts from uninvolved psoriatic sites are most responsive. To determine if fibroblasts from psoriatics could induce the psoriasiform phenotype on normal keratinocytes, an interactive skin equivalent system has been developed. With this system, fibroblasts from uninvolved and involved sites cause normal keratinocytes to have an enhanced outgrowth. Uninvolved fibroblasts cause the greatest changes. The nature of the skin equivalent system calls for this to occur via message over distance. We conclude that fibroblasts from psoriatic subjects can induce a psoriasiform phenotype via a soluble message. ",16 1047,"Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia. ",9 2262,"Surgical management of palmar hyperhidrosis. Hyperhidrosis is an idiopathic pathologic condition characterized by excessive sweating beyond that required to cool the body. Disturbance of the central nervous system, endocrine system, or obesity has been associated with this condition. Patients have a history of several years of occupational or social embarrassment. Individuals of Japanese ancestry and Jews of Northern African, Yemeni, or Balkan descent are predisposed to the condition. Nonoperative therapy is merely temporizing and unacceptable because of lack of efficacy or side effects. Surgical intervention provides effective and permanent control. The key to surgical correction appears to be the division of the sympathetic chain above the T-2 ganglion and below the T-3 ganglion of the involved side with removal of the entire T2-3 segment with its corresponding spinal nerves. This paper presents our experience with the dorsal thoracic approach for interruption of sympathetic innervation for severe palmar hyperhidrosis. We also review surgical efficacy of various approaches to the sympathetic chain, as well as possible side effects of operative intervention. ",16 2896,"The hippocampus and parahippocampus in schizophrenia, suicide, and control brains [published erratum appears in Arch Gen Psychiatry 1991 May;48(5):422] Recent postmortem studies in schizophrenia have shown abnormalities in medial temporal lobe structures, including the hippocampus and parahippocampus. We tried to replicate previous studies and to explore the specificity of this finding to schizophrenia. The anterior hippocampus and parahippocampal cortex were evaluated for area and shape in postmortem tissue from 12 schizophrenic, 17 nonschizophrenic suicide, and 10 nonpsychiatric control brains. No significant differences were found in hippocampal area, but the parahippocampal cortex was significantly smaller in the schizophrenic group than in the control group. When parahippocampi from right and left sides were analyzed separately, both the suicide and schizophrenic groups had smaller parahippocampi on the right side than did the controls [corrected]. The suicide group exhibited greater parahippocampal areas in the left than in the right tissue samples within the group, while such a difference did not exist in the schizophrenic or control groups. This study demonstrated changes in temporal lobe structures in both schizophrenic and nonschizophrenic suicide groups. ",20 2088,"The real impact of mechanical bridge strategy in patients with severe acute infarction. Results obtained in the past 3 years in patients referred with acute myocardial infarction (AMI) and cardiogenic shock for a mechanical bridge to urgent transplantation permit one to assess the real impact of the present strategy in clinical practice. Ten patients (mean age = 49) were admitted in serious condition (CI = 1.8 +/- 0.2 L/min/m2, PCWP = 28 +/- 6 mmHg, systolic aortic pressure = 88 +/- 20 mmHg, urine output 11 +/- 20 ml/hr) and were treated by maximal sympathomimetic support and i.v. enoximone. Two had to be implanted with a total artificial heart (TAH) and one with a left ventricular assist device (LVAD) for recurrent fibrillation despite hemodynamic improvement, within 8 hr. Two have received transplants and are living well after 20 months. Seven who initially improved markedly have been listed as urgent transplant candidates: two of these have been successfully transplanted, and three died suddenly after 6, 25, and 45 days, respectively. One has undergone successful coronary surgery. One patient (age 62, diabetic) was secondarily rejected for a transplant and died. This experience clearly shows that despite initial spectacular hemodynamic improvement, which was due to optimized medical management, death rate before transplant because of sudden ventricular fibrillation remains unacceptably high. This should prompt early mechanical support, with less invasive systems, in patients with AMI. ",13 3342,"Total perinatal wastage. A clarification of priorities. The pregnancy outcome of 16,971 women carrying 17,352 living fetuses after 16 weeks gestation was studied. As well as recording perinatal deaths, all losses before 28 weeks and up to one year after delivery were recorded to give a total perinatal wastage rate of 21.6 per 1000 fetuses alive at 16 weeks compared with a perinatal mortality rate (stillbirths plus early neonatal deaths) of 7.8 per 1000 births. All deaths were then classified according to pathological sub-groups. The concept of auditing perinatal care using perinatal mortality was then compared with that using total perinatal wastage. ",22 2097,"ECMO assisted angioplasty for cardiomyopathy patients with unstable angina. Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy. ",13 3197,"Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor alpha/delta locus. The gene encoding angiogenin, a potent inducer of blood vessel formation, has been localized within the human genome. It is present as a single copy per haploid genome and is located on chromosome 14, on the basis of discordancy analysis of human-rodent hybrid cell lines. This localization was refined to 14q11 by in situ hybridization of an angiogenin probe to metaphase chromosomes prepared from both normal human lymphocytes and RPMI 8402 cells. The results from the RPMI 8402 cells also establish that the angiogenin gene resides proximal to a translocation breakpoint within the T cell receptor alpha/delta locus and therefore upstream from that locus. An AvaII RFLP, present at a frequency of 29% in an unselected collection of human placental DNAs, was identified in the coding region of the gene and results from a single silent transversion. ",22 1970,"Differentiation of ventricular tachyarrhythmias. Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm ""organization."". ",13 2649,"Cytomegalovirus infection in children with AIDS. Data for 38 children perinatally exposed to human immunodeficiency virus (HIV) were evaluated to determine the impact of cytomegalovirus (CMV) infection on the course of perinatally acquired HIV infection. Thirteen children belonged to the P0 (indeterminate) group, one to the P1 (asymptomatic) group, and 24 to the P2 (symptomatic) group, per the classification of the Centers for Disease Control. Of the 24 children in the P2 group, 10 died. The mean follow-up time was 22.8 months for the 10 children who died and 16.3 months for the 13 children in the P0 group. Serial cultures of urine were performed for all 38 patients. CMV was isolated from seven of 10 children who died and from four of 14 children who survived (P less than .05). Only one of the 13 P0 children was culture-positive for CMV, as compared with 11 of 24 P2 children (P less than .05). All CMV-infected children continued to demonstrate CMV viruria in serial cultures. The mean age at the time of the first culture positive for CMV was 13 months. Microcephaly was present in 15 (65%) of 23 P2 children but in none of the P0 and P1 children (P less than .05). Eight of 11 CMV-infected children were microcephalic; seven of 12 children not infected with CMV were microcephalic (P greater than .05). These data suggest that the prevalence of active CMV infection is significantly higher in P2 children than in P0 and P1 children. In addition, there is a significant association between CMV infection and mortality among P2 children. ",19 1029,"Bilateral semicircular canal aplasia with near-normal cochlear development. Two case reports. Congenital malformations of the vestibular labyrinth (pars superior) are rare. We present two patients with computed tomographic findings of bilateral semicircular canal aplasia with normal or near-normal cochleas. Initial bone conduction thresholds were within normal limits, although both patients had significant conductive hearing losses due to congenital middle ear malformations. Bithermal caloric responses were absent in both. To our knowledge these are the first reports of vestibular aplasia concomitant with normal or near-normal cochlear development. These findings conflict with conventional hypotheses that state that inner ear malformations result from arrested development during the normal stages of inner ear embryogenesis. ",8 2792,"Is arterial proximity a valid indication for arteriography in penetrating extremity trauma? A prospective analysis. Three hundred seventy-three patients with a penetrating extremity injury were studied to assess the yield of arteriography. Patients underwent arteriography if any of the following was present: bruit, history of hemorrhage or hypotension, fracture, hematoma, decreased capillary refill, major soft-tissue injury, or nerve or pulse deficit. In the absence of these findings, arteriography was performed if the injury was in ""proximity"" to a major neurovascular bundle. In 216 patients, arteriography was performed when an abnormal finding was noted. Sixty-five injuries were identified, 19 requiring intervention. Proximity was the indication for arteriography in 157 patients. Seventeen injuries were identified, of which one required repair. In penetrating extremity trauma, the need for arteriography is based on clinical findings. The use of arteriography to screen for an arterial injury when proximity alone is the indication rarely identifies a significant injury and should be abandoned. ",20 1003,"Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis. The effect of acute oral administration of 2 g vitamin C on bronchial responsiveness to inhaled histamine in 16 patients with allergic rhinitis was compared with placebo on two consecutive days in a double-blind, crossover design. The PC15FEV1 was significantly increased one hour after treatment with vitamin C but not after placebo. ",8 526,"Posterior mediastinal teratoma with abdominal extension. Posterior mediastinal benign teratomas are uncommon neoplasms in infancy; nine cases have been reported so far. A one month old baby was found to have a benign posterior mediastinal teratoma infiltrating the lower oesophagus from the level of the carina through the oesophageal hiatus into the upper abdomen. Partial oesophagectomy provided a successful outcome. ",3 2868,"The acute effects of alcohol on the blood pressure of young, normotensive men. Alcohol's acute effects on arterial blood pressure (BP) were examined. To separate the effects of alcohol on BP from those of fluid volume and expectancy, normotensive men were divided into three groups. The alcohol group received 1.0 ml of absolute alcohol/kg of body weight. The expectancy group expected alcohol but received only tonic. The control group expected and received only tonic. With age as a covariate, significant changes in systolic BP were found only in the alcohol group, indicating that the changes in systolic BP were not attributable to subject expectancy or volume of fluid consumed. The expectancy control groups did not differ from each other. A significant quadratic trend was found for systolic BP in the alcohol group, suggesting that alcohol may have an acute biphasic effect on systolic BP, with an initial decrease as the alcohol is ingested followed by an increase toward the basal level during detoxication. No significant effects were found for diastolic BP. ",20 3355,"En bloc transplantation of kidneys from donors weighing less than 15 kg. into adult recipients. En bloc transplantation of kidneys from donors who weighed less than 15 kg. into 20 adult patients is described. Intraperitonealization of the medial kidney allowed adequate renal positioning and growth. Graft venous thrombosis occurred in 1 patient and irreversible graft rejection occurred in 4 patients. Graft survival was 65% with excellent function at a mean followup of 8.8 months. En bloc transplantation of pediatric cadaver kidney grafts in adults is an acceptable procedure. ",22 2582,"Dust mite assays in clinical allergy practice: mite antigen exposures among skin test positive patients in Kansas. We have attempted to determine whether sensitive monoclonal antibody assays for Dermatophagoides mite antigens Der p I and Der f I can be carried out in a private clinical allergy practice laboratory, to ascertain incidence of significant home mite exposure in dust samples from patient homes in Kansas, and to consider whether such information impacts on patient management. We analyzed 152 dust samples from 62 patient homes. All patients were skin prick test positive for one or both common mite species available for skin testing, and had potentially relevant histories. Der p I and Der f I antigen levels were added together, and levels above 2 micrograms/g of dust were considered ""positive."" By this definition, elevated levels were found in at least one sample from 48 of 62 homes tested (77%); however, 61% of mattress samples tested, 41% of carpet samples, and 54.5% of furniture samples had levels below those considered likely to cause symptoms. Only 13 of 152 samples yielded Der p I levels above 2 micrograms/g. We conclude that monoclonal antibody assays for Der p I and Der f I antigens can be performed in a well-equipped office laboratory staffed by trained medical technologists, that Der f I is the predominant mite species in Kansas, and that data derived from mite assays may be important in treatment planning for patients suspected of having mite-related allergy symptoms. ",19 2151,"Hypergammaglobulinemic purpura of Waldenstrom. Hypergammaglobulinemic purpura of Waldenstrom is characterized by hypergammaglobulinemia, recurring purpura, an elevated erythrocyte sedimentation rate, and the presence of rheumatoid factor indicative of circulating immune complexes. There is a significant association with autoimmune diseases, especially Sjogren's syndrome and lupus erythematosus. Hypergammaglobulinemic purpura is considered primary when there is no other associated disease or secondary when associated with other diseases, usually autoimmune. Immune derangements are fundamental in its pathogenesis, although its cause is still unknown. Therapy is unrewarding and is probably unnecessary for this usually benign condition. Three cases are presented that are representative of patients with hypergammaglobulinemic purpura. ",14 2902,"Pediatric penetrating head and neck trauma. Penetrating head and neck trauma in children causes uncommon and potentially life-threatening injuries. We reviewed the charts of 21 patients who sustained penetrating injuries to the face or upper neck. Seventeen males and 4 females, aged 32 weeks' gestation to 19 years (mean = 10.2 years) comprised the study population. There were 15 gun-shot wounds, 1 shotgun injury, and 5 stab wounds. Significant problems included 7 vascular injuries, 6 central nervous system injuries, 5 ocular injuries, 3 airway compromises, 2 facial nerve injuries, 1 cervical esophageal penetration, and 2 cases of pneumothorax. Three deaths occurred, but the majority of the patients survived and sustained minimal permanent disability. Included in this review is a unique case of an intrauterine gunshot wound to the face at approximately 32 weeks' gestation. The treatment protocol, differences from adult patients, and management highlights are reviewed. ",20 495,"Melanoma and soft tissue sarcoma in seven patients. Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between melanoma and sarcoma, the nature of which remains unknown. ",3 2918,"Endotracheal tube cuff pressure assessment: pitfalls of finger estimation and need for objective measurement. Estimation of endotracheal (ET) cuff pressure by finger palpation is one of the methods currently used in the clinical setting. We compared the accuracy of this method with instrumental intracuff pressure measurement in tracheal model tests by 20 members of our ICU team. Four different ET tubes at three different pressure levels were examined. Accuracy for the estimated method by finger palpation was 69% for high pressures, 58% for normal pressures, and 73% for low pressures. We observed differences in terms of sensitivity, specificity, and positive predictive power between different tubes reflecting differences in tube characteristics and interobserver variability. We conclude that precise intracuff pressure measurement is mandatory to prevent complications of over- or underinflation. ",20 173,"Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin. ",3 620,"Spondyloepiphyseal dysplasia of Maroteaux. The cases of four patients who had an unusual clinical entity of disproportionately short stature, referred to as spondyloepiphyseal dysplasia of Maroteaux, are described. In patients who have this syndrome, the abnormalities are confined to the musculoskeletal system. The patients do not have corneal opacities or increased excretion of keratosulphate. The mode of transmission appears to be autosomal dominant. Platyspondylysis is present but there are no anterior tongue-like deformities of the vertebral bodies. Because of the presence of spondyloepiphyseal dysplasia and normal intelligence, and the lack of abnormalities at birth, this entity seems to mimic Morquio syndrome. However, unlike Morquio syndrome, the disorder involves no biochemical abnormalities. Thus, the entity may be classified as new. ",4 287,"Giant cell tumor of bone. A clinicopathologic and DNA flow cytometric analysis. Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior. ",3 2449,"Pursuing mild elevations of liver enzyme values to exclude hemochromatosis. To determine whether physicians in an academic medical center excluded hemochromatosis as a diagnosis in a population of patients with mildly elevated liver enzyme values, we reviewed 100 charts of patients with both aspartate aminotransferase and alkaline phosphatase levels that were less than twice the upper limit of normal. We analyzed each chart to determine if hemochromatosis would have been excluded by a subsequent workup. Those patients who did not have a complete workup were assigned to one of three categories: (1) no mention was made of abnormal liver enzyme values; (2) liver enzyme values were ascribed to some condition other then hemochromatosis and no definitive workup was done; and (3) the condition of the patient was so poor that assessment did not seem indicated. Ninety of 100 patients were not given a workup to exclude hemochromatosis. Physicians often ignore mild elevations in liver enzyme values. ",17 2391,"Serial evaluation of lipid profiles and risk factors for development of hyperlipidemia after cardiac transplantation. To determine the prevalence, time course and factors responsible for hyperlipidemia after heart transplantation, 83 consecutive 1-year survivors were studied. By 1 year, 83% of patients had serum total cholesterol levels greater than 5.2 mmol/liter (200 mg/dl) and 28% of the patients had serum total cholesterol higher than the age- and sex-matched ninety-fifth percentile. At the end of 1-year follow-up, serum total cholesterol correlated with the recipient age (p less than 0.0001), the preoperative cholesterol level (p less than 0.001), the actual dose of maintenance prednisone at 1 year (p less than 0.02) and the cumulative 1-year steroid dose (p less than 0.03). Similarly, the serum triglyceride level at 1 year correlated with the pretransplant level of serum triglycerides (p less than 0.0001), recipient age (p less than 0.03) and cumulative 1-year steroid dose (p less than 0.03). Patients with a pretransplant diagnosis of coronary artery disease had a significantly higher level of serum total cholesterol and triglyceride levels at 1 year (p less than 0.02 and p less than 0.03, respectively). Heart transplant recipients with body mass index greater than or equal to 25 kg/m2 also presented with significantly elevated serum total cholesterol and triglyceride levels at 1 year compared with nonobese patients (p less than 0.01 and p less than 0.002, respectively). Hyperlipidemia occurs frequently and is detected within the first month after heart transplantation. Optimal management of this problem requires further study. ",17 1541,"The establishment of an ovum donation program using a simple fixed-dose estrogen-progesterone replacement regimen. Most ovum donation (OD) programs involve cycle synchronization between recipient and donor for normally cycling recipients and a complex estrogen-progesterone replacement regimen for recipients with ovarian failure. In 1987, Serhal and Craft (1) suggested the use of a fixed-dose estrogen-progesterone regimen for recipients who were normally ovulatory and to those with ovarian failure. Following this protocol, and simplifying it still, the authors administered 6 mg estradiol valerate (E2) daily orally starting on day 2-6 of induced withdrawal bleeding, augmented with 100 mg progesterone in ethyl oleate (P) intramuscularly daily, starting any time between 4 days prior to and the day of oocyte pickup. All recipients underwent embryo transfer at a 2-pronuclei (2PN)-10-cell stage. A group of 21 patients underwent 26 treatment cycles, resulting in 16 pregnancies. Twelve of the patients gave birth, one to triplets, two to twins, and nine to singletons. Four patients miscarried in the first trimester of pregnancy. ",12 3351,"Role of membrane proteins in monosodium urate crystal-membrane interactions. II. Effect of pretreatments of erythrocyte membranes with membrane permeable and impermeable protein crosslinking agents. Intact, human erythrocytes were pretreated with membrane permeable, dimethyl adipimidate (DMA) and dimethyl suberimidate (DMS) and membrane impermeable 3,3' dithiobis (sulfosuccinimidylpropionate) (DTSSP) protein crosslinking agents and incubated with monosodium urate monohydrate (MSUM) crystals. The percent inhibition of lysis values for pretreated cells relative to untreated cells were determined. All 3 agents caused a concentration dependent inhibition of MSUM induced hemolysis that was not due to a decrease in MSUM binding to the pretreated membranes. It was proposed that the inhibition of lysis was due to crosslinking of integral and cytoskeletal membrane proteins, resulting in a reduced mobility of the proteins, inhibition of lateralization of integral proteins into aggregates and decreased ""pore"" formation in the membrane. ",22 2936,"Efficacy of tetracaine-adrenaline-cocaine topical anesthetic without tetracaine for facial laceration repair in children [published erratum appears in Pediatrics 1991 Feb;87(2):185] To determine whether the tetracaine component traditionally used in tetracaine-adrenaline-cocaine (TAC) is necessary to obtain effective topical anesthesia, a prospective study was performed to compare TAC and adrenaline-cocaine preparations for the repair of facial lacerations in children. Physicians were ""blind"" to which preparation was being used. Of 55 patients studied, 24 received TAC (103 sutures placed) and 31 received adrenaline-cocaine (151 sutures placed). The anesthetic efficacy of each preparation was approximately 95%; there were no adverse reactions related to administration of either medication or complications of wound healing noted in either group. The tetracaine component of TAC is superfluous for obtaining topical anesthesia of minor dermal lacerations of the face in children. The TAC formulation can be simplified by omitting tetracaine without compromising anesthetic efficacy. ",20 1764,"Percutaneous popliteal approach for angioplasty of superficial femoral artery occlusions. Angioplasty using the percutaneous popliteal approach was utilized in 50 patients (PTS) to recanalize 59 occluded superficial femoral arteries which had been unsuccessfully canalized by using the antegrade approach because of either a flush origin occlusion or inability to maintain the guide wire in the true lumen. All PTS had claudication; 8 had rest pain; 3 had non-healing ulcers. The laser Probe was used in 17 cases and the Rotablator in 3 cases. Occlusion length varied between 1 and 40 cm: 7 lesions were less than 10 cm (group 1); 9 were between 10 and 20 cm (group 2); and 43 were greater than 20 cm (group 3). An angiographic success was obtained in 48/59 lesions (81%): 14/16 (87%) in groups 1 and 2 and 34/43 (79%) in group 3. Three PTS needed complementary common femoral endarterectomy and one required percutaneous aspiration of a thromboembolus. Complications included: arterial perforation and/or dissection (without clinical sequelae) in 11 and a popliteal hematoma in 1 PT. One patient with a severely ischemic leg underwent successful emergency vascular surgery, while another limb salvage patient required below-knee amputation. There was no worsening of limb ischemia from any popliteal approach attempt. At discharge, 39 patients (78%) whose outcome would have been unsuccessful with the traditional antegrade approach were clinically improved after utilizing the popliteal approach to achieve a successful angioplasty procedure. ",13 1188,"Innervation territories for touch and pain afferents of single fascicles of the human ulnar nerve. Mapping through intraneural microrecording and microstimulation. The peripheral distribution of the fibre content of individual ulnar nerve fascicles supplying skin and muscles of the hand in human volunteers was indirectly mapped by tracing the fields of projected sensation evoked by intraneural electrical microstimulation (INMS) and by tracing receptive fields delineated through intraneural recording of afferent impulse activity elicited by natural stimulation of end organs. Moderate intensity suprathreshold INMS, delivered in cutaneous fascicles, induced nonpainful sensations projecting to stereotyped and coherent areas of skin, the fascicular projected fields (FPFs). Fascicular receptive fields (FRFs) were mapped during microneurographic recording by determining the area of skin which, when activated by light tactile stimuli, elicited afferent neural discharges recorded intraneurally. It was found that at a given electrode position in a skin nerve fascicle, moderate intensity INMS induced nonpainful sensations projecting to a cutaneous field (FPF) that coincides with the FRF, while high intensity INMS induced painful sensations projecting within the cutaneous field of nonpainful sensations. Pain induced by INMS in muscle nerve fascicles was projected to the muscles innervated by that fascicle and, in most instances, to areas beyond the muscular receptive field. The study demonstrates that individual ulnar nerve fascicles, at wrist levels, subserve well-defined cutaneous territories in the hand, and that the area of skin covered by the sum of all ulnar fascicular receptive or projected fields matches the maximal possible cutaneous distribution of the ulnar nerve. Insights of practical relevance regarding clinical expression of fascicular nerve injuries are also brought up by this study. ",9 824,"Carcinoma of the gallbladder. Gallbladder cancer remains difficult to diagnose preoperatively. However, recent work suggests that ultrasound may be effective. Gallbladder cancer remains highly lethal despite aggressive therapy. Extension of the disease beyond the mucosa predicts a poor chance of long-term survival. ",5 2878,"Controlled tissue expansion of a groin flap for upper extremity reconstruction. A large upper extremity defect in an 8-year-old girl was resurfaced with an expanded groin flap. Tissue expansion allowed complete coverage of the defect while minimizing the donor deformity. Pretransfer expansion of pedicled flaps offers an alternative to free-flap reconstruction of complex upper extremity defects. This is especially valuable in the pediatric patient, in whom donor-site morbidity can be significant. ",20 2296,"Interleukin-1 in human skin: dysregulation in psoriasis. Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1 alpha levels, and an IL-1 beta that lacked function in T-cell assays. IL-1 beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1 beta precursors, both normal and psoriatic skin process IL-1 beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1 beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis. ",16 2224,"Ultrasonic forms of posterior staphyloma. The most frequent deformations of the globe encountered in pediatric ophthalmology are staphylomas and colobomas. In this paper we reviewed 16 ultrasonographically diagnosed staphylomas and classified the ultrasonographic patterns produced by staphyloma cases into four types: (1) staphylomas involving the posterior pole but not the optic nerve head, (2) staphylomas involving the posterior pole and the optic nerve head, (3) peripapillary staphylomas, and (4) giant peripapillary staphylomas. Morphologic and ultrasonographic characteristics are described. ",15 430,"Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil. Using a prospective, randomized, and double-blind study design, alfentanil (n = 15), fentanyl (n = 14), or sufentanil (n = 16), in combination with N2O, were administered to patients undergoing craniotomy for supratentorial tumor resection. Physicians were given two syringes, one of which was labeled as ""load"" for the initial loading dose and the other as ""maintenance"" for continuous infusion. The concentration of drug in each syringe was adjusted to permit administration on a milliliter per kilogram basis. The target loading doses for alfentanil, fentanyl, and sufentanil were 75, 10, and 1 microgram/kg, respectively, and initial infusion rates were 33.5, 2.0, and 0.3 microgram.kg-1.h-1, respectively. Additional supplementary boluses and changes in maintenance infusion rate were made according to predetermined guidelines. Isoflurane, in increasing 0.2% inspired increments, was used only when the maximum allowed opioid dose had been given (i.e., supplementary bolus doses equal to 75% of the calculated loading dose or supplementary bolus doses equal to 50% of the calculated loading dose combined with a 50% increase in the maintenance infusion rate). Opioid infusions were stopped at the time of bone flap replacement. Antihypertensive medications and naloxone were subsequently given at the discretion of the anesthesiologist. Group demographics were not different. Total volumes of drug were similar among groups indicating equipotent preparations. Administration of isoflurane, antihypertensive medications, and naloxone were not different among groups. Although decreases in blood pressure seen with induction were similar among groups, alfentanil-treated patients received ephedrine more frequently before intubation. Thirty minutes after entry into the postanesthesia recovery area, respiratory rate and pH were lowest in sufentanil-treated patients. ",3 1559,"Simplified method for estimating true aortic valve mean gradient from simultaneous left ventricular and peripheral arterial pressure recordings. Estimation of the aortic valve gradient by simultaneous recording of left ventricular and peripheral arterial pressures is subject to error due to delay and modulation of the arterial pressure contour as it propagates from the ascending aorta. This error can be corrected by averaging the mean gradients derived from unaltered and temporally aligned simultaneous left ventricular-peripheral arterial pressure tracings. In 26 patients with aortic stenosis and simultaneous recordings of ascending aortic and femoral arterial pressure we compared this method with a simplified approach in which the peripheral arterial pressure is partially aligned by advancing it against the left ventricular pressure by 50% of the time delay of the simultaneously recorded upstrokes. Gradients measured this way predicted the true aortic valve gradients (left ventricular-ascending aortic) with a mean difference of +1.1 mm Hg (range = +10 to -5 mm Hg). We recommend use of this simplified method of correction because it predicts true aortic valve gradient equally well as the averaging technique (r = 0.977 vs. 0.979) and requires half the time and effort. ",13 1230,"Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder. Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylphenidate compared with placebo. Dependent measures included behavioral ratings, classroom work output, laboratory measures of attention and learning, and direct observations of social behavior. Improvement with medication on the Conners Hyperactivity Index was observed in 75% of subjects. Significant increases in work output, on-task behavior, and attentional skills were associated with methylphenidate. However, gains in measures of attention were not associated with improvement in learning, as measured by a paired associate learning task. Additionally, no significant increases in appropriate social interactions during free play were associated with methylphenidate. The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylphenidate at similar rates and in similar domains to that of the nonretarded population. ",9 992,"Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. We tested the hypothesis that surfactant replacement would be beneficial in the acid-aspiration model of acute lung injury. HCl (0.1 N, 2 ml/kg) was injected into the trachea of excised rabbit lungs (n = 8). Control lungs (n = 4) had no intervention. All were perfused with Tyrode's solution mixed 1:1 with autologous whole blood at 40 ml/min/kg for 30 min, and then degassed. A modified natural surfactant (Survanta, Ross Laboratories) was then injected into the trachea of four lungs injured with HCl (100 mg/kg at 25 mg/ml). Two quasi-static pressure-volume curves were determined. The mean alveolar pressures at 50, 60, 70, 80, and 90% of TLC were greater in the HCl group than in the control group (p less than 0.05). However, no difference was observed between the control lungs and those that received HCl + Survanta. In 13 anesthetized, paralyzed, and ventilated rabbits, deflation pressure-volume curves were determined from TLC to FRC (measured by helium dilution). Then, 0.1 N HCl (3 ml/kg) was injected into the trachea and, in seven, Survanta was instilled 5 min later. The mean alveolar pressures at 60, 70, 80, and 90% TLC were higher at 15 and 60 min in the HCl group compared with their pre-HCl time point (p less than 0.05). In the HCl + Survanta group, no differences were seen at 15 min, and only slight increased were seen at 60 min. No effect of surfactant replacement on arterial blood gases was observed. HCl aspiration increased recoil in both excised and in vivo lungs, and surfactant replacement with Survanta returned recoil to normal. ",7 2143,"HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Agranulocytosis develops in approximately 1% of patients with chronic schizophrenia treated with the atypical neuroleptic drug clozapine. Previous studies have not identified the mechanism or risk factors for this adverse reaction. Because of an observed association between Jewish ethnic background and the development of agranulocytosis in our patient sample treated with clozapine for refractory symptoms, HLA typing was performed in 31 patients (19.4% of whom had developed agranulocytosis). The HLA-B38 phenotype was found in 83% of patients who developed agranulocytosis and in 20% of clozapine-treated patients who did not develop agranulocytosis. Because B38 is part of a haplotype known to occur frequently in the Ashkenazi Jewish population, the frequencies of the combined alleles HLA-B38, DR4, and DQw3 were examined. The incidence of HLA-B38, DR4, DQw3 was significantly increased in patients with agranulocytosis (five of five patients) compared with control patients of Ashkenazi Jewish ancestry (two of 17 patients). These findings indicate that genetic factors marked by major histocompatibility complex haplotypes may be associated with the susceptibility of Jewish schizophrenic patients treated with clozapine to develop agranulocytosis. We postulate that gene products contained in the haplotype may be involved in mediating drug toxicity. ",14 2298,"Lymphocyte adhesion to psoriatic dermal endothelium: mechanism and modulation. Psoriasis is characterized by the hyperproliferation of keratinocytes in the epidermis and the accumulation of activated CD4+ T lymphocytes in the upper dermis. We have recently tested the hypothesis that the abnormal endothelial proliferation in the dermal papillae of psoriatic lesions may be mechanistically linked to the expression of endothelial ligands capable of promoting lymphocytes binding and extravasation. The results indicated that specialized endothelial cells lining the post-capillary venules of psoriatic lesions are capable of promoting the selective adherence of human CD4+ T cells and its memory subset. In contrast, B cells, CD8+ T cells, and CD45RA+ T cells are deficient in their capacities to bind. The adhesion process is energy and calcium dependent and involves tissue-specific lymphocyte receptors, with LFA-1 molecules playing an accessory role. We concluded that transformation of the dermal endothelium into a lymphocyte-receptive phenotype by defined growth factors or cytokines may represent a positive feedback mechanism promoting lymphocyte migration into the diseased sites. ",16 2950,"Improved trauma care in a rural hospital after establishing a level II trauma center. A study of motor vehicle accident deaths occurring in Napa County, California, from 1979 through 1983 showed that there was a preventable death rate of 42% for deaths that were not related to central nervous system injuries. After developing a Level II trauma center at our hospital, the preventable death rate decreased to 14%. This was statistically significant (total chi-square, 0.01 less than p less than 0.025). There was a significant increase in the average Injury Severity Score (34 versus 45, p less than 0.005) as well as significant improvements in the surgeon's response time (32 minutes versus 11 minutes, p less than 0.005) and in the time from hospital arrival to the start of surgery (3.6 hours versus 1.9 hours, 0.01 less than p less than 0.025). We conclude that these changes are indicative of improved trauma care and reflect favorably upon the effectiveness of a rural trauma center that meets Level II trauma center guidelines established by the American College of Surgeons Committee on Trauma. ",20 981,"Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist BACKGROUND. Exercise is a common stimulus of bronchoconstriction in subjects with asthma, who also have bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced bronchoconstriction. METHODS. In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), a selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from bronchoconstriction. RESULTS. Treatment with MK-571 attenuated exercise-induced bronchoconstriction in all the subjects. The mean (+/- SEM) maximal percent decrease in FEV1 after exercise was 25.2 +/- 3.5 percent in the subjects taking placebo and 9.2 +/- 2.5 percent in the subjects taking MK-571 (P less than 0.001). The mean percent inhibition for the entire group was 69.5 percent. The mean time to recovery after exercise was 33.4 +/- 4.0 minutes in the placebo group and 8.4 +/- 2.5 minutes in the MK-571 group (P less than 0.001). CONCLUSIONS. This study demonstrates that pretreatment with a potent and selective LTD4 antagonist markedly attenuates exercise-induced bronchoconstriction, and it suggests that LTD4 is a major mediator of this type of bronchoconstriction. ",7 1478,"The role of tubal pathology and other parameters in ectopic pregnancies occurring in in vitro fertilization and embryo transfer. Contradictory findings were reported concerning the role of tubal disease in the genesis of ectopic pregnancy in in vitro fertilization and embryo transfer (IVF-ET). We report on six ectopics that occurred in 141 IVF-ET pregnancies (4.3%). All of the six cases were among 84 patients with tubal disease, and none occurred in the remaining 57 patients with other etiological factors. No correlation was found in other parameters including: ovulation induction, number of embryos transferred, and luteal support. A comparison between the ectopics and six matched controls demonstrated similar estradiol levels, but beta-hCG levels on day 15 to 17 after ET were lower. Homolateral salpingectomy was performed in all six cases, but a contralateral resection was carried out in three of them. More comprehensive studies are needed to clarify whether tubal pathology really increases the risk for ectopic gestation in IVF-ET. ",12 2570,"Failure of T cell receptor-anti-CD3 monoclonal antibody interaction in T cells from marrow recipients to induce increases in intracellular ionized calcium. There are multiple immune defects in T cells from recipients after bone marrow transplantation (BMT). This study examines recipient T cells for increases in intracellular ionized calcium concentration [( Ca2+]i) after binding the T cell receptor-CD3 complex with anti-CD3 MAb. PBL from 10 of 23 short-term recipients (less than 1 yr after BMT) responded poorly (less than 35% of control) to anti-CD3 stimulation and PBL from 9 of 23 had blunted calcium flux responses (35-70% of control). Purified CD2+, CD56- cells from seven additional short-term recipients including three autologous marrow recipients were closely examined, and a sizable proportion of CD3+ cells from six of seven recipients did not increase [Ca2+]i after anti-CD3 stimulation. The decreased magnitude of the responses was due to decreased numbers of responding cells and not to a decrease in mean CD3 fluorescent intensity or in calcium flux responses on a single cell basis. Five of seven long-term recipients (greater than 1 yr after BMT) had PBL that responded normally and two of seven had PBL with blunted calcium flux responses. The data show that the signal transduction response mediated by the CD3-antigen receptor as measured by calcium flux is defective early after autologus or allogeneic BMT. ",19 1153,"Relief of injection pain in adults. EMLA cream for 5 minutes before venepuncture. The effectiveness of skin anaesthesia after 5 minutes' topical application of a lignocaine-prilocaine cream was evaluated. One hundred and twenty patients estimated the pain of antecubital venepuncture both on a linear scale and verbally after use of the cream for either 5 or 60 minutes, a placebo cream or no treatment. Reported pain was significantly less after only 5 minutes of the lignocaine-prilocaine cream (p = 0.002). The cream can be used to relieve the pain of all routine injections. ",9 782,"Interventional gallbladder procedures. Interventional radiologic procedures in the gallbladder are influencing both the diagnosis and therapy of many gallbladder disorders. Current diagnostic and therapeutic percutaneous techniques offer important alternatives for their management. This article highlights the spectrum of interventional radiologic techniques available for gallbladder diseases. ",5 1539,"A morphological and immunological study of human placental bed biopsies in miscarriage. Placental bed biopsies were examined in three groups of pregnant women for maternal vascular response to placentation as well as for the presence of cells associated with local immunosuppression activity. In the group of women undergoing legal abortion, the histological appearance of trophoblastic invasion was normal in all but one, and the proportion of immunosuppressor cells was also normal. In the missed miscarriage group the histological appearances were abnormal except in one patient. In women with a history of recurrent miscarriage who had miscarried after immunization, placentation was normal in some and defective in others. Immunosuppressor cells appeared to be diminished in number, although there was no correlation between the cytotoxic status of their sera and their pregnancy outcome. ",12 3131,"Observer reliability in detecting surreptitious random occlusions of the monaural esophageal stethoscope. The esophageal stethoscope is used often during anesthesia to monitor ventilation and cardiac function. Deficiencies in observer vigilance may limit the effectiveness of this monitoring instrument. The aim of this study was to determine how long it took for an observer to detect a surreptitiously occluded monaural esophageal stethoscope in the setting of clinical anesthesia. During routine anesthesia, where an esophageal stethoscope was in use, a computer-guided device would artificially, silently, and at random time intervals, occlude the stethoscope tubing. Personnel using the stethoscope noted when they perceived the absence of stethoscope sounds. We studied 320 stethoscope occlusions in 32 patients. The time between stethoscope occlusion and detection was 34 +/- 59 seconds (mean +/- SD). Eighty-seven percent of detections were made in less than 60 seconds. However, 13% of detections were delayed for more than 60 seconds, and 2.3% for more than 240 seconds. While anesthesia personnel using an esophageal stethoscope could detect most stethoscope occlusions, failure to appreciate such episodes occurred in a small but significant number of cases. This suggests that the esophageal stethoscope has some definite limitations as a continuous monitor and that other monitoring techniques, such as oximetry, capnography, and ventilator disconnect alarms, as well as visual/tactile inspection of the patient, should be used as well. ",22 432,"Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location PURPOSE: To examine studies of normal colon and colorectal cancer for evidence that the location of the primary tumor proximal or distal to the splenic flexure of the colon may determine distinct genetic categories of this disease. DATA IDENTIFICATION: Studies were identified through a manual search of journals, through MEDLINE, and through review of bibliographies in identified articles. STUDY SELECTION: Approximately 300 articles were examined. About 150 articles were excluded because tumor location was not reported or was reported in a way that did not permit correlation with results or conclusions. DATA EXTRACTION: Articles were selected either because the presentation of data permitted correlation of results with anatomic regions of the colon or because they were relevant to inherited colorectal cancer. RESULTS OF THE ANALYSIS: Differences were noted in biologic properties of proximal and distal segments of normal fetal and adult colonic epithelium and in the epidemiologic, pathologic, cytogenetic, and molecular features of proximal and distal colorectal cancer. Some differences correlated with the features of inherited colorectal cancer (proximal, nonpolyposis or distal, and polyposis forms). CONCLUSIONS: Developmental and biologic differences in proximal and distal colon may reflect differing susceptibilities to neoplastic transformation. Differences in proximal and distal colorectal cancer suggest that each may arise through different pathogenetic mechanisms. Proximal tumors appear to represent a genetically more stable form of the disease and may arise through the same mechanisms that underlie inherited nonpolyposis colon cancer. Distal tumors show evidence of greater genetic instability and may develop through the same mechanisms that underlie polyposis-associated colorectal cancer syndromes. ",3 2780,"Effects of alcohol on the import of aldehyde dehydrogenase precursor into rat liver mitochondria. We previously showed that incubation of rat liver mitochondria with alcohols resulted in the inhibition of the import of aldehyde dehydrogenase precursor but not that of ornithine transcarbamylase precursor (Wang TTY, Farres J, and Weiner H: Arch Biochem Biophys 272:440-449, 1989). The time required for inhibition of import to occur was now measured with ethanol (200 mM) and butanol (100 mM) at 0 degree and 30 degrees C. It required approximately 30 min to achieve 50% inhibition with butanol and 50 min with ethanol. To further substantiate the membrane perturbing effects of alcohols, we also examined the effect of oleic acid on import. We found that incubation of mitochondria with oleic acid (0-100 microM) resulted in inhibition of aldehyde dehydrogenase precursor import in a dose response fashion. In addition to in vitro effects of alcohols on import, we conducted a preliminary study on import of protein into liver mitochondria isolated from rats fed ethanol. We found that the rate of aldehyde dehydrogenase precursor import into liver mitochondria isolated from ethanol fed rats was identical to that from control. The results are consistent with finding that the activity and amount of aldehyde dehydrogenase was the same in mitochondria isolated from the alcohol-fed or control animals. ",20 542,"Expression of placental alkaline phosphatase in gastric and colorectal cancers. An immunohistochemical study using the prepared monoclonal antibody. The authors developed monoclonal antibodies (MoAb) against human placental alkaline phosphatase (PLAP). Four specific MoAb reacting only with PLAP and two nonspecific MoAb reacting equally with isozymes of alkaline phosphatase (hepatic, intestinal, and placental) were obtained. Immunohistochemical staining with the specific MoAb showed that the cell membrane and cytoplasm of cancer cells were stained in gastric and colorectal carcinoma. The incidence of PLAP positivity was 23% (25 of 107) of all gastric carcinomas. Among gastric carcinomas, the 42% (13 of 31) positivity of highly differentiated carcinoma (papillary adenocarcinoma and well-differentiated tubular adenocarcinoma) was a significantly higher rate than that found in poorly differentiated carcinoma (poorly differentiated adenocarcinoma and signet-ring cell carcinoma, five of 41, 12%). The incidence of PLAP positivity was 11% (four of 35) in colorectal carcinoma. In contrast, gastric adenoma, intestinal metaplasia, and noncancerous tissue adjacent to cancer did not show staining. These results indicated that expression of PLAP was apt to occur in more highly differentiated gastric carcinoma and was highly specific for carcinoma in the gastrointestinal tract, although its incidence was not high. ",3 1619,"Hemodynamics in internal carotid artery occlusion examined by positron emission tomography. Using positron emission tomography in nine patients with minor strokes, unilateral internal carotid artery occlusion, and good collateral circulation through the anterior portion of the circle of Willis, we analyzed regional cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume. These studies allowed quantification of the regional hemodynamic status, especially in relation to watershed areas. Compared with eight normal controls, the patients had significantly (p less than 0.01) decreased regional cerebral blood flow in the middle cerebral artery territory and the surrounding watershed areas of the occluded hemisphere. The oxygen extraction fraction rose with the distance from the anterior portion of the circle of Willis, attaining the highest value in the superior parietal and posterior temporo-occipital watershed area. A concomitant decrease in the cerebral blood flow/cerebral blood volume ratio suggested reduction in the mean blood flow velocity, whereby elevated blood viscosity would be more liable to reduce cerebral blood flow. These findings suggest hemodynamic vulnerability of the watershed areas after internal carotid artery occlusion in persons with good collateral circulation through the anterior portion of the circle of Willis. Our results also emphasize the importance of systemic hemodynamic factors such as blood pressure and circulating blood volume in the genesis of watershed infarction. ",13 1324,"Basic evaluation of female urinary incontinence. Urinary incontinence is a common disorder that is frequently underreported because of its social implications. Although several types of urinary incontinence are recognized, they can be generally classified as failure of the bladder to store or failure of the urethral mechanism. A systematic approach for the evaluation of incontinence that includes history, physical examination, basic laboratory tests, and often urodynamic evaluation, offers the most comprehensive assessment of the etiology of incontinence. ",11 3301,"Diclofenac for day-care arthroscopy surgery: comparison with a standard opioid therapy. Sixty unpremedicated patients presenting for day-care arthroscopy surgery were allocated randomly to receive diclofenac 1 mg kg-1 i.m., fentanyl 1 microgram kg-1 i.v. or no analgesic during the course of anaesthesia. Patients receiving fentanyl had slightly, although not significantly prolonged recovery times. Patients receiving diclofenac had significantly improved postoperative visual analogue pain scores compared with patients receiving placebo medication (P less than 0.05). With fentanyl, pain scores were reduced also, but the effect was not statistically significant. Both fentanyl and diclofenac produced significant reduction in postoperative analgesic requirements (P less than 0.05). We conclude that diclofenac 1 mg kg-1 i.m. was an effective analgesic for arthroscopic procedures on the knee and is a useful alternative to opioids for day-care patients. ",22 3123,"Feasibility and cost savings of outpatient electrophysiologic testing. The feasibility of outpatient electrophysiologic testing was examined by reviewing 100 consecutive outpatient tests performed in 95 patients. Seventy-one of the patients (75%) had no underlying heart disease. The electrophysiologic tests were performed to evaluate supraventricular tachycardias (n = 47), nonsustained ventricular tachycardia (n = 20), unexplained syncope (n = 21), palpitation (n = 9) or intermittent heart block (n = 2). A mean of 2.8 +/- 0.5 6F electrode catheters were inserted through a femoral vein. An electrode catheter was inserted into a subclavian or internal jugular vein in 28 tests and a 5F cannula was inserted into a femoral artery to monitor the blood pressure in 20 tests. The results of 61 tests (61%) were abnormal. Patients were monitored for a mean of 3.8 +/- 1.2 h after the procedure and then discharged. No complications occurred. For cost analysis a subgroup of 60 of these patients was matched for age, gender, heart disease and indication for electrophysiologic testing with a group of 60 patients who underwent electrophysiologic testing as inpatients. Physicians' fees for the two groups were similar; however, the mean hospital charge was $5,845 +/- 3,763 for the inpatient group compared with only $2,120 +/- 1,244 for the outpatient group (p less than 0.001). Thus, outpatient electrophysiologic testing is feasible and safe and results in substantial cost savings in patients without life-threatening arrhythmias. ",22 601,"Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel-Dubousset instrumentation. One hundred sixty patients with idiopathic scoliosis treated with Cotrel-Dubousset instrumentation (CDI) underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine. The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible. When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appear to provide the most physiologic sagittal contour. Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis. ",4 2666,"Differentiating agents facilitate infection of myeloid leukemia cell lines by monocytotropic HIV-1 strains [published erratum appears in Blood 1991 Apr 1;77(7):1624] Monocytotropic human immunodeficiency virus type 1 (HIV-1) isolates from patients with acquired immunodeficiency syndrome (AIDS) infect mononuclear phagocytes as well as activated T cells, but do not usually infect immature human myeloid cell lines in vitro. The HL-60 promyelocytic/myeloblastic cell line and the promonocytic line, U937, were susceptible to productive infection by monocytotropic HIV-1 isolates (HIV-1JR-FL and HTLV-IIIBa-L) after treatment with retinoic acid, dimethyl sulfoxide, dibutyryl cAMP, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Virus production was only detected when these compounds were added before virus infection. Virus replication did not correlate with CD4 receptor expression because undifferentiated HL-60 cells express CD4 and the level of CD4 expression did not increase after differentiation in the presence of retinoic acid, 1,25(OH)2D3, or TPA. A mature monocytic cell line (THP-1) was capable of infection without pretreatment, and treatment with differentiating agents enhanced virus production. A chronically infected cell line (J-HL-60) was isolated after HIV-1JR-FL infection of HL-60 cells treated with retinoic acid. Virus production in this cell line was enhanced more than 10-fold after differentiation in the presence of 1,25(OH)2D3 or TPA. The majority of virus production by 1,25(OH)2D3-treated J-HL-60 cells was associated with the mature, adherent population. Molecular analysis of a cloned line of J-HL-60 showed integration of a single DNA provirus. These results suggest that cellular factors associated with precursor cell differentiation along the myelomonocytic pathway are required for optimal replication of monocytotropic HIV-1 strains in vitro. ",19 1063,"Rehabilitation of chronic stroke patients: changes in functional performance. Forty stroke patients who were at least one year post-onset completed a one-month intensive rehabilitation program. The month before the program served as a control period. During the program, patients received individual sessions in occupational and physical therapy four days a week, and they participated in group activities on the fifth day. Therapy emphasized instruction in motor planning, balance and weight shift, and the use of adaptive equipment; these motor abilities were then practiced within real life situations. The patients demonstrated significant improvement in the outcome measures of weight shift, balance, and ADL scores after the one-month rehabilitation program (weight shift: F = 16.1, p = .0001; balance: F = 6.26, p = .0007; ADL: F = 13.8, p = .0001). They retained these new skills during a three-month follow-up period. ",9 148,"Effects of albendazole on Echinococcus multilocularis infection in the Mongolian jird. Albendazole chemotherapy of larval Echinococcus multilocularis was studied in the Mongolian jird by administration of medicated feed at various concentrations and durations. The effects were evaluated by comparison of treated and control groups in terms of host mortality, larval metastases to the lungs, and final weight and histologic appearance of larval tissue. Viability of larval tissue at necropsy of each animal was tested by inoculation into two noninfected jirds. Albendazole-medicated feed (0.05%-0.10%) significantly inhibited larval growth. Other effects of the drug included larval degeneration and necrosis, inhibition of protoscolex formation, decreased pulmonary metastases, and reduced mortality of hosts. Adverse effects on the parasite correlated significantly with serum albendazole metabolite levels and duration of therapy. However, serum albendazole levels in jirds equal to or exceeding concentrations achieved in humans receiving daily doses of 10 mg/kg of body weight did not kill the parasite. ",2 1601,"Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation. Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability. ",13 3116,"Surveillance of in situ infrainguinal bypass grafts: conventional vs. color flow duplex ultrasonography. Surveillance of in situ saphenous vein bypass grafts with duplex scanning detects graft abnormalities which may lead to graft thrombosis. Correction of these defects, while grafts are still patent, potentially improves overall graft patency. In this study we compared color flow and conventional duplex to determine whether color flow provided additional information not obtainable by conventional duplex examination. The primary patency rate (patency maintained without intervention) for all 51 cases was 76% (39/51). The secondary patency rate (patency maintained by identification and correction of graft defects before failure) was 88% (45/51). Duplex scanning reduced the graft failure rate by 50%. Color flow and conventional duplex examination provided the same information regarding incipient graft failure. In 20 patients monitored with both techniques, the same number of proximal (100%) and distal (90%) anastomoses were imaged. The same number of graft defects (three vein graft stenoses, one proximal femoral artery stenosis) were identified. Velocity data obtained using the two techniques (peak systolic velocity in an area of stenosis and the duplex velocity ratio) were not always the same, making calculation of percent stenosis from this data inaccurate. Color flow duplex is useful in monitoring graft patency, but provides no additional information over that provided by conventional scanning. ",22 1867,"Adult open heart surgery in New York State. An analysis of risk factors and hospital mortality rates This study analyzes data from New York State's new Cardiac Surgery Reporting System, which contains information about cardiac preoperative risk factors, postoperative complications, and hospital discharge. The purposes of the study were to determine the set of significant clinical risk factors and to identify cardiac surgical centers most likely to have serious quality-of-care problems. Significant risk factors for in-hospital death were age, gender, ejection fraction, previous myocardial infarction, number of open heart operations in previous admissions, diabetes requiring medication, dialysis dependence, disasters (acute structural defect, renal failure, cardiogenic shock, gunshot), unstable angina, intractable congestive heart failure, left main trunk narrowed more than 90%, and type of operation performed. Four of the 28 hospitals had significantly higher mortality rates than expected, given the risk factors of their patients. Subsequent site visits and medical record reviews confirmed that these facilities had high percentages of quality-of-care problems among cases resulting in mortality. ",13 2769,"Fatal high cervical spinal cord injury in an automobile accident complicating os odontoideum. We report a case where spinal instability from incomplete fusion of the dens of C2 (os odontoideum) allowed anterior displacement of the skull and first cervical vertebra following right frontal impact against the A pillar in an automobile accident. Resultant crushing and laceration of the spinal cord occurred at the level of C1 and C2. Without either radiographic investigation or detailed examination of the spine, the fatal injury might have been overlooked and death attributed to acute alcoholic poisoning because the blood alcohol level was .613%. ",20 663,"Intra-osseous pressure and oxygen tension in avascular necrosis and osteoarthritis of the hip. The intra-osseous pressure, PO2, and PCO2 were measured in 32 hips (21 patients) which were painful but showed no severe degenerative changes. Pre-operative scintigraphy and radiography was performed in all patients. Thirteen hips showed early osteoarthritis, eight had early osteonecrosis, and 11 had no changes. Core biopsies were performed and the bone was examined histologically and graded for necrosis. Histologically, necrosis was present in 27 specimens. Scintigraphic findings did not correlate with the histological results but were more closely related to the radiographic findings. The intra-osseous pressure in hips with histological necrosis (mean 47 mmHg) was significantly higher than in hips without necrosis (mean 26 mmHg). The PO2 was lower in bone with histological necrosis (mean 44 mmHg) than in bone without (mean 71 mmHg). PO2 increased and intra-osseous pressure decreased after decompression. The results confirm that ischaemia plays a central role in the development of necrotic changes in bone. Histological necrosis was found in hips with radiographic signs of osteonecrosis and in those with osteoarthritis. Radiography, and scintigraphy are shown to be insensitive methods for differentiating between those disorders. ",4 701,"Loss of duodenal folds allows diagnosis of unsuspected coeliac disease. We report three patients with coeliac disease who presented without the classic features of malabsorption and who underwent biopsy and were diagnosed only because of the endoscopic finding of the disappearance of Kerckring's folds in the descending duodenum. This sign constitutes a new and valid aid for the identification of patients with otherwise unsuspected coeliac disease. ",5 3314,"Differential regulation of human immunodeficiency viruses (HIVs): a specific regulatory element in HIV-2 responds to stimulation of the T-cell antigen receptor. The human immunodeficiency viruses (HIVs) types 1 and 2 have similar genetic organization but differ significantly in nucleic acid sequence. Although infection by either agent leads to symptoms of immunodeficiency, recent studies suggest potential differences in the time course and severity of these diseases. In this report, the transcriptional regulation and induction of these retroviruses were analyzed. We report that the regulation of HIV-2 differs from that of HIV-1: a distinct T-cell activation pathway, triggering of the CD3 component of the T-cell receptor complex, stimulates HIV-2 but not HIV-1 gene expression. The response to T-cell receptor stimulation in HIV-2 is mediated partly by an upstream regulatory element, termed CD3R, which is recognized by a sequence-specific DNA binding protein, NF-CD3R. Jurkat T leukemia cell lines containing HIV-2 provirus also showed increased viral replication after stimulation of the T-cell receptor complex, in contrast to HIV-1. These findings suggest that transcriptional regulation and induction of HIV-2 differ from HIV-1 and raise the possibility that different cofactors contribute to the activation of HIV-1- and HIV-2-associated AIDS. ",22 2457,"Vitamin A status in preschool-age Indonesian children as assessed by the modified relative-dose-response assay. The modified relative-dose-response (MRDR) assay has been validated in rats as a function of vitamin A status and tested in a group of American children. In this study the MRDR assay was applied to West Javan children who are at risk of being vitamin A deficient. Of 86 children enrolled, 75 were tested. In a time-course study involving 22 children aged 3.7-5.3 y, blood samples were taken at different times after doses of 0.35 mumol 3,4-didehydroretinyl acetate/kg body wt. Generally, the ratio of dehydroretinol to retinol (DR-R ratio) peaked between 4 and 8 h. Thereafter, in a survey of 53 children aged 0.6-4.8 y, single blood samples were drawn 5 h after the dehydroretinyl acetate dose. The DR-R ratio ranged from 0.0028 to 0.169. With a DR-R ratio of 0.03 as the cutoff value, 62% of the children were judged to be of marginal vitamin A status. ",17 1530,"C-reactive protein in assessing antimicrobial treatment of acute pelvic inflammatory disease. Serial serum C-reactive protein (CRP) determinations were used in the evaluation of antimicrobial treatment of acute pelvic inflammatory disease (PID) as proven by laparoscopy and endometrial biopsy or microbiologic findings in the upper genital tract in 36 women. Sixteen patients were treated with ciprofloxacin and 20 with doxycycline plus metronidazole. The mean CRP levels did not differ significantly in patients with severe and moderate salpingitis in comparison with mild salpingitis on admission or during treatment, nor was there any significant difference between the mean CRP levels in patients with acute chlamydial/gonococcal and nonchlamydial/nongonococcal PID. The mean CRP levels decreased by the third day of treatment in all treatment groups, and the decrease by the sixth day of treatment was significant (P less than .05), reflecting the clinical response to therapy faster than did serial ESR determinations. After the documentation of acute PID, serial serum CRP determinations were a useful predictor of the short-term response to antimicrobial therapy. ",12 277,"Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells. Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood. ",3 1556,"Cardiac catheterisation with 5 French catheters. From the beginning of November 1987 to the end of January 1989, 526 coronary arteriograms and left ventricular angiograms were performed with 5 French coronary catheters. In 448 (85%) patients diagnostic pictures were obtained with three standard types of 5 French catheters (No 4 Judkins): that is, left coronary, right coronary, and pigtail catheters. In 60 patients (11.4%) various other 5 French catheters were required to complete the study. In nine patients (1.7%), a 7 or 8 French catheter was used. Major complications causing cardiac arrest or requiring urgent operation developed in five patients. Sixty two patients (11.77%) had minor complications that required sublingual nitrates or a single bolus of atropine, or developed a haematoma that did not need intervention or had a mild reaction to the contrast material. Complications of moderate severity developed in 17 patients (3.2%): severe chest pain, arrhythmia requiring a temporary pacemaker, contrast reaction associated with hypotension, haematoma requiring blood transfusion, or a transient ischaemic episode. There were no deaths. 5 French catheters were used for routine coronary angiography and left ventriculography in 98.3% of patients. There were no major complications related to femoral artery puncture. The routine use of 5 French coronary catheters should increase the feasibility of safe coronary angiography in outpatients and should reduce the cost of this investigation. ",13 3148,"Multiple-pulse stimulation and dantrolene in malignant hyperthermia. A potentially fatal condition, yet preventable, malignant hyperthermia (MH) lacks a satisfactory noninvasive diagnostic test. Studying the effects of intravenous dantrolene (3 mg/kg) on electrically stimulated skeletal muscle, we found that this approach does not conclusively distinguish between normal humans and those susceptible to malignant hyperthermia but nonetheless yielded important information about the action of dantrolene in man and in MH. Supramaximal single- and multiple-pulse stimulation of the common peroneal nerve produced stable torque responses of the dorsiflexor muscles (monitored in vivo), which dantrolene suppressed. With the multiple-pulse stimulation (5-6 pulses) this torque suppression was significantly less in MH-susceptible subjects than in control subjects. This distinction, also observed in MH swine, confirms this animal as a good model for human MH. That dantrolene's effect in MH can be more completely reversed with high frequency stimulation is intriguing; presumably, excitation-contraction coupling differs in MH and normal muscle. ",22 23,"Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection. Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P less than 0.01). ",0 2440,"Is exogenous fructose metabolism truly insulin independent? Although fructose is widely regarded as an insulin-independent fuel source, its in vivo conversion to glucose represents a theoretical limitation to its clinical usefulness in diabetics, particularly if given in large doses. To determine whether small amounts of fructose can be well utilized in the setting of insulinopenia, we administered a low-dose fructose infusion (4.2 g/hr) to a fasting type 1 diabetic patient receiving continuous subcutaneous insulin at a dose that had previously maintained stable euglycemia for 72 hr (plasma glucose = 80-110 mg/dl). Despite the low infusion rate (less than 20% of calorie requirement), fructose caused an immediate and marked rise in plasma glucose (to 370 mg/dl after 27 hr). Glucose loss in the urine and accumulation in plasma could account for fully half of the administered hexose load. Thus, the utilization of even small quantities of exogenous fructose is profoundly impaired under hypoinsulinemic conditions. It is misleading to regard fructose as a truly insulin-independent fuel source. ",17 3174,"Interventional radiology of the biliary tract. Metallic stents. Biliary metallic stents were placed in 18 patients with bile duct obstruction. Six patients received Gianturco stents and 14 Wall-stents. Results of these tests are discussed. ",22 2076,"Temporal relation between left ventricular dysfunction and chest pain in coronary artery disease during activities of daily living. Forty-three ambulatory patients with angina of increasing frequency underwent continuous monitoring of left ventricular (LV) function for an average of 2.9 +/- 1.9 hours to determine the incidence and temporal sequence of LV dysfunction, ST-segment depression and chest pain. Indicators of ischemia were: a decrease in ejection fraction greater than 5% lasting greater than 1 minute; horizontal or downsloping ST-segment depression of greater than or equal to 1 mm; or onset of the patient's typical chest pain complex, or a combination of these. During the monitoring interval, subjects performed daily activities such as sitting, walking, climbing stairs and eating. In 11 patients, 22 episodes of chest pain or ST-segment depression, or both, were observed. Eighteen episodes were accompanied by a decrease in ejection fraction (9 patients); chest pain accompanied the decrease in ejection fraction during 13 episodes, whereas ST-segment changes occurred during 7. In 12 of 13 episodes the decrease in ejection fraction began earlier than the onset of chest pain, whereas in 1 patient ejection fraction decrease and chest pain onset started at the same time. The average interval from a decrease in ejection fraction to the onset of chest pain was 56 +/- 41 seconds (range 0 to 120). ST changes occurred after the onset of a decrease in ejection fraction in 6 of 7 episodes. The average interval from the onset of ejection fraction decrease and the onset of ST change was 99 +/- 91 seconds. These data suggest that LV dysfunction manifested by a decrease in ejection fraction is an earlier indicator of myocardial ischemia than is angina pectoris or electrocardiographic evidence of ischemia. ",13 2914,"Reappraisal of pancreatic and duodenal injury management based on injury severity. We evaluated the effectiveness of treatment protocols for pancreatic and duodenal injuries according to the severity of injury. Of 81 patients, 65 survived initial injury. Pancreatic injuries without ductal involvement occurred in 21 patients and were treated by drainage. No late deaths occurred. Pancreatic injuries with ductal disruption occurred in 18 patients and were treated by pancreatic resection. Abscesses developed in seven (39%) of the patients, but no late deaths occurred. Nineteen patients had duodenal injuries without pancreatic injury, and no duodenal complications occurred. Simple closure sufficed for injuries affecting up to 40% of the duodenal circumference. Wounds affecting up to 40% of the duodenal circumference can be treated by suture closure alone. Adjunctive duodenal tube decompression should be reserved for wounds affecting greater than 40% of the duodenal circumference, closure under tension, and associated injuries to the head of the pancreas. Pyloric exclusion was rarely necessary in our patients. ",20 1698,"Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial. The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h. ",13 2282,"Contact dermatoses from disposable glove use: a review. Contact dermatoses from disposable gloves are being reported with greater frequency. A variety of eruptions can occur. These have become increasingly relevant for dermatologists, who for most procedures now use disposable gloves. This article represents a review of the relevant issues about the use of disposable gloves by dermatologists. Methods of management and prevention of morbidity associated with disposable glove use will also be discussed. ",16 961,"Pleuropulmonary morbidity: internal thoracic artery versus saphenous vein graft. Although use of the internal thoracic artery (ITA) for coronary artery bypass grafting results in superior graft patency and improved patient survival, our initial clinical observations suggested an increased incidence of pleuropulmonary morbidity with its use. One hundred consecutive patients with left ITA grafts were studied prospectively and compared with a consecutive retrospective group of 100 patients undergoing coronary artery bypass grafting with saphenous vein grafts only. Preoperative, postoperative day (POD) 2, POD 6, and postoperative week 8 chest roentgenograms were analyzed for atelectasis and effusion. Postoperative left lower lobe atelectasis was common in both groups on both POD 2 (saphenous vein, 43%, versus ITA, 53%; not significant) and POD 6 (saphenous vein, 40%, versus ITA, 41%; not significant). There was a significantly higher incidence of pleural effusion on POD 6 in the ITA group (84% versus 47%; p less than 0.05) but most of these were small. There was more chest tube drainage (1,413 versus 1,028 mL; p less than 0.01) and a greater need for secondary thoracostomy or thoracentesis (4% versus 0%) in the ITA group. The left pleural space was opened in 67 of the 100 ITA patients but pleurotomy did not appear to influence postoperative morbidity. We conclude that use of the internal thoracic artery for coronary artery bypass grafting results in a small but significant increase in pleuropulmonary morbidity. ",7 268,"A signet-ring cell carcinoma of the ampulla of Vater. We describe a variant of carcinoma of the ampulla of Vater, which, to our knowledge, has not been previously described. Classic signet-ring cells represented the predominant cell type, and were admixed with more poorly differentiated tumor cells that were chromogranin positive. These findings raise the possibility of an amphicrine tumor of the ampulla. ",3 1488,"Ectopic pregnancy in adolescents: a clinical review for pediatricians. Pediatricians caring for sexually active female adolescents and young adults need to be aware of the history, symptoms, and signs of an ectopic pregnancy. A thorough history and physical examination, including the pelvic examination, as well as specific diagnostic tests such as repeated quantitative hCG measurements, and ultrasonography when indicated, are crucial to proper and early diagnosis of a nonruptured ectopic pregnancy manageable by laparoscopy. The key to early diagnosis is to include ectopic pregnancy in the differential diagnosis in any sexually active female patient who has abnormal vaginal bleeding or abdominal pain. With early diagnosis, close observation, and appropriate management, the outcome is more likely to be favorable, with minimal morbidity and risk of death. ",12 450,"Potent toxicity of 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo. A novel approach to immunosuppressive therapy. Lymphoid cells were thought to be uniquely susceptible to excess 2'-deoxyadenosine (dAdo), when exposed to inhibitors of adenosine deaminase (ADA). However, we now find that human monocytes are as sensitive as lymphocytes to dAdo or to the ADA-resistant congener 2-chloro-2'-deoxyadenosine (CldAdo). Monocytes exposed in vitro to CldAdo, or to dAdo plus deoxycoformycin rapidly developed DNA strand breaks. Both the DNA damage and the toxicity of CldAdo or dAdo toward monocytes were blocked by deoxycytidine, but not by inhibitors of poly(ADP-ribose) polymerase. A partial decrease in RNA synthesis and a gradual decline of cellular NAD were early biochemical events associated with monocyte DNA damage. Low CldAdo concentrations (5-20 nM) inhibited monocyte phagocytosis and reduced the release of interleukin 6. Higher CldAdo concentrations led to a dose- and time-dependent loss of monocyte viability. Circulating monocytes disappeared within 1 wk in patients with cutaneous T cell lymphoma or with rheumatoid arthritis during continuous CldAdo infusion. The marked sensitivity of human monocyte function and survival to CldAdo in vitro, together with the monocyte depletion in patients receiving CldAdo chemotherapy, suggests that CldAdo or other dAdo analogues offer a novel therapeutic strategy for chronic inflammatory and autoimmune diseases characterized by inappropriate monocyte deployment or function. ",3 1653,"Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring. In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin-converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of ""office"" BP control, different antihypertensive regimens do not confer the same degree of ""nonoffice"" BP control. ",13 812,"Pathogenesis and therapy of peptic ulcer disease. The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H2-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H2-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H2-receptor antagonists for the majority of patients with peptic ulcer. ",5 2617,"Normal responsiveness of superficial hand veins to alpha- and beta-adrenergic stimuli in allergic asthma: effects of terbutaline and prednisolone on beta-adrenergic responsiveness. Impaired function of the adrenergic-receptor system has been postulated to contribute to the pathogenesis of bronchial asthma. Using the dorsal hand-vein compliance technique, we compared the changes in diameter of superficial hand veins in response to phenylephrine, an alpha-adrenoceptor agonist, and to isoproterenol, a beta-adrenoceptor agonist, in 14 untreated patients with allergic asthma and in 16 nonatopic control subjects. There were no significant differences in the median effective dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) or in the maximal response (Emax) between the two groups. Bronchial hyperreactivity (assessed by methacholine-challenge tests) in the patients with asthma was uncorrelated with the ED50 or Emax of isoproterenol. These results demonstrate no evidence for a generalized change in alpha- or beta-adrenergic responsiveness on smooth muscle cells in asthma. Hand-vein responsiveness to isoproterenol was unchanged after treatment for 7 days with oral terbutaline (5 mg three times per day). Thus, unlike leukocytes, smooth muscle appears not readily susceptible to beta-adrenoceptor desensitization in vivo. Local infusions of prednisolone or dexamethasone during 2 hours and systemic administration of dexamethasone (24 hours) caused a significant fall in the Emax for isoproterenol. The mechanism of attenuation of beta-adrenoceptor responsiveness by corticosteroids remains to be determined. ",19 2204,"Cardiac teratogenesis of trichloroethylene and dichloroethylene in a mammalian model. Recent epidemiologic studies have demonstrated a greater than expected number of pediatric patients with congenital heart disease in areas where drinking water was contaminated by halogenated aliphatic hydrocarbons. Trichloroethylene, trichloroethane and dichlorethylene were the principal contaminants in the groundwater. A previous study of chick embryos demonstrated that when injected into the air sacs of fertilized eggs trichloroethylene produced more than three times the number of cardiac defects that are found in control embryos. This mammalian study demonstrates similar effects of trichloroethylene and dichloroethylene when applied under provocative circumstances (that is, solutions delivered through a catheter into the gravid uterus from an intraperitoneal osmotic pump) to the developing rat fetus in utero during the period of organ differentiation and development. Furthermore, the effect is dose dependent for both agents. Although only a very small number of congenital heart anomalies (3%) were found in the control group, 9% and 12.5% were found in the lower dose trichloroethylene and dichloroethylene groups and 14% and 21% in the higher dose groups, respectively (p less than 0.05). A variety of cardiac defects were found. Dichloroethylene appears to be at least as great a cardiac teratogen as trichloroethylene even though it was administered at a 10-fold lower concentration. These agents appear to be specific cardiac teratogens because only a single noncardiac anomaly was found. This study in a rat model demonstrates a dose-dependent relation between fetal exposure to trichloroethylene and dichloroethylene in utero during the period of organogenesis and the appearance of a variety of congenital cardiac defects. ",15 2027,"Fish oil amplifies the effect of propranolol in mild essential hypertension. Forty-seven male patients with mild essential hypertension were randomly allocated to three subgroups. After a run-in period of 4 weeks, the first subgroup (n = 16) received propranolol (80 mg/day) for 36 weeks followed by a placebo period of 4 weeks. The second subgroup (n = 15), after a run-in period of 4 weeks, was given a supplement of encapsulated fish oil (9 g/day) for 36 weeks with a subsequent period of 4 weeks in which fish oil placebo was given. The third subgroup (n = 16), after a run-in period of 4 weeks, was given propranolol (80 mg/day) for 12 weeks, propranolol (80 mg/day) plus fish oil capsules (9 g/day equivalent to 1.8 g/day of eicosapentaenoic acid and 1.1 g/day of docosahexaenoic acid) for 12 weeks, propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent period of 4 weeks when propranolol placebo was administered. The results indicate a blood pressure-lowering effect of fish oil, which was comparable with that of propranolol. The simultaneous intake of fish oil plus propranolol was more effective than propranolol or fish oil alone. Propranolol treatment resulted in a decrease of plasma norepinephrine, plasma renin activity, and thromboxane B2 formation. After fish oil supplementation, plasma norepinephrine and thromboxane B2 formation were likewise reduced, whereas plasma renin activity appeared increased. The decrease of serum triglycerides, total and low density lipoprotein cholesterol as well as the rise of high density lipoprotein cholesterol are concomitant beneficial effects, which justify the consideration of fish oil alone or in combination with antihypertensive drugs for the treatment of mild hypertension. ",13 1021,"Head stability and gaze during vertical whole-body oscillations. To understand head and eye stabilities during upright locomotion, we investigated head and eye movements during vertical whole-body oscillations of various amplitudes (1 to 10 cm) and frequencies (1 to 3 Hz) in both normal subjects (n = 10) and patients with bilateral labyrinthine loss (n = 5). Vertical oscillations produced pitching motions of the head, of which the amplitude was markedly altered by a change in the oscillation frequency or the displacement. Vertical eye movements, being correlated with pitching head movements, were scarcely modified by gaze at 2 and 3 Hz. Acquired bilateral lesions presented deteriorated head stability and physically induced eye movements under stronger stimulations. However, significant increase of head movement upon stepping and suppression of pitching motion upon running, both characteristically found in bilateral lesions, were not reproduced by passive oscillations. Thus, these features during active locomotion may result from imbalance produced by alternate bipedal motions and from adaptation to minimize oscillopsia, respectively. ",8 3153,"Observer variability in the scoring of colpophotographs. Colposcopy and cervicography are accepted tools for assessing the cervix for an atypical transformation zone. We studied the validity of the colpophotograph as a measurement tool by determining the agreement of experienced colposcopists using colpophotographs of 50 women. Interobserver agreement was generally fair to good (kappa greater than or equal to 0.40) for the presence of the squamocolumnar junction and the area of ectopia but it was poor (kappa less than 0.40) for the area, border, and color characteristics of an atypical transformation zone. Intra-observer agreement was fair to good for the color characteristics of an atypical transformation zone, but it was poor for the area and border characteristics. We conclude that observer agreement studies should play a role in the validation of methods used in the visual diagnosis of cervical intraepithelial neoplasia. Considerable lack of agreement in reporting cytologic findings is a well-known problem, and lack of agreement might be an even bigger problem in reporting colposcopic findings. ",22 134,"Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys. Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes. ",1 722,"Fibronectin-related substance located in the chief cells of human and rat gastric mucosa. A novel substance located in the chief cells of human and rat gastric mucosa, which was detected immunologically by either polyclonal or monoclonal antihuman fibronectin (FN) antibodies, is reported. All three polyclonal antihuman FN antibodies used in this study reacted immunohistologically exclusively with the chief cells. Monoclonal antibody against C-terminal peptide or cell binding peptide reacted clearly with the human chief cells, but monoclonal antibodies against FN N-terminal and midmolecule failed to react with the cells. Western blot analysis of the rat gastric mucosal extract with polyclonal antihuman FN antibody showed that this substance has a molecular weight of about 70,000 Da. Therefore, this substance appears to be a fragment containing the C-terminal peptide of whole molecule FN and thus in the present study is named FN-related substance (FNRS). In a further study with ethanol-induced ulcer model of the rat, the physiological significance of FNRS was examined. The FNRS decreased remarkably, in a dose-dependent manner, in the fundic mucosa of the rats that ingested ethanol. The FNRS appeared to be associated with development of mucosal damage and repair, subsequently playing, in part, an important role in the gastric mucosal protection mechanism. ",5 3247,"Evaluating hematuria in children. Where to start and how to proceed. Bleeding from somewhere along the urinary tract is not unusual in children. Of the many causes, systemic infection and trauma are among the most common. History taking and physical examination should be careful and complete, because the results obtained help direct the laboratory evaluation. Diagnostic testing always begins with urinalysis but may progress to intravenous urography, voiding cystourethrography, endoscopic procedures in the upper and lower urinary tract, sonography, arteriography, or renal biopsy. Some cases remain unexplained and require follow-up to assess renal function. ",22 2762,"Puffer fish poisoning. Regarded by many as a delicacy, puffer fish can be the source of lethal food poisoning in humans. The syndrome is caused by tetrodotoxin, one of the most potent poisons known. Intoxication produces a constellation of symptoms, with paresthesias and generalized muscle weakness being common complaints. Treatment is symptomatic and often needs to be aggressive. Life support may be required. In some series, the mortality rate has approached 60 percent. ",20 2150,"Pulse oximetry. Uses and abuses. Pulse oximetry has made a significant contribution to noninvasive monitoring in a wide variety of clinical situations. It allows for continuous reliable measurements of oxygen saturation while avoiding the discomfort and risks of arterial puncture. As the extent of hypoxic episodes during various procedures and clinical settings is better appreciated, the role of continuous noninvasive monitoring will undoubtedly expand. An understanding of the principles and technology of pulse oximetry will allow physicians to obtain maximal clinical benefit from its use. ",14 2694,"Effect of continuous-infusion zidovudine therapy on neuropsychologic functioning in children with symptomatic human immunodeficiency virus infection. Neuropsychologic function was assessed in 13 children with symptomatic human immunodeficiency virus disease (Centers for Disease Control Class P2), ranging in age from 14 months to 12 years. Before the initiation of treatment, eight patients were classified as having encephalopathy. Psychologic tests were administered both before and after 6 and 12 months of continuous-infusion azidothymidine (AZT; zidovudine) treatment. After 6 months of treatment a significant increase of 15.5 (+/- 3.3) IQ points was demonstrated in general cognitive functioning (p less than 0.001). Follow-up for 10 of these patients indicated that after 12 months of AZT therapy, they had maintained their gains in IQ points. Improvements in adaptive behavior after 6 months of therapy, assessed with a standardized interview, paralleled the findings on the IQ data. No significant differences in the amount of change was observed for the different subgroups. The magnitude of these improvements could not be explained by practice effects, environmental changes, or general improvement in physical state. We conclude that neuropsychologic function was significantly improved with continuous infusion AZT treatment. ",19 2477,"Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney. Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study. ",17 2783,"Separation of a ruptured angioplasty balloon with successful percutaneous retrieval--a case report. A case of ruptured angioplasty balloon with complete separation from the catheter is presented. Successful percutaneous retrieval of the balloon with endoscopic biopsy forceps was performed. ",20 2953,"Inhalation injury to tracheal epithelium in an ovine model of cotton smoke exposure. Early phase (30 minutes). The purpose of this study was to evaluate lung cell injury during the acute phase of smoke inhalation injury. A group of 10 sheep were anesthetized with halothane and pancuronium followed by endotracheal intubation. In the first experiment 5 sheep were given air (sham group) and 5 were insufflated with cooled cotton smoke with a modified bee smoker. In the second part of our study (Experiment 2) the animals were insufflated with the following number of smoke breaths: 1 x 12 (n = 3); 2 x 12 (n = 4); 3 x 12 (n = 4) 4 x 12 (n = 4); and sham control (n = 1). After 30 min the animals were killed with KCl and the trachea prepared for scanning, transmission electron, and light microscopy. Our initial observation with scanning electron microscopy revealed a large amount of mucus on the surface of the epithelia. Numerous ciliated cells had been sloughed from the epithelium and were observed on the surface of the remaining ciliated cells. The sloughed cells were intact, and the cilia remained on the apical cell surface. Light and transmission electron microscopy revealed that most goblet cells were in the process of extruding mucus. The cytoplasm of goblet and basal cells appeared normal. Ciliated cells had a slightly vesiculated cytoplasm, and many were in the process of being sloughed from the epithelial surface. In these cells desmosomal attachment had been separated. The light microscope evaluation of the tracheal epithelium showed there was no dose-dependent effect between the four treatment groups. ",20 2847,"Bilateral simultaneous fractures of the femoral neck: case report. A case of bilateral fractures of the femoral neck resulting from high-voltage electric injury is reported. Surgeons caring for patients with electrical injuries must be aware of the possibility of this injury as well as other skeletal injuries which may result from muscle contraction or falls related to electric shock. Without vigilance for these injuries, diagnosis may be delayed. ",20 1038,"Ethyl chloride and venepuncture pain: a comparison with intradermal lidocaine. One hundred and twenty unpremedicated patients undergoing gynaecological surgery were randomly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula. They received either no anaesthetic, 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site. Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture. However, it was not as effective as intradermal lidocaine. It had no effect on vein visualisation or ease of cannulation. Ethyl chloride can be recommended as a method of producing instant skin anaesthesia. ",9 1783,"Optimizing the exercise test for pharmacological investigations Exercise trials in cardiology are often hindered by inconsistent approaches to exercise testing. These inconsistencies include the choice of exercise protocol, exercise end points, points of analysis, and absence or misuse of gas exchange data. Gas exchange techniques greatly enhance the accuracy with which cardiopulmonary function is assessed by exercise. Commonly used protocols are not always appropriate for all patients or all studies. Both cardiovascular disease and the exercise protocol can have an important impact on the relation between changes in work rate and oxygen uptake. Ramp protocols appear to offer the greatest promise for assessing cardiopulmonary function. Analyzing hemodynamic and gas exchange responses at several points submaximally, in addition to those at peak exercise, can add important information concerning the efficacy of a drug. A great deal of confusion continues to hinder the application of the gas exchange anaerobic threshold, and many of the commonly used testing end points are not reliable. ",13 3083,"Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. Whereas xenogeneic collagen has provided a safe and effective biomaterial for numerous medical applications, there are few instances in which data permit the correlation of the immunologic profile of well-defined devices with their clinical sequelae. A major exception is the use of injectable bovine dermal collagen for soft-tissue contour correction. The low incidence of hypersensitivity has been studied in the context of clinical efficacy and safety with several devices. The findings indicate that such immunity usually results in the manifestation of local symptoms of dermal inflammation at sites of treatment that resolve as the implant is resorbed by the host. In contrast, more immunogenic hemostatic agents may elicit a more frequent or vigorous immune response that is not clinically visible or relevant in that application. Recent experiences with collagen-based devices for the repair and regeneration of bone have also demonstrated that the presence of immunity to their collagenous or non-collagenous components does not necessarily predict adverse clinical sequelae. Indeed, numerous specific data indicate that this immunity can exist as an epiphenomenon with no effect on osteogenesis. To get a true composite picture of biocompatibility, significant steps must be taken to characterize biomaterials properly and to ensure that immunologic, clinical, histologic, and other pertinent laboratory data are viewed in relation to one another and not in isolation. ",22 225,"Carcinoma of the thyroglossal duct. A review of 39 instances of excision of a cyst of the thyroglossal duct performed at St. Paul Medical Center, Dallas, Texas, revealed two patients with carcinoma of the thyroglossal duct. A review of the English literature yielded 146 instances of this uncommon tumor. Eighty-four per cent were papillary adenocarcinoma of thyroid type and 5 per cent were squamous cell carcinoma. The patients were from six to 81 years old with a 2:1 female to male ratio. Metastatic disease to lymph nodes was noted in 11 per cent and invasion of overlying strap muscles was found in 4 per cent. Carcinoma of the thyroid gland occurred in 14 per cent. Preoperative diagnosis was rare. The Sistrunk procedure is recommended for initial surgical therapy with further surgical or adjuvant therapy dependent on associated clinical findings. Prognosis for carcinoma of the thyroglossal duct of thyroid type parallels that of carcinoma of the thyroid gland. ",3 3056,"Prolonged paralysis following suxamethonium and the use of neostigmine. A case of prolonged neuromuscular block following the administration of suxamethonium is reported. Three hours after administration of suxamethonium, a well defined, recovering phase II block was demonstrated with a T4:T1 ratio of 0.25, and neostigmine was administered. Although the T4:T1 ratio was improved to 0.9, T1 remained at 25% of control, and significant paralysis persisted which responded to administration of cholinesterase. It is concluded that neuromuscular monitoring cannot reliably predict reversibility in such cases and that, even after 3 h, antagonism of prolonged suxamethonium block should commence with cholinesterase, followed by neostigmine if necessary. ",22 2137,"Detection of drug-dependent, platelet-reactive antibodies by antigen-capture ELISA and flow cytometry. The effectiveness of flow cytometry in the detection of drug-dependent, platelet-reactive antibodies was investigated. In studies of seven sera known to contain quinine- or quinidine-dependent, platelet-reactive antibodies, flow cytometry was 5 to 10 times more sensitive in detecting drug-dependent antibodies (DDAbs) than the 51Cr release assay, antigen-capture enzyme-linked immunosorbent assay (ELISA), and indirect immunofluorescence microscopic assay. With flow cytometry, DDAbs could be detected at drug concentrations as low as 0.1 microM, or less than one-tenth the level required with other methods. Antigen-capture ELISA was not as sensitive as flow cytometry in DDAb detection, but it did allow identification of the DDAbs' target molecules. With this assay, five of the seven DDAbs recognized both the glycoprotein Ib/IX (GPIb/IX) and glycoprotein IIb/IIIa (GPIIb/IIIa) complexes, while the remaining two sera reacted only with GPIb/IX. Of 44 consecutive patients who developed thrombocytopenia while taking quinidine, DDAbs were detected by flow cytometry in 11 (25%), more than twice the number detected by other methods. In one patient who developed thrombocytopenia while taking trimethoprim/sulfamethoxazole, DDAbs could be detected only by flow cytometry. It can be concluded that flow cytometry is highly sensitive in detecting DDAbs and allows their detection at pharmacologic concentrations of the drug. Most quinidine-dependent antibodies recognize at least two different glycoprotein complexes in the platelet membrane. ",14 2831,"Field performance of the Intoxilyzer 5000: a comparison of blood- and breath-alcohol results in Wisconsin drivers. Intoxilyzer 5000 and blood-alcohol results from drivers arrested for operating a motor vehicle while intoxicated and for related offenses were compared during a two-year period. Three hundred and ninety-five pairs of results were studied. The breath- and blood-alcohol specimens in this study were collected within 1 h of each other. The mean blood-alcohol concentration obtained was 0.180 g/dL, with a range from zero to 0.338 g/dL. By comparison, the mean Intoxilyzer 5000 result was 0.16 g/210 L with a range from zero to 0.32 g/210 L. Compared with the blood-alcohol result, Intoxilyzer 5000 results were lower by more than 0.01 g/210 L 67% of the time, within 0.01 g/210 L 31% of the time, and higher by more than 0.01 g/210 L 2% of the time. ",20 1006,"Informed consent in head and neck surgery. Informed consent is the fastest growing problem in the medical negligence debate. It was highlighted recently in the United Kingdom in the Sidaway case. Informed consent comprises the advice you would give the patient, the consequences of not taking your advice, the specific risks of the surgery or treatment you have in mind, and the risks of surgery in general. In an attempt to identify what the present practice in otolaryngology was, a postal survey was carried out of the members of the Scottish and North of England Otolaryngological Societies. ",8 3329,"Another way of pumping blood with a rotary but noncentrifugal pump for an artificial heart. This article describes an alternative mode of pumping blood inside the body. The device is a non centrifugal, valveless, low speed rotary pump, electrically powered, based on Wankel engine principle. The authors developed an implantable electrical actuator resulting in a compact, sealed motor-pump unit with electrical and magnetic components insulated from fluids. The results in the flow curve and in the pumping action show some common points but also some basic differences compared to classical pulsatile pumps or centrifugal pumps. The blood coming from the atrium follows a continuous movement without any stop flow but with variations creating pulsatility. Ejection and filling of the pump are simultaneous. It is always an active filling. Hydraulic efficiency depends on clearance in the pumping chamber and outlet port pressure. A 60 cc device allows flows up to 8-9 liters. The implantable motor is cyclindrical in shape, has a moderate weight (490 grams) and presents a good efficiency (32% for a rotary speed of 90 rpm against a mean aortic pressure of 150 mm of Hg). The authors conclude that their device could be proposed after further experimental studies, as an LVAD for shortterm assistance with a good promise for permanent application. ",22 3045,"Reoperations on heart valve prostheses: an analysis of operative risks and late results. To evaluate risks and complications of reoperations on heart valve prostheses, we reviewed data on 183 patients who underwent reoperation because of prosthetic valve malfunction. The incremental effect of the redo procedure on hospital mortality and morbidity was studied by comparing primary and reoperative procedures and analyzing a series of possible predisposing factors. Late survival after first and second reoperations was computed, and possible determinants of late mortality were examined. Overall operative mortality was 8.7%; emergency operation (p = 0.0001), previous thromboembolism (p = 0.05), and advanced New York Heart Association functional class (p = 0.031) were the independent determinants. In a series of 1,355 patients having primary or secondary isolated valve replacement, the redo procedure was a significant risk factor in the univariate analysis (p = 0.025) but not in the multivariate analysis except for the subset of patients having mitral valve replacement (p = 0.052). The postoperative course was quite complicated, as evidenced by the long mean stay in the intensive care unit (mean stay, 3.8 days; longer than 2 days for 26% of the survivors). Nevertheless, postoperative complications were not significantly greater after a redo procedure than after a primary operation. Actuarial survival at 7 years was 57.3% +/- 8%. A comparison with a nonhomogeneous series from our institution did not demonstrate significant differences. In the subset of 16 patients having a second reoperation, late survival was 37.8% +/- 16% at 2 years. Advanced New York Heart Association class (p = 0.0001), double prosthetic valve dysfunction (p = 0.003), and any indication other than primary tissue failure (p = 0.06) were determinants of late mortality. ",22 930,"Developmental expression of plasminogen activator inhibitor type 1 by human alveolar macrophages. Possible role in lung injury. Urokinase activity is regulated by the specific endogenous plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). One of these inhibitors, PAI-1, has been directly implicated in connective tissue metabolism by virtue of its ability to bind extracellular matrix proteins. Because the normal lung is relatively rich in urokinase and abnormalities in urokinase activity have been associated with fibrotic lung diseases, we have explored the possibility of local production of PAI-1 and PAI-2 in human lung. Reverse transcription and subsequent amplification by the polymerase chain reaction of total lung RNA revealed PAI-1 mRNA in each of three normal samples and in two specimens from patients with the adult respiratory distress syndrome (ARDS). In situ hybridizations of lung biopsy specimens from a patient with ARDS with cRNA probes to PAI-1 and PAI-2 indicated that alveolar macrophages express PAI-1 mRNA during the acute injury phase. Subsequent reverse transcription and PCR amplification of normal human monocyte and alveolar macrophage mRNA revealed that neither cell type expressed mRNA for urokinase inhibitors. However, after 24 h stimulation with endotoxin in vitro, monocytes were strongly positive for PAI-2 but negative for PAI-1 mRNA whereas, under the same conditions, alveolar macrophages exhibited mRNA for both PAI-1 and PAI-2. Metabolic labeling of endotoxin-stimulated alveolar macrophages with 35S-methionine followed by immunoprecipitation with PAI-1 and PAI-2 antibodies revealed that macrophages synthesized both PAI-1 and PAI-2. As judged by immunoprecipitation and functional studies, PAI-2 was found to be the major intracellular PA inhibitor whereas PAI-1 was found to predominate outside the cell. Thus, mononuclear phagocytes exhibit a developmental potential for PAI-1 expression. The release of PAI-1 by stimulated macrophages, as observed in the setting of ARDS, may be one mechanism by which these cells promote connective tissue accumulation. ",7 130,"HIV seroconversion in two homosexual men after receptive oral intercourse with ejaculation: implications for counseling concerning safe sexual practices. Seroconversion for HIV antibody occurred in two homosexual men who reported no anal intercourse for greater than or equal to 5 years and multiple episodes of receptive oral intercourse with ejaculation. Neither man reported intravenous drug use or receipt of blood products. The last antibody-negative specimen was also negative by the polymerase chain reaction and p24 antigen assays. All sexually active persons should be clearly counselled that receptive oral intercourse with ejaculation carries a potential risk of HIV transmission. ",1 307,"Early gastric cancer. Endoscopic diagnosis of depth of invasion. In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth. ",3 1577,"Time course of hemodynamic responses to sodium in elderly hypertensive patients. Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients. ",13 2363,"Combined insulin-sulfonylurea therapy in treatment of NIDDM. For the past few years, interest has focused on the combination of insulin and sulfonylurea in the search for effective treatments for non-insulin-dependent diabetes mellitus (NIDDM) patients who fail on oral hypoglycemic agents. Although several studies have demonstrated beneficial effects of such therapy in NIDDM patients, the average effect is small and is observed in only about half of the patients. However, there are several problems with most previous studies, including small sample size, selection of patients, and simultaneous use of several end points. First, residual beta-cell function has been considered to be a prerequisite for a beneficial effect of combination therapy. Therefore, most studies have failed to demonstrate improved glycemic control after adding sulfonylurea to insulin therapy in patients with insulin-dependent diabetes mellitus. Inclusion of patients with impaired beta-cell function will therefore attenuate the effect of combination therapy. Second, most studies have used glycemic control as an end point. Nevertheless, the insulin dose has been reduced by 20-30% to avoid hypoglycemia after adding sulfonylurea to insulin. Thus, the comparison has been made between treatments with a smaller insulin dose with sulfonylurea and a larger insulin dose without sulfonylurea. The patient most likely to benefit from combination therapy is slightly obese, has had NIDDM for a relatively short period, and has preserved beta-cell function. In such a patient, combined insulin-sulfonylurea therapy predominantly stimulates basal insulin secretion, resulting in more effective suppression of hepatic glucose production and lower fasting plasma glucose. The side effects are few, most notably more frequent but mild hypoglycemic reactions. ",17 1210,"Long-term potentiation of electrotonic coupling at mixed synapses. Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described. Here we report that at mixed synapses between sensory afferents and an identified reticulospinal neuron, the electrotonic coupling potential can be potentiated, as well as the chemically mediated excitatory postsynaptic potential, for a prolonged time period using a stimulation paradigm like that which produces long-term potentiation in hippocampus. The effect on coupling is due to an increase in gap-junctional conductance. Our data indicate that the potentiation of both synaptic components requires an increase in intracellular calcium, involves activation of NMDA (N-methyl-D-aspartate) receptors, and is specific to the tetanized pathway. ",9 691,"Can clinicians accurately assess esophageal dilation without fluoroscopy? This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation. ",5 1019,"Artificial restoration of voice. I: Experiments in phonatory control of the reinnervated canine larynx. Coordinated electronic pacing of implanted nerve pedicles into paralyzed laryngeal muscles has allowed selective dynamic control of abduction, adduction, and elongation of the vocal cords. Modifications of the original circuit in a cervical muscle model has added fine tuning to basic ""all-or-none"" pacing. Rehabilitation of phonation illustrated the sophisticated nature of voice and the need for restoration of fine tuning. Five mongrel dogs received nerve-muscle pedicles into the thyroarytenoideus, cricothyroideus, and posterior cricothyroideus after denervation of one hemilarynx. Following appropriate reinnervation time, pedicles and intact recurrent laryngeal nerves were injected with currents of variable amplitudes and pulse widths to achieve graded vocal fold control while air was blown intratracheally towards the glottic chink. Videoscopic and spectral analyses indicated that artificial phonation could be restored to frequencies measured in the normal state. These experiments suggested that rehabilitation of the impaired voice by servocontrol might eventually be feasible. ",8 2230,"Tolerance and dependence in neonates sedated with fentanyl during extracorporeal membrane oxygenation. We undertook a retrospective chart review of 37 neonates who received fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation (ECMO) between May 1986 and October 1988. We quantified the doses of all sedatives utilized, determined the incidence of neonatal abstinence syndrome (NAS), and identified risk factors associated with NAS. We determined peak fentanyl infusion rate, mean fentanyl infusion rate, total fentanyl dose, and duration of ECMO therapy. NAS was observed in 21 of 37 neonates (57%). In both the NAS and non-NAS neonates, mean infusion rate increased steadily during ECMO therapy, from a mean of 11.6 +/- 6.9 (SD) micrograms.kg-1.h-1 on day 1 to a mean of 52.5 +/- 19.4 (SD) micrograms.kg-1.h-1 by day 8. Total fentanyl dose and duration of ECMO were significantly greater in neonates with NAS. We found that neonates with a total dose greater than 1.6 mg/kg or an ECMO duration greater than 5 days had a significantly greater incidence of NAS (chi-squared test, P less than 0.01 and P less than 0.005; odds ratios = 7.0 and 13.9, respectively). With multiple logistic regression, ECMO duration was found to be the most powerful predictor of the occurrence of NAS. We also measured plasma fentanyl concentrations in a separate group of 5 neonates receiving fentanyl by continuous infusion for sedation. Fentanyl concentrations increased steadily during the period of infusion, suggesting the development of tolerance to the sedating effects. We conclude that continuous administration of fentanyl for sedation is associated with the uniform development of tolerance and a significant incidence of dependence. Alternative approaches to sedation should be investigated. ",15 3073,"Mechanical myocardial actuation during ventricular fibrillation improves tolerance to ischemia compared with cardiopulmonary bypass. Direct mechanical ventricular actuation (DMVA) is a unique non-blood-contacting biventricular assist device that provides circulatory support during ventricular fibrillation without demonstrating adverse effects on the myocardium. The purpose of this study was to assess the preservation of myocardial energy stores and myocardial responses to ischemia after circulatory support during ventricular fibrillation with direct mechanical ventricular actuation versus cardiopulmonary bypass. Twenty adult mongrel dogs were randomized to receive circulatory support with either cardiopulmonary bypass or direct mechanical ventricular actuation. After 4 hours of ventricular fibrillation, hearts were defibrillated and left ventricular transmural biopsies were obtained. Hearts were then excised and subjected to 90 minutes of normothermic total ischemia. Serial biopsies were obtained at 15-minute intervals to determine regional depletion of high energy phosphates. The time-to-peak ischemic contracture was recorded by using needle-tipped Millar catheters placed in the left ventricular endocardium, epicardium, septum, and right ventricle. Time-to-peak ischemic contracture of the endocardium (62.6 +/- 1.4 vs. 58.8 +/- 1.0 minutes, p less than 0.05) and septum (61.1 +/- 6.9 vs. 46.9 +/- 6.2 minutes, p less than 0.004) were significantly prolonged after direct mechanical ventricular actuation versus cardiopulmonary bypass, respectively. Similar trends were noted in the epicardium and right ventricular regions; however, these differences were not statistically significant. Left ventricular adenosine triphosphate (ATP) levels were better preserved after direct mechanical ventricular actuation (22 +/- 1.5 mumols/g dry wt) compared with cardiopulmonary bypass (17 +/- 1.9 mumols/g dry wt). The depletion of left ventricular endocardium ATP during normothermic ischemia was significantly delayed after direct mechanical ventricular actuation compared with cardiopulmonary bypass. ",22 249,"Limbal autograft reconstruction after conjunctival squamous cell carcinoma. Two patients who had squamous cell carcinoma with extensive limbal and corneal involvement were treated with surgery and cryotherapy. Rarely large areas of the cornea are involved by this tumor. Visual prognosis in such patients is poor. In these two patients, autologous limbal transplants were effective in restoring an excellent corneal surface and good visual function. This technique may be useful in the reconstruction of eyes with extensive neoplastic involvement of the corneoscleral limbus and cornea. ",3 1787,"Relative risks of left ventricular aneurysmectomy in patients with akinetic scars versus true dyskinetic aneurysms. From 1971 to 1988, 303 patients underwent left ventricular aneurysm resection. We analyzed preoperative and procedure-related variables to ascertain risk factors for surgery. A distinction was made between akinetic and dyskinetic aneurysms to assess potential relation with postoperative outcome. Indications for surgery were arrhythmia in 20 patients, congestive heart failure in 81, angina in 133, congestive heart failure and angina in 42, and other combinations in the remaining 27 patients. The left ventricular aneurysm was dyskinetic in 180 patients and akinetic in 121. Risk factors and surgical procedures were similar in both groups. Left ventricular ejection fraction was less than or equal to 30% in 98 patients. Coronary bypass grafting was performed in 269 patients, with an average of 2.3 grafts per patient. Mitral valve replacement, the most common concomitant procedure, was performed in 16 patients. Intra-aortic balloon assist was required postoperatively in 47 patients. Overall operative mortality was 13% (38 patients) and was due to low cardiac output in 23 patients and arrhythmia in 12 patients. Univariate and multivariate analyses related early mortality to New York Heart Association functional classification of heart failure, the predominant indications of arrhythmia or congestive heart failure, left ventricular ejection fraction less than or equal to 30%, the need for intra-aortic balloon support, and the excision of an akinetic (18%) rather than dyskinetic (8%) left ventricular aneurysm. Over a follow-up period averaging nearly 5 years, the actuarial survival at 5 years was 63% in the dyskinetic group and 51% in the akinetic group. ",13 98,"Bird attack on milk bottles: possible mode of transmission of Campylobacter jejuni to man A case-control study was carried out to test the hypothesis that the rise in the rate of Campylobacter jejuni infection in the Brigend area of South Wales during May was due to the consumption or handling of milk from bottles that had been attacked by birds. 32 of 36 cases meeting the case definition were interviewed, along with 2 controls per case, matched for age, sex, and area of residence. There were strong associations between campylobacter infection and doorstep delivery of milk bottles, a history of milk bottle attack by birds, milk bottle attack by birds during the week before illness, and consumption of milk from attacked bottles during the week before illness. There was a very strong dose-response relation between frequency of bird attack and illness. Controls with a history of milk bottle attack by birds were more likely than cases to have taken preventive measures against bird attack and consumption of contaminated milk. Although few people witnessed the attacks, the likely culprits are magpies (Pica pica) and jackdaws (Corvus monedula). ",0 1529,"Ultrasound-guided transcervical metroplasty. A new technique of metroplasty is described. The septum is divided with 4-mm endoscopic scissors introduced into the uterine cavity through the cervix. The whole procedure is monitored by a real-time ultrasound scanner. Twenty-four patients were operated on with this technique. No complication was encountered. Fifteen patients had third trimester deliveries or ongoing pregnancies. Among 12 patients who had suffered repetitive pregnancy losses, 11 desired pregnancy: 10 have been successfully pregnant beyond the second trimester (91.7%), 8 are delivered, and the living birth rate is 72.7%. These results equal those obtained after hysteroscopic metroplasty. The procedure is short, safe, requires no special equipment, and does not necessitate concomitant laparoscopy. ",12 2739,"Pulmonary functional impairment associated with pleural asbestos disease. Circumscribed and diffuse thickening. To define the pulmonary functional impairment associated with pleural asbestos signs (PAS), we compared 738 men with only circumscribed (plaques) or diffuse pleural thickening on chest roentgenograms but no irregular opacities by ILO pneumoconiosis criteria (1980) with 738 age-matched asbestos-exposed men without any roentgenographic signs and with 228 men unexposed to asbestos. All men were white. Spirometry and total thoracic gas volumes (TGV) were measured and expressed as percentage of predicted of white Michigan men who have been modeled for spirometric values thereby adjusting for height, age, and in current and ex-smokers for duration of smoking. Asbestos-exposed men who never smoked had reduced FEF75-85 (p less than 0.01) and increased TGV (p less than .0001) as compared with unexposed men. The 155 men with PAS who had never smoked had reduced flows (p less than .0001), FVC (p less than 0.0056), and TGV (p less than .0001) when compared with 155 age-matched asbestos-exposed men. The 325 asbestos-exposed current smokers with normal chest roentgenograms compared with unexposed smokers had reduced expiratory airflows (p less than 0.0001), reduced FEV1 (p less than 0.004), and increased TGV (p less than 0.0001). The 325 current smokers with PAS had additional air trapping that further reduced vital capacity. Thus, PAS were associated with significant pulmonary dysfunction in men who never smoked, and current and ex-smokers had additional dysfunction even after adjustment for duration of smoking. ",20 1966,"Functional chiral asymmetry in descending thoracic aorta To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion. ",13 2334,"Arthropathy of Down syndrome. A juvenile rheumatoid arthritis-like arthropathy has previously been documented in 12 patients with Down syndrome. An additional 9 patients are described and the literature is reviewed. It is unknown whether these patients have juvenile rheumatoid arthritis or a unique arthropathy in light of the genetic and immunologic abnormalities associated with Down syndrome. Most of the patients had a progressive course with polyarticular disease complicated by subluxations and a long lag time to diagnosis. The purpose of reporting these children is to increase awareness of this association and facilitate more appropriate and timely diagnosis of arthritis in Down syndrome patients. ",16 2228,"Results of a 25-year screening programme for neonatal hip instability. From 1962 to 1986, 117,256 neonates were screened for congenital dislocation of the hip (CDH). When the primary physical examination was performed by the junior paediatric staff there was a persistent late diagnosis rate of 0.5 per 1000 live births. When the primary examination was undertaken by experienced orthopaedic personnel (1982 to 1984) the late diagnosis rate fell and fewer infants were splinted. ",15 1464,"Prenatal diagnosis of congenital cytomegalovirus infection by virus isolation from amniotic fluid. Cytomegalovirus was isolated antenatally from the amniotic fluid of two pregnant women. In both cases prenatal diagnosis of the fetal virus infection aided the subsequent management of the mother and newborn infant. ",12 3288,"Postoperative bile duct strictures. Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs. ",22 1752,"Haemostatic changes during continuous oestradiol-progestogen treatment of postmenopausal women. To identify changes in haemostatic balance during continuous oestradiol-progestogen treatment, 60 postmenopausal women with climacteric complaints, mean age 55.4 years (range 44-68) were randomly allocated to receive one of four hormone replacement regimens for one year. All four formulations were administered daily and continuously, each contained 2 mg of 17 beta-oestradiol in combination with either norethisterone acetate, 1 mg (group A) or 0.5 mg (group B) or megestrol acetate, 5 mg (group C) or 2.5 mg (group D). No significant changes occurred during treatment within or between the groups in platelet count, fibrinogen and 2-antiplasmin. Activated partial thromboplastin time was shortened (P less than 0.05) in group D and a decline in factor VII activity and antigen (P less than 0.001) and in ATIII activity (P less than 0.05) was noted in group A. Protein C tended to decline in all treatment groups but statistically significant changes were noted only in groups A and C. Two women developed crural thrombosis during the observation period. ",13 902,"Effects of albuterol and procaterol on exercise-induced asthma. Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well. ",7 3179,"Comparison of structure, mechanical properties, and functions of lumbar spinal ligaments. The organization of collagen in the supraspinous, interspinous, and longitudinal ligaments, as well as the ligamenta flava, in lumbar spines from human cadavers has been investigated by polarized light microscopy, scanning electron microscopy, and x-ray diffraction. These experiments were performed on ligaments in situ, with their bony attachments undisturbed, and on excised ligaments at a range of applied strains. Results were related to the composition (investigated by standard histologic techniques) and gross structures (investigated by light microscopy) of the ligaments. More importantly, the results were related to the mechanical properties of the ligaments, which include stiffness, failure conditions, stress relaxation, and hysteresis. Where necessary, results were supplemented by or compared with those obtained from pig ligaments. Mechanical properties were related to postural changes by ligament strains induced in cadaveric specimens, using results from the literature. Thus, ligament structures could be related to their physiologic functions. ",22 2487,"Acylation-stimulatory activity in hyperapobetalipoproteinemic fibroblasts: enhanced cholesterol esterification with another serum basic protein, BP II. Cultured fibroblasts from patients with familial hyperapobetalipoproteinemia (hyperapoB) were used to determine if a defect in lipid metabolism was present. Three basic proteins (BP I, BP II, and BP III) were isolated from normal human serum by preparative isoelectric focusing, preparative SDS/PAGE, and reversed-phase HPLC. The Mr and pI values of these proteins were 14,000 and 9.10 for BP I, 27,500 and 8.48 for BP II, and 55,000 and 8.73 for BP III. These proteins differed significantly in their content of arginine, cysteine, proline, histidine, serine, and methionine. BP I appears to be the same protein as acylation-stimulating protein, but BP II and BP III appeared different from acylation-stimulating protein and other lipid carrier proteins. BP I, BP II, and BP III stimulated the incorporation of [14C]oleate into lipid esters in normal fibroblasts, an effect that was time and concentration dependent. In hyperapoB cells, BP II markedly increased (up to 9-fold) the incorporation of [14C]oleate into cholesteryl ester compared with that in normal cells; in addition, there was a 50% decrease in the stimulation of triglyceride acylation and cholesterol esterification with BP I. No difference between normal and hyperapoB cells was observed with BP III. In summary, the identification of another serum basic protein, BP II, led to the elucidation of another cellular defect in hyperapoB fibroblasts, enhanced cholesterol esterification, which may be related to the precocious atherosclerosis and abnormal lipoprotein metabolism seen in hyperapoB. ",17 2903,"Excess injury mortality among children in the United States: comparison of recent international statistics. Using data from the National Center for Health Statistics and the World Health Organization, child injury death rates in the US were compared to those of Canada, England and Wales, France, Netherlands, and Norway. Except for the 1981 Canadian figure, overall US childhood injury mortality was greater than childhood injury mortality rates of all countries studied during each year from 1980 to 1986. Injury mortality steadily declined in most other countries, whereas the US rate appears to be increasing. Attention to specific causes reveals that much of the difference is explained by motor vehicle injuries and homicide, but in every childhood age group US death rates due to drowning, firearms, homicide, poisoning, and fire are among the highest. Excess US injury mortality is largely attributable to deaths among children younger than 5 and older than 14 years of age, the most vulnerable groups in all countries. Especially high rates among US minorities account for little of the observed differences; for many injuries, the mortality rate of US nonblacks is several times those reported by the comparison nations. Behavioral strategies are inadequate to deal with excess death rates of this magnitude. Limiting exposure through regulation of handguns, greater use of public transportation, and affordable and accessible day care are among the measures that should be implemented. ",20 3183,"Spreading depression-like depolarization and selective vulnerability of neurons. A brief review. If oxygen is withdrawn from rat hippocampal slices, a spreading depression-like response occurs earlier and is of larger amplitude in the CA1 area than in the dentate gyrus. After reoxygenation, recovery of synaptic transmission correlates inversely with the time spent in spreading depression. Recovery occurs more frequently in dentate gyrus than in CA1. Chlorpromazine and the gangliosides GM1 and AGF2 promote recovery from hypoxic depression of synaptic transmission in CA1. Prevention of irreversible loss of function correlates closely with a shortening of the time spent in spreading depression. If Ca2+ is withdrawn before hypoxia, then synaptic function recovers upon restoration of oxygen and [Ca2+]o, despite prolonged spreading depression. When spreading depression lasting more than 6-9 minutes is induced in fully oxygenated slices by superfusion with high-K+ solution, then transient recovery is followed by long-lasting loss of synaptic function. In intact brain of anesthetized rats, synaptic transmission in CA1 recovers after spreading depression-like depolarization lasting more than 30 minutes, but is lost irreversibly after 60 minutes. We conclude that entry of Ca2+ into neurons caused by spreading depression-like depolarization is important in the selective vulnerability of neurons; the duration of depolarization is critical to cell survival; and in the presence of a normal blood supply, neurons resist protracted spreading depression-like depolarization. ",22 1714,"Long-term amiodarone administration protects against global myocardial ischemia. Reports on the effects of amiodarone on cardiac function have been variable. This study addresses the effect of long-term amiodarone administration on recovery of cardiac function after a period of global ischemia. Normotensive and spontaneously hypertensive rats were used. Normotensive rats (n = 6) received 240 mg/kg amiodarone for 4 weeks, for a total of 72 +/- 3 mg. Hypertensive rats (n = 6) received 500 mg/kg amiodarone for 4 weeks, for a total of 116 +/- 5 mg. Final myocardial concentrations of amiodarone and desethylamiodarone were 1.85 +/- 1.75 and 0.50 +/- 0.61 micrograms/g wet weight for the normotensive rats and 1.30 +/- 0.58 and 0.31 +/- 0.17 micrograms/g for the hypertensive rats (p = nonsignificant). Equal numbers of controls received sterile saline solution for 4 weeks. The hearts were excised and perfused in a Langendorff apparatus. The results indicate that, after 15 minutes of normothermic ischemia, hearts treated with this relatively low dose of amiodarone recovered a greater percentage of preischemic work (97% +/- 13%) as compared with the controls (76% +/- 17%) (p less than 0.005). ",13 3286,"Filler DNA is associated with spontaneous deletions in maize. We have determined the structure of five spontaneous deletions within the maize waxy (Wx) gene. Of these, four were found in spontaneous wx mutants (wx-B, wx-B1, wx-B6, wx-C4) and include exon sequences; the fifth is restricted to an intron and represents a restriction fragment length polymorphism of a nonmutant allele (Wx-W23). The deletions, which range in size from 60 to 980 base pairs (bp), cluster in a G+C-rich region of approximately 1000 bp that is capable of forming stable secondary structures. Most striking is our finding that all of the alleles have DNA insertions (filler DNA) of 1-131 bp between the deletion endpoints. For three of the five deletions, the filler DNA and sequences at the deletion termini appear to be derived from sequences near one deletion endpoint. A previously reported spontaneous deletion of the maize bronze gene (bz-R) also contains filler DNA. The association of filler DNA with maize deletion endpoints contrasts dramatically with the rarity of similar events in animal germ-line and bacterial mutations. ",22 2317,"Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis. Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued. ",16 1160,"Substantia nigra: a site of action of muscle relaxant drugs. Sites of action of centrally active muscle relaxant drugs are not well defined. Clinical experience with such drugs suggests that the spinal cord may be one of the important regions from which pathologically increased muscle tone may be relieved. Supraspinal centers that may also be involved in the expression of muscle relaxant action have not yet been defined. We report here that microinjections of therapeutically relevant muscle relaxants into the midbrain tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra is the region from which midazolam, baclofen, and tizanidine (drugs used clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7-phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs active in animal models of spasticity), reduce muscle tone in genetically spastic rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs are topographically restricted to the substantia nigra pars reticulata and are receptor specific. These observations disclose a previously unknown function of the substantia nigra in mediating muscle relaxation. ",9 2630,"Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection. OBJECTIVE: To determine whether a short course of 2',3'-dideoxycytidine (ddC) could provide safe antiretroviral activity in children with symptomatic human immunodeficiency virus infection and whether it could be used with azidothymidine (AZT, zidovudine). The goal was to maintain uninterrupted antiretroviral therapy while sparing AZT-related myelosuppression and ddC-related neuropathy. METHODS: In a pilot study, we evaluated four dosage levels of ddC--0.015, 0.02, 0.03, and 0.04 mg/kg, given orally every 6 hours--in 15 children between 6 months and 13 years of age with Centers for Disease Control P2 (i.e., symptomatic) human immunodeficiency virus infection. Thirteen patients had not had any prior antiretroviral therapy; two patients had received and benefited from AZT, but dose-limiting neutropenia had developed. At each dosage level, ddC was given for 8 consecutive weeks and then stopped. After a 30-day rest, a schedule of ddC for 1 week was followed by 3 weeks of AZT therapy (180 mg/m2 every 6 hours); this alternating schedule was repeated for as long as tolerated. Age-appropriate psychometric testing was performed before the start of ddC therapy and after 8 weeks. RESULTS: During the 8 weeks of therapy with ddC alone, no neutropenia or anemia was observed; 6 of 9 patients had decreases in p24 antigen levels, and 8 of 15 had an increased CD4 cell count. At the 0.04 mg/kg level, a rash developed in three patients; mild mouth sores developed in 9 of 15 patients. On the alternating ddC/AZT schedule, no neuropathy was observed. CONCLUSIONS: 2',3'-Dideoxycytidine has antiretroviral activity in some children and appears to be safe for short intervals. Longer courses of ddC at lower dosage levels, and schedules integrating ddC into combination regimens, deserve to be explored. ",19 2763,"Wounding effects of the AK-47 rifle used by Patrick Purdy in the Stockton, California, schoolyard shooting of January 17, 1989. The limited disruption produced in tissue simulant by the rifle and bullets used in the Stockton, California, schoolyard shooting is entirely consistent with the autopsy reports on the five children who died of their wounds. It is also entirely consistent with well-documented battlefield studies and with previous tissue-simulant studies from many laboratories. It is inconsistent with many exaggerated accounts of assault-rifle wounding effects described by the media in the aftermath of this incident. This information should be documented for the historical record. However, the critical reason for correcting the misconceptions produced by media reaction to this incident is to prevent inappropriate gunshot-wound treatment. ",20 3347,"Evaluation of 13C-urea breath test in the detection of Helicobacter pylori and in monitoring the effect of tripotassium dicitratobismuthate in non-ulcer dyspepsia Sixty nine patients with non-ulcer dyspepsia have been studied with endoscopy, biopsy, quick urease (CLO) test, Helicobacter pylori culture, and the 13C-urea breath test before and after treatment with tripotassium dicitratobismuthane (DeNol) two tablets twice daily for four weeks. Symptoms of non-ulcer dyspepsia were recorded using a standard questionnaire. Using H pylori culture as the gold standard, the sensitivity of the 13C-urea breath test was 90%, the specificity 98.6%, and the accuracy 94.8% with a positive predictive value of 98.2% and a negative predictive value of 92.5%. Conversion rate from H pylori positive to negative status after treatment with tripotassium dicitratobismuthate was 17.9%. Symptoms of non-ulcer dyspepsia improved appreciably after treatment irrespective of H pylori status. The 13C-urea breath test is an accurate research tool suitable for serial testing and population surveys. ",22 360,"Laparoscopic management of ovarian cysts. One hundred two women with ovarian cysts were managed laparoscopically over a 13-year period. Thirteen were treated with laparoscopic inspection followed by laparotomy, 6 with laparoscopic fine needle aspiration followed by laparotomy and 83 with laparoscopic fenestration and biopsy, with or without coagulation or removal of the cyst lining. Satisfactory results were noted in patients treated completely with laparoscopy. Only 1 of 56 functional, simple or paraovarian cysts recurred during the study period. Two of the 18 ovarian endometriomas treated with fenestration and coagulation or removal of the lining recurred, whereas 8 of 9 such lesions recurred when treated with fenestration alone. There were no surgical complications. ",3 93,"Absence of significant bacteremia during urinary catheter manipulation in patients with chronic indwelling catheters. The objective of this study was to quantify the microorganisms present in blood at urinary catheter removal and at reinsertion in patients with chronic indwelling urinary catheters. This was a prospective study during a 4-month period at a university-affiliated geriatric medical center. Our subjects were 33 patients with chronic indwelling urinary catheters and positive urinary cultures; the urinary catheter was usually changed once a month. A peripheral vein line was used for blood withdrawal and urinary cultures and quantitative blood cultures (Isolator) were performed during and shortly after urinary catheter removal and insertion. All patients had significant bacteriuria (greater than 10(5) cfu/mL) with an average of 2.3 microorganisms. Among the 46 sequential quantitative blood cultures performed, only two patients had bacteremia from the urinary source and at a very low concentration; one patient had 0.13 cfu/mL Str. faecalis in blood 5 minutes after removal of the urinary catheter, and the other 0.1 cfu/mL Proteus mirabilis 5 minutes after reinsertion of a new urinary catheter. None of the patients had any subjective or objective clinical problem during the 36 hours after the urinary manipulation. Clinical symptoms and bacteremia are rare events, and prophylactic antibiotics do not appear necessary during urinary catheter removal and reinsertion in elderly institutionalized patients. Further studies are necessary to identify risk factors in the rare instances of patients with bacteremia. ",0 1777,"Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables. To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available. ",13 1325,"Treatment of renal calculi in the elderly. The management of renal calculi in the geriatric patient population poses some unique problems that include anesthetic risks, underlying medical disease, and general risk/benefit concerns. A variety of relatively noninvasive procedures are available, including extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrostolithotomy (PCNL). A practical management plan is presented that is based primarily on stone size and takes into consideration problems unique to the elderly patient. ",11 2049,"Compensation and overcompensation in congestive heart failure. The compensatory mechanisms that develop in response to heart failure have been well defined. In this review, it is argued that each compensatory mechanism leads to overcompensation and that there is no way to distinguish between the beneficial aspects of the former and the harmful effects of the latter. Therapeutic agents that maintain rather than decrease blood pressure might perhaps be more beneficial because of the crucial role of hypotension in initiating both compensation and overcompensation. ",13 1721,"Angioscopy for intraoperative management of thromboembolectomy. Our experience with angioscopy suggests that direct visualization of the arterial lumen during thromboembolectomy procedures would provide a more reliable method of assessing luminal morphologic characteristics than angiography alone. We inspected 32 grafts (seven aortobifemoral, 18 infrainguinal bypass, and seven dialysis access fistula grafts) in 32 patients. Thirty-one patients had thrombotic events and one patient had an acute embolus. Angioscopy following standard catheter thrombectomy revealed significant amounts of retained thrombus or neointima in all thrombectomies. Angioscopic information from 18 patients with an infrainguinal bypass graft led to graft revision in six cases and placement of a new graft in 10 cases. One graft limb was replaced in seven aortobifemoral grafts, and multiple repeated thrombectomies were employed to extract debris in the remaining six cases. Repeated graft thrombectomy was also beneficial in dialysis access fistulas. Angioscopy allowed us to omit the completion angiogram and led to an improved technical result. We conclude that angioscopy is useful during thromboembolectomy procedures. ",13 2876,"The radial forearm flap for reconstruction of the upper extremity. The radial forearm flap, owing to its good-caliber arteries of long length and equally well distributed venous system, has proved very reliable. It has not only earned its place and recognition in reconstructive hand surgery, but also has emerged as a workhorse for the microvascular surgeon. We have used 14 radial forearm flaps for upper extremity reconstruction, and we present herein our experience. The technique of extracorporeal tissue transfer, which has been published elsewhere, was used in two patients and is detailed. Four representative patients are presented. ",20 721,"Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat. ",5 2989,"Gastrointestinal bleeding in a 15 month old male. A presentation of Munchausen's syndrome by proxy. Munchausen's syndrome by Proxy is a well-described entity that may not always be immediately considered in a complicated case. We describe this syndrome being portrayed through the guise of gastrointestinal bleeding in a 15 month old male and discuss not only the difficulty involved in solidifying this diagnosis but also the consequences that may occur should this diagnosis not be entertained. Failure to diagnose Munchausen's syndrome by proxy often results from failure to consider the diagnosis. These cases frequently have specific characteristics that allow seasoned clinicians to suspect the diagnosis. Once the diagnosis is considered, it is crucial to take steps to protect not only the index patient but also siblings who not infrequently are also recipients of this life threatening form of child abuse. ",22 1380,"Angiotensin II receptor regulation in anti-glomerular basement membrane nephritis. The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody. ",11 384,"Brain stem and spinal metastases of supratentorial glioblastoma multiforme: a clinical series. Although the spread of supratentorial glioblastoma multiforme to the brain stem and spine has been extensively described in published autopsy series, information on the diagnosis, treatment, and subsequent clinical course of patients manifesting symptoms of glioblastomatous dissemination ante mortem remains scant. We report a series of 11 patients having the signs and symptoms of neuraxis dissemination of supratentorial glioblastoma multiforme. All patients had radiographic documentation of metastases by either contrast-enhanced myelograms or enhanced magnetic resonance imaging scans. Ten presented with spinal involvement, whereas one presented with lower cranial neuropathies secondary to diffuse involvement of the basal cisterns. The mean age of the patients was 38.5 years, and the mean time interval between diagnosis of intracranial disease and diagnosis of metastases was 14.1 months. After diagnosis of tumor spread, subsequent mean survival time was 2.8 months. All patients received additional radiotherapy to the areas of metastasis, but the clinical response to radiotherapy was quite poor. This study confirms previous reports in the literature suggesting that metastases occur in younger patients and in patients with extended survival. The findings suggest that the relatively infrequent clinical incidence of the symptomatic spread of glioblastoma multiforme, as compared with the frequent incidental discovery of such spread at autopsy, may be the result of the limited survival of the affected patients, and not due to the biology of the tumor. ",3 3192,"Primary abscess of the omentum. A 65-yr-old man presented with upper abdominal pain and fever due to a primary abscess of the omentum. The finding of microscopic-size foreign particles within the abscess raised the possibility of antecedent clinically silent perforation of the bowel or appendix. Surgical resection and antibiotic therapy were curative. ",22 2520,"Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. Preproparathyroid hormone (preproPTH) gene mutation has been proposed as a cause of familial isolated hypoparathyroidism (FIH). We cloned the preproPTH alleles of a patient with autosomal dominant FIH and sequenced the coding regions, 5' flanking regions, and splice junctions. The putatively abnormal (based on previous linkage studies) allele differed from the other allele's normal sequence at only one nucleotide. This T to C point mutation changes the codon for position 18 of the 31 amino acid prepro sequence from cysteine to arginine, disrupting the hydrophobic core of the signal sequence. Because the hydrophobic core is required by secreted proteins for efficient translocation across the endoplasmic reticulum, the mutant protein is likely to be inefficiently processed. Indeed, in vitro studies demonstrated dramatically impaired processing of the mutant preproPTH to proPTH. In summary, we observed a point mutation in the signal peptide-encoding region of a preproPTH gene in one FIH kindred and demonstrated a functional defect caused by the mutation. Mutation of the signal sequence constitutes a novel pathophysiologic mechanism in man, and further study may yield important insights both into this form of hormone deficiency and into the role of signal sequences in human physiology. ",18 2394,"Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. To clarify its physiologic role, alkaline phosphatase (ALP) was examined in normal skin fibroblasts and was shown to be the tissue-nonspecific (TNS) isoenzyme type (as evidenced by heat and inhibition profiles) and to be active toward millimolar concentrations of the putative natural substrates phosphoethanolamine (PEA) and pyridoxal-5'-phosphate (PLP). Fibroblast ALP has a low-affinity activity, with a distinctly alkaline pH optimum (9.3), toward 4-methylumbelliferyl phosphate (4-MUP), PEA, and PLP but a more physiologic pH optimum (8.3) toward physiologic concentrations (micromolar) of PEA and PLP. Normal fibroblast ALP is linked to the outside of the plasma membrane, since in intact cell monolayers (1) dephosphorylation rates of the membrane-impermeable substrates PEA and PLP in the medium at physiologic pH were similar to those observed with disrupted cell monolayers, (2) brief exposure to acidic medium resulted in greater than 90% inactivation of the total ALP activity, and (3) digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) released about 80% of the ALP activity. Hypophosphatasia fibroblasts were markedly deficient (2%-5% control values) in alkaline and physiologic ALP activity when 4-MUP, PLP, and PEA were used as substrate. The majority of the detectable ALP activity, however, appeared to be properly lipid anchored in ecto-orientation. Thus, our findings of genetic deficiency of PEA- and PLP-phosphatase activity in hypophosphatasia fibroblasts, as well as our biochemical findings, indicate that TNS-ALP acts physiologically as a lipid-anchored PEA and PLP ectophosphatase. ",17 2094,"Pulmonary artery counterpulsation with a skeletal muscle power source. We evaluated the feasibility of using skeletal muscle (SM) to provide pulmonary artery (PA) counterpulsation in an acute pulmonary hypertension (PHT) model. PA counterpulsation was achieved in six dogs with a dual chambered pump powered by the latissimus dorsi muscle. A rate-responsive stimulator was used to make the muscle contract in counterpulsation. Graded PHT was induced by infusing 150 microns glass beads into the PA, while RV and PA pressures were monitored. With PA pressures ranging from 19/10 to 115/62 mmHg, effective counterpulsation was observed. The degree of counterpulsation was influenced by the extent of PHT induced, with the amount of RV tension-time index (TTI) unloading correlated with the level of PA systole (r = 0.92). Therefore, results were divided into two groups (Group 1: PA systole less than or equal to 40 mmHg, and Group 2: PA systole greater than 40 mmHg). In Group 1, RV TTI decreased from 11.29 +/- 0.76 to 9.99 +/- 0.72 mmHg.sec, PA diastole increased from 20 +/- 2.3 to 31 +/- 3.0 mmHg, and PA mean increased from 24 +/- 2.2 to 2.9 +/- 2.2 mmHg (all p less than 0.05). In Group 2, RV TT1 decreased from 15.12 +/- 1.83 to 10.99 +/- 0.90 mmHg.sec, PA diastole increased from 41 +/- 3.5 to 64 +/- 6.2 mmHg, and PA mean increased from 49 +/- 4.8 to 55 +/- 5.7 mmHg (all p less than 0.05). ",13 1277,"Graves' ophthalmopathy. Correlation of saccadic eye movements with age, presence of optic neuropathy, and extraocular muscle volume. Quantitative infrared oculography was used to record saccadic eye movements of 49 patients with Graves' ophthalmopathy. Peak saccadic velocities were decreased in those patients who developed or presented with optic neuropathy. This effect was more pronounced for larger eye movements. Peak saccadic velocity also decreased as total extraocular muscle volume and limitation of ocular motility increased. For any given extraocular muscle volume, peak saccadic velocity was 40 degrees/s slower in patients 40 years or older than in younger patients. The relationship between velocity and motility limitation was most pronounced for intermediate muscle volumes (8% to 15% of total orbital volume). Saccadic velocities in those patients with optic nerve compression often improved following treatment. This study demonstrated that eye movement recording was a useful adjunct in evaluation of patients with Graves' ophthalmopathy. Furthermore, age-related lowering of peak saccadic velocities implicated changes of extraocular muscle structure as a factor in the development of optic neuropathy. ",10 2466,"Amniotic fluid insulin concentration as a predictor of obesity. Longitudinal correlations were obtained between amniotic fluid insulin concentration at 32 to 38 weeks' gestation and anthropometric characteristics at the age of 6 years in 56 children of diabetic mothers. The prospective studies indicated that at the age of 6 years, as at birth, the greatest increase in weight in relation to height (relative obesity) was seen in children who experienced the greatest exposures to insulin in the uterus (as judged by amniotic fluid insulin concentration). Significant correlations between amniotic fluid insulin and relative obesity at the age of 6 years were found after adjustment for maternal obesity and macrosomia at birth. The highest amniotic fluid insulin values are clustered in the subgroup of 14 children who were obviously obese by the age of 6 years. These findings are consistent with the hypothesis that there is an association between anthropometric development and intrauterine metabolism, and suggest that premature and excessive exposure to insulin during gestation may predispose to obesity in childhood. The amniotic fluid insulin concentration may predict this eventuality. ",17 903,"Exercise-induced biphasic responses and methacholine reactivity in asthma. Biphasic (early and late) asthmatic responses to exercise occurred in seven of 43 children with reproducible exercise-induced asthma. As biphasic allergen-induced asthma is associated with a prolonged increase in nonspecific bronchial hyperreactivity, this effect was not sought in the 43 asthmatic children. There was no significant change in methacholine PD20 FEV1 before and after exercise challenge, either in children who had early, or early and late, exercise responses. Late reactions after allergen exposure are likely to be of considerable clinical significance in relation to the enhancement of bronchial responsiveness. It is reassuring that this is not the case for exercise challenge, as it would have major implications in relation to the recommendations that asthmatics should participate in normal activities and even in training programs. Furthermore, it suggests that there are differences between the pathophysiology of asthma induced by exercise and that produced by allergens. ",7 286,"Distribution of immunoglobulins and secretory component in gastric cancer of the aged. The secretory immune system plays an important role in the local humoral immunity of the gastrointestinal tract. In order to evaluate humoral immunity in gastric cancer, distribution of immunoglobulins (Ig) and secretory component was immunohistochemically studied in 74 early and 15 advanced primary gastric cancers. In non-cancerous gastric mucosa, IgA and IgM, and secretory component were mainly identified in the cytoplasm of the intestinal metaplasia. In early gastric cancer of well-differentiated type, the localization of IgA and IgM, and secretory component was similar to that of intestinal metaplasia. In advanced gastric cancer, they were faintly observed and showed low positivity. The number of Ig-containing cells infiltrating cancerous stroma was enumerated. Immunoglobulin A-containing cells were dominant in the stroma of early gastric cancer. On the other hand, there were few Ig-containing cells in the stroma of advanced gastric cancer, and the number of IgA-containing and IgM-containing cells was also decreased. These results suggest that local humoral immunity is suppressed in gastric cancer, especially in advanced gastric cancer. ",3 2180,"Intravenous immunoglobulin in virus associated haemophagocytic syndrome. A 1 year old boy with virus associated haemophagocytic syndrome caused by cytomegalovirus infection is described. Persistent severe thrombocytopenia responded to repeated intravenous infusions of immunoglobulin. ",14 1945,"Transtelephonic defibrillation. STUDY OBJECTIVES: This study was undertaken to assess the safety and reliability of a device for transtelephonic defibrillation. DESIGN: The transtelephonic system consists of a patient unit and a base station. The patient unit contains a monitor-defibrillator, electrode pads, microphone, microprocessor, and DC defibrillator. The base station comprises a control panel, computer, and ECG display. SETTING: Fifteen patients who were treated in our emergency department for cardiac arrest were placed on patient units that activated our base station in a remote location within the ED. TYPE OF PARTICIPANTS: Thirteen patients were treated for ventricular fibrillation, and two patients were treated for ventricular tachycardia. INTERVENTIONS: Thirty-one shocks were delivered transtelephonically. MEASUREMENTS AND MAIN RESULTS: In all cases, voice and ECG transmission were established without difficulty. CONCLUSIONS: We conclude that this system represents a safe and reliable method for the treatment of ventricular fibrillation, and we advocate additional use to study the prehospital applications of transtelephonic defibrillation. ",13 2492,"Health of homeless children and housed, poor children. Homeless children in families are increasing in numbers across the country and have been noted to have frequent health problems. The health status of homeless children was assessed on multiple dimensions through parental report in a survey conducted with 196 homeless families in 10 shelters in Los Angeles and 194 housed poor families after March 1987 through January 1988. During the month before the survey, the homeless and housed poor children experienced high rates of illness symptoms, disability, and bed days. Homeless and housed poor children were frequently rated by their parents to be in fair or poor health (17% vs 13%, P = .14). Homeless children, however, were reported to have more behavior problems and school failure [30% vs 18%, P = .06] than housed poor children. Homeless children also had high rates of other health problems such as developmental delay (9%) and overweight (13%). The diets of homeless children were frequently imbalanced, dependent on food from ""fast-food"" restaurants, and characterized by repeated periods of deprivation. Family problems were more common among homeless families, especially among single-parent homeless families compared with single-parent housed families (spousal abuse, 68% vs 41%, P less than .01; parental drug and alcohol abuse, 60% vs 39%, P less than .01). It is concluded that homeless children have significant child behavior and developmental problems and disorders of nutrition and growth, which are associated with multiple risk factors in their environment. ",17 2015,"Baroreflex control of renal sympathetic nerve activity is potentiated at early phase of two-kidney, one-clip Goldblatt hypertension in conscious rabbits. Conscious normotensive and two-kidney, one-clip Goldblatt hypertensive rabbits were studied to determine the sensitivity of the arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate. The relations of the mean arterial pressure-RSNA and mean arterial pressure-heart rate were examined over a wide range of blood pressures produced by infusions of phenylephrine and nitroglycerin. The maximum slope obtained by logistic function analysis was considered to represent the baroreflex sensitivity. In the early hypertensive group (n = 8; mean arterial pressure +/- SEM, 88 +/- 2 mm Hg) on day 5 after renal clip application, the maximum slope of the mean arterial pressure-RSNA relation was -11.3 +/- 1.2, which was significantly greater than that of the sham normotensive group (-6.9 +/- 0.3, p less than 0.05). The maximum slope (-4.3 +/- 0.2) of the mean arterial pressure-RSNA relation in the late hypertensive group (n = 8; mean arterial pressure, 96 +/- 3 mm Hg) on day 21 after renal clipping was significantly smaller than that of another sham group (-7.2 +/- 0.2, p less than 0.05). In contrast to these changes in the baroreflex control of RSNA, the control of heart rate was attenuated according to the magnitude of mean arterial pressure. To elucidate the mechanisms underlying the potentiated baroreflex, the effects of endogenous neuropeptides were investigated. First, plasma concentrations of angiotensin II and arginine vasopressin that are known to affect the baroreflex were determined. Plasma concentrations of vasopressin (3.1 +/- 0.6 pg/ml) as well as of angiotensin II (34 +/- 7 pg/ml) were increased in the early hypertensive group, and the plasma vasopressin returned to a similar level to the sham group in the late hypertensive group (1.3 +/- 0.4 pg/ml). Second, to study endogenous effects of these neuropeptides on the baroreflex, the maximum slopes of the baroreflex curves during infusions of antagonists for the peptides were determined in the early hypertensive group. The maximum slope of mean arterial pressure-RSNA during intravertebral arterial [Sar1, Ala8]-angiotensin II (-16.4 +/- 1.5) was significantly greater (p less than 0.05), whereas the maximum slope during intravertebral arterial infusion of d(CH2)5Tyr(Me)arginine vasopressin (-4.7 +/- 0.5) was significantly smaller (p less than 0.05) than that during vehicle infusion (-11.3 +/- 1.2).(ABSTRACT TRUNCATED AT 400 WORDS). ",13 1900,"Transesophageal echocardiography in the awake elderly patient: its role in the clinical decision-making process. To assess the impact on the management and safety of transesophageal echocardiography (TEE) in the elderly population, the results and limitations of this technique were retrospectively analyzed in 88 patients. TEE was indicated whenever the transthoracic approach was not diagnostic or was inconsistent with the clinical setting. The most frequent clinical indications were to investigate the source of emboli, assess valvular regurgitation, and identify valvular vegetations. In 72 patients (82%) TEE significantly influenced management decisions. In selected patients TEE avoided the use of more invasive diagnostic procedures. Adverse effects included occasional premature atrial or ventricular beats (11 patients), sinus bradycardia (six patients), and protracted nausea (one patient). We conclude that in elderly patients with cardiovascular diseases, TEE plays a significant role in the decision-making process without adding a significant risk. ",13 1347,"Psychological assessment and follow-up after in vitro fertilization: assessing the impact of failure. The present study was conducted to assess the immediate psychological impact of failed in vitro fertilization (IVF). Emotional status and marital functioning were also examined pre-IVF, and both demographic information and psychological test scores were evaluated as predictors of reaction to treatment failure. After a failed first cycle, both males and females showed significant increases in anxiety and depressive symptoms. Although group means were not clinically elevated and most participants were coping adequately, the prevalence of both mild and moderate depression increased substantially, particularly among women. In addition, women without children were a subgroup particularly vulnerable to the stress of failure. Predisposition towards anxiety, pre-IVF depressive symptoms, and fertility history were the most important predictors of emotional response. Treatment implications of these findings were discussed. ",11 2046,"Epidemiologic aspects of heart failure. The prevalence of heart failure in Northwest London is 0.4%, a lower figure than that quoted for the United States. Heart failure is a common reason (5%) for medical admission to the hospital in the London area. The problem of heart failure is predominantly in persons over 65 years. Coronary artery disease is the most frequent cause, and hypertension is relatively uncommon. In those patients admitted to the hospital, the prognosis is poor. ",13 3019,"Urothelial grafts in mice. Mouse bladder epithelium has been successfully transplanted to the bladders of syngeneic mice and has survived for at least twenty weeks. The fate of the transplanted tissue was followed using a fluorescein label. The recipient bladders were prepared by stripping the urothelium either by a surgical or a chemical method. The possibility of adopting a comparable technique for the treatment of early bladder cancer in man is discussed. ",22 1780,"Excretion of thromboxane A2 and prostacyclin metabolites before and after exercise testing in patients with and without signs of ischemic heart disease. We addressed the hypothesis that platelets are not activated in association with effort-induced myocardial ischemia in stable coronary disease. Seventy-two patients undergoing a diagnostic bicycle exercise test were stratified according to the development of chest pain (yes/no, 33/39) and of exercise-induced ST-segment depression of at least 200 microV in the electrocardiogram (yes/no, 12/60). Noninvasive indexes of platelet activation and of platelet/vessel wall interaction (urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 [Tx-M] and prostacyclin [PGI-M], respectively) were analyzed in samples collected in the basal state and after the test. Basal Tx-M and PGI-M did not differ in patients with (236 +/- 35 and 131 +/- 22 pg/mg creatinine, respectively) and without (185 +/- 16 and 101 +/- 13 pg/mg creatinine, respectively) chest pain, or in those with (178 +/- 45 and 162 +/- 41 pg/mg, respectively) and without (216 +/- 22 and 104 +/- 11 pg/mg, respectively) ST-segment depression during the test. Patients without chest pain or without ST-segment depression moderately increased (p less than 0.05) their urinary Tx-M (by 21% and 13%, respectively) and PGI-M (by 28% and 23%, respectively) after exercise. No significant increases were observed in those developing chest pain or ST depression during exercise. These data indicate that effort-induced myocardial ischemia is not associated with an increase in platelet activation or platelet/vessel wall interaction in patients with stable coronary disease. ",13 226,"An unusual epidural, vascular spinal lipoma in a 3-year-old child: a case report and review of the literature. Epidural lipomas are usually benign tumors affecting the spinal cord. We report the unusual presentation of a cervicothoracic spinal lipoma associated with a cervical dysraphism in a young boy. Diagnostic options using magnetic resonance imaging and gadolinium-diethylenetriaminepentaacetic acid are discussed as a pathway to early diagnosis of these and other occult spinal lesions. ",3 2525,"Structural abnormality in LDL from diabetic patients as revealed by resonance Raman spectroscopy. Resonance Raman spectra of low-density lipoprotein (LDL) isolated from the plasma of diabetic patients (age range 13-77 yr, mean age 37 yr) and age- and sex-matched control subjects were recorded in the 1000- to 1600-cm-1 region as a function of temperature (0-50 degrees C). Both nondiabetic and diabetic LDL yield spectra characterized by two major bands near 1160 and 1530 cm-1 due to the carotenoid component of lipoproteins. The relative intensity of 1530- and 1160-cm-1 bands, assigned to -C = C- and = C-C = stretchings, respectively, i.e., I1530-I1160 ratio, was plotted against temperature. For nondiabetic control subjects, the plots showed an inflection in the temperature range of 30-39 degrees C, which corresponded to the thermal transition of LDL. This transition was abolished in the LDL of diabetic patients (P less than 0.001), suggesting an altered lipid structure. The transition (30-39 degrees C) was also abolished in the in vitro glycosylated nondiabetic LDL. Lipid analysis did not show any appreciable change between nondiabetic control subjects and diabetic patients. The change in the thermal transition properties of diabetic LDL has been attributed to the organizational change in the LDL protein. ",18 3291,"Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Intraoperative administration of the proteinase inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 x 10(5) KIU/h during surgery. Additionally, 2 x 10(6) KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P less than 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P less than 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P less than 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly increased until heparin was neutralized after cardiopulmonary bypass (CPB). ",22 1891,"Persistent uptake of indium-111-antimyosin monoclonal antibody in patients with myocardial infarction. Indium-111(111In)-antimyosin scintigraphy was investigated in 27 patients with myocardial infarction. 111In-antimyosin Fab was administered intravenously, and planar and single photon emission computed tomographic images were obtained 48 hours later. Uptake of 111In-antimyosin was present in 9 of 10 patients (90%) studied within 6 days of infarction. During the second week positive scans were seen in 16 of 16 patients (100%) including 13 (81%) who had normal creatine kinase levels. The mechanism of persistent positive antimyosin images in the subacute stage of myocardial infarction remains to be clarified. 111In-antimyosin scintigraphy may be useful as a noninvasive method for the detection of myocardial injury late and early after a suspected acute myocardial infarction. ",13 379,"Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. BACKGROUND. The rates of colon cancer in various countries are strongly correlated with the per capita consumption of red meat and animal fat and, to a lesser degree, inversely associated with the consumption of fiber. METHODS. We conducted a prospective study among 88,751 women 34 to 59 years old and without a history of cancer, inflammatory bowel disease, or familial polyposis who completed a dietary questionnaire in 1980. By 1986, during 512,488 person-years of follow-up, 150 incident cases of colon cancer had been documented. RESULTS. After adjustment for total energy intake, animal fat was positively associated with the risk of colon cancer (P for trend = 0.01); the relative risk for the highest as compared with the lowest quintile was 1.89 (95 percent confidence interval, 1.13 to 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95 percent confidence interval, 1.24 to 5.03), as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was particularly strongly associated with an increased incidence of colon cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95 percent confidence interval, 1.50 to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but this relation was not statistically independent of meat intake. CONCLUSIONS. These prospective data provide evidence for the hypothesis that a high intake of animal fat increases the risk of colon cancer, and they support existing recommendations to substitute fish and chicken for meats high in fat. ",3 289,"Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records. The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma. Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records. Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur. ",3 1562,"Percutaneous valvuloplasty in a patient with mitral stenosis following surgical annuloplasty. A case is described in which a patient with a Carpentier-Edwards annuloplasty ring developed mitral stenosis and was treated with percutaneous mitral valvuloplasty. Possible mechanisms for the development of mitral stenosis are briefly discussed. ",13 3021,"The nuclear pacemaker: is renewed interest warranted? From 1973 through 1987, 155 radioisotope-powered ""nuclear"" pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p less than 0.001). Power-source failure was observed in only 1 case, but 47 nuclear pacemakers were removed for other reasons, including component malfunction (15 units), mode change (12 units), high pacing thresholds (8 units) and lead or connector problems (5 units). The actuarial survival at 15 years was 99% for power sources and 82% for the entire pacing systems (pulse generators plus leads). The frequency of malignancy was similar to that of the population at large and primary tumor sites were randomly distributed. Deaths most commonly were due to cardiac causes (68%). Thus, nuclear pacemakers are safe and reliable and their greater initial cost appears to be offset by their longevity and the resulting decrease in the frequency of reoperations. It is reasonable to suggest that further use be made of long-lasting nuclear power sources for modern pacemakers and other implantable rhythm-management devices. ",22 847,"Lipid peroxidation and hepatic antioxidants in alcoholic liver disease. The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation. ",5 790,"Oral dissolution therapy for cholelithiasis: mix and match. The authors conducted a prospective, randomized trial of chenodeoxycholic and ursodeoxycholic acid versus ursodeoxycholic acid alone in patients with cholelithiasis to determine their efficacy for dissolution of gallstones. One hundred and twenty patients with radiolucent gallstones, less than or equal to 15 mm and who had a functioning gallbladder were enrolled. The patients were divided into two groups based on the diameter of their largest stones. Seventy patients had stones larger than 5 mm but less than 15 mm, whereas 50 patients had stones that measured 5 mm or less. The patients were randomly assigned to treatment with chenodeoxycholic acid plus ursodeoxycholic acid (5 mm/kg of each) or ursodeoxycholic acid (10 mm/kg) alone. Oral cholecystography, plain abdominal x-rays, and ultrasonography of the gallbladder were done at 6, 12, and 24 months. Dissolution was deemed to be complete if not stones were visualized on two examinations. partial dissolution was defined as a 50% reduction in stone size and/or number. Stones that were not detected by cholecystography but still detected during ultrasonography were considered to be partially dissolved. Plasma triglycerides, serum cholesterol, HDL, and serologic liver function tests were determined at 1, 3, 6, 12, 18, and 24 months. In a select group of patients, bile-rich duodenal aspirates were aspirated and analyzed for biliary lipid contents. In the group with small stones, defined as less than or equal to 5 mm, complete stone dissolution occurred significantly more often utilizing combination therapy at 6 months (52% vs 24%), and this trend persisted, although no longer significant, at 12 and 24 months. Combination therapy also achieved an improved rate of dissolution for large stones within 6 months; however, this did not persist at 12 and 24 months. Although not statistically significant, stone calcification occurred less often with combined therapy. All treatment regimens were well tolerated, with only minor changes in bowel habits and mild elevations in serum transaminase levels. Serum lipid levels did not change with either therapy. The authors concluded that the combination of chenodeoxycholic acid and ursodeoxycholic acid was the preferred therapy for gallstone dissolution, because it dissolves stones more rapidly, with a lower incidence of stone calcifications, and thus might reduce the long-term cost of treatment. ",5 114,"Suppression of herpes simplex virus type 1 reactivation from latency by (+-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) in vitro. Latent herpes simplex virus type 1 (HSV-1) infection was induced in human embryonic lung cells in vitro by using a combination of viral replication inhibitors and elevated temperature. Under reactivating conditions (superinfection by human cytomegalovirus or temperature manipulation), a nonantiviral thymidine kinase inhibitor (L-653,180) was found to suppress or delay reactivation of HSV-1 from latently infected human embryonic lung cells. L-653,180 alone or in combination with interferon was ineffective as a primary or acute viral replication inhibitor and was unable to induce latent HSV-1 infection in cell culture. These data suggest that initial or acute virus replication and replication resulting from reactivation from latency are separate events. ",1 1209,"Involvement of the central nervous system in chronic inflammatory demyelinating polyneuropathy: a clinical, electrophysiological and magnetic resonance imaging study. In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in six. It is concluded that subclinical evidence of central nervous system (CNS) involvement is common, at least in patients with CIDP in the United Kingdom, but that clinically evident signs of CNS disease are infrequent. The association of a multiple sclerosis-like syndrome with CIDP is rare. ",9 1058,"Cholinergic deficiency and frontal dysfunction in Parkinson's disease. To investigate the influence of central cholinergic deficit on cognitive function in Parkinson's disease (PD), we compared the neuropsychological performance of a group of 20 patients who were treated with anticholinergic drugs (mean daily dose, 10.2 mg) with that of a group of 20 patients who received no anticholinergics. The two groups were matched for all the variables of parkinsonism and levodopa therapy. At the dose used, there was no significant difference between the two groups of patients for intellectual, visuospatial, instrumental, and memory function. In contrast, in the group that received anticholinergics severe impairment was observed on tests believed to assess frontal lobe function. These results suggest that the lesion of the ascending cholinergic neurons, which has been demonstrated post mortem in PD, may play a role in the subcorticofrontal behavioral impairment of this disease. ",9 2188,"Placental histology in fetuses between 18 and 23 weeks' gestation with abnormal karyotype. Placentas from karyotypically abnormal fetuses (18 to 23 weeks' gestation) were analyzed prospectively at the light microscopic level. Group I consisted of 14 control placentas. Group II consisted of 14 placentas from fetuses with an abnormal karyotype. Secondary and tertiary stem villi counts, small muscular artery counts, and total vessel counts were determined per 100 x field. There were no differences in secondary and tertiary stem villi counts between groups. A significant decrease in small muscular artery counts (p less than 0.01) and total vessel counts (p less than 0.01) was noted in group II. Placental and fetal weights were comparable between groups. This undervascularization may represent placental immaturity as a result of arrested or delayed angiopoiesis. It appears that this abnormality is established before the third trimester and may be enhanced by late vascular obliteration as reported by others. These data substantiate the concept that the structure and function of the placenta is determined to a great degree by fetal karyotype and may help explain the morbidity and mortality seen in these fetuses. ",15 2515,"Comparison of HbA1 and fructosamine in diagnosis of glucose-tolerance abnormalities. Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance. ",18 885,"Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients. Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking habits and the degree of airway obstruction were investigated. Specimens of peripheral lung parenchyma, free of tumor tissue, were taken and the malondialdehyde (MDA) content was measured in the S-12 fractions. Airway obstruction was assessed by flow-volume curves, and data were expressed as percentage of the predicted values. Cigarettes smoked were expressed as pack-years. The patients with LC and NLC did not differ by MDA content, age, and number of pack-years. On the contrary, FEF75-85 and MEF75 were significantly lower in LC than in NLC patients (p less than 0.05). The MDA content was inversely correlated to number of days patients had refrained from smoking (r = -0.66, p less than 0.001). The MDA content was higher in recent smokers (ie, people smoking during the last 30 days before surgery) than in the other patients (0.136 +/- 0.007 vs 0.116 +/- 0.007 mumol/g of tissue, p less than 0.05) and, by considering only recent smokers, MDA content was higher in LC patients (0.144 +/- 0.008 mumol/g of tissue) than in NLC patients (0.113 +/- 0.014 mmol/g tissue, p = 0.059). When patients were divided into ""high MDA"" and ""low MDA"" groups, MEF75 was much lower in the high MDA group (35.1 +/- 3.4 percent) than in the low MDA group (55.1 +/- 8.1 percent) (p less than 0.01). These results suggest the following: (1) enhanced level of prooxidant state in the lungs is associated with recent cigarette smoking; (2) LC patients may be more prone than respective NLC patients to oxidative stress; (3) MDA level and degree of small airway obstruction were associated and differed between LC and NLC patients even though these groups did not differ in the percentage of recent smokers; and (4) a common free-radical mediated pathway may be active for both LC and small airway obstruction. ",7 865,"Epithelial rests' function in replantation: is splinting necessary in replantation? The problem of resorption during replantation in relationship to the epithelial rests and a lack of splinting was studied. Ten mongrel dogs were used. Two dogs served as control subjects, while eight had their mandibular incisors intentionally replanted and studied histologically. It was observed that where rests of Malassez were present we did not see resorption, and the lack of splinting did not result in resorption or loss of teeth. It appears we can stain epithelial rests of Malassez with immunofluorescent antibodies and use this technique for further study of this tissue. ",6 2348,"Randomized crossover study of effect of resistance training on glycemic control, muscular strength, and cholesterol in type I diabetic men. The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors, blood glucose management, and overall strength in diabetic subjects. A randomized crossover design was performed on eight male type I (insulin-dependent) diabetic subjects (mean +/- SD age 31 +/- 3.5 yr, height 176 +/- 5.6 cm, body wt 80 +/- 15 kg, duration of diabetes 12.3 +/- 9.8 yr, and insulin dose 24 U NPH/day and 21 U regular/day). The program consisted of heavy-resistance weight training 3 days/wk for 10 wk, concentrating on the strengthening of major muscle groups through progressive resistance. Blood tests included total cholesterol, triglycerides, very-low-density lipoprotein and high-density lipoprotein cholesterol, and HbA1c. These tests were repeated at three time points during the program. Field-strength testing was performed before and after training. An improvement was seen in the squat (93.6% increase, P less than 0.0001) and bench press (58% increase, P less than 0.005). HbA1c and triglyceride levels showed no change during the resting portion of the experiment but showed a significant change with the training program: HbA1c 6.9 +/- 1.4 vs 5.8 +/- 0.9% (P = 0.05) and triglyceride 5.044 +/- 1.06 vs. 4.628 +/- 0.88 mM (P = 0.01). Self-monitored glucose (taken pre- and postexercise) showed a decrease from 7.85 +/- 3.13 to 7.05 +/- 2.91 mM (P = 0.0001). Very-low-density lipoprotein cholesterol and triglycerides did not change after training. Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c. ",17 327,"Insulinoma after streptozotocin therapy for metastatic gastrinoma: natural history or iatrogenic complication? Islet cell carcinoma frequently produces more than one chemical product, although its clinical expression is usually restricted to a single hormone. We describe an unusual patient who presented with full-blown metastasizing gastrinoma. He was treated with cimetidine for five years and then streptozotocin therapy, which resulted in a regression in hepatomegaly and a fall in serum gastrin levels. Following one year's therapy with streptozotocin, he was admitted in hyperinsulinemic hypoglycemic stupor. This appears to be the first reported case of a ""shift"" from clinical gastrinoma to insulinoma possibly related to prolonged streptozotocin therapy. ",3 2658,"Effect of education on the use of universal precautions in a university hospital emergency department. STUDY OBJECTIVES: To determine if an educational program would improve both knowledge and practice of universal precautions by nursing personnel. DESIGN: Participants were given a 14-question test and observed for their, practice of universal precautions during routine IV catheter placement or phlebotomy and trauma care before and six months after an education in-service. SETTING: University hospital emergency department. TYPE OF PARTICIPANTS: Nursing personnel. INTERVENTIONS: One-hour lecture addressing the occupational risk of human immunodeficiency virus (HIV) infection and the recommended use of universal precautions. MEASUREMENTS AND MAIN RESULTS: The mean overall correct response rates to the questionnaire before and after the in-service were 70% and 73%, respectively (P = NS). The pattern of incorrect responses suggested that the perceived risks of HIV transmission are underestimated, particularly among healthy-appearing patients. For care of critical trauma patients, there were significant increases between the frequency rates before and after the in-service of glove and protective eyewear use (66.7% vs 87.7%, P less than .025; 0.0% vs 17.3%, P less than .05, respectively). The frequency rates of glove use for IV placement or phlebotomy in noncritical patients and of gown use for trauma patient care also increased (52.6% vs 65.2% and 25% vs 39.5%, respectively); however, these changes were not statistically significant. CONCLUSION: An intensive educational program was associated with a modest increase in the compliance of ED nursing personnel with universal precautions and had no long-term effect on their general knowledge of HIV risk. The practice of universal precautions is still far from universal in this ED. ",19 29,"Seven-day administration of recombinant human granulocyte colony-stimulating factor to newborn rats: modulation of neonatal neutrophilia, myelopoiesis, and group B Streptococcus sepsis. Single-pulse administration of rhG-colony-stimulating factor (CSF) to neonatal rats was previously demonstrated to induce peripheral neutrophilia and modulate bone marrow (BM) neutrophil storage and proliferative pools (NSP + NPP). In this study, we investigated the prolonged effects of 7 days of rhG-CSF therapy (5 micrograms/kg/per day). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneally (IP) (daily for 7 days) with rhG-CSF or phosphate-buffered saline/human serum albumin (PBS/HSA). RhG-CSF induced a significant early and late peripheral neutrophilia: 6,905 +/- 1,625 (day 1) and 9,223 +/- 515 microL (day 7) v 1,275 +/- 90/microL (P less than or equal to .0001). In addition, 7 days of rhG-CSF resulted in a significant increase in the BM NSP: 3,247 +/- 190/microL v 1,677 +/- 339/microL (P less than or equal to .001). There was, however, no depletion or significant change in the BM NPP. Seven days of rhG-CSF also induced a mild increase in BM CFU-GM colony formation (P less than or equal to .01). There was, however, no significant change in liver/spleen CFU-GM colonies or in the CFU-GM proliferative rate in either the BM or liver/spleen cultures. Finally, 7 days of prophylactic rhG-CSF therapy resulted in a synergistic response with antibiotic therapy and significantly modulated the mortality rate during experimental group B streptococcal sepsis (GBS) (100% v 50%) (GvsC) (P less than or equal to .001). Pulse rhG-CSF administered at 6 hours or 18 hours after GBS inoculation, however, failed to act synergistically with antibiotics to improve survival or prevent peripheral neutropenia. This study suggests that 7 days of prophylactic rhG-CSF therapy induces peripheral neutrophilia, myeloid maturation, increases neutrophil BM reserves and also may provide immunologic enhancement of neonatal host defense during experimental GBS in term neonatal rats. ",0 3129,"Electroencephalographic activity related to palatal myoclonus in REM sleep. Polysomnography, including electroencephalography, electromyography and electro-oculography was performed in three patients with palatal myoclonus (PM). The amplitude of the myoclonus decreased during sleep. The frequency did not change during non-REM sleep, but increased during REM sleep in two patients. Ocular myoclonus synchronized with PM disappeared during deep sleep stages in two patients and reappeared during REM sleep in one of them. In the other patient, ocular myoclonus was noted only in REM sleep, being absent even when the patient was awake. All patients showed episodic EEG activities synchronous with myoclonic jerks only in REM sleep. These episodes were noted 5-15 times throughout the night, and each episode lasting for 1-7 s. They were negative or positive waves of saw-tooth appearance which were distributed predominantly in the central region. During the episodes, the frequency of myoclonic jerks increased in two patients. Although it is known that REM sleep influences PM and ocular myoclonus, this is the first report demonstrating the electroencephalographic activity associated with PM. ",22 2526,"Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes. Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an approximately 2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume approximately 2400 kcal/day, whereas the calorie-restricted group consumed approximately 1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 +/- 0.8 mM wk 1 vs. 6.8 +/- 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 +/- 1.0 mM wk 1 vs. 5.4 +/- 0.5 mM wk 2, P less than 0.01). Fasting plasma insulin also declined in the calorie-restricted group (265 +/- 165 pM wk 1 vs. 145 +/- 130 pM wk 2), resulting in a significant change between groups (P less than 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of beta-hydroxybutyrate rose in the calorie-restricted group (290 +/- 240 microM wk 1 vs. 780 +/- 30 microM wk 2) but not in the control group (P less than 0.01). Finally, urine ketones increased significantly (P less than 0.02) in the calorie-restricted group, whereas they remained absent in the control group. ",18 1319,"Flow cytometry in carcinoma of the prostate. Flow cytometry is a quantitative cytologic technique with demonstrated utility in the assessment of prostate cancer as well as other tumors. The authors summarize current data on its use in disease detection and diagnosis, prognostic evaluation, and monitoring of response to therapy. They also project future developments. ",11 489,"The concept of locally advanced gastric cancer. Effect of treatment on outcome. The Gastrointestinal Tumor Study Group. In previous Gastrointestinal Tumor Study Group (GITSG) reports, gastric cancer patients with locally unresectable disease, treated with combined radiation and chemotherapy had a shorter median survival (40 weeks) but more remained alive at 4 years (18%) when compared to those randomized to receive chemotherapy alone (76 weeks and 6%, respectively). To further test the concept that combined modality therapy might increase the number of long-term survivors, a second protocol was designed, but with three major modifications. A course of chemotherapy would precede the 5-fluorouracil-potentiated radiation therapy. Doxorubicin would be added to the 5-fluorouracil plus methyl-CCNU combination. Radiation therapy would be given as a single course of 4320 cGy, with 5-fluorouracil given daily for 3 days at the beginning and end of the course. Median survival of 46 patients treated with chemotherapy alone was 59 weeks, with 11% alive after 3 years. Following combined modality therapy, median survival was 62 weeks, but only 7% lived 3 years. Although the problem of early deaths in the combined modality group was resolved, long-term survival with combination therapy was not demonstrated in this study. ",3 1211,"Indications for thymectomy in myasthenia gravis. Fifty-six board-certified neurologists with interest and expertise in myasthenia completed a survey of indications for thymectomy in myasthenia gravis. Thymectomy was advocated for virtually all patients with thymoma, for a variable subset of patients with generalized myasthenia without thymoma, and occasionally for selected patients with disabling ocular myasthenia. ",9 3065,"Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine. ",22 777,"Cyclic pelvic pain. Cyclic pelvic pain is a common gynecologic problem caused by relatively few diseases, which usually can be diagnosed and remedied quickly. Some complaints reflect normal physiologic aspects of the menstrual cycle (mittelschmerz, menstrual awareness). Premenstrual syndrome can be diagnosed, but an effective and convenient treatment is lacking. Dysmenorrhea is the commonest source of cyclic pain, diagnosed by its characteristic history and rapid relief on administration of antiprostaglandin agents. Endometriosis is diagnosed surgically and best treated either surgically then, or medically by danazol or GnRH agonists. In contrast, adenomyosis is a problem commonly encountered in later life, and hysterectomy is usually needed for both definitive diagnosis and treatment. ",5 1997,"B-mode imaging and histomorphometric evaluation of carotid atherosclerosis. The quantitative and qualitative evaluation of atherosclerotic lesions by the ultrasonography has presented several problems, above all, the determination of accuracy and reproducibility of this methodology in humans. The present study aims to evaluated the results of B-mode imaging of extracranial carotid arteries in patients selected for surgery as compared with histologic results of the observations of the samples obtained by endarterectomy. Shrinkage effects of the histologic samples were taken into consideration. Several bidimensional images of atherosclerotic lesions, as obtained by ultrasound at different incident angles, were used to establish their maximum thickness. The maximum degree of the vessel stenosis calculated by ultrasound showed a high correlation (Y = 0.47X + 42.4, se = 0.11, r = 0.5, p less than 0.001) compared with the one obtained by histology. The imaging methodology provided however, a mean overestimation of the stenosis of about 7%. Relationships among the amount of calcium (p less than 0.03); necrotic core p less than 0.056); and echogenic types, ie, soft, mixed, and hard; have been suggested by a statistical trend. The results suggested that of the vascular lumen due to advanced atherosclerotic lesions. Qualitative interpretation of atherosclerosis by B-mode imaging, ie, morphologic characteristics, seem, at present, to be of value, but more investigations in depth are needed. ",13 2168,"Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies. Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti-LIBS1) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the thrombasthenic platelets, suggesting a primary defect in ligand binding. Chromatography of detergent-solubilized platelets on a KYGRGDS affinity column confirmed that the patient's GPIIb-IIIa lacked the fibrinogen binding site. In another patient with myelofibrosis and defective aggregation, PAC1 failed to bind to adenosine diphosphate-stimulated platelets, but did bind when protein kinase C was directly activated with phorbol myristate acetate. Furthermore, the binding of PMI-1 and anti-LIBS1 increased in response to GRGDSP, confirming a defect in agonist-mediated fibrinogen receptor activation rather than in fibrinogen binding or events distal to binding. These studies indicate that this immunochemical approach is useful in classification of clinical abnormalities of platelet aggregation as defects in either (a) fibrinogen receptor activation, (b) fibrinogen binding, or (c) postoccupancy events. ",14 1201,"Lateralized effects of subclinical epileptiform EEG discharges on scholastic performance in children. The interaction between lateralization of subclinical epileptiform discharges and cognitive tasks was investigated in 21 children (12 girls and 9 boys, mean age 10.6 years). Seventeen had a diagnosis of epilepsy (partial or secondarily generalized). Testing was by reading, arithmetic, and intelligence subtests during continuous telemetric EEG and video monitoring. Children with left-sided discharges had significantly lower reading performance than children with right-sided discharges. During reading, epileptiform discharges occurred relatively less frequently and with a shorter total duration over the left hemisphere than the right. This supports the view that cognitive tasks suppress epileptiform discharges when they activate a region of the brain within the epileptogenic zone. Discharges from other epileptogenic zones not directly activated by the tasks are increased, however. ",9 1383,"Urinary incontinence. Symptoms of urinary incontinence are distressing and disruptive to everyday life. They can also be indicative of more serious underlying disorders. Many methods of symptom management are available. Matching the affected person to the most effective and appropriate treatment method is a significant challenge for nursing. Just as pressing is the need to develop and test a cogent conceptual model for symptom management that includes primary prevention. ",11 1892,"Coronary perfusion catheter: its effectiveness in an experimental model of acute coronary occlusion. The effectiveness of a coronary perfusion catheter was studied in an animal model of acute coronary occlusion. Systemic hemodynamic variables, regional myocardial blood flow (RMBF) in the subepicardium and subendocardium, and regional systolic function (systolic segmental shortening) of the area perfused by the circumflex coronary artery (CX) were measured in eight anesthetized dogs. After baseline measurements, the CX coronary artery was occluded with a silk snare and measurements were repeated after 5 minutes of ischemia (occlusion No. 1). The snare was released and 1 hour later the snare occlusion was repeated after placement of a perfusion catheter in the CX coronary artery. After 5 minutes, measurements were repeated (occlusion No. 2). To determine the long-term effectiveness of the catheter, hemodynamic variables and regional function measurements were then obtained every 15 minutes for a total of 60 minutes. During occlusion No. 1, RMBF decreased from 1.30 +/- 0.20 to 0.41 +/- 0.13 ml.min-1.gm-1 (p less than 0.01), and subendocardial RMBF decreased from 1.44 +/- .24 to 0.34 +/- 0.15 ml.min-1.gm-1 (p less than 0.01). After insertion of the perfusion catheter (occlusion No. 2), subepicardial RMBF was maintained at 0.97 +/- 0.16 and subendocardial RMBF was maintained at 0.78 +/- 0.13 ml.min-1.gm-1; during occlusion No. 2 subepicardial RMBF was greater (p less than 0.05) than occlusion No. 1 and was not different from baseline. ",13 1747,"Post-transplant hypertension. Post-transplant hypertension remains an important risk factor for cardiovascular mortality and graft function. There are multiple mechanisms responsible for post-transplant hypertension. The details of these mechanisms are poorly understood. Steroids, acute and chronic rejection, recurrent renal disease, native kidney disease, and renal artery stenosis have all been implicated in causing post-transplant hypertension. With the addition of cyclosporine, a known hypertensive agent, to the immunosuppressive armamentarium, the evaluation of post-transplantation hypertension has become difficult. Presently, medical therapy is initially directed toward the complications of cyclosporine nephrotoxicity. Empirically, converting enzyme inhibitors are added to the antihypertensive regimen. Further management is aimed at identification of specific causes of post-transplant hypertension. Unfortunately, because of the multifactorial etiology of post-transplant hypertension and a lack of detailed information about the mechanisms, medical and surgical therapy are often unrewarding. Further study is needed to clarify the mechanisms involved in post-transplant hypertension, and thus direct therapy. ",13 3068,"Electrotonic influences on action potentials from isolated ventricular cells. This work combines a theoretical study of electrical interactions between two excitable heart cells, using a variable coupling resistance, with experimental studies on isolated rabbit ventricular cells coupled with a variable coupling resistance to a passive resistance and capacitance circuit. The theoretical results show that the response of an isolated cell to an increased frequency of stimulation is strongly altered by the presence of a coupling resistance to another cell. As the coupling resistance gradually is decreased, the stimulated cell becomes able to respond successfully to more rapid stimulation, and then, at levels of coupling resistance that allow conduction between the two cells, the coupled pair of cells exhibits arrhythmic interactions not predicted by the intrinsic properties of either cell. The experimental results show that the isolated rabbit ventricular cell is extremely sensitive to even a very small electrical load, with shortening of the action potential by 50% with electrical coupling to a model cell (of similar input resistance and capacitance to the ventricular cell) as high as 1,000 M omega, even though the action potential amplitude and current threshold are very insensitive to the electrical load. ",22 1743,"Increase of calmodulin activator in hypertension. Modulation by dietary sodium and calcium. The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly-discovered hydrophobic compound that increases CaM activity in SHR and spontaneously hypertensive mice (SHM) tissues (J Clin Invest 82:276, 1988). The CaM activator was assessed by its capacity to stimulate a CaM-dependent phosphodiesterase (CaM-PDE). In Wistar rats, which were fed a high sodium diet (3.5%), BP significantly increased (P less than .01) from 106 +/- 4 to 128 +/- 8 mm Hg in parallel to an elevation of the CaM activator from 1.57 +/- 0.14 to 2.80 +/- 0.18 U. WKY, SHR, and Dahl salt-sensitive (DS/JR) and salt-resistant (DR/JR) rats were given low (0.15%) or high (2.5%) Ca diets, both with 1% sodium. In rats receiving high dietary Ca the progression of hypertension diminished and BP was lower in SHR (156 +/- 4 mm Hg) and young DS/JR rats (125 +/- 3 mm Hg) than in those receiving low dietary Ca (192 +/- 10 and 183 +/- 2 mm Hg). There was a concomitant decrease of CaM activator in these animals to levels indistinguishable from those of WKY or DR/JR rats. The activator was also found in the heart, kidneys and erythrocytes from SHM. In the presence of exogenously added CaM, lipidic extracts from the SHM heart showed augmented CaM-PDE activity relative to normotensive preparations. This difference was eliminated by trifluoperazine. ",13 407,"Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects. ",3 1218,"Quantitative evaluation of hypnotically suggested hyperaesthesia and analgesia by painful laser stimulation. The ability to reduce both clinically and experimentally induced pain by hypnotic suggestion of analgesia is well known. However, the nature of hypnotic analgesia still remains uncertain. Attempts to demonstrate and identify specific psychophysiological mechanisms have, so far, been unsatisfactory. Methodological problems in inducing pain and monitoring physiological responses may be the reason for this lack of success. In the present study, we have attempted to eliminate some of these methodological problems. The sensory and pain thresholds to laser stimulation were determined, and the laser-evoked brain potentials were measured for 8 highly hypnotically susceptible subjects in 3 conditions: (1) waking state, (2) suggestion of hyperaesthesia, (3) suggestion of analgesia. The thresholds were reduced during induced hyperaesthesia and increased during analgesia. During hyperaesthesia sensations could be evoked by laser intensities which were below intensities that could be perceived in the awake state. The amplitude of the evoked brain potentials increased during hyperaesthesia and decreased during analgesia. The latency of the potential remained constant. The perception of pain during hypnosis can change very fast, indicating that slow endogenous mechanisms may play only a minor role in suggested hyperaesthesia/analgesia. ",9 306,"Survival in patients with large-bowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study. Five-year survival data were obtained in 97 percent or 1105 of 1140 new patients with histologically confirmed colorectal adenocarcinoma during a 12-month period in 1981 and 1982, as part of a large comprehensive population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Fifteen percent of patients were Dukes' A stage, 32 percent were Dukes' B, 25 percent were Dukes' C, and 29 percent were Dukes' D. At five years after diagnosis, the observed survival rate was 36 percent and the adjusted rate was 42 percent. Dukes' staging was a highly discriminating factor in survival (P less than 0.001). Survival rates were better in women than in men and better for patients with colon cancer than for patients with rectal cancer. Survival by Dukes' staging was not affected by colon subsite or by the tumor being the first and single tumor, metachronous tumor, or synchronous tumor. The survival of younger patients was better for Dukes' stages A, B, and C, and worse for Dukes' D. Survival was worse in the presence of bowel perforation in Dukes' C and D stages. Within Dukes' D (incurable cases), survival was best in the absence of hepatic metastases, slightly worse when only hepatic metastases were present, and poorest in the presence of both hepatic and extrahepatic metastases. Statistical modeling of survival determinants other than staging indicated that cell differentiation had the largest effect (survival decreasing with poor cell differentiation), followed by site (survival worse for rectal cancer than colon cancer), then age (survival better for younger patients), while bowel perforation had the smallest effect on survival. ",3 478,"Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin-embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion. ",3 652,"The effect of early fronto-orbital advancement on frontal sinus development and forehead aesthetics. The frontal sinuses make an important contribution to normal forehead and glabellar contour. This study was designed to test our clinical impression that early fronto-orbital (""frontal bone"") advancement could have an adverse effect on frontal sinus development and consequently on forehead aesthetics. A retrospective study was conducted on 11 patients who had undergone fronto-orbital advancement and also had a long period of follow-up at the Institute of Reconstructive Plastic Surgery at New York University. The longitudinal cephalometric data were compared with unoperated controls. With one exception, no patient who underwent bilateral fronto-orbital advancement developed a frontal sinus, and all such patients had a flattened brow contour when compared with unoperated patients, of whom 82 percent developed at least one frontal sinus. Of the three patients who underwent unilateral fronto-orbital advancement for plagiocephaly (flattened forehead), two developed a frontal sinus but only on the unoperated side and one developed bilateral frontal sinuses. The two patients with unilateral frontal sinus development had a particularly obvious deformity resulting from normal glabellar projection on the unoperated side and a flattened contour on the operated side. Fronto-orbital advancement affects forehead aesthetics and should be performed only in infant patients with moderate to severe deformities. patients with plagiocephaly whose deformity is sufficiently severe to warrant surgery should preferably undergo bilateral fronto-orbital advancement (by the technique described) rather than unilateral advancement in order to avoid the brow asymmetry that results from unilateral frontal sinus development. ",4 799,"Pharmacology of pravadoline: a new analgesic agent. Pravadoline is a new chemical entity with analgesic activity in humans. This report describes the pharmacology of pravadoline and compares the activity of pravadoline with that of two major classes of analgesics, the opioids and the nonsteroidal anti-inflammatory drugs (NSAIDs). Like the NSAIDs, pravadoline inhibited the synthesis of prostaglandins (PGs) in mouse brain both in vitro (IC50, 4.9 microM) and ex vivo (ED50, 20 mg/kg p.o.) and displayed antinociceptive activity in rodents subjected to a variety of chemical, thermal and mechanical nociceptive stimuli. Administration of pravadoline prevented the writhing response induced by i.p. administration of acetylcholine (ED50, 41 mg/kg p.o.) or PGE2 (ED50, 24 mg/kg p.o.) and prolonged the response latency induced by tail immersion in hot water at a temperature of 55 degrees C (minimum effective dose, 100 mg/kg s.c.). In the rat, treatment with pravadoline prevented acetic acid-induced writhing (ED50, 15 mg/kg p.o.), brewer's yeast-induced hyperalgesia (Randall-Selitto test) (minimum effective dose, 1 mg/kg p.o.), the nociceptive response induced by paw flexion in the adjuvant-arthritic rat (ED50, 41 mg/kg p.o.) and bradykinin-induced head and forepaw flexion (ED50, 78 mg/kg, p.o.). The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1 mg/kg s.c.) and pravadoline did not bind to opioid receptors at concentrations up to 10 microM. However, like the opioid analgesics, pravadoline diminished the electrically induced twitch response of mouse vas deferens preparations, but, in contrast to opioids, this action of pravadoline was not attenuated by naloxone. The possibility is discussed that this effect of pravadoline upon isolated tissues may contribute to its antinociceptive activity. In contrast to NSAIDs, pravadoline was more potent ex vivo as an inhibitor of the formation of PGs in brain vs. stomach. In addition, pravadoline failed to produce gastrointestinal lesions when administered p.o. to rats or mice, and did not possess significant anti-inflammatory activity at antinociceptive doses. Also unlike NSAIDs, pravadoline inhibited rat gastrointestinal transit when administered at doses similar to those which were antinociceptive. The overall pharmacologic profile of pravadoline suggests that the compound may be capable of managing more diverse or more severe pain than is achieved by anti-inflammatory analgesics, without producing side effects commonly associated with either the opioid or the nonopioid analgesics. ",5 3060,"Graft stenosis: justification for 1-year surveillance. In all, 412 femorodistal grafts (femoropopliteal and femorocrural), performed between 1984 and 1988, have been prospectively studied at 6 weeks and 3, 6, 9 and 12 months after operation and at intervals of 6 months thereafter by duplex scanning and intravenous digital subtraction angiography. The overall incidence of stenoses was 16 per cent (femorocrural 20 per cent, femoropopliteal 15 per cent). All stenoses were detected in the first year after operation and none occurred after this. Twenty-four non-haemodynamically significant stenoses were not treated but were followed at intervals of 3 months. Forty-two haemodynamically significant stenoses were detected and secondary procedures were performed in 30 grafts at a mean of 8 months after surgery. Thirteen had percutaneous balloon dilatation and six (46 per cent) remain patent at a mean follow-up of 22 months. Two grafts which occluded within 30 days and three which restenosed at a mean of 8 months had tertiary procedures. Seventeen grafts were surgically revised, nine with patch grafts and eight with bypass grafts. Eleven of these remain patent at a mean follow-up of 30 months. One occluded immediately and three occluded late. Two grafts which restenosed at a mean of 19 months had successful tertiary procedures. In total, seven grafts had tertiary procedures (two had balloon dilatation and five had surgery) and six of these remain patent at a mean follow-up of 13.5 months. In conclusion, 37 procedures have been performed on 30 grafts, of which 23 (77 per cent) remain patent at a mean follow-up of 12 months. Approximately one-quarter of femorodistal grafts will develop graft-related stenoses and graft surveillance is worthwhile, but only for the first year after operation. ",22 1066,"Geographic patterns of parkinsonism-dementia complex on Guam. 1956 through 1985. Average annual age-adjusted incidence rates of parkinsonism-dementia complex were obtained for the 19 election districts of Guam from 1956 through 1985. The highest rates were found in the southern and central districts, and the lowest rates were found in the northern and western districts. Geographic and temporal patterns of incidence were associated with socioeconomic status but not with geochemical factors. The risk of parkinsonism-dementia complex in susceptible sibships was much higher than that in the general population--even in districts with the highest incidence rates, but especially in districts with the lowest incidence rates. Our evidence tends to support the hypothesis that multiple factors linked to cycad use play an important role in the cause of PDC. Hypotheses related to metal exposure and simple genetic factors were unsatisfactory explanations for the epidemiologic patterns observed. ",9 1946,"Dissecting aneurysm of the pulmonary artery with pulmonary hypertension. Pulmonary artery dissection was observed in a 64-yr-old female patient with severe pulmonary hypertension, which was probably primary (pulmonary vascular resistance, 817 dyn.s.cm-5; normal range less than or equal to 200 dyn.s.cm-5). The patient was admitted to the hospital because of severe dyspnea on exertion. Echocardiography demonstrated a dissecting aneurysm of the pulmonary artery. Right heart catheterization revealed severe pulmonary hypertension (mean pulmonary artery pressure, 64 mm Hg; normal range, 10 to 22 mm Hg); dissection of the pulmonary artery was confirmed by pulmonary arteriography. One-year follow-up was uneventful. In the literature, 28 patients with dissecting aneurysm of the pulmonary artery are reviewed. The dissection has only been diagnosed in life in one patient (by echocardiography). ",13 1528,"Repair of the uterine cavity after hysteroscopic septal incision. We performed a follow-up hysteroscopy with multiple biopsies at different intervals after surgery in 19 women who underwent hysteroscopic septal incision. Seven days after operation the sectioned areas were very evident and not epithelialized (3 patients). At 14 days, the incised zone was depressed with scattered epithelialization (5 subjects). At 1 month, the sectioned surfaces were still depressed and uniformly covered by thin endometrium (5 cases). After 2 months the uterine cavity was almost normal with minimal tendency to central fundal adhesions (6 women). Thus, spontaneous healing processes after hysteroscopic metroplasty progressed regularly and completely and there is probably no reason to delay attempts at pregnancy for longer than two cycles after surgery. ",12 848,"Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test. The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration. ",5 1264,"Glaucomatous optic nerve atrophy in small discs with low cup-to-disc ratios Glaucomatous optic nerve damage has generally been associated with high cup-to-disc ratios. Fifteen eyes of nine patients with increased intraocular pressure and glaucomatous visual field loss but low cup-to-disc ratios are reported. The optic disc area was significantly (P less than 0.01) smaller than in 429 normal subjects and 556 glaucoma patients with high cup-to-disc ratios. Parapapillary chorioretinal atrophy was significantly larger and retinal nerve fiber bundles were significantly less visible than in the normal group. The latter two parameters were not significantly different in the glaucoma groups with low and high cup-to-disc ratios when the groups were matched for mean perimetric loss. The authors conclude that in eyes with small optic discs, glaucomatous optic nerve damage may be indicated more sensitively by parapapillary changes than by cup-to-disc ratios. Glaucomatous eyes with small optic nerve heads can have misleadingly low cup-to-disc ratios. ",10 1520,"Evaluation of the stimulated menstrual cycle by magnetic resonance imaging. Changes in uterine zonal anatomy in six women during a cycle of treatment with clomiphene citrate is studied by magnetic resonance imaging. There was a rapid rate of increase in endometrial thickness during the periovulatory period that was similar to the pattern seen in a prior study of women with normal (nonstimulated) cycles. Junctional zone thickness did not parallel the endometrial pattern and differed from the response seen in nonstimulated cycles. Results of large scale studies may help to further understand the effects of these medications. ",12 588,"Polypoid melanoma: a virulent variant of nodular melanoma. Report of three cases and literature review. We report the cases of three patients with polypoid melanoma. In no case was there microscopic evidence of melanoma cell invasion below the papillary dermis. In the polypoid variant of nodular melanoma, melanoma cells accumulate in large volume above the skin's surface. This increase in tumor volume encourages dislodgment of melanoma cells that are carried to superficial lymphatic vessels without invading the reticular dermis; this feature differentiates polypoid melanoma from the nonpolypoid nodular variant. Although polypoid melanoma is considered the most malignant form of melanoma, our findings, albeit limited to three cases, suggest that early diagnosis and prompt surgical excision may provide a favorable 5-year survival rate. ",3 710,"Pathogenesis of biliary sludge. The increasing application of ultrasonography in biliary tract disease had led to more frequent recognition of an old disorder--""biliary sludge."" Sludge is detected on ultrasound as low-amplitude echoes without acoustic shadowing. It layers in the most dependent part of the gallbladder and shifts with positioning. Particulate matter in bile, such as cholesterol monohydrate crystals, has been shown to be echogenic. Agglomeration of these crystals in biles with high mucus content accounts for the layering and the characteristic appearance of the movement of sludge with alteration in patient position. Within the gallbladder, the stability of the vesicular form of cholesterol and protein-lipid interactions are important determinants of cholesterol precipitation. In mixed and pigment gallstones, the equilibrium between ionized and unionized calcium and the hydrolysis of conjugated bilirubin are also important factors. Although the risk factors contributing to the formation of gallbladder sludge have not been critically examined, it is now known that in some instances sludge can produce biliary pain and can be associated with acalculous cholecystitis, recurrent pancreatitis and, ultimately, the formation of gallstones. A better appreciation of the pathogenesis of sludge formation can help in the understanding of the genesis of gallstones and also perhaps in understanding other documented but poorly understood biliary and pancreatic disorders. ",5 906,"Tumor necrosis factor-alpha mediates acid aspiration-induced systemic organ injury. Acid aspiration-induced systemic organ injury is mediated by the sequestration of activated neutrophils (PMN). In other settings cytokines have been shown to increase neutrophil-endothelial adhesion, a requisite for injury. This study tests whether the systemic leukosequestration and permeability following localized aspiration is mediated by tumor necrosis factor (TNF)-alpha-induced synthesis of an adhesion protein. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the instillation of either 0.1 mL 0.1 N HCI (n = 18) or 0.1 mL saline in control rats (n = 18). Localized aspiration induced generalized pulmonary leukosequestration with 95 PMN/10 high-power fields (HPF) in the aspirated lung and 46 PMN/10 HPF in the nonaspirated lung, higher than control values of 7 PMN/10 HPF and 5 PMN/10 HPF in saline- and nonsaline-aspirated sides, respectively (p less than 0.05). The leukosequestration was associated with permeability edema shown by increased protein concentrations in bronchoalveolar lavage (BAL) of 3900 micrograms/mL in the aspirated and 2680 micrograms/mL in the nonaspirated side, higher than saline with 482 micrograms/mL and 411 micrograms/mL, respectively (p less than 0.05). There was generalized pulmonary edema following aspiration measured by increase in wet-to-dry weight ratios (w/d) of 6.6 in the aspirated and 5.1 in the nonaspirated lung, higher than control values of 3.5 and 3.4, respectively (p less than 0.05). Localized aspiration led to systemic leukosequestration documented by increases in myeloperoxidase activity (units/g tissue) of 2.2 and 1.7 in heart and kidney, higher than control values of 0.3 and 0.4, respectively (p less than 0.05). This event was associated with edema of these organs with w/d ratios of 4.6 and 4.3, relative to control values of 3.0 and 3.4 (p less than 0.05). Treatment of animals (n = 18) 20 minutes after aspiration with anti-TNF-alpha antiserum (rabbit anti-murine) but not normal rabbit serum (n = 18) reduced lung leukosequestration in the aspirated and nonaspirated segments (61 and 32 PMN/10HPF), BAL protein concentration (1490 and 840 micrograms/mL), and w/d ratio (4.3 and 3.7) (all p less than 0.05). In the heart and kidney there were reductions in myeloperoxidase activity (0.7 and 0.6) and w/d ratio (3.5 and 3.6) (both p less than 0.05). Treatment of rabbits (n = 18) with the protein synthesis inhibitor cycloheximide, 0.2 mg/kg/hr was as effective as TNF-alpha antiserum in modifying aspiration injury.(ABSTRACT TRUNCATED AT 400 WORDS). ",7 1253,"Clinical and morphometric results of penetrating keratoplasty with one-piece anterior-chamber or suture-fixated posterior-chamber lenses in the absence of lens capsule. The clinical records and serial corneal endothelial images of 25 acapsular, pseudophakic eyes with Kelman-style, one-piece, anterior-chamber intraocular lenses and 24 acapsular, pseudophakic eyes with suture-fixated, posterior-chamber intraocular lenses following penetrating keratoplasty were reviewed to determine clinical success and endothelial survival after 1 year. Twenty-two (88%) of 25 grafts in the anterior-chamber intraocular lens group and 23 (96%) of 24 grafts in the sutured posterior-chamber intraocular lens group were clear after 1 year; best corrected visual acuity of 20/40 or better was noted in 25% of the eyes in the anterior-chamber intraocular lens group and 29% of the eyes in the sutured posterior-chamber intraocular lens group. The mean intraocular pressure for the anterior-chamber intraocular lens group was significantly lower than for the sutured posterior-chamber intraocular lens group at 3 months (17 +/- 4 vs 21 +/- 7 mm Hg) and at 6 months (17 +/- 3 vs 20 +/- 5 mm Hg); but did not differ at 1 year. The mean percent of endothelial cell loss after 1 year did not differ between the anterior-chamber intraocular lens group (32% +/- 26%) and the sutured posterior-chamber intraocular lens group (27% +/- 26%). No clinical or endothelial morphometric advantages were noted after 1 year for the suture-fixated, posterior-chamber intraocular lens over the Kelman-style, one-piece anterior chamber, intraocular lens following pseudophakic penetrating keratoplasty; however, a long-term, prospective, randomized study of these two intraocular lens types is recommended. ",10 1205,"Delirium: masquerades and misdiagnosis in elderly inpatients. Delirium is an organic mental disorder defined as transient, fluctuating global dysfunction of cognition. It is common in elderly medical inpatients, yet its varied presentation is often missed or misdiagnosed. ",9 2219,"Norwood operation for univentricular heart with subaortic stenosis in the neonate. In the setting of a single ventricle, subaortic stenosis may be enhanced by pulmonary artery banding and may later contraindicate a Fontan operation. The Norwood operation may prove a preferable alternative in some infants as a preparatory procedure. We have successfully used this procedure as the initial operation to palliate a newborn with tricuspid atresia, transposition of the great arteries, coarctation, and severe arch hypoplasia secondary to a restrictive bulboventricular foramen. ",15 1482,"Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone. Pulsatile GnRH therapy has yet to achieve widespread acceptance as an alternative to exogenous gonadotropin therapy in women with hypothalamic amenorrhea and complete GnRH deficiency. However, when a physiologically based replacement regimen of pulsatile GnRH is used, a high rate of ovulation and conception can be anticipated in patients with complete GnRH deficiency and hypothalamic amenorrhea. Women with polycystic ovarian syndrome may also benefit from pulsatile GnRH, although rates of ovulation are lower. Pretreatment with a GnRH agonist may improve these rates considerably, but experience is limited. Whether an iv or sc route of administration is chosen, a simplified clinical monitoring protocol can be created which requires a minimum of patient monitoring while assuring maximum safety. Seventy five nanograms per kg appears to be a reasonable initiating dose, with subsequent increases in those who do not respond. The frequency of GnRH administration is best based on the GnRH pulse frequency in normal women. However, further information is needed to determine whether such a variable frequency is clearly superior to a fixed frequency regimen. When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion. Most importantly, and as opposed to exogenous gonadotropin therapy, pulsatile GnRH can be administered by most physicians in the office setting without the necessity of on-line E2 monitoring. This feature will enable more patients to receive treatment by their local physicians, whereas exogenous gonadotropin therapy should be administered by appropriately equipped referral centers. In the future, further studies will be required to determine which other categories of patients might benefit from pulsatile GnRH. ",12 3325,"Was CEPOD right? This retrospective study found that the long-term (greater than 6 months) postoperative survival in ASA 4E and 5E patients was 41% and 21% respectively, in 1986. This supports the Confidential Enquiry into Peri-operative Deaths' recommendation that life-saving surgery should not be withheld from patients who present in so serious a condition that they are unlikely to survive surgery. ",22 768,"Mallory-Weiss syndrome after cardiopulmonary resuscitation. We report hematemesis from Mallory-Weiss tears after successful cardiopulmonary resuscitation (CPR). A computer search of the English language literature disclosed only 3 similar cases, and we review them. This complication of CPR may occur more frequently than recognized and should be prevented by careful technique. ",5 2696,"Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. The airway response and cardiovascular and hypokalaemic effects of fenoterol, salbutamol, and terbutaline given in multiples of standard doses from metered-dose inhalers were studied in ten patients with mild asthma. In a double-blind, crossover, placebo-controlled study the subjects received 2, 6, and 18 puffs of each drug with intervals of 90 min, and forced expiratory volume in 1 s, heart rate, QTc interval, plasma potassium concentration, tremor, and bronchial reactivity to histamine were measured. All three drugs produced similar bronchodilatation. However, the rises in heart rate, QTc interval, and tremor and the fall in plasma potassium were greater after fenoterol than after salbutamol or terbutaline. The maximum mean (SD) increases in heart rate for fenoterol, salbutamol, and terbutaline were 29 (24) bpm, 8 (9) bpm, and 8 (14) bpm, respectively; falls in plasma potassium were 0.76 (0.62) mmol/l, 0.46 (0.32) mmol/l, and 0.52 (0.39) mmol/l, respectively. Fenoterol afforded no additional protection against histamine compared with salbutamol. These findings suggest that at doses based on those used in clinical practice fenoterol causes more adverse effects than salbutamol or terbutaline. The most likely explanation for these effects is that fenoterol has been marketed at a higher dose than the other beta 2-agonists; fenoterol may in addition be less selective for beta 2 receptors. ",19 1557,"Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography. Mitral valve cusp separation on M mode echogram, the mitral valve opening artefact, and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation, while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people, 14 patients with mitral stenosis, 21 patients with left ventricular hypertrophy, and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve, and pulsed and continuous wave Doppler spectra of transmitral flow, with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However, when the onset of Doppler flow was regarded as the end of isovolumic relaxation, the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals, by 25 (15) ms in patients with left ventricular hypertrophy, and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure ""isovolumic relaxation time"". ",13 1668,"Timing and mechanism of in-hospital and late death after primary coronary angioplasty during acute myocardial infarction. The effect of early myocardial reperfusion on patterns of death after acute myocardial infarction (AMI) is unknown. Thus, the mechanism and timing of in-hospital and late deaths among a group of 614 patients treated with coronary angioplasty without antecedent thrombolytic therapy for AMI were determined. Death occurred in 49 patients (8%) before hospital discharge. Four patients died in the catheterization laboratory. Death was due to cardiogenic shock in 22 patients, acute vessel reclosure in 5 patients, was sudden in 8 patients and followed elective coronary artery bypass surgery in 8 patients. Cardiac rupture was observed in only 2 patients after failed infarct angioplasty, and did not occur among the 574 patients with successful infarct reperfusion. Intracranial hemorrhage did not occur. Multivariate predictors of in-hospital death included failed infarct angioplasty, cardiogenic shock, 3-vessel coronary artery disease and age greater than or equal to 70 years. During a follow-up period of 32 +/- 21 months (range 1 to 87), 55 patients died. The cause of death was cardiac in 36 patients, including an arrhythmic death in 23 patients and was due to circulatory failure in 13 others. One patient died of reinfarction due to late reclosure of the infarct artery. Actuarial survival curves demonstrated overall survival after hospital discharge of 95 and 87% at 1 and 4 years, respectively. Freedom from cardiac death at 1 and 4 years was 96 and 92%. Multivariate predictors of late death included 3-vessel disease, a baseline ejection fraction of less than or equal to 40%, age greater than 70 years and female gender. ",13 2010,"Operative findings after percutaneous pulmonary balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Since 1983 percutaneous balloon dilatation of the right ventricular outflow tract has been performed as an alternative to surgical palliation in selected cases of tetralogy of Fallot at the Royal Liverpool Children's Hospital. From 31 December 1984 to 31 December 1988, 27 of these patients underwent subsequent surgical correction. Age at operation ranged from 7 to 58 months (median 2.7 years). The mean interval between balloon dilatation and correction was 15.6 months (range 3-39 months). Two patients had a systemic pulmonary shunt operation performed before dilatation and a further five required one afterwards. Overall 20 (74%) patients had some anatomical alteration as the result of balloon dilatation, while in seven (26%) there was no discernible change in the right ventricular outflow tract. There was no consistent relation between the ratio of balloon size to pulmonary annulus diameter and the morphological findings. Balloon dilatation may obviate the need for systemic-pulmonary shunt at the expense of some structural damage, particularly to the posterior cusp. The present data suggest that dilatation does not bring about growth of the annulus to such an extent that transannular patch is no longer needed at intracardiac repair. ",13 3356,"Afferent nipple valve malfunction caused by anchoring collar: an unexpected late complication of the Kock continent ileal reservoir. In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered. ",22 1729,"Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade. Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems. ",13 3164,"Assessment of patient laboratory data in the acutely ill. Laboratory test results are a valuable source of information. Nurses need to assess laboratory test results as part of the physical assessment of their patients. Comparison of laboratory test results and changes with abnormal physical findings provides the basis for changes in the nursing care plan. Progressive monitoring of laboratory results and prompt interventions might lessen the seriousness of the health problem. In acute care units, the initial group of laboratory tests serves as a baseline for assessing additional test results. Several reference values should be remembered, particularly the electrolytes (potassium, sodium, and calcium), glucose, BUN, creatinine, and albumin. Specific group profiles assist in identifying and in monitoring the patient's health status. Incorporating laboratory test results into the plan and evaluation of care will result in safer and more effective patient care. Referring to laboratory test findings and comparing them with physical assessment findings are required for the delivery of professional nursing care. ",22 2877,"Calcium carbonate gel therapy for hydrofluoric acid burns of the hand. Hydrofluoric acid is used extensively as an industrial cleaning agent for metals and glass. Many workers are injured by cutaneous contact of the acid with exposed skin surfaces, particularly hands. Hydrofluoric acid burns are characterized by delayed onset of symptomatology with skin ulceration, and severe pain may be of extended duration. Treatment of hydrofluoric acid burns traditionally has consisted of local infiltration or intraarterial injections of calcium solutions. These injections are painful and frequently require retreatment. A new treatment utilizing a topical gel of calcium carbonate is described. Nine patients have been treated for hydrofluoric acid burns of the hand with calcium carbonate gel applied topically and covered with occlusive glove dressings. A gel slurry is compounded from calcium carbonate tablets and K-Y Jelly. Fingernails of the affected fingers are removed if a subungual burn is obvious. The gel is put into a surgeon's glove and placed over the burned hand. The patient replaces the glove and slurry every 4 hours for 24 hours. After the first day, the glove is discontinued unless there is resumption of painful symptoms. Full range of motion is encouraged during this interval. The calcium carbonate gel technique was successfully utilized in nine patients with no further need for injection therapy. In these patients, pain relief was obtained within 4 hours of treatment, with no further progression of skin ulceration. No reconstructive procedures were required in any patient, and only one patient did not return to full-duty work within 1 week. There were no long-term sequelae from burns treated with this topical therapy, except one patient, who presenting 24 hours after the burn, developed a digital tip neuroma that was excised. ",20 889,"Changes in self-concept during pulmonary rehabilitation, Part 1. The purpose of this two-part study was to describe changes in self-concept during and after a formal pulmonary rehabilitation program. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future selves on program admission, on program discharge, and 2 to 6 months after home discharge. Mean total self-concept score for the present self significantly increased between program admission and home discharge 3 weeks later (mean change 31.32 +/- 22.04, p less than 0.0001). No significant declines in self-concept were found 2 to 6 months after home discharge (p = 0.39). Men showed a significantly higher change in total self-concept score than women during the 3-week program (p = 0.03). However, the men's change score dropped significantly after home discharge (p = 0.02), suggesting a need for more intensive follow-up care than with women. The self-concept tool in this study provided an easy way to monitor subjective changes in psychologic status. ",7 259,"Delayed reconstruction following Mohs' chemosurgery for skin cancers of the head and neck. The case records of 52 patients with 55 cutaneous neoplasms treated by Mohs' chemosurgery and subsequently reconstructed by plastic surgeons were reviewed to determine if delay between resection and reconstruction adversely affected the outcome of reconstruction. Reconstruction was performed from 5 to 61 days after Mohs' chemosurgery for 45 basal cell carcinomas and 10 other cutaneous neoplasms. There were no complications during the interval between resection and reconstruction. Following reconstruction, minor wound complications occurred in 6% of patients; there were no major complications. Microscopic examination of the re-excised wound revealed residual disease in 2 of 45 cases of basal cell carcinoma and 0 of 10 other cutaneous malignancies. Both patients with residual basal cell carcinomas (i.e., false-negative margins after Mohs' surgery) had presented to the Mohs' surgeon with recurrent tumors. During a follow-up period of 3 months to 3 years after complete resection, recurrent tumor developed in 2 of 45 cases of basal cell carcinoma and 3 of 8 cases of squamous cell carcinoma. Delayed reconstruction, usually 5 to 20 days after Mohs' chemosurgery, can be performed without significant morbidity. Re-excision of the Mohs' chemosurgical wound for pathologic examination can detect residual disease and may be especially indicated for large recurrent wounds. ",3 2439,"Primary hypertriglyceridemia with borderline high cholesterol and elevated apolipoprotein B concentrations. Comparison of gemfibrozil vs lovastatin therapy A common pattern of dyslipidemia is elevated levels of plasma triglyceride, borderline high total cholesterol, reduced high-density lipoprotein, and increased apolipoprotein B. This pattern of dyslipidemia frequently is associated with premature coronary heart disease. Nicotinic acid is the drug of first choice for this pattern. In this study, gemfibrozil and lovastatin were compared for their effects on the overall lipoprotein profile in 13 men with this type of dyslipidemia. Both drugs significantly reduced very-low-density lipoprotein and intermediate-density lipoprotein cholesterol levels, and both modestly raised high-density lipoprotein cholesterol levels. Gemfibrozil therapy, however, failed to reduce total cholesterol or total apolipoprotein B levels, whereas lovastatin therapy lowered levels of total cholesterol by 28%, low-density lipoprotein cholesterol by 33%, and total apolipoprotein B by 32%. Moreover, lovastatin therapy caused greater declines in lipoprotein cholesterol ratios than gemfibrozil therapy. Lovastatin thus seems to have certain advantages over gemfibrozil for treatment of elevated plasma triglyceride levels accompanied by borderline high total cholesterol and raised apolipoprotein B levels; therefore, lovastatin therapy should be considered as one approach for management of this condition. ",17 2804,"The influence of prophylactic orthoses on abdominal strength and low back injury in the workplace This study was designed to determine the effect of multimodal intervention and the prevention of back injury, and to evaluate the adverse side effects of using a lumbosacral corset in the workplace. Subjects were 90 male warehouse workers randomly selected from over 800 employees at a grocery distribution center. Subjects were assigned to three groups: true controls, no back school, no brace orthoses; back school only; and back school plus wearing a custom molded lumbosacral orthosis. Comparisons of pre-testing and 6-month follow-up post-testing for abdominal strength, cognitive data, work injury incidence and productivity and use of health care services were evaluated. Controls and training-only group showed no changes in strength productivity or lost time. Orthoses and training-group showed no changes in strength productivity or accident rate; however, they showed substantially less lost time. This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss. It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries. ",20 147,"Diagnosis of intestinal amebiasis using salivary IgA antibody detection. This investigation sought to determine whether detection of salivary IgA antibodies to Entamoeba histolytica could identify intestinal amebic infections among 223 school children. Four groups of children were identified through coproparasitoscopic examination: E. histolytica as other parasites only (20%); and parasite-free (25%). The diagnostic accuracy of salivary IgA antibodies to an E. histolytica membrane extract was 91.5% (sensitivity, 85%; specificity, 98%), maintaining high predictive value at different prevalences. Also, a positive correlation (r = .753, P less than .001) was observed between fecal E. histolytica membrane antigen levels and salivary IgA antibody activity. Measurement of IgA antibodies in saliva may be useful in diagnosing intestinal infections with E. histolytica within a wide range of prevalences. Moreover, sampling of saliva may be a useful non invasive test for immunoepidemiologic surveys. ",2 829,"Esophageal motility in an adult with a congenital H-type tracheoesophageal fistula. Congenital H-type tracheoesophageal fistulas (TEF) are rare. Long-standing respiratory symptoms are the most common presenting complaints. Patients with these fistulas have a congenital esophageal motor abnormality characterized by uncoordinated, low-amplitude peristalsis of the esophageal body; both low and normal lower esophageal sphincter pressures have been described. These findings persist despite fistula repair. A case history of an adult patient with congenital TEF is presented and the literature is reviewed. This patient is unusual in that esophageal symptoms (dysphagia) were more prominent than the usual respiratory symptoms. ",5 2667,"Cell membrane expression and functional role of the p75 subunit of interleukin-2 receptor in lymphoproliferative disease of granular lymphocytes. The cell membrane expression and functional role of the interleukin-2 receptor (IL-2R) was analyzed in nine patients with lymphoproliferative disease of granular lymphocytes (LDGL) using monoclonal antibodies (MoAbs) specific for the p75 (TU27) and the p55 (anti-Tac) subunits of IL-2R. Four patients were characterized by the proliferation of CD3+CD8+ granular lymphocytes (GL) expressing the alpha/beta T-cell receptor (T alpha beta) and one case by the proliferation of CD3+CD4-CD8- GL expressing the gamma/delta T-cell receptor (T gamma delta); in four additional cases proliferating cells were CD3 negative GL. Consistent with data observed on normal GL, phenotypic analysis demonstrated that patients' GL lack the expression of the p55 IL-2R, whereas the p75 subunit is constitutionally expressed by expanding GL of both T-cell (either T alpha beta and T gamma delta) and natural killer (NK) origin in variable proportions (11% to 94% of cells). The analysis of the cytotoxic and proliferative activity demonstrated that the anti-p55 MoAb failed to inhibit IL-2-mediated activation, whereas a marked inhibition of both cytotoxicity and proliferation were obtained using the anti-p75 chain specific MoAb. These data indicate that the p75 chain of IL-2R is responsible for IL-2 signal transduction in both CD3+ and CD3- LDGL patients' GL. ",19 1099,"Foci of increased T2 signal intensity in MR images of healthy elderly subjects. A follow-up study. An 18-month follow-up study was conducted on 26 healthy elderly subjects with and without foci of increased T2 signal intensity on MR imaging. The subjects did not differ with respect to health status or cognitive performance as measured by the Cognitive Subscale of the Cambridge Mental Disorders of the Elderly Examination and the Mini Mental State Examination at follow-up. There was a significant decline in performance on the Digit Symbol Substitution Test in subjects who had evidence of T2 foci compared to the performance of subjects without T2 foci. This may indicate that the presence of T2 foci is correlated with subtle difficulties in learning and memory. ",9 2766,"Carbon monoxide poisoning. Five-years' experience in a defined population. A review is presented of 302 cases in East Denmark in 1982-1986 in which the manner of death was fatal carbon monoxide (CO) poisoning. The incidence of this far too frequent single-substance poisoning has as yet not decreased over the years despite preventive measures. The number of fatal CO poisoning cases may diminish as a result of a natural gas project in progress. The purpose of this survey, therefore, is to contribute to the evaluation of the actual causes of these fatal poisonings in East Denmark, and to discuss existing measures that prevent gas poisonings, in the expectation of a decline both in gas suicides and in accidental gas poisonings within the next few years. ",20 462,"Metabolism of human gliomas: assessment with H-1 MR spectroscopy and F-18 fluorodeoxyglucose PET Localized hydrogen-1 magnetic resonance (MR) spectroscopy and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were employed to obtain metabolic information from intracranial gliomas. Advantages and difficulties associated with comparison of results from the two modalities were realized. Forty patients were studied with H-1 MR spectroscopy. MR signal intensities from lactate, N-acetylaspartate (NAA), choline, and creatine from a volume of interest containing the tumor and a contralateral volume were obtained and evaluated. NAA signal intensities were generally decreased in the tumor spectra, and choline signal intensities were elevated. H-1 MR spectroscopy was unsuccessful in eight patients, and FDG PET scans were not obtained in four of the patients with successful MR spectroscopic examinations. Lactate signal intensity was detected in 10 of the 28 patients who had successful H-1 MR spectroscopic and FDG PET studies. Lactate signal intensities were observed in lesions shown at FDG PET to be hypermetabolic, as well as in lesions found to be hypometabolic. ",3 11,"Individualizing treatment of vaginal candidiasis. Clinicians have a vast array of effective antimycotics for the treatment of vaginal candidiasis. Multiple topical formulations are available, yet there is little evidence to suggest that formulation per se influences outcome. A growing number of highly effective oral systemic antimycotic agents provide the practitioner with additional options. Treatment regimens have also changed with the introduction of shorter, often single-day/single-dose courses of therapy. Not all therapeutic agents have the same activity against vaginal fungal pathogens in that topical azoles tend to be more active than nystatin. Differences in patient characteristics, however, are more important than the differences between antimycotic agents and therapeutic regimens in determining selection of the appropriate antimycotic. Patients with vaginal candidiasis vary with regard to duration and severity of symptoms and past frequency of attacks, distribution of inflammation, and pregnancy status. The clinician should consider all these variables both in selecting the appropriate antimycotic agent and the route of administration and in planning the duration of therapy. Individualized therapy offers additional benefits to patients, who may then enjoy the maximum advantages of antimycotics now available. ",0 1561,"Use of a guiding catheter for contralateral femoral artery angioplasty. We describe a unique method employing a transseptal sheath as a ""guiding catheter"" that allows contralateral retrograde femoral artery access to perform balloon angioplasty of proximal superficial femoral artery lesions. This technique simplifies arterial access, provides support for crossing lesions, and allows angiographic visualization of target lesions during the procedure. ",13 2358,"Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients. Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia. ",17 2362,"Metabolic effects of combination glipizide and human proinsulin treatment in NIDDM. The effects of 3 mo of treatment with a combination of glipizide and human proinsulin were studied in a small group of closely monitored patients. The patients had non-insulin-dependent diabetes mellitus (NIDDM) and poor glucose regulation, despite maximal sulfonylurea therapy. This was a randomized double-blind placebo-controlled trial in which there were three treatment groups who received either 20 mg glipizide given 30 min before breakfast and dinner and human proinsulin given subcutaneously at bedtime (n = 5), glipizide and human proinsulin placebo (n = 5), or glipizide placebo and human proinsulin (n = 5). Glycemic regulation was assessed by measurements of 24-h plasma glucose profiles and glycosylated hemoglobin. Our observations demonstrate that the combination of glipizide plus human proinsulin was more effective than either agent alone in controlling overall glycemia in patients with NIDDM. The data support the concept of use of an agent during the day that has its major effects postprandially and another agent at bedtime that is relatively hepatospecific. ",17 3106,"Cerebral blood flow in acute mountain sickness. Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS. ",22 120,"Measles antibody: reevaluation of protective titers. A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level. ",1 257,"Flow cytometric evaluation of chemosensitive and chemoresistant head and neck tumors. For patients with head and neck squamous carcinoma, a clinical response to induction chemotherapy has correlated with a survival advantage. Similarly, patients with diploid tumors have displayed a survival advantage when compared with patients with aneuploid tumors. This study examined DNA content in 33 patients who had undergone induction chemotherapy as part of two clinical protocols to determine if there was a correlation between the patients with diploid tumors and the patients with a clinical response to chemotherapy. Although patients with stage III tumors had a longer disease-free survival than stage IV patients (p less than 0.0002), the addition of DNA content information did not improve the ability to predict response. Specifically, there was no correlation between DNA content and the response to chemotherapy. In addition, for this group of patients, a diploid DNA content was not correlated with a survival advantage. We conclude that DNA content information did not add significantly to the prediction of clinical outcome in these patients who received induction chemotherapy. ",3 612,"Giant-cell reparative granuloma of the hand and foot bones. Giant-cell reparative granuloma (GCRG) is an uncommon benign reactive intraosseous lesion. It occurs in the skull, jaw, hand, foot, and facial bones and rarely in other skeletal sites. It is a solitary, lytic, expanded lesion and infrequently may extend into the surrounding soft tissue. Histologically, it is composed of fibrous stroma with spindle-shaped fibroblasts, multinucleated giant cells, and inflammatory mononuclear cells. Areas of hemorrhage are uniformly present. It may be difficult to distinguish this entity from an aneurysmal bone cyst, giant-cell tumor, or brown tumor of hyperparathyroidism because of roentgenographic and histologic similarities. Accurate diagnosis is essential for appropriate treatment; serum calcium, phosphorus, and parathyroid hormone levels should be measured. Curettage and bone graft are effective treatments for both primary lesions and recurrences. Second recurrences are rare. ",4 2825,"Unexpected geographic variation in rates of hospitalization for patients who have fracture of the hip. Medicare enrollees in the United States. With the use of data from hospitals for fiscal year 1985, we calculated the rates of hospitalization for fracture of the hip, by state of residence, for all enrollees in Medicare who were sixty-five years old or older; we adjusted for age and race. The rate of fracture of the hip was highest in the South and lowest in the Northeast, especially in women. The cause of this difference is not known. ",20 1311,"Economics of screening for carcinoma of the prostate. The proposition of whether to adopt a system of mass screening for carcinoma of the prostate in the U.S. is well suited to the clinical decision analysis approach. The authors demonstrate this by using available data, which suggest that offering a screening program to all men ages 50 to 70 would be prohibitively expensive. The method also permits calculation of the eventual morbidity of screening and its costs. This analysis demonstrates the importance of attempting to predict ultimate patient outcomes before implementing any health care strategy as standard. ",11 1237,"Synaptic transmission in human neocortex removed for treatment of intractable epilepsy in children. Synaptic transmission to pyramidal cells was studied in slices of neocortex resected from infants and children (n = 10, age 8 months to 13 years) undergoing surgical treatment for intractable epilepsy. Most specimens were from the least abnormal area of the resection. Stable intracellular recordings could be obtained for up to 8 hours. Most of the recorded neurons had electrophysiological characteristics similar to those of regular-firing pyramidal cells and were in layers III to V, which was confirmed by intracellular staining with Lucifer yellow. Local extracellular stimulation evoked a sequence of excitatory and inhibitory postsynaptic potentials. After application of the gamma-aminobutyric acid antagonist, bicuculline (10-30 microM), extracellular stimulation induced large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous bursts occasionally occurred in bicuculline. This effect of bicuculline was observed in all the tissue samples, even those from infant patients (n = 4, age 8-16 months). Kynurenic acid depressed or abolished both spontaneous and stimulation-induced bursts. The competitive antagonist for N-methyl-D-aspartate receptors, DL-2-amino-5-phosphonopentanoic acid decreased the duration of bicuculline-induced bursts. These data provide evidence that, similar to rat and cat neocortex, excitatory and inhibitory amino acids are important transmitters to pyramidal cells in immature human neocortex. ",9 492,"Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. Clinical, histopathologic, and immunohistochemical analyses. An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which usually shows the same phenotype as CTCL, i.e., a helper/inducer T-cell phenotype (CD4+CD8-), and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. In this study, we demonstrated differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i.e., CD4-CD8-, CD4+CD8-, and CD4-CD8+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL-2R), CD71 (OKT9), HLA-DR, and HLA-DQ was higher in the skin-infiltrating ATL cells than in CTCL cells. Expression of CD29 (4B4) was high, and that of CD45RA (2H4) was low in both the skin-infiltrating ATL and CTCL cells compared with the peripheral blood and lymph node ATL cells. Expression of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotypic difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin-infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL is a disease distinct from CTCL. ",3 1600,"The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 AM, 9 AM, 11 AM, 1 PM, 2 PM, 4 PM, 6 PM and 7 PM. On one day each patient received isosorbide dinitrate at 8 AM, 1 PM and 6 PM in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 AM dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 AM exercise time had returned to control level. One hour after the 1 PM dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later. ",13 3066,"Neurological phenomena during emergence from enflurane or isoflurane anaesthesia. During emergence from anaesthesia, transient neurological signs that would usually be considered pathological may appear. The objective of this randomized, patient (n = 30) and observer-blinded study was to compare prospectively the incidence and duration of post-anaesthetic neurological abnormalities in healthy patients undergoing minor elective procedures following thiopentone and succinylcholine induction, and enflurane-N2O or isoflurane-N2O anaesthesia. Patients were studied for 60 min after anaesthesia. Arousal state, muscle tone, deep tendon reflexes, plantar reflex, sustained clonus, shivering, intense muscular spasticity and temperature were assessed. Results of neurological examination were correlated with the patient's state of arousal. Transient emergent neurological abnormalities occurred more frequently following enflurane-N2O anaesthesia than isoflurane N2O anaesthesia. This was statistically significant (P less than 0.05) for quadriceps hyperreflexia, upgoing toes (positive Babinski reflex) and intense muscular spasticity. Neurological abnormalities occurred most commonly 5-20 min after anaesthesia and all abnormalities resolved within 60 min. Following enflurane anaesthesia, as patients became more alert the incidence of abnormalities declined, while the arousal state did not affect the incidence of abnormalities after isoflurane. There was no significant difference between axillary temperatures of those patients who shivered and those who did not. In conclusion, temporary emergent neurological abnormalities occurred more often following enflurane-N2O than after isoflurane-N2O anaesthesia. ",22 1422,"Non-heparin hemodialysis with oral administration of newly developed antiplatelet agent. Non-heparin hemodialysis (HD) was successfully done in anuric dogs with the oral administration of a newly developed antiplatelet agent, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, (E5510, Eisai Pharmaceutical Co., Japan). In the current study, the antithrombotic effect of E5510 during HD was investigated. Eleven mongrel dogs with bilateral ureteral ligation were given 0.1 mg/kg of E5510 orally 1 hr before undergoing 4 hr HD using hollow fiber dialyzers, (PMMA 5, regenerated cellulose 6) without heparin and under general anesthesia. Blood samples were taken before the administration of E5510 and before and 1, 2, 3, and 4 hr after starting HD; blood counts, hematocrits, blood chemistries, and plasma thromboxane levels (TxB2) were examined. Platelet aggregation, activated clotting times (ACT), and activated partial thrombin times (APTT) were also measured, and sequential plasma E5510 concentrations were determined. In 10 of 11 anuric dogs, non-heparin HD was successfully done with minimal clotting in the dialyzer and drip chambers. The maximum aggregation rate was depressed to less than 20% of the initial value throughout HD. Plasma TxB2 concentration was depressed, and ACT and APTT were mildly, but not significantly prolonged. Neither hemorrhagic complications nor other side effects of E5510 were observed. ",11 150,"Geographical distribution of Plasmodium falciparum erythrocyte rosetting and frequency of rosetting antibodies in human sera. Uninfected erythrocytes bind spontaneously to those infected with certain strains of Plasmodium falciparum. This is known as spontaneous erythrocyte rosetting. We have studied the occurrence and frequency of rosetting in 75 fresh patient isolates and have identified rosetting strains from Africa, South America, and Asia. Rosetting was present in 49% of the isolates tested; the frequency of rosetting red blood cells (RBC) in individual isolates was 0-75% when scored during the first cycle of in vitro growth. Rosetting antibodies were found in 15 out of 73 (21%) Liberian sera as measured by disruption of rosettes in vitro. However, antibodies able to inhibit CD36 dependent cytoadherence of P. falciparum-infected RBC were not detected in these sera. Erythrocyte rosetting is a geographically widespread phenomenon. Rosetting antibodies seem to be induced by natural infection and the molecular mechanism of rosette formation seems distinct from that of endothelial cytoadherence. ",2 3077,"Late results with Carpentier-Edwards porcine bioprosthesis. From 1977 to 1984, 429 patients underwent aortic valve replacement (AVR), and 339 underwent mitral valve replacement (MVR) with a Carpentier-Edwards bioprosthesis. Early mortality for AVR was 4.6% (isolated AVR, 1.9%) and for MVR was 5.3% (isolated MVR, 4.1%). Follow-up was 99.3% complete at a mean of 5.9 years. Actuarial event-free rates at 10 years for AVR and MVR were, respectively, 1) for structural valve deterioration, 91.4 +/- 3.2% versus 75.1 +/- 4.0% (p less than 0.01); 2) for nonstructural dysfunction, 100% versus 97.8 +/- 1.6% (p = NS); 3) for thromboembolism, 90.6 +/- 2.3% versus 87.3 +/- 2.6% (p = NS); 4) for anticoagulant-related bleeding, 95.3 +/- 1.1% versus 88.6 +/- 2.4% (p = 0.05); 5) for endocarditis, 87.8 +/- 5.7% versus 90.6 +/- 2.4% (p = NS); 6) for reoperation, 91.0 +/- 2.5% versus 74.4 +/- 3.7% (p less than 0.01); 7) for valve-related mortality, 76.1 +/- 6.9% versus 71.4 +/- 5.2% (p = 0.01); 8) for permanent physical impairment, 85.0 +/- 3.0% versus 71.5 +/- 3.6% (p less than 0.01); and 9) for combined operative mortality, valve-related mortality, and reoperation, 68.7 +/- 6.4% versus 51.5 +/- 4.9% (p = 0.01). No structural valve dysfunction was observed in any AVR patient whose valve was inserted after age 70. Age at operation was the only factor that predicted structural valve deterioration (p less than 0.01). ",22 221,"Male breast cancer. Male breast cancer is uncommon but important. The diagnosis is easily made by breast biopsy, and patients are presenting earlier in the course of the disease than in the past. Despite this, patients are often first seen with tumors that have metastasized to the axillary nodes, which markedly decreases the survival rate. Therapy of localized disease includes simple excision, modified radical mastectomy, and radical mastectomy, but there is no consensus for which operation is appropriate. Radiation therapy should be strongly considered in patients with metastases to the axillary nodes, but the role of adjuvant hormonal therapy or chemotherapy is unclear. For treatment of disseminated disease, tamoxifen seems to be replacing orchiectomy. The favorable response rate, especially in patients with estrogen-receptor-positive tumors, the lack of side effects, and the high level of patient acceptability make it an attractive therapeutic choice. ",3 424,"Increase of beta 1-6-branched oligosaccharides in human esophageal carcinomas invasive against surrounding tissue in vivo and in vitro. The -GlcNAc beta 1-6Man- (beta 1-6) branched N-glycosidic oligosaccharides expressed on tumor cells have been found to contribute to malignant and metastatic potential in experimental tumor models. Phaseolus vulgaris leukoagglutinin (L-PHA) requires the beta 1-6-linked lactosamine antenna for high-affinity binding and was used histochemically to characterize the distribution of these sugar structures in human esophageal squamous cell carcinomas from 42 patients. Leukoagglutinin-reactive carcinoma cells in the invasive tumors were distributed predominantly on the outer surface of the tumor adjacent to the surrounding tissue. Furthermore, when TE 1 cells, a human esophageal squamous cell carcinoma line, were cultured in a collagen gel matrix to obtain colonies in a three-dimensional form, these colonies exhibited high affinity for L-PHA binding only in the outer cell layer facing the collagen matrix, unrelated to the cell growth cycle. These findings suggest that the increase in beta 1-6-branched oligosaccharides in esophageal carcinomas is an important trait of the tumor in the invasion into the surrounding tissue. ",3 2823,"Alcohol and trauma. Countermeasures to alcohol-related trauma are essential. The public perception that there is low risk of detection and punishment for alcohol-precipitated violence is being addressed. Current legislation is aimed at decreasing the availability of alcohol (e.g., adjusting legal drinking age, decreasing the serum alcohol intoxication limit, restricting the sale of alcoholic beverages at public events), increasing detection (e.g., greater driver surveillance, increased number of dedicated personnel), strengthening legal penalties for alcohol-related offenses, and mandating rehabilitative therapy. Physicians can intervene in the alcohol-trauma cycle. Unfortunately, they are notably poor in detecting the patient with alcohol-related injury. Moreover, physicians infrequently refer these patients to facilities and personnel that are expert in alcohol detoxification and rehabilitation. Recidivism can be positively impacted by physicians who are sensitive to and versed in the medical and social patterns of alcohol abuse. ",20 1248,"Phenotypic and functional characterization of T cells from patients with myasthenia gravis. A study of cell surface phenotypes of PBL of myasthenia gravis (MG) patients showed that their T cells had a significantly higher percentage of 4B4+ T cells (the helper/inducer subset) than age- and sex-matched controls. The PBL of MG patients proliferated significantly higher than those of normal subjects (NS) in response to the purified alpha chain of the acetylcholine receptor (AChR). Anti-AChR antibody was present in sera of 88% of MG and none of the NS. The PBL B cells from MG only, when cultured with autologous T cells and stimulated with either pokeweed mitogen (69%), or AChR-alpha chain (38%), secreted antibody to AChR-alpha chain, whereas T and B cells alone secreted no antibody. T cells from PBL of MG patients were more readily cloned than T cells of NS, by limiting dilution, in the presence of recombinant IL-2 and in the absence of AChR-alpha chain. About 50% of T cell clones from MG patients, compared to none from NS, proliferated to AChR-alpha chain. This response was HLA-DR restricted. MG T cell clones did not display significant cytotoxic activity, as compared to control T cell clones. Our results indicate that in MG, 4B4+ regulatory T cells play their role in the pathogenesis of MG, not by cytotoxicity, but more likely by their ability to stimulate specific antibody production by B cells. ",9 2089,"Complement activation and use of a cell saver in cardiopulmonary bypass. Complement activation was evaluated in ten patients undergoing cardiopulmonary bypass (CPB) and intraoperative blood salvage with a cell saver (CS) to assess the inflammatory response related to the CS. The washed red blood cell concentrate was reinfused after protamine injection. Plasma C3a was measured by radioimmunoassay preoperatively, 5 min before CPB, at 5, 60, and 90 min during CPB, 5 min after protamine infusion, at the end of surgery, and after 24 hr. In addition, a clinical score based on renal, pulmonary, neurologic, and myocardial postoperative evolution was given (0-8) to every patient. Results were compared with the C3a changes and clinical scores obtained from 26 routine (no CS) cardiac surgical patients. Results showed maximal C3a generation after protamine and no further activation in cases of CS concentrate reinfusion, which ranged from 400 ml to 2,000 ml. No difference in clinical score was observed between the CS (1 +/- 1) and control (0.85 +/- 0.6) groups. The authors conclude that the CS does not enhance complement activation resulting from extracorporeal circulation and can be safely used as a blood saving strategy in cardiac surgery. ",13 1394,"Extracorporeal removal of anti-HLA antibodies in transplant candidates. We report on the results of a clinical trial in which 14 transplant candidates were treated with an extracorporeal immunoadsorption system using Protein A that selectively removes immunoglobulin from plasma; we also assessed the dynamics of anti-HLA antibody as a model of IgG removal and re-equilibration, as well as the clinical safety of the procedure. At the end of a treatment course, plasma IgG levels were reduced by 90% +/- 8% of control values (P less than 0.01). In contrast, albumin levels were reduced by only 15% (P less than 0.05). Specific cytotoxic anti-HLA antibody titers were reduced by approximately 18-fold. Panel reactivity was measured as the proportion of a 40-member cell donor panel killed by patients' serum in the presence of complement; in nine of the 14 patients, there was a significant reduction in this parameter (range, 23% to 87%). During the 4-week follow-up period, anti-HLA antibody titers returned to baseline levels. There were no remarkable changes observed in blood chemistries, nor were there any unanticipated adverse reactions seen in the patients treated. We conclude that selective extracorporeal immunoadsorption is a safe and effective way of removing IgG-type antibodies, with potential application to reduction of HLA antibodies in transplant candidates. ",11 2179,"Rheologic properties of mixed hemoglobin gels: deoxyhemoglobins S and F. To obtain new information concerning the behaviors--and in turn, the structures--of gels formed from mixtures of S and F hemoglobins, their rheologic properties have been characterized by stress relaxation. The variables manipulated were (1) initial total hemoglobin concentration; (2) mole fraction of hemoglobin S present in the mixture; (3) hemoglobin F as only intact tetramer or as both tetramers and hybridized hemoglobin; (4) hemoglobin F as predominantly G gamma, A gamma, or a mixture of gamma chain types; (5) annealing time; (6) shear history, (7) temperature; and (8) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin S and F gels were less solid than pure hemoglobin S gels of similar initial total hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by annealing time, shear history, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin S and F gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. Pathophysiologic implications of these findings for various sickle cell disorders are proposed. ",14 1659,"Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease. Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts. ",13 2412,"Reduced insulinotropic effects of glucagonlike peptide I-(7-36)-amide and gastric inhibitory polypeptide in isolated perfused diabetic rat pancreas. The pathophysiological role of incretin in diabetes mellitus has not been established. We therefore examined the effects of glucagonlike peptide I-(7-36)-amide (truncated GLP-I) and gastric inhibitory polypeptide (GIP) on insulin and glucagon release from isolated perfused pancreases of diabetic rats (12-14 wk of age, mean +/- SE fasting plasma glucose 8.9 +/- 0.6 mM, n = 25) after an injection of 90 mg/kg streptozocin on the 2nd day after birth and compared the results with those of nondiabetic control rats. In diabetic rats, the infusion of 1 nM GLP-I or GIP in perfusates with varying glucose concentrations (2.8, 5.6, 8.3, 11.1, or 22.2 mM) caused a nearly equal degree of insulin stimulation from a similar basal insulin level. Meanwhile, basal and GLP-I- or GIP-stimulated insulin release increased in correlation with the ambient glucose concentration in nondiabetic rats. The degree of stimulation of insulin release at glucose concentrations of 5.6 mM in diabetic rats was approximately 33% that of nondiabetic rats. The stimulation potency was the same between GLP-I and GIP. The insulin treatment for diabetic rats (5 U/kg NPH insulin at 0900 and 2100 for 6 days) brought only a slight improvement in the glucose dependency of GLP-I-stimulated insulin release. The effects of GLP-I and GIP on glucagon release were completely opposite. GLP-I suppressed release; GIP stimulated it. In diabetic rats, the degree of suppression by GLP-I and stimulation by GIP were almost the same with similar basal glucagon levels in the perfusate with varying glucose concentrations. ",17 573,"Internists' practices in health promotion and disease prevention. A survey. OBJECTIVE: To estimate internists' use of disease prevention and health promotion activities, and to explore demographic, professional, behavioral, psychological, cognitive, and organizational factors associated with the use of such practices. DESIGN: Mail survey. SETTING AND SUBJECTS: A sample of 2610 members and fellows of the American College of Physicians (ACP) participated in the study. They engaged in patient care activities more than 20 hours per week and were stratified by gender and region. They lived in four geographic areas of the United States (Northeast, Southeast, Central, and West), comprising 21 ACP regions. MEASUREMENTS: A questionnaire requesting background information as well as information about personal health; record keeping; use of immunizations (pneumococcal, influenza, tetanus, hepatitis B); use of screening tests and procedures for detecting cancer (breast examination, Papanicolaou smear, stool occult blood test) and other diseases (electrocardiograms, cholesterol level tests, chest radiographs); and behavioral counseling to promote health (in the areas of smoking, exercise, and alcohol and seat belt use). MAIN RESULTS: Internists used effective preventive interventions less frequently and ineffective practices more frequently than experts recommend. Internists' use of health promotion and disease prevention activities is associated with habit, attitude, and a lack of adequate knowledge. Younger physician age, general internal medicine practice, and personal health promotion and disease prevention practices were strongly associated with more appropriate use of recommended practices (P less than 0.01). CONCLUSIONS: Internists' use of disease prevention and health promotion activities falls short of expert recommendations. Programs to improve the delivery of preventive services might be aimed at improving physicians' personal health practices, might be directed toward patients, and might include the development of effective systems to remind physicians. ",3 2791,"Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines. ",20 942,"Chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease is indeed a multifaceted illness. The obstructive picture is the result of multiple pathologic processes. The most common cause is cigarette smoking. The key to decreasing the incidence of this disease is education to prevent people from starting to smoke and to educate those who do smoke to stop. The therapeutic management involves numerous medications, oxygen, and physiotherapy. Unfortunately, the pharmacologic management remains largely empiric with sympathomimetics, anticholinergics, methylxanthines, and corticosteroids. These agents, especially methylxanthines and corticosteroids, are not without considerable toxicity. Therefore, embarking on a pharmacologic plan requires weighing the risk to benefit ratio carefully and having a comprehensive plan to assess subjectively and objectively the efficacy and toxicity of the chosen therapy. ",7 2662,"Clearance of 99mTc-DTPA in pigeon fancier's hypersensitivity pneumonitis. The rate of clearance of inhaled 99mTc-DTPA was measured in 20 nonsmoking pigeon fanciers and 7 control subjects. The degree of their avian contact and pigeon-related symptoms were noted, humoral immune response in the form of IgG antibody to pigeon gamma globulin was quantified, and diffusing capacity and total lung capacity were measured. Thirteen fanciers who had a high level of antibody had increased rates of clearance of 99mTc-DTPA (mean half-time clearance of 16.8 [+/- SEM 2.02] min [p = 0.001]) even if they were asymptomatic and even if their diffusing capacity and total lung capacity were normal. Seven control subjects without exposure to pigeon-derived antigens had normal clearance (mean 72.6 [+/- 5.98] min), and seven fanciers with antigen exposure but without an antibody response had intermediate rates of clearance (mean 42.57 [+/- 5.11] min). Clearance was not directly related to the indices of intensity and duration of antigen exposure. The measurement of rate of clearance of 99mTc-DTPA in pigeon fanciers can identify an alteration in pulmonary integrity more subtle than found with conventional pulmonary function tests and may therefore be a useful test for studying the pulmonary response to inhaled antigen and for detecting the earliest stages in the evolution of hypersensitivity pneumonitis. ",19 1382,"Bidirectional incompatibility between conspecific populations of Drosophila simulans Cytoplasmic incompatibility (CI) describes the phenomenon whereby eggs fertilized by sperm from insects infected with a rickettsial endosymbiont fail to hatch. Unidirectional CI between conspecific populations of insects is a well documented phenomenon. Bidirectional CI has, however, only been described in mosquito populations, and recently between closely related species of parasitic wasps, where it is of interest as both an unusual form of reproductive isolation and as a potential means of insect population suppression. Here we report on the first known example of bidirectional CI between conspecific populations of Drosophila simulans. Further, we show that defects as early as the first cleavage division are associated with CI. This observation suggests that the cellular basis of CI involves disruption of processes before or during zygote formation and that CI arises from defects in the structure and/or function of the sperm during fertilization. ",11 2465,"Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. OBJECTIVE: To determine whether insulin resistance or insulin deficiency is primary in the pathogenesis of type II diabetes. DESIGN: Cohort analytic study of persons with normal glucose tolerance but with a high risk for developing type II diabetes (average follow-up time, 13 years). SETTING: Outpatients had an intravenous glucose tolerance test and were contacted periodically to ascertain diagnoses of diabetes. PARTICIPANTS: One hundred and fifty-five normal offspring, ranging in age from 16 to 60 years, of two parents with type II diabetes and 186 normal control subjects in the same age range who had no family history of diabetes. MEASUREMENTS AND MAIN RESULTS: Two phenotypic characteristics distinguished the offspring of diabetic parents from control subjects. They had slower glucose removal rates (Kg) (P less than 0.01) and higher insulin levels (fasting and during the second phase of insulin response to intravenous glucose; P less than 0.0001) than did control subjects, even after adjustment for differences in obesity. Sixteen percent of the offspring developed type II diabetes. Mean Kg at baseline was 1.7%/min among offspring who subsequently developed diabetes, 2.2%/min among offspring who remained nondiabetic, and 2.3%/min among control subjects. Corresponding means for first-phase insulin were 498, 354, and 373 pM, respectively, whereas second-phase insulin means were 329, 117, and 87 pM, respectively. In multivariate analysis, low Kg and high serum insulin levels independently increased the risk for developing diabetes among the offspring of diabetic parents. CONCLUSIONS: One to two decades before type II diabetes is diagnosed, reduced glucose clearance is already present. This reduced clearance is accompanied by compensatory hyperinsulinemia, not hypoinsulinemia, suggesting that the primary defect is in peripheral tissue response to insulin and glucose, not in the pancreatic beta cell. ",17 2860,"Anomie, alcohol abuse and alcohol consumption: a prospective-analysis. Cross-sectional and 36-month prospective analyses of the relationships among anomie and both alcohol abuse and alcohol consumption patterns provided little support that anomie was directly associated with ethanol ingestion patterns in a sample of 302 male air traffic controllers. This lack of association was observed for self-reported alcohol consumption, interview-established alcohol abuse and biochemical markers of alcohol intake. In addition, anomie was not predictive of change in alcohol use/abuse over 36 months, controlling for baseline levels of alcohol use and abuse and for relevant demographic factors. Measurement of anomie and alcohol use/abuse, the relative importance of anomie in various socioeconomic groups and issues related to prospective research on this topic are discussed. ",20 3250,"Treatment of chronic facial palsy by transplantation of the neurovascularized free rectus abdominis muscle. We performed neurovascularized free rectus abdominis muscle transplantations in two patients with chronic facial palsy. In one patient, the postoperative course was uneventful, but the patient died from rupture of esophageal varices. In the other patient, both morphologic and functional results were satisfactory. Therefore, the rectus abdominis muscle is considered to be a suitable donor for muscle transplantation for the treatment of chronic facial palsy. The rectus abdominis muscle is advantageous in that (1) simultaneous operations by two teams are possible with the patient in the supine position, (2) it is supplied by long nerves and long and large vessels, (3) it is flat and consists of segments with appropriate lengths, (4) the force and distance of contraction are appropriate, and (5) the tendinous intersections are suitable for anchoring sutures. ",22 3107,"Distribution of pulmonary capillary transit times in recruited networks. When pulmonary blood flow is elevated, hypoxemia can occur in the fastest-moving erythrocytes if their transit times through the capillaries fall below the minimum time for complete oxygenation. This desaturation is more likely to occur if the distribution of capillary transit times about the mean is large. Increasing cardiac output is known to decrease mean pulmonary capillary transit time, but the effect on the distribution of transit times has not been reported. We measured the mean and variance of transit times in single pulmonary capillary networks in the dependent lung of anesthetized dogs by in vivo videofluorescence microscopy of a fluorescein dye bolus passing from an arteriole to a venule. When cardiac output increased from 2.9 to 9.9 l/min, mean capillary transit time decreased from 2.0 to 0.8 s. Because transit time variance decreased proportionately (relative dispersion remained constant), increasing cardiac output did not alter the heterogeneity of local capillary transit times in the lower lung where the capillary bed was nearly fully recruited. ",22 1630,"Contribution of transesophageal echocardiography to patient diagnosis and treatment: a prospective analysis. The capability of transesophageal (TEE) versus transthoracic (TTE) echocardiography as a diagnostic tool in clinical practice was prospectively examined in 86 consecutive cases. A conclusive diagnosis was possible in 95% with TEE, whereas the same result was achieved in 48% by TTE. Specifically, TEE provided a conclusive diagnosis in 14 of 16 cases of infective endocarditis, while TTE gave this result in 4 of the 16 cases (p less than 0.001). Similarly, TEE allowed a conclusive diagnosis in 11 of 11 instances of aortic dissection, while TTE gave this indication in two cases (p less than 0.001). TEE was similarly effective in eight of eight cases of atrial thrombi, whereas TTE gave the diagnosis in three of eight cases (p less than 0.01). In five subjects with intracardiac masses, TEE gave a conclusive diagnosis in all five, whereas TTE was able to diagnose conclusively in one subject (p less than 0.02). In seven patients with mitral regurgitation, TEE gave the conclusive diagnosis in all seven and TTE was able to provide this information in four (p = NS). TEE was able to provide a conclusive diagnosis in four patients with aortic insufficiency, and TTE gave the same information in two of the four (p = NS). In 14 patients with prosthetic valve dysfunction, TEE gave the diagnosis in 12 and TTE gave it in eight patients (p = NS). Both methods gave a conclusive diagnosis in 13 out of 13 cases of mitral stenosis (p = NS). Also, TEE provided a conclusive diagnosis in eight of eight patients with adult congenital heart disease and TTE gave this information in four (p = NS). ",13 3125,"The Senior Care Study. The optimal use of medications in acutely ill older patients. Geriatric assessment units have improved pharmacotherapy for their patients by decreasing the number of medications prescribed. The Senior Care Study, a randomized controlled trial, compared a multidisciplinary-team approach to patient care to the standard medical practice of the institution. As a part of the trial, the effectiveness of an interdisciplinary team intervention in improving the use of medications was studied. Study goals were to decrease medications used, decrease unnecessary medications, and improve medication choices in our acutely ill inpatient population. A pharmacist interviewed all experimental patients and patient records, and presented medication concerns and recommendations at a team conference. Medications were counted on admission and on the third day, sixth week, and third month after randomization. Medications were paired with patient problems. Medication:problem pairs were judged as inappropriate choices if there were potential side effects that would affect patient function, and if better alternatives were available. The 215 control and 221 experimental patients in the study were similar in age, sex, place of origin, and number of medications on admission. Experimental patients took fewer medications than controls on the third day (5.3 versus 5.9, P less than .05). Experimental patients received fewer multiple unpaired medications (11% versus 19%, P less than .025) and fewer inappropriate medication choices (20% versus 37%, P less than .005). The results suggest that the team intervention was effective in improving pharmacotherapy in the acute-care setting. ",22 730,"Exacerbation of chronic active hepatitis type B after short-term corticosteroid therapy resulting in fatal liver failure. The case of a 36-yr-old male with chronic active type B hepatitis in whom 4-wk prednisone therapy resulted in prolonged and fatal exacerbation of liver disease is described. Thus, short-term corticosteroid therapy may in some patients have disastrous effects on the course of chronic active hepatitis B. ",5 2102,"Comparison of right ventricular and biventricular circulatory support in a porcine model of right heart failure. The effects of right ventricular (RVAD) and biventricular assist devices (BVAD) in an acute porcine model of right heart ischemic failure produced by occluding the right coronary artery for 2 min (RCAO) were compared. Right and left ventricular pressures were measured with Millar transducers and respective septal-to-free wall dimensions (RVSFWD, LVSFWD) with ultrasonic crystals. RCAO alone resulted in significant right heart failure, marked by a 36 +/- 5% reduction in cardiac output (pulmonary artery flow) and a 54 +/- 16% reduction in RV stroke work. Isolated RVAD significantly improved the hemodynamic conditions by restoring pulmonary blood flow and left heart filling to control levels. RVAD also resulted in reduced RVSFWD to control levels and increased LVSFWD via a rightward septal shift due to right heart unloading. Biventricular support resulted in the same hemodynamic improvement, but estimated LV peak systolic wall stress was reduced by 65 +/- 15% compared with control, due to concomitant LV unloading and reductions in LVSFWD. Therefore, either right or biventricular devices are effective in treating RV failure. The advantage of biventricular support is that the left ventricle is also unloaded, thus allowing improved circulatory support with minimal LV wall stress. ",13 668,"Incidence of cervical spinal stenosis in professional and rookie football players. Sagittal canal/vertebral body ratios were measured on cervical spine lateral radiographs of 124 professional football players and 100 rookie football players. A total of 894 levels were measured in 224 players. Thirty-two percent (40) of the 124 professional football players, and 34% of the 100 rookies had a ratio of less than 0.80 at one or more levels from C3 to C6. The 0.80 ratio has been considered indicative of cervical spinal stenosis. This is the first time that the incidence of spinal stenosis, as determined by Torg's ratio, has been demonstrated in a population of professional and rookie football players. Because one-third of this population has cervical spinal stenosis as determined by the Torg ratio, other factors should be considered in the evaluation of a player with a transient quadriplegic episode when making continued play decisions. ",4 2428,"Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulin-stimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800-1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = -0.43; P less than 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = -0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin-stimulated glucose uptake in the patients we studied. ",17 2562,"Formoterol in the treatment of nocturnal asthma. Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared with that of 200 micrograms of albuterol (salbutamol) in a single-center, double-blind, randomized within-patient study. The drugs were given as aerosols by MDI to 16 patients with nocturnal asthma in a stable phase. The inhalations were given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2, 6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of formoterol was significantly higher than that after albuterol (ANCOVA: p = 0.008), and this was still the case 12 hours after the test dose at 10 AM the following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic starting value after albuterol, whereas it remained at least 10 percent above the formoterol inhalation. Five patients required rescue therapy after albuterol and two after formoterol. We conclude that formoterol in a dose of 12 micrograms via MDI confers good protection against nocturnal asthma; this was only insufficient for some patients with severe asthma, and further studies with higher dosages in these patients are clearly indicated. ",19 1459,"Contraception and ectopic pregnancy risk. Studies of the association of ectopic pregnancy with contraception have generated a conflicting array of results because of methodologic differences between studies. We estimated the absolute incidence rates of ectopic pregnancy for various contraceptives by multiplying the pregnancy rate by the proportion of pregnancies with ectopic implantation for each method. Our results indicated a more than 500-fold difference in ectopic pregnancy incidence, from a low of 0.005 ectopic pregnancies per 1000 women years of oral contraception or vasectomy to a high of 2.6 per 1000 women years of no contraception. These estimated incidence rates should be useful for clinicians and patients seeking to better understand the risks and benefits of contraceptives. ",12 3265,"Relation between transcardiac and transthoracic current during defibrillation in humans. Conceptually, transthoracic defibrillation threshold current can be considered a function of at least two quantities. It is directly proportional to the transcardiac threshold current and inversely proportional to the transcardiac current fraction (FC) or the ratio of transcardiac and transthoracic current. Although experimental and theoretical estimates of FC have been as high as 45%, previous measurements in humans have not been made. This study was designed to quantify FC in humans. During intraoperative testing of the automatic implantable cardioverter defibrillator, transthoracic rescue shocks of 200-400 J were delivered when the device failed to defibrillate. Simultaneous transthoracic voltage (VT) and transcardiac voltage (VC) between two implanted epicardial patch electrodes were measured. The ratio, VC/VT, was 0.04 +/- 0.03 (mean +/- SD) in 10 patients. In 16 dogs, a comparison was made between direct measurement of FC and VC/VT. FC was determined with a specially designed electrode system, which was calibrated to account for field distortion introduced by the electrodes. There was no significant difference between FC and VC/VT, which were both approximately 0.05, suggesting that VC/VT was statistically equivalent to FC. The results of this study, therefore, indicate that during transthoracic defibrillation in humans, approximately 4% of transthoracic current traverses the heart. This relatively small percentage of current results from the existence of parallel pathways, such as the thoracic cage and lungs, which shunt current around the heart. ",22 1286,"A miniaturized vitrectomy system for vitreous and retinal biopsy. The author has developed a miniaturized vitrectomy system and its accessories with the size of a 23-gauge needle. The hand-piece can be inserted inside the eye through a Ziegler knife track. This instrument can be used for ""atraumatic"" removal of vitreous biopsy specimens and for removal of small pieces of retina. The system also seems to have application in vitreous surgery in premature infants' eyes. ",10 179,"Lewis system alterations in gastric carcinogenesis. Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis. Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals. ",3 1229,"The influence of warning signal timing and cognitive preparation on the aversiveness of electric shock. Many medical and dental procedures are noxious. Finding an optimal way of warning patients concerning the aversive procedures could help them to cope better. A model for the effective use of a warning signal in coping with pain posited that a person needs enough time to be able to react and should possess the skills necessary to utilize the time effectively. It was felt that a very short warning period, e.g., 5 sec, could not be long enough, while a 180 sec warning period would in and of itself become aversive. Reactions to electric shock were obtained from 36 paid, volunteer subjects who were each tested on a within-subject, counterbalanced order at 4 different warning periods: 5, 30, 60, and 180 sec. The subjects were divided into 3 groups: (1) the experimental group was provided with a pretested self-instructional booklet to learn a variety of pain control techniques; (2) the placebo group was provided with a self-instructional booklet on citizenship; (3) the control group waited quietly for 13 min. No significant results were obtained for the different pain-coping conditions. Significant differences, however, were obtained for the various warning periods. Maximum skin resistance changes, higher ratings of pain and of anxiety were obtained for the 60 and 180 compared to the 5 and 30 sec warning periods. Maximum heart rate was obtained for the 30 sec warning. Results were discussed in terms of the psychological meaning of the various measures as well as their clinical implications. ",9 2737,"Critical care for clonidine poisoning in toddlers. Clonidine may be a source of serious toxicity when ingested by toddlers. We describe 11 cases of clonidine ingestion by toddlers (mean dose 0.15 mg/kg; range 0.01 to 0.57). The source of the clonidine was a grand-parent in six of 11 cases. Symptoms included altered level of consciousness (n = 11), miosis (n = 5), bradycardia (n = 8), hypotension (n = 5), apnea and respiratory depression (n = 6), hypothermia (n = 5) and hypertension (n = 3). Therapeutic interventions included naloxone (n = 8) and atropine (n = 4), dopamine (n = 1), fluid resuscitation (n = 4), and endotracheal intubation (n = 1). There were no deaths. Symptoms of clonidine ingestion were typically mild if the dose ingested was less than 0.01 mg/kg, while bradycardia and hypotension occurred usually with doses of greater than 0.01 mg/kg. Apnea and respiratory depression were common when the dose exceeded 0.02 mg/kg. More effective measures are needed to prevent these potentially serious intoxications. ",20 3168,"Estrogen receptor level determines sex-specific in vitro transcription from the Xenopus vitellogenin promoter. Female-specific expression of the Xenopus laevis vitellogenin gene was reconstituted in vitro by addition of recombinant vaccinia-virus-produced estrogen receptor to nuclear extracts from male livers, in which this gene is silent. Transcription enhancement was at least 30 times and was selectively restricted to vitellogenin templates containing the estrogen-responsive unit. Thus, in male hepatocytes, estrogen receptor is the limiting regulatory factor that in the female liver controls efficient and accurate sex-specific expression of the vitellogenin gene. Furthermore, the Xenopus liver factor B, which is essential in addition to the estrogen receptor for the activation of this gene, was successfully replaced in the Xenopus extract by purified human nuclear factor I, identifying factor B of Xenopus as a functional homolog of this well-characterized human transcription factor. ",22 3122,"Balloon expandable stent implantation in stenotic right heart valved conduits. Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model was used, in which the pulmonary artery was ligated and a right ventricular to pulmonary artery 14 mm bioprosthetic Dacron valved conduit implanted. In five baboons, at an average of 40 months after valved conduit implantation, fibrointimal stenosis at the valve site resulted in narrowing and a mean transconduit pressure gradient of 49 mm Hg (range 33 to 65). A tubular slotted steel stent (1.2 cm long) was deployed within the valved conduit after inflation of an 8 to 15 mm diameter balloon catheter that was introduced through the femoral vein. A stent was delivered to all valved conduits; however, in two baboons, balloon undersizing resulted in stent dislodgment. In the remaining three baboons, the transconduit gradient was reduced by 59% (49 to 20 mm Hg) and right ventricular systolic pressure decreased acutely by 35% (77 to 50 mm Hg). It is concluded that stent deployment is feasible in right ventricular to pulmonary artery stenotic valved conduits and may result in significant hemodynamic improvement. However, successful stent delivery is critically dependent on the proper selection of stent length and balloon diameter. ",22 3295,"Simultaneous 'dual system' rehabilitation in the treatment of facial paralysis. Simultaneous dual system rehabilitation of facial paralysis involves using two independent reanimation techniques to optimize facial movement in both a quantitative and qualitative manner. These techniques involve the use of nerve grafting or crossover procedures combined with a dynamic muscle transfer. A group of 37 patients who underwent five different combinations of reanimation was analyzed. The techniques were evaluated using a standard rating scheme for judging success of reanimation procedures. The combination of a masseter muscle transfer to the lower region of the face and a cable graft of the upper facial nerve division appeared to offer excellent results in terms of independent motion of the upper and lower regions of the face and good eye closure, while allowing spontaneous mimetic function in 50% of cases. The advantages and disadvantages of the other techniques are described. The clinical situations in which these techniques have advantage over single reanimation techniques are outlined. ",22 1051,"Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Recent neuropathologic investigations in schizophrenia report smaller volume of medial temporal lobe structures. These findings are confirmed by preliminary magnetic resonance imaging (MRI) studies. Direct stimulation of lateral temporal lobe structures in the region of the superior temporal gyrus provokes hallucinations. The authors' MRI study of young schizophrenic patients demonstrates smaller volume of the superior temporal gyrus (an auditory association area) and of the left amygdala. Smaller size of the left superior temporal gyrus and left amygdala is not accounted for by smaller size of the overall brain or temporal lobe. Shrinkage of the left superior temporal gyrus is strongly and selectively correlated with severity of auditory hallucinations. ",9 1576,"Caliber-persistent artery of the stomach (Dieulafoy's vascular malformation). Caliber-persistent artery of the stomach (also known as cirsoid aneurysm, Dieulafoy's lesion, and submucosal arterial malformation) is clinically manifested as recurrent, massive, often fatal hematemesis. The lesion often is not seen endoscopically. Left gastric angiography in one patient with hematemesis showed a convoluted and ectatic artery in the gastric fundus, which proved to be caliber-persistent artery of the stomach on pathological examination. The tortuosity of the abnormal vessel in this condition has been attributed to artefactual contraction of the stomach following excision and formalin fixation. This is the first reported case in which a pathologically proven lesion has been clearly visualized by angiography. This demonstrates that the submucosal vessel is truly and not artifactually sinuous. It is proposed that angiographic demonstration of a nontapering, convoluted artery in the territory of the left gastric artery is highly suggestive of caliber-persistent artery of the stomach. ",13 493,"von Willebrand factor in head and neck cancer. Laboratory abnormalities in blood coagulation factors are common in patients with cancer but the significance is unknown. Twenty-eight patients with head and neck cancer were studied at the time of diagnosis. Twenty-five were advanced-stage (III or IV) patients. Levels of clotting factors, antithrombin III, and plasminogen were normal. Levels of von Willebrand factor (vWF), both antigenic and functional (ristocetin cofactor), were elevated. This group of patients were followed for a minimum of 41 months (median, 48 months). Fifteen patients died within the follow-up period. von Willebrand factor levels were significantly higher in these 15 than the 13 survivors. Extreme elevation of ristocetin cofactor (greater than 300 U/dl) was seen in six of the 15 patients who died and in none of the survivors. Plasma vWF is elevated in head and neck cancer and the level measured at the time of diagnosis may have prognostic and potentially therapeutic implications. ",3 1014,"Dysequilibrium and otitis media with effusion: what is the association? An association between non-suppurative otitis media (NSOM) and symptoms of dysequilibrium has been observed but not previously quantified in children (Gates, 1980; Busis, 1983; Blayney and Coleman, 1984). This study compared the incidence of balance related problems in 154 children with surgically proven glue ear and 51 children with normal ear function. Symptoms ranging from true vertigo to mild ataxia were discovered in 22 per cent of the children with NSOM but in none of those within the control group (p less than 0.001). Periods of dysequilibrium were associated with episodes of otalgia in 64 per cent of the children but were not increased in those with unilateral compared to those with bilateral effusions. Complete resolution of symptoms occurred in 85 per cent of children following the insertion of grommets. A history of balance disturbance should be actively sought in all children with otitis media with effusion, and when present, provides a strong indication for early operative intervention. ",8 1517,"A new method for the dressing of free skin grafts. Using adhesive drapes and a disposable suction drain, a new method for the dressing of free skin grafts has been devised. The graft is compressed by pressure that is equivalent to the negative pressure of the suction drain. This method can apply uniform and constant pressure on the graft. Moreover, the graft can be observed through a transparent drape so that the existence of hematomas can be detected easily. ",12 3145,"Acute hypervolaemic haemodilution to avoid blood transfusion during major surgery 16 patients underwent acute hypervolaemic haemodilution with dextran 40 and Ringers lactate, to see whether this procedure could avoid preoperative blood transfusion. Packed cell volume (PCV) and oxygen extraction decreased, and cardiac index and pulmonary wedge pressure increased, although end-systolic area was unchanged. PCV was not significantly different between patients who lost less than or greater than 20% of their initial blood volume. This preoperative manoeuvre, which reduces loss of red blood cells, allowed major surgery to be completed safely without blood transfusion. ",22 382,"Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy. This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity. ",3 2116,"Apical segmental dysfunction in hypertrophic cardiomyopathy: subgroup with unique clinical features. A segmental wall motion abnormality is an unusual finding in patients with hypertrophic cardiomyopathy. To clarify its clinical significance, 48 patients with hypertrophic cardiomyopathy were analyzed. Eight patients (Group A) had apical segmental dysfunction; 40 (Group B) had normal wall motion. No patient in either group had coronary artery stenosis on selective coronary arteriography. In all patients in Group A, apical segmental dysfunction was revealed by left ventriculography; however, it could be detected by echocardiography in only two patients in Group A. Left ventricular hypertrophy by electrocardiogram (ECG) was more common in Group B (p less than 0.05). Abnormal Q waves were more frequently discovered in Group A (p less than 0.005) and were recognized predominantly in the lateral leads. On serial ECGs, a gradual development of abnormal Q waves was noted in six of eight patients in Group A. Malignant arrhythmias were more common in Group A (p less than 0.001). In two patients in Group A, left ventricular dilation and congestive heart failure developed during the follow-up period. Thus, the presence of a Q wave in the lateral leads on an ECG in patients with hypertrophic cardiomyopathy may indicate the presence of apical segmental dysfunction. Left ventriculography should be performed to examine the presence of this abnormality and 24 h ambulatory ECG monitoring should be done to detect malignant arrhythmias in patients who have abnormal Q waves in the lateral leads. Patients with this unique type of hypertrophic cardiomyopathy need careful follow-up evaluation. ",13 2429,"Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years. The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity. ",17 1590,"Multiple breakpoint method for measuring effect of antibiotics on endocarditis strains of streptococci. The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency. ",13 1695,"Does isoflurane lead to a higher incidence of myocardial infarction and perioperative death than enflurane in coronary artery surgery? A clinical study of 1178 patients To examine if the choice of volatile agents influences cardiac outcome in coronary artery surgery, 1178 patients undergoing elective coronary artery bypass grafting without additional operations received enflurane (608) or isoflurane (570) as their primary anesthetics. The inspired concentration of volatile agent (administered with 50% nitrous oxide) was adjusted depending on the level of blood pressure at the discretion of the anesthesiologist. In addition to the volatile agent assigned, each patient received small doses of fentanyl at induction and before sternotomy (total 0.006-0.008 mg/kg). The groups did not differ in preoperative and surgical characteristics except for a more frequent history of renal dysfunction in patients given isoflurane. The rates of postoperative myocardial infarction, administration of positive inotropic agents at the time of weaning from cardiopulmonary bypass, and in-hospital deaths in the enflurane and isoflurane groups were 1.8% and 4.0% (P less than 0.05), 4.9% and 8.1% (P less than 0.05%), and 0.3% and 2.1% (P less than 0.01), respectively. Although the mechanism of the adverse effects of isoflurane could not be clarified in this study, these results demonstrate that the use of isoflurane could be inappropriate in patients undergoing coronary artery bypass grafting. ",13 2406,"Insulin use in NIDDM. Rationale based on pathophysiology of disease. Because basal hyperglycemia is a major feature in non-insulin-dependent diabetes mellitus, diabetes control can be monitored by the fasting blood glucose concentration. A hierarchical sequence of therapies is proposed in which the major aim is to maintain near-normal fasting blood glucose concentrations, in the expectation that this will help prevent development of long-term complications. When diet and tablet therapy are no longer effective in keeping the fasting blood glucose level less than 6 mM, a basal insulin supplement from a long-acting insulin such as ultralente can be added. When monitored by fasting blood glucose concentration, there is little risk of hypoglycemia, and the patient can continue a normal life-style without restrictions concerning exercise or the size of individual meals. A basal insulin supplement does not induce marked weight gain. The dose of insulin required can be predicted from the level of the fasting blood glucose and the degree of obesity, which provides an index of the accompanying insulin resistance. Based on current evidence, insulin therapy is equally appropriate in patients with insulin deficiency and insulin resistance, because the benefit from maintaining near-normal glucose concentrations probably outweighs a putative risk of hyperinsulinemia. In more severely affected patients, additional regular insulin to cover meals is needed. Lowering fasting blood glucose to normal with a basal insulin supplement reduces endogenous insulin production, and this may be advantageous if accompanying production of islet amyloid polypeptide and islet amyloid formation are also reduced. ",17 2580,"Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin-antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative. ",19 2239,"Prevalence of additional cardiovascular anomalies in patients referred for transcatheter closure of patent ductus arteriosus. Catheter closure of the patent ductus arteriosus is now a reality. The purpose of this study was to establish the prevalence of associated cardiovascular defects and the accuracy of echocardiography in patients referred for transvenous ductal closure. This study reviewed 146 patients seen from 1981 to 1988: 126 with only a patent ductus arteriosus (Group I) and 20 with additional cardiovascular anomalies (Group II). Groups I and II did not differ significantly in age, gender or physical examination except for the presence of a continuous murmur (Group I 100% versus Group II 80%, p less than 0.001). A left patent ductus arteriosus was visualized by two-dimensional echocardiography in 96% of patients and was evident by Doppler study in 100%. A patent ductus arteriosus was not seen in six patients including a patient who was found to have only a collateral network from the aorta to the main pulmonary artery. The 12 patients with noncardiovascular abnormalities such as Down's syndrome were more likely than the overall group to have additional cardiovascular anomalies (6 of 12, p = 0.001). The cardiovascular anomalies encountered were varied. Eight of the 20 patients with such anomalies had only a restrictive ventricular septal defect in addition to the patent ductus arteriosus. Significant anomalies found at catheterization included two thoracic arteriovenous malformations and an isolated right carotid artery draining into the right pulmonary artery by way of a right ductus arteriosus. This study indicates that echocardiography is an effective diagnostic technique in this patient group. A thorough cardiac catheterization with angiography should be performed before implantation of a ductal device. ",15 342,"Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient. ",3 127,"Impact of cytomegalovirus infection on organ transplant recipients. Cytomegalovirus (CMV) is the single most important infectious agent affecting recipients of organ transplants, with at least two-thirds of these patients having CMV infection 1-4 months after transplantation. Latently infected allografts are the major exogenous source of CMV infection in transplant recipients, although leukocyte-containing blood products can also transmit the virus. Three patterns of CMV infection are recognized: primary infection, reactivation infection, and superinfection. Primary infection has the greatest clinical impact. The clinical effects of CMV infection include infectious disease syndromes such as pneumonia and chorioretinitis; an immunosuppressed state that predisposes to potentially lethal opportunistic infection; and the initiation of a process that can result in allograft injury. Progress has been made in controlling CMV infection; hyperimmune anti-CMV globulin and certain antiviral drugs appear promising for prophylaxis, and the combination of hyperimmunoglobulin and ganciclovir appears promising for therapy. ",1 1807,"The effects of phenylephrine on right ventricular performance in patients with pulmonary hypertension Pulmonary hypertension causes right ventricular ischemia and failure as a result of increased afterload combined with reduced coronary blood flow. Increasing coronary driving pressure by raising aortic pressure with phenylephrine has been shown to reverse right ventricular ischemia from pulmonary hypertension in animals. Since vasodilators often fail to reduce afterload, we tested whether raising the coronary driving pressure would improve right ventricular function in man. Ten patients with pulmonary hypertension had hemodynamics and right ventricular coronary driving pressure measured before and 10 minutes after a steady state was reached with a phenylephrine infusion titrated to raise aortic pressure by 25 percent. Phenylephrine caused a significant (p less than .01) increase in mean aortic pressure (84 to 108 mm Hg) and right ventricular coronary driving pressure (46 to 69 mm Hg). In response, there was a significant (p less than .01) rise in mean pulmonary artery pressure (58 to 67 mm Hg), right ventricular end-diastolic pressure (10 to 16 mm Hg) and wedge pressure (5 to 9 mm Hg), and an insignificant fall in cardiac output (3.26 to 3.09 L/min) and pulmonary artery O2 saturation (57 to 49 percent). Although phenylephrine increased right ventricular coronary driving pressure, it worsened right ventricular function as manifest by a rise in end-diastolic pressure and fall in cardiac output. Any benefit of raising right ventricular coronary driving pressure may have been offset by alpha vasoconstriction of right ventricular coronary blood flow and/or pulmonary arterial vasoconstriction. Phenylephrine does not appear to be a useful therapy of right ventricular failure from pulmonary hypertension in patients who fail vasodilators. ",13 2484,"Hydroquinone-induced localized exogenous ochronosis treated with dermabrasion and CO2 laser. Exogenous localized ochronosis can result from the repeated use of hydroquinone-containing creams, many of which are available over the counter. We report a case that was managed by dermabrasion and CO2 laser. The incidence and proposed etiologies of hydroquinone-induced exogenous ochronosis are reviewed. ",17 2351,"WHO Multinational Project for Childhood Diabetes. WHO Diamond Project Group. Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries, most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990-1999), this study will collect population-based data concerning IDDM in greater than 90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated with IDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programs in diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae. ",17 1120,"Fibrillation potential amplitude and muscle atrophy following peripheral nerve injury. Maximum peak-to-peak fibrillation potential amplitude was measured in 69 subjects between 7 days and 10 1/2 years post complete or partial peripheral nerve injury. Mean amplitude during the first 2 months was 612 muV; third and fourth months 512 muV, fifth and sixth months 320 muV. After the first year, no population of fibrillation potentials greater than 100 muV was recorded. The sciatic nerve was sectioned in 13 guinea pigs and animals studied up to 17 weeks. Fibrillation potential amplitude in gastrocnemius muscles declined paralleling that in humans. By the end of the study, type I fibers had lost almost half of their initial diameter and type II fibers had atrophied more than twice this amount. Fibrillation potential amplitude may be useful in estimating the time post nerve injury and appears to correlate with the surface area and fiber diameter of a type I muscle fiber. ",9 2414,"Insulinlike activity of new antidiabetic agent CP 68722 in 3T3-L1 adipocytes. We examined the in vitro effects of CP 68722, a novel antidiabetic agent, in 3T3-L1 adipocytes. CP 68722 stimulated 2-deoxyglucose uptake in the absence of insulin. At least 30 min of incubation were required for stimulation of uptake. This effect increased over 5 h and was sustained up to 72 h. The stimulation of 2-deoxyglucose uptake by CP 68722 could be inhibited approximately 60% by inhibition of protein synthesis with cycloheximide. Half-maximal and maximal responses to CP 68722 at 72 h of incubation were observed at 10 and 100 microM of drug, respectively, with a threefold stimulation of uptake at 100 microM approximating the maximal response of these cells to acute insulin stimulation. CP 68722 was able to overcome insulin resistance induced by dexamethasone in 3T3-L1 cells. The effect of drug, like that of insulin, was primarily to increase the Vmax of 2-deoxyglucose uptake. The stimulation of uptake by CP 68722 or insulin could be prevented by incubating the cells at 10 degrees C, a temperature that impedes translocation of glucose transporters to the plasma membrane. Therefore, it appears that CP 68722, like insulin, stimulates glucose uptake by a mechanism that involves translocation of intracellular glucose transporters to the plasma membrane and de novo protein synthesis. We compared the effect of CP 68722 with the sulfonylureas, the primary drugs used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). CP 68722 was a more potent and effective stimulator of 2-deoxyglucose uptake in 3T3-L1 cells than either first- or second-generation sulfonylureas. ",17 546,"Extrahepatic metabolism of morphine occurs in humans. The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half-life was 92 +/- 9 minutes, total body clearance was 1260 ml.min-1, and the hepatic extraction ratio was 0.65 +/- 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney. ",3 1785,"Early and late results after isolated coronary artery bypass surgery in 159 patients aged 80 years and older. We have studied 159 patients 80 years of age or older who have had isolated coronary artery bypass grafting (CABG) since 1977. Eighty-seven percent have had surgery since 1984. Two thirds of the patients were male, and the mean age was 82 years. Most patients (97%) were in New York Heart Association (NYHA) functional class III or IV, 89% had unstable/postinfarction angina pectoris, and 67% had rest pain. Almost half (47%) required preoperative admission to the coronary care unit, 6% required preoperative use of an intra-aortic balloon pump, and 20% were operated on emergently. Significant left main coronary artery disease (greater than or equal to 50% stenosis) was present in 41%. Ten patients (6.3%) died within 30 days of surgery, with seven more patients dying during the same hospital admission or soon after transfer to another institution. This resulted in an overall hospital mortality of 10.7%. The median hospital stay was 10 days. On univariate analysis, the significant predictors of hospital mortality were NYHA IV, angina at rest, preoperative admission to the coronary care unit, emergency operation, ejection fraction less than 0.50, and the presence of mitral regurgitation. On multivariate analysis, ejection fraction less than 0.50 was the only significant risk factor (p less than 0.01). Of hospital survivors, 98% have been followed for a mean of 29 months. The estimated 5-year survival (+/- SEM) of all patients was 71 +/- 4.5%, and for hospital survivors, 80 +/- 4.5%. The most important predictor of adverse survival was an ejection fraction less than 0.50. Seventy-nine percent are angina-free, and 89% are in NYHA classes I and II. The majority of patients felt that they were improved by surgery. We conclude that CABG in patients 80 years or older, although associated with increased operative risk, gives excellent relief of symptoms and good 5-year survival. Patients should not be denied CABG because of age alone. ",13 2782,"Examination of Cloninger's type I and type II alcoholism with a sample of men alcoholics in treatment. Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking. ",20 2799,"Prospective evaluation of gastric emptying in the self-poisoned patient. The authors prospectively studied the effect of gastric emptying (GE) and activated charcoal (AC) upon clinical outcome in acutely self-poisoned patients. Presumed overdose patients (n = 808) were treated using an alternate day protocol based on a 10-question cognitive function examination and presenting vital sign parameters. Asymptomatic patients (n = 451) did not receive GE. AC was administered to asymptomatic patients only on even days. GE in the remaining symptomatic patients (n = 357) was performed only on even days. On emptying days, alert patients had ipecac-induced emesis while obtunded patients received gastric lavage. AC therapy followed gastric emptying. On nonemptying days, symptomatic patients were treated only with AC. No clinical deterioration occurred in the asymptomatic patients treated without GE. AC use did not alter outcome measures in asymptomatic patients. GE procedures in symptomatic patients did not significantly alter the length of stay in the emergency department, mean length of time intubated, or mean length of stay in the intensive care unit. Gastric lavage was associated with a higher prevalence of medical intensive care unit admissions (P = .0001) and aspiration pneumonia (P = .0001). The data support the management of selected acute overdose patients without GE and fail to show a benefit from AC in asymptomatic overdose patients. ",20 3006,"An effective and adaptable transvenous defibrillation system using the coronary sinus in humans. With use of a coronary sinus catheter electrode, a right ventricular catheter electrode and a chest wall patch electrode system, defibrillation threshold voltage, current and energy were measured with four distinct transvenous defibrillation techniques delivered in random sequence in each of 12 survivors of cardiac arrest immediately before implantation of a standard epicardial patch defibrillation system. The four transvenous defibrillation techniques were 1) single pathway monophasic pulsing, 2) single pathway biphasic pulsing, 3) dual pathway sequential pulsing, and 4) dual pathway simultaneous pulsing. A transvenous defibrillation method was considered to be potentially useful only if the defibrillation threshold was less than or equal to 500 V (less than or equal to 15 J delivered energy). The 500 V value would allow a 2:1 defibrillation safety margin for a device with a maximal output of 30 J. No single transvenous pulsing technique was uniformly superior in efficacy. However, by choosing the best pulsing technique for each patient, it was possible to obtain an average defibrillation threshold of 410 +/- 135 V leading edge voltage, 7.2 +/- 2.5 A leading edge current and 11.3 +/- 7.4 J delivered energy for the group of 12 patients. With the ability to vary defibrillation technique, transvenous antiarrhythmic device implantation would have been possible in 10 (83%) of the 12 patients at or below a 15 J defibrillation threshold cutoff point. In contrast, if only one transvenous defibrillation method had been used, as few as 5 and at most 8 of the 12 patients would have been candidates for a transvenous defibrillation system given a 15 J defibrillation threshold cutoff point for insertion. ",22 2911,"Treatment of digitalis intoxication with emphasis on the clinical use of digoxin immune Fab. Many studies and cases of digitalis intoxication have been reported since the time of William Withering's first publication in 1785. Recognition and management of digitalis toxicity is challenging. Before digoxin immune Fab was commercially available, treatment consisted of managing the signs and symptoms of toxicity until the digitalis was eliminated. Digoxin immune Fab offers a safe, effective, and specific method of quickly reversing digitalis toxicity. Factors that must be considered with the clinical use of this agent include the dosage calculation, administration technique, postdose monitoring, pharmacokinetics, mechanism of action, interference with commercially available digoxin assays, partial neutralizing dosing, rebound of free digoxin, and indications for use. For severe, life-threatening toxicity, digoxin immune Fab is the treatment of choice. ",20 936,"Serologic evidence of subclinical pertussis in immunized children. Incidental to a vaccine study involving 783 immunized children conducted at two study sites, inner city children had significantly higher geometric mean pertussis agglutinin titers compared with suburban children just before the fourth dose of diphtheria-tetanus-whole cell pertussis vaccine (47 vs. 25; P less than 0.001). Higher titers in the inner city were correlated with residence in census tracts where cases of pertussis were reported. Three hundred thirty-two children in a placebo arm of the study who were clinically observed and had paired serum samples taken during a 2- to 4-month period were analyzed for evidence of natural Bordetella infection. Twelve (11%) inner city children and three (1.3%) suburban children had spontaneous 4-fold or greater rises in at least two different pertussis antibodies measured (agglutinin, antitoxin or enzyme-linked immunosorbent assay for IgG to pertussis toxin, IgG and IgA to filamentous hemagglutinin). Eighty percent of these children had IgA to filamentous hemagglutinin. Nine of 12 inner city children with serologic evidence of pertussis lived within 6 blocks of a case of pertussis reported within 1 month of the observed antibody rise in study subjects; none had a household member with pertussis and none had symptomatic disease. ",7 491,"The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. MaxEPA (MA), a fish oil high in omega-3 fatty acids, was combined with various levels of corn oil (CO), rich in omega-6 fatty acids, and fed to female CF1 mice. The three fish oil blends with CO and the two CO levels of the diets studied were as follows: 16.0% CO + 4.4% MA (Diet 1); 10.2% CO + 10.2% MA (Diet 2); 4.4% CO + 16.0% MA (Diet 3); 20.4% CO (Diet 4); and 4.4% CO (Diet 5). The diets were provided 2 weeks before weekly subcutaneous injection of saline or azoxymethanol (AOM). Studies of epithelial cell proliferation and the incidence of focal areas of dysplasia (FAD) involved six weekly AOM injections. One week after the last AOM injection and 1 hour before killing, mice were injected with tritiated thymidine (3HTdR). No differences in any proliferative parameters were found among the five groups of saline-treated mice. Among the AOM-treated animals, those fed Diet 3 showed significantly fewer cells per crypt and significantly fewer labeled cells/gland than CO Diets 4 and 5. Additionally, the distribution of S-phase cells in crypts of AOM-treated mice fed Diet 3 most closely resembled that of the saline controls. The greatest alteration in the distribution of proliferative cells was observed in the high-CO diet (Diet 4) and the lowest MA level (Diet 1). Mice fed Diets 2 and 3 had significantly fewer FAD/500 microns of distal colonic serial sections than those fed the high CO diet (Diet 4). Mice involved in chronic tumor incidence studies received only three weekly injections of the same dose of AOM. Regardless of diet, approximately 88% of all tumors arose in the distal colon. A significantly larger tumor-bearing population was observed in both the high-CO Diet 4 and the lowest MaxEPA (MA) diet (Diet 1) compared with the incidence in MA Diets 2 and 3 and the low-CO Diet 5. A diet with a ratio of omega-6 to omega-3 fatty acids of approximately 1.0 apparently prevented the development of an adenoma-type proliferative pattern thereby reducing FAD numbers and subsequent tumor incidence. ",3 2479,"Role of two types of glucose transporters in enlarged adipocytes from aged obese rats. The mechanism of insulin-resistant glucose-transport activity in enlarged aged adipocytes was examined. Glucose-transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of HepG2 erythrocyte/glucose transporter (GLUT1), and the muscle/adipose tissue transporter (GLUT4) was estimated by immunoblotting. Basal glucose-transport activity increased 6.3-fold/cell but remained constant per unit cellular surface area due to cell enlargement. Maximal insulin-stimulated transport activity remained constant per cell but decreased per unit cellular surface area. On a per protein basis, GLUT1 and GLUT4 from aged rats decreased to approximately 60 and 10% of those from young rats, respectively. However, when the protein content of each fraction and the recoveries of marker enzymes were used for estimating the amount of transporters in intact adipocytes, the amount of GLUT1 per cell remained relatively constant, whereas that of GLUT4 decreased. In basal cells from young rats, 31% of the total GLUT1 per cell was located in the plasma membrane, whereas in those from aged rats, 63% was located in the plasma membrane. Thus, in comparing basal adipocytes from aged rats with those from young rats, GLUT1 per cell in the plasma membrane increased 2.8-fold, but this increase was less than that of transport activity (6.3-fold). In basal cells from young rats, 8% of the total GLUT4 was located in the plasma membrane, and a 4.5-fold increase was observed with insulin treatment, but the amount of GLUT4 in each fraction from aged rats markedly decreased. ",17 2301,"The expression of retrovirus-like particles in psoriasis. Retrovirus-like particles have been isolated from patients with psoriasis. Antigens crossreacting with the major internal protein, pso p27, of these particles have been demonstrated in the wall of dermal vessels and in a subfraction of cells in psoriatic lesions. The antigen has also been observed in blood lymphocytes from psoriatic patients. Pso p27 antigen and anti-pso p27 antibodies are present as complement-activating immune complexes in psoriatic scale and in the blood of patients with psoriasis and psoriatic arthritis. The potential contribution of the circulating immune complexes to the inflammatory process in psoriasis is discussed. ",16 2382,"Hyponatremia in rats induces downregulation of vasopressin synthesis. Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality. ",17 1060,"Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine. ",9 1679,"Efficacy of acebutolol after acute myocardial infarction (the APSI trial). The APSI Investigators. A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of beta blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether beta-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (greater than or equal to 20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol-treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors. ",13 105,"Risk factors for Staphylococcus aureus nosocomial pneumonia in critically ill patients. Staphylococcus aureus nosocomial pneumonia has become an important infection not only because of an apparently increasing incidence but also because of its high mortality rate. A total of 50 episodes of nosocomial pneumonia in critically ill patients in which etiologic diagnosis was well established were prospectively followed in a medical-surgical intensive care unit (ICU). S. aureus was isolated in a total of 13 episodes. In the univariate analysis the variables significantly associated with S. aureus nosocomial pneumonia were below 25 yr of age, coma, nonuse of corticosteroids, and antecedent trauma. A step-forward logistic regression analysis defined only coma as significantly influencing the risk of developing S. aureus nosocomial pneumonia. We suggest that antimicrobial drugs active against S. aureus must be included in the initial empirical antimicrobial regimen for treating nosocomial pneumonia in patients with coma. The identification of factors influencing the etiology and the possibility of earlier effective antimicrobial treatment may represent a further step in the control of nosocomial pneumonia in critically ill patients by improving its prognosis. ",0 3330,"Improved biocompatibility by postfixation treatment of aldehyde fixed bovine pericardium. Long-standing release of locally cytotoxic aldehyde concentrations is responsible for lack of spontaneous endothelialization and increased calcification of glutaraldehyde fixed bovine pericardium. Postfixation treatment with amino acids made in vitro endothelialization of bioprosthetic heart valves possible. Such treated pericardium calcified significantly less (13 +/- 4 micrograms/mg dry weight) than did conventionally processed pericardium (114 +/- 25 micrograms/mg) after 63 days of subcutaneous implantation in rats. To test the ability for spontaneous in vivo endothelialization, 5 sheep had 6 mm grafts made from postfixation treated pericardium (PTP) implanted into the carotid artery, compared to PTFE grafts on the contralateral side, which spontaneously endothelialize in animal models. In a pregnant animal, both grafts occluded. All remaining pericardial grafts remained patent, but one additional PTFE graft occluded and another one was stenosed. The area covered with red thrombus was significantly smaller in the PTP grafts (3.05 +/- 3.9%) than in the PTFE grafts 42 +/- 14% (p = 0.0036); TEM and SEM showed endothelial cells growing directly on the PTP, but only on myofibroblasts in PTFE grafts. Postfixation treatment of glutaraldehyde fixed pericardium aids spontaneous endothelialization and decreases tissue calcification. ",22 211,"Results of conservative surgery and radiation therapy for breast cancer. For stage I or II breast cancer, conservative surgery and radiation therapy are as effective as modified radical or radical mastectomy. In most cases, cosmetic considerations and the availability of therapy are the primary concerns. The extent of a surgical resection less than a mastectomy has not been a subject of a randomized trial and is controversial. It appears that removal of a quadrant of the breast for small lesions is safe but excessive. Using histologic findings in the biopsy as a guide, it may be possible to limit the breast resection to gross tumor removal for most patients while using wider resections for patients with an extensive intraductal component or for invasive lobular carcinoma. It also appears that excluding patients from breast conservation on the basis of positive margins on the first attempt at tumor excision may be unnecessarily restrictive. Although patients with an extensive intraductal component or invasive lobular carcinoma should have negative margins, it appears that a patient with predominantly invasive ductal carcinoma can be treated without re-excision if all gross tumor has been resected and there is no reason to suspect extensive microscopic disease. Patients with indeterminate margins should have a re-excision. Axillary dissection provides prognostic information and prevents progression of the disease within the axilla. Axillary dissections limited to level I will accurately identify a substantial number of patients who have pathologically positive but clinically negative nodes. When combined with radiation therapy to the axilla, a level I dissection results in a limited number of patients with progressive axillary disease. Patients with pathologically positive axillas and patients at particularly high risk for systemic disease because of the extent of axillary node involvement can be identified by dissections of levels I and II. Radiation therapy can be avoided safely in patients who have pathologically negative axillas by level I and II dissection. There appears to be no advantage to routine dissection of level III lymph nodes. Lymphedema of the arm and breast increases with more extensive dissections and with radiation therapy. ",3 1341,"Comparison of pathological lesions on repeated renal biopsies in 73 patients with primary IgA glomerulonephritis: value of quantitative scoring and approach to final prognosis. In order to improve our possibility of establishing a long-term prognosis in IgA nephritis, 73 patients out of a cohort of 282, followed over a mean period of 12 years at the same institution for an IgA nephritis, had a prospective second renal biopsy 5 years later. For all biopsies (RB1 and RB2), we developed a quantitative scoring for all elementary lesions with a glomerular, an interstitial, a tubular and a vascular index. The sum of these 4 indexes gave a global optical score (GOS). Pathological improvement on light microscopy (delta GOS less than or equal to -2) was noticed only in 3 patients (4%), stability (-2 less than delta GOS less than +2) in 30 patients (41%), mild deterioration (+2 less than or equal to GOS less than 5) in 23 patients (32%) and major progression (delta GOS greater than or equal to 5) in 17 patients (23%). We observed no pathological remission, even in the 14 patients with complete clinical remission. The pathological progression was characterized by an increase in all elementary lesions, mainly the tubulo-interstitial and vascular ones. By immunofluorescence mesangial IgA deposits remained stable with no disappearance; however, the number and intensity of vascular C3 deposits were significantly greater on RB2. Chronic renal failure (serum creatinine greater than 1.5 mg/dl) correlated best with major pathological progression and mainly with the progression of extraglomerular lesions. IgA nephritis is a slowly progressive disease with no pathological remission, and its evolution is characterized by progression of extraglomerular lesions, mainly vascular, which might play a major role in the ultimate development of chronic renal failure. ",11 1548,"Prevalence of aortic regurgitation by color flow Doppler in relation to aortic root size. To determine whether there is a correlation between aortic root size and the prevalence of aortic regurgitation, we performed color flow Doppler echocardiographic studies on 1015 consecutive patients during a 3-month period. Patients were grouped according to their M-mode aortic root diameter as measured in the left parasternal position. The measured groups ranged from 2.0 to 4.5 cm, grouped at 0.1 cm intervals. As the aortic root size enlarged, the prevalence of aortic regurgitation increased linearly (p less than 0.001; correlation coefficient, r = 0.75). At an aortic root size in the ""small normal"" range of 2.0 to 2.4 cm, the prevalence of aortic regurgitation was 0% to 15%. In the ""intermediate"" and ""top normal"" ranges of 2.9 to 3.7 cm, the prevalence of aortic regurgitation increased linearly from 15% to 47%. With aortic root dilation, the prevalence of aortic root regurgitation was generally more than 50%. The severity of aortic regurgitation was semiquantified. Aortic root size was not a good indicator for the severity of aortic regurgitation. Patients with moderate and severe aortic regurgitation had variable aortic root sizes. Throughout the range of aortic root sizes, mild aortic regurgitation predominated. We conclude that aortic regurgitation is a common finding in patients with aortic roots that are dilated or are in the ""top normal"" size range, that the prevalence of aortic regurgitation increases linearly with aortic root size, and that aortic root size does not correlate with the severity of aortic regurgitation. ",13 1846,"Transesophageal echocardiography to detect atrial clots in candidates for percutaneous transseptal mitral balloon valvuloplasty. Left atrial thrombi are common in patients with mitral stenosis. When percutaneous balloon mitral valvuloplasty is performed on such patients, there is a potential risk of thrombus dislodgment and embolization. In this study conventional transthoracic echocardiography and transesophageal echocardiography were performed for percutaneous balloon mitral valvuloplasty on 19 consecutive candidates (6 men, 13 women, 23 to 81 years old). In five patients (26%), transesophageal echocardiography revealed a left atrial thrombus; in only one of these was there a suspicion of left atrial thrombus on transthoracic echocardiography. Balloon mitral valvuloplasty was canceled in four of the five patients. Three underwent mitral valve surgery that confirmed the echocardiographic findings. Transesophageal echocardiography is better than conventional transthoracic echocardiography in detecting left atrial clots in candidates for balloon mitral valvuloplasty. Because of the potential risk of embolization, transesophageal echocardiography is recommended in all candidates for balloon mitral valvuloplasty. ",13 1256,"Topical timolol and serum lipoproteins. Oral timolol taken for the treatment of systemic hypertension has been shown to affect adversely serum lipoprotein levels. In a 15-week study on 19 patients topical timolol therapy for raised intraocular pressure was found to have no significant adverse effect on serum lipoprotein levels. This is reassuring in view of the large number of patients on this form of long term therapy, and selection of the type of beta blocker to use should not be influenced by lipid changes associated with the oral form of the drug. ",10 2366,"Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men. The Japanese-American population of King County, Washington, is known to have a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a community-based study, we reexamined 146 second-generation Japanese-American men who had been initially classified as nondiabetic. At a mean follow-up period of 30 mo, 15 men had developed NIDDM, and 131 remained nondiabetic. The variables measured at the initial visit that distinguished the 15 diabetic men from the 131 nondiabetic men were older age, higher serum glucose level at 2 h after 75 g oral glucose, higher fasting plasma C-peptide level, and increased cross-sectional intra-abdominal fat area as determined by computed tomography. Both older age and higher 2-h glucose levels are variables that have been associated with the development of NIDDM, but the association of higher fasting C-peptide level and greater intra-abdominal fat area with subsequent development of NIDDM were new observations. The elevated fasting C-peptide level persisted after adjustment for fasting serum glucose. The elevated C-peptide level represents hypersecretion of insulin and was interpreted to reflect a compensatory response to an underlying insulin-resistant state that antedates the development of NIDDM. The fasting C-peptide level was correlated with the intra-abdominal fat area, suggesting that the intra-abdominal fat area may be associated with insulin resistance. Thus, in individuals who develop NIDDM, insulin resistance, increased insulin secretion, and increased intra-abdominal fat are present before diabetic glucose tolerance can be demonstrated. ",17 2579,"Morphometric analysis of follicular center cell lymphomas. The Lukes/Collins classification of non-Hodgkin's lymphomas subdivides follicular center cell (FCC) lymphomas into four categories based on nuclear size, shape, and state of transformation. Because of the well-recognized difficulty in making these subdivisions in routine histologic sections, a morphometric analysis of typical small cleaved (SC), large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) FCCs was performed to describe and compare these four categories using objective parameters. The following features, which had been previously tested on normal follicles, were measured and calculated: nuclear area (NA), nuclear contour index of ellipticity (NCIe), nuclear contour index of nuclear irregularity (NCIni), and a relative chromatin dispersal index (CDI). The presence of nucleoli also was recorded. Mean values for the NA, NCIe, NCIni, and CDI were significantly different among all four FCC lymphoma subtypes, except that the CDI, which reflects transformation, was similar for the SC and LC cell groups. Comparison using the proportion of cells with nucleoli in each case revealed significant differences between all but the SNC and LNC groups. The LC group had the highest mean nuclear ellipticity and nuclear irregularity values. Mean nuclear area was smallest for the SC group followed by the LC, SNC, and LNC groups. Despite these many differences, all parameters showed a broad spectrum of values when either mean values for individual cases of each FCC subtype or distribution curves for all cells within a certain subtype were compared. This morphometric data demonstrates that the four histologically recognized types of FCC lymphomas are distinctive using a more analytic technique. This study also provides further insight into the differences among them. Evidence of nuclear transformation (nuclear size, chromatin dispersal, and frequent nucleoli) is a more important criterion than nuclear contours in distinguishing LNC from LC lymphomas. Although LC lymphomas have some features intermediate between SC and the noncleaved FCC lymphomas, they more closely resemble SC lymphomas. Finally morphometric analyses such as these provide an objective morphologic foundation for future prospective investigations of transformation-related phenomena; these studies may facilitate comparison of morphologic data with immunophenotype and genotype in non-Hodgkin's lymphomas and comparison of various other B-cell neoplasms with follicular center cell neoplasms. ",19 3162,"Low dose amitriptyline in chronic pain: the gain is modest. In the double-blind placebo-controlled study presented here, the effects were investigated of a low dose of amitriptyline (75 mg) in patients with chronic pain of various origins. The active drug was superior to placebo in reducing pain intensity. The reduction was small. In the second treatment week, the amitriptyline treated patients slept longer. No differences between active drug and placebo were found with respect to daily activities or use of analgesics. Based on our data and those of other studies, it is concluded that amitriptyline (and other antidepressants) in low doses does have a positive effect on the intensity and some other aspects of chronic pain, but that the effect is modest. It must be kept in mind that chronic pain is a very treatment-resistant condition. Therefore, even modest positive effects may be worthwhile. ",22 3053,"Comparison of four pulse oximeters: effects of venous occlusion and cold-induced peripheral vasoconstriction. The ability of four pulse oximeters (the Ohmeda 3700, Nellcor N100 and N200 and the Datex Oscar) to detect hypoxaemia was determined in the presence of venous obstruction and cold-induced peripheral vasoconstriction. Significant increases in detection time for hypoxaemia were found in both cases. There were no significant differences in detection time between the instruments, although the Ohmeda 3700 displayed smaller values of SaO2 under certain conditions. Peripheral vasoconstriction was induced using three differing methods which gave differing results, thus emphasizing the importance of methodology in assessments of pulse oximetry. ",22 871,"Histopathologic grading of salivary gland neoplasms: III. Adenoid cystic carcinomas. Histopathologic grading of adenoid cystic carcinomas can provide valuable prognostic information, particularly when the presence or absence of a solid growth architecture is noted. Other growth patterns, exemplified by a tubuloductal or cribriform-cylindromatous differentiation, are associated with a more protracted biologic course and less rapid mortality. A three-tiered grading system based on the three growth patterns of the carcinoma is presented. ",6 2853,"The effects of fluoxetine in the overdose patient. Fluoxetine (Prozac) is a new antidepressant, first marketed in the United States in January 1988. Only limited toxicologic information during a fluoxetine overdose is available. The goal of this prospective multi-center study was to develop a toxicity profile of initial signs and symptoms observed in fluoxetine overdose. A standardized data collection form was used on all patients ingesting fluoxetine as reported to four poison centers. Information obtained included age, dose, co-ingested drugs, presenting symptoms, vital signs, EKG abnormalities and lab values. Of the 127 cases of acute fluoxetine overdose collected, 106 cases met the criteria of the study. Of these, 69/106 ingested other drugs, including ethanol and 37/106 ingested fluoxetine alone. Of the latter group, the amounts ingested ranged from 20 to 1500 mg. It was observed that 48.6% (18/37) remained asymptomatic, 16.2% (7/37) were sleepy, 24.3% (9/37) had a sinus tachycardia (of 100 beats per minute or greater), and 8.1% (3/37) had a diastolic pressure over 100 mm Hg. Data collection is ongoing. Based upon our initial experience, fluoxetine in overdose appears to be relatively benign. ",20 162,"Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study. A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases, as previous studies have indicated a trend toward the superiority of CT scanning over palpation. The respective values of neck examination, CT scanning, and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections. The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning. A retrospective analysis of the CT findings failed to reveal greater accuracy. We found nodes measuring 10 mm or more with central low density always to be malignant. Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck, it should not be regarded as an essential tool in the staging of nodal disease. After radiation therapy, as neck dissection is only performed because of clinical or radiologic suspicion, CT scanning is of utmost importance. ",3 2379,"Diabetes and the myo-inositol paradox. To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical techniques in layers of the cornea, the aortic myointima, the cardiac left ventricle and atrioventricular node (AVN), and retina and kidney after 19 days or 2 mo (mildly diabetic non-insulin-treated [MD] and severely diabetic insulin-treated [SD] groups) in the alloxan-induced diabetes model. In the aqueous humor, glucose rose linearly with increased serum glucose, sorbitol was markedly increased in the MD and SD groups, and myo-inositol did not change in any diabetic group. There was no change in glucose or sorbitol in aortic myointima in any group, but myoinositol was decreased in 19-day diabetic rabbits by 26%, unchanged in MD rabbits but paradoxically increased by 60% in SD rabbits. Glucose, sorbitol, and myo-inositol increased in all three corneal layers in SD rabbits but only in epithelium and stroma in 19-day and MD rabbits. AVN glucose and sorbitol did not change in 19-day diabetic, MD, or SD diabetic rabbits. AVN myo-inositol was three times higher than ventricular myo-inositol and did not appear to change in SD rabbits. Retinal pigmented epithelium myo-inositol was decreased 30% in SD rabbits. Glomerular myo-inositol was also decreased, but not significantly, in SD rabbits. We conclude that the paradoxical increase in corneal and aortal myo-inositol raises fundamental questions about the general applicability of the myo-inositol-depletion hypothesis. ",17 52,"Positive Lyme serology in subacute bacterial endocarditis. A study of four patients. Lyme borreliosis is a multisystem inflammatory disorder caused by the tick-borne spirochete Borrelia burgdorferi. Clinical manifestations are protean, involving the skin, joints, peripheral and central nervous systems, and the heart. However, the presentation of Lyme disease often overlaps with that of other conditions. We describe four patients from a region endemic for Lyme disease who had elevated levels of antibodies reactive to B burgdorferi and whose signs and symptoms were initially attributed to Lyme borreliosis but whose subsequent blood cultures established a diagnosis of nonspirochetal subacute bacterial endocarditis. Although immunoblots on serum samples from three of the four patients were consistent with prior infection from B burgdorferi, a positive immunoblot does not establish active infection. Similarly, seropositivity to B burgdorferi only indicates possible exposure to this organism. The occurrence of positive serologies to B burgdorferi in the presence of other diseases can lead to diagnostic confusion. ",0 3303,"Late postoperative episodic and constant hypoxaemia and associated ECG abnormalities. Twenty-two patients without cardiopulmonary disease and undergoing elective major abdominal surgery were monitored continuously with a Holter tape recorder and a pulse oximeter on one night before operation and the first two nights after operation (23:00 to 07:00), without oxygen therapy. Mean heart rate increased 16 beat min-1 (P less than 0.001) and mean oxygen saturation (SaO2) decreased 2.6% (P less than 0.001) after operation. Episodic oxygen desaturation to less than 80% occurred in four patients before operation, but in 13 patients after operation (P less than 0.05). ECG abnormalities were observed in 10 patients before operation and in 16 patients after operation (ns). Individual maximum ST depression was more pronounced after than before operation (P less than 0.05). Episodic desaturation was related closely to tachycardia in six patients before operation and one patient after operation; before operation to atrioventricular block in one patient, and after operation to ST depression in two patients. Mean SaO2 on the second night after operation correlated with total dose of opioid for pain relief (rs = -0.48; P less than 0.05), and postoperative decrease in SaO2 correlated with postoperative increase in heart rate (rs = -0.43; P less than 0.05). No patient had postoperative cardiac complications indicating treatment. ",22 2734,"Isolated avulsion of the biceps femoris insertion. A case report. The clinical, roentgenographic, and operative findings of an isolated biceps femoris avulsion in a 21-year-old man demonstrated the significance of the static stabilizers about the knee, menisci, and articular cartilage. Examination of the dynamic structures about the knee, however, may present a diagnostic problem. A systematic examination of the musculature (hamstrings, quadriceps, and patellofemoral mechanism) should be included in the evaluation of every acute knee injury. Special attention should be given to the surface anatomy as well as function of the knee. ",20 3328,"Monitoring platelet interactions with prosthetic graft implants in a canine model. This study shows that prosthetic arterial grafts stimulate platelets for as long as 1 year after implantation in a canine model. Carotid-to-distal aorta Dacron (DuPont, Wilmington, DE) grafts (0.8 x 50.0 cm) were tunneled subcutaneously over the right dorsal side, allowing for percutaneous arterial sampling. Thromboxane B2 (TxB2) levels were evaluated at the proximal anastomosis (w), 5.0 (x), 25.0 (y), and 50.0 (z) cm distal from w, and platelet counts and mean platelet volumes were monitored at sites w and z. TxB2 levels increased after blood entered the graft and progressively increased until the blood exited at the distal anastomosis. Platelet counts did not significantly change across the graft. Over time, systemic platelet counts decreased to approximately 50% of each dog's pregraft baseline levels and remained depressed over a 1 year period. Mean platelet volumes peaked 1-3 weeks after implant and remained greater than pregraft levels. Examination of the graft luminal surface showed a developed pseudointima characteristically similar to that which develops in mature human vascular grafts. These results suggest that healed vascular grafts in canines continue to stimulate platelet release of TxB2, reduce systemic platelet counts, and increase mean platelet volumes over 1 year. These data further suggest that platelets are stimulated by the graft and consumed. ",22 145,"Transmission indices of Loa loa in the Chaillu Mountains, Congo. A longitudinal entomological survey of the vectors of loiasis was conducted in the Missama area (Lekoumou region) in the Congo from September 1987 to August 1989. The principal catching site was a palm grove surrounded by forest 3 km from the village. Landing/biting densities of Chrysops were measured by standardized fly catches lasting 11 hr carried out twice a month. Vector landing densities were also assessed in the Bantu and Pygmy villages and in the fields. Populations of Chrysops from the palm grove were examined 6 times a month for infection with the infective stage of Loa loa. Chrysops silacea was the predominate vector except at the beginning of the rainy season, when C. dimidiata was the prevailing species. Chrysops were caught throughout rainy season, from October to June. The host-seeking activity of C. silacea was greatest in the middle of this season (February), but occurred sooner (October) for C. dimidiata. The following variables associated with transmission were calculated from our observations in the palm grove (the first figure corresponds to the first year of the study and the figure in parentheses corresponds to the second year). It was calculated that 2.658 (2.185) C. silacea and 1.412 (1.182) C. dimidiata could bite a person in the palm grove per year, including an average of 14.4 (12.7) infective C. silacea and 9.8 (7.2) infective C. dimidiata. The percentage of all dissected flies with third stage larvae in the head and the mean number of larvae in the head/infective fly were 0.57% and 10.1 +/- 6.8 for C. silacea and 0.66% and 11.2 +/- 6.5 for C. dimidiata, respectively. The estimated annual transmission potentials were 171.1 (102.9) for C. silacea and 116.1 (73.8) for C. dimidiata. In the palm grove, transmission was ensured by 2 effective vectors during the rainy season (October to May). Although the annual biting rate for both species was twice as low in the village as in the forest, our data suggest that effective transmission occurs there also. ",2 2850,"Cranial electrostimulation (CES) use in the detoxification of opiate-dependent patients. This paper reviews the scientific literature on cranial electrostimulation (CES) as a non-chemical means to alleviate opiate withdrawal symptoms. CES involves applying small amounts of electrical stimulation through electrodes applied to the skin surface over the cranium. The paper summarizes major theories (gate, endorphin, and Chinese acupuncture) which attempt to explain how CES may help alleviate drug withdrawal and craving. Two of the studies reviewed show that CES patients experienced more severe withdrawal during the early part of treatment than comparison groups of methadone patients. Other studies show that CES patients did better than methadone patients. The findings from all studies reviewed, however, were limited because of low participation rates, high dropout rates, difficulties in blinding subjects and evaluators, and the absence of standardized procedures and equipment. The evidence reviewed suggests that CES is a promising line of inquiry for continued efforts to develop nonchemical ways to detoxify opiate-dependent individuals. Improved research designs, larger sample sizes, more integrity in data collection, and improved data analysis are needed in the future. ",20 1620,"Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage. We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm. ",13 2006,"Evidence of hibernating myocardium by a new transesophageal echocardiographic technique. Reversal of resting wall motion abnormalities after successful coronary angioplasty were documented in a patient with the use of a novel approach to stress testing. Transesophageal stress echocardiography utilizes transesophageal atrial pacing to provoke myocardial ischemia while the left ventricular contractility is being monitored by means of transesophageal echocardiography. The potential use of this technique is illustrated in this report. ",13 1254,"A survey of the initial referral of children to an ophthalmology department. We report on a survey of the referral of 525 children making their first visit to an ophthalmology department. Information was gathered by interviewing the parents and reviewing the case notes. Parents and relatives initiated the referrals in 223 cases (42%) and health visitors initiated a further 123 cases (23%). General practitioners were rarely the first to notice a condition, though they played a major part in the subsequent referral process. Of 556 reasons for referral squint was the most important (319 cases, 57%), followed by poor vision (106 cases, 19%). There were 44 confirmed cases of amblyopia, of which 15 (34%) were not detected until the child was aged 5 years or over. The overall accuracy of referral was 66% (367 reasons for referral confirmed). In 109 cases (21%) the child was found to be normal. Parents and relatives first noticed 54% of cases of confirmed squint but only 15% of the cases of poor vision. Health professionals, especially health visitors, were of great importance in first detecting poor vision. ",10 2504,"Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver. ",17 704,"Duodenal ulcer and refined carbohydrate intake: a case-control study assessing dietary fibre and refined sugar intake An association between duodenal ulceration and a low fibre intake and a high refined carbohydrate diet has been reported. We therefore compared the current diet, smoking habits, social class, and possible other risk factors of 78 patients with duodenal ulcer and a community control group matched for age and sex. Logistic regression for matched sets was used to calculate the relative risks for successive quintiles of dietary fibre and sugar intake before and after adjustment for total calorie intake and for the possible confounding effect of other known risk factors. Relative risks did not differ materially or consistently for total dietary fibre or for the cereal moiety whether adjusted or not for calorie intake. By contrast, relative risks tended to be reduced with high vegetable fibre intake and with low refined sugar intake. After controlling for smoking and social class, both of which were associated with ulcer disease, and for relative weight (Quetelet's index), the relation between ulcer disease and low refined sugar intake persisted, while that with high vegetable fibre intake was reduced. The results of this study indicate that a lack of cereal or total fibre intake plays no part in duodenal ulcer development but that a low refined sugar intake may be a protective factor. ",5 1371,"Prospective comparison of plain abdominal radiography with conventional and digital renal tomography in assessing renal extracorporeal shock wave lithotripsy patients. Most publications citing the effectiveness of renal extracorporeal shock wave lithotripsy have used plain abdominal radiography to assess residual calculi after treatment. We compared radiologist sensitivity and specificity in the detection of calculi on plain abdominal radiographs versus conventional film-screen and digital renal tomograms in extracorporeal shock wave lithotripsy patients. Of the patients 50 were imaged before and within 24 hours after lithotripsy. Six radiologists evaluated the resultant 300 studies for the presence and location of calculi. The mean sensitivity for digital tomograms was 83% for pre-lithotripsy and post-lithotripsy studies, which was significantly higher than for plain abdominal radiography and conventional tomography after lithotripsy. However, there were significantly more false positive stone diagnoses associated with digital tomogram interpretation. Signal detection analysis verified the over-all superiority of digital tomography for post-extracorporeal shock wave lithotripsy imaging. Calculus detection by conventional and digital tomography is superior to detection by plain abdominal radiography. However, because we did not perform delayed imaging, it is not possible to say what impact digital tomography might have on the management of extracorporeal shock wave lithotripsy patients. ",11 2165,"Prenatal diagnosis of laryngeal atresia. In a patient in whom preeclampsia developed at 23 weeks' gestation, ultrasonographic examination of the fetus showed enlarged edematous lungs, a compressed fetal heart, severe ascites, fetal hydrops, and placental edema. Autopsy of the hydropic stillborn infant showed laryngeal atresia. The ultrasonographic appearance of this rare malformation is presented. ",14 798,"Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. Whether parenchymal or nonparenchymal liver cells play a predominant role in the pathophysiology of hepatic fibrosis has not been firmly established in vivo. We have addressed this question by quantitating the relative abundance of specific mRNAs for collagen types I, III, and IV, and laminin in purified populations of hepatocytes, sinusoidal endothelial cells, and lipocytes from normal and fibrotic rat liver. In normal liver, type I collagen gene expression was minimal in all cell types; mRNA for types III and IV collagen were apparent in endothelial cells and lipocytes, but not in hepatocytes. Laminin mRNA was present in all cell types. Induction of fibrogenesis by either bile duct ligation or carbon tetrachloride administration was associated with a substantial increase in mRNA for types I and III collagen in nonparenchymal cells. Lipocytes from fibrotic animals exhibited a greater than 30-fold increase in type I collagen mRNA relative to normal lipocytes, and greater than 40-fold relative to hepatocytes. Type III collagen mRNA reached 5 times that in normal lipocytes and greater than 120 times that in hepatocytes. Endothelial cells exhibited an isolated increase in type I collagen mRNA, reaching five times that in normal liver. Type IV collagen and laminin gene expression were not significantly increased in nonparenchymal cells during fibrogenesis; in fact, mRNA for type IV collagen and laminin decreased by up to 50% in endothelial cells. Despite the pronounced changes that occurred in matrix gene expression in nonparenchymal cells during fibrogenesis, no change was noted in hepatocytes. We conclude that nonparenchymal liver cells, particularly lipocytes, are important effectors of hepatic fibrosis in vivo. ",5 2998,"High dietary fiber and low saturated fat intake among oligomenorrheic undergraduates. Numerous functional risk factors are associated with the occurrence of secondary amenorrhea in young women. Less is known regarding factors associated with the more prevalent problem of oligomenorrhea. We have evaluated nutrient intake, body composition, perceived psychological stress, 24-hour urinary cortisol, and urinary C peptide (UCP) in 35 eumenorrheic, 11 mildly oligomenorrheic, and 10 oligomenorrheic nonathletic undergraduate women. Nutrient intake was evaluated by a validated food frequency questionnaire. Oligomenorrheic women were found to consume significantly more dietary fiber, crude fiber, and polyunsaturated fat, and significantly less saturated fat than their eumenorrheic classmates. Oligomenorrheic women had significantly lower 24-hour UCP excretion than mildly oligomenorrheic women. The groups did not differ in any aspect of body composition, body weight, age of menarche, perceived psychological stress, or urinary cortisol excretion. The data suggest that higher intake of fiber and lower intake of saturated fat may be associated with oligomenorrhea among otherwise healthy undergraduate nonathletic women. ",22 2888,"Rapid visual colorimetry of peritoneal lavage fluid. STUDY HYPOTHESIS: That visual colorimetry can be used to rapidly and precisely estimate the erythrocyte count of 1:5 dilutions of simulated peritoneal lavage fluid. POPULATION: Fifty-four normal adult human subjects. METHODS: The automated or chamber RBC count is often used on fluid obtained by peritoneal lavage in patients with abdominal trauma to help determine the need for surgery. Unfortunately, this method sometimes results in excessive delay. We designed and built a simple colorimeter that facilitated rapid direct visual comparison of unknown samples with known color standards. A radiograph view box was used as a light source. Standards were prepared in 16-mm glass tubes to simulate peritoneal lavage fluid with RBC counts ranging from 0 to 140,000 in 10,000 cell/microL increments; 1:5 dilutions with water were used throughout to reduce opacity. Thimerosal was added to unknowns and standards to stabilize color; all samples were kept refrigerated at 4 C when not in use. In a double-blind in-vitro study, each subject matched 20 randomly distributed unknowns ranging from 12,000 to 131,000 erythrocytes/microL to the nearest standard. RESULTS: The mean absolute error for all 1,080 determinations was 3,560 RBC/microL (95% CI = 4,290-4,830; SD = 4,560; t = 39.6; df = 1,079; P less than .001). This method correctly predicted the RBC count to within 9,000 cells/microL 95% of the time. CONCLUSION: Visual comparison of 1:5 dilutions of simulated peritoneal lavage fluid with known color standards can be used to rapidly and precisely estimate the erythrocyte count. ",20 1526,"Establishment of pregnancies in humans after transcervical transfer of gametes immediately after oocyte retrieval. This study, like that of Veersema et al. demonstrates the feasibility of direct intrauterine transfer of gametes in initiating pregnancy. Whether the success of this procedure can be further improved with modification (preincubation, in vitro insemination) remains the subject of continued investigation. Notwithstanding this uncertainty, we feel that transcervical transfer of gametes may be an alternative to IVF for patients with ethical concerns regarding IVF. ",12 2924,"A survey of wound monitoring and topical antimicrobial therapy practices in the treatment of burn injury. A survey was done to determine how burn wound microbial monitoring is performed and how topical antimicrobial agents are employed. The survey was sent to 90 burn-care facilities, which comprised most of the major burn centers in the United States. The survey contained questions concerning frequency and techniques of wound monitoring, personnel involved in monitoring, as well as questions about how decisions were made to initiate topical antimicrobial therapy, which agents were selected, and how they were administered. Sixty of 90 facilities (66%) responded to the survey. Although there were few areas of unanimous agreement, several trends did emerge. Most facilities monitored burn wounds for microbes (92%). Wound monitoring was typically done at least twice weekly by either surface swab or quantitative biopsy. Nursing staff played a significant role in specimen collection in 69% of facilities and were solely responsible for obtaining biopsy specimens in 29% of facilities that used biopsies exclusively. All responding facilities used topical antimicrobial agents; silver sulfadiazine was the most popular (95%). Only 33% of facilities surveyed had their own laboratory for microbial monitoring. Rapid techniques for early diagnosis of wound sepsis were used in 20% of units, and topical antimicrobial testing was used in 17% of facilities surveyed. ",20 294,"Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma. ",3 953,"Determination of serum concentrations of type III procollagen peptide in mechanically ventilated patients. Pronounced augmented concentrations in the adult respiratory distress syndrome. Type III procollagen peptide (PCP) is a byproduct of type III collagen synthesis and a potential marker of collagen secretion. In chronic diffuse interstitial lung diseases, elevated PCP concentrations have been found in serum as well as in bronchoalveolar lavage fluid. It has been proposed that PCP is a marker of early, active stages of fibrosis. As severe fibrosis is a frequent complication in adult respiratory distress syndrome (ARDS), we investigated PCP in patients with ARDS and compared the results with those from patients requiring mechanical ventilation because of heart failure and after neurosurgical and surgical interventions, and those from spontaneously breathing patients, including healthy volunteers and patients with pneumonia, liver cirrhosis, and renal failure. PCP concentrations in patients with ARDS were extremely elevated compared with those in control subjects (p less than 0.001) and correlated positively with FiO2 (r = 0.71, p less than 0.01). These results support the pathophysiologic concept of early fibrogenesis in ARDS. As preventing pulmonary fibrosis in ARDS is essential in improving survival rate, we believe PCP can be a valuable diagnostic tool in ARDS. ",7 56,"The use of prophylactic furazolidone to control a nosocomial epidemic of multiply resistant Salmonella typhimurium in pediatric wards. The nosocomial spread of enteric pathogens is often difficult to control in overcrowded pediatric wards. During 1983 and 1984, despite cohorting of patients and enforced hand washing, more than 200 cases of nosocomial multiply resistant Salmonella typhimurium phage type R-9 were observed on two adjacent pediatric wards. Most cases occurred during the summer months. After 19 new cases were detected early in the summer of 1985, oral administration of furazolidone throughout their entire hospital stay (2.5 mg/kg twice daily) was recommended for all subsequently hospitalized infants. Among the 114 (65%) infants who were appropriately treated, only one additional case (1%) was detected. In contrast 11 (19%) cases occurred among the 59 infants who were inappropriately treated: 5 of 35 (14%) of those who were not treated and 6 of 24 (25%) in whom treatment with furazolidone was delayed greater than 24 hours (P less than 0.001 between the appropriately and inappropriately treated groups). In pediatric wards where infection control measures cannot be optimally applied, prophylactic furazolidone administration may be helpful in preventing the spread of enteric pathogens. ",0 99,"Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock. ",0 3256,"Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings. ",22 729,"Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux. A total of 36 patients with grade 2 or greater erosive esophagitis and an abnormal 24-h pH monitor study, were treated in a randomized, double-blind fashion to assess the efficacy of sucralfate suspension as adjunctive therapy to cimetidine for severe esophagitis secondary to gastroesophageal reflux. Treatment consisted of cimetidine, 300 mg qid and either sucralfate suspension (1 g/10 ml) or an identical placebo suspension, 10 ml after meals and 20 ml hs. Patients were treated for 12 wk unless endoscopic healing occurred earlier. Initial evaluation and monthly follow-up consisted of symptom monitoring, endoscopic evaluation and pre- and post-therapy esophageal manometry, Bernstein test, and 24-h pH monitoring. The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation. Sucralfate plus cimetidine improved the overall endoscopic outcome of esophagitis more than cimetidine alone (p less than 0.05). More patients exhibited endoscopic healing in the adjunctive sucralfate group than in the cimetidine-only group. Endoscopic healing, however, was not statistically different between groups. We conclude that sucralfate used as adjunctive therapy to cimetidine resulted in improvement of some of the symptoms of reflux, and probably increases the likelihood of complete healing of esophagitis, compared with cimetidine alone. ",5 241,"Estimation of PR and ER by immunocytochemistry in breast cancer. Comparison with radioligand binding methods. Immunocytochemical assays for progesterone receptor (PR) using monoclonal antirabbit PR antibodies (PR-ICA) and for estrogen receptor (ER) (ER-ICA) were compared with radioligand binding (dextran-coated charcoal [DCC]) methods for receptor determination in patients with breast cancer. Immunocytochemical staining for PR was exclusively nuclear in localization. In this regard, PR staining is similar to previous findings for ER; PR-ICA showed a sensitivity of 89% and specificity of 100%. ER-ICA was also 89% sensitive and similarly specific. There was good correlation between the degree and intensity of staining and quantitative binding of radioligand. Receptor-positive tumors, however, show considerable variation of immunocytochemical staining, suggesting heterogeneity of cellular PR content. The availability of an immunocytochemical assay for PR increases the discriminatory potential for these methods of receptor determination. ",3 195,"Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials. ",3 3130,"Placement of esophageal stethoscope by acoustic criteria does not consistently yield an optimal location for the monitoring of core temperature. The esophageal stethoscope has evolved into a device for both acoustic and core temperature monitoring. To test whether routine placement according to acoustic criteria results in placement of the core temperature sensor in the region of contiguity between the esophagus and the heart, we determined the depth of placement electrocardiographically. All patients were undergoing nonthoracic elective operations requiring general anesthesia and tracheal intubation. First, we established that different observers selected the same esophageal depth within +/- 1 cm electrocardiographically, using the criterion of a symmetric biphasic P wave of maximal amplitude (7 patients). Then, in 30 more patients, we compared routine acoustic placements with the depths of the maximal-amplitude biphasic P wave. Stethoscopes placed according to acoustic criteria were within +/- 3 cm of P-wave depths in 15 of 30 patients. In the remaining patients, measured discrepancies ranged up to 13.5 cm. We conclude that the prevailing stethoscope design, with a thermistor at the tip, below the acoustic window, does not ensure placement of the thermistor within the optimal region for monitoring of core temperature. A modification in design that would take advantage of the reliability of electrocardiographic positioning is suggested. ",22 2304,"Cyclosporine A in the treatment of psoriasis: a clinical and mechanistic perspective. Cyclosporine A, a unique immunomodulatory agent, has been used increasingly over the last 5 years in the management of severe psoriasis. The remarkable efficacy of this drug coupled with its known immunosuppressive properties have enabled a further appreciation of the role of the immune system in the induction and maintenance of psoriatic plaques. Although acting primarily on T lymphocytes, there is also evidence for an effect of cyclosporine A on other constitutive cell types within the skin. The future use of systemically administered cyclosporine A in the treatment of psoriasis and other cutaneous diseases is dependent on the successful balance of efficacy and side-effect profile; namely, the dose-related problems of hypertension and nephrotoxicity. As a result of the toxicity encountered with systemically administered cyclosporine A, attempts to formulate a successful topical preparation for use in cutaneous disease are being made. The advent of cyclosporine A provides the dermatologist with a new therapeutic strategem in the management of psoriasis, although the long-term safety of such interventional therapy remains to be discerned. ",16 504,"Growth factor-dependent differentiation along the myeloid and lymphoid lineages in an immature acute T lymphocytic leukemia. Bone marrow cells from a child with an immature (CD2+, CD5+, CD7+) acute T lymphocytic leukemia (T-ALL) were cultured in the presence and absence of human rIL-2, IL-3, or granulocyte-macrophage (GM)-CSF. Cells cultured without growth factors failed to divide and those initiated in the presence of IL-2 or GM-CSF underwent maturation and terminal T lymphoid or myelomonocytic differentiation, respectively. In contrast, a permanent growth factor-dependent cell line, designated TALL-103/3, was established upon culture in IL-3. The TALL-103/3 cells gradually lost the T cell-specific markers and acquired a myeloid phenotype (CD15+, CD33+). Switching of the IL-3-dependent cells at an early passage to medium containing only human rIL-2 resulted in the establishment of a subline, named TALL-103/2, with a T lymphoid phenotype (CD3+, CD8+, TCR-gamma delta +, CD7+). The TALL-103/2 cells strictly require IL-2 for growth, are irreversibly committed to the lymphoid lineage, and cannot survive in the presence of any other hemopoietic growth factor tested so far. In contrast, the IL-3-dependent TALL-103/3 cells could be adapted to grow in synthetic (serum-free) medium also in the presence of either GM-CSF or IL-5, in which they retain a myeloid phenotype. Interestingly, after 18 mo in culture in IL-3, the TALL-103/3 cells can still be phenotypically converted to the lymphoid lineage upon addition of IL-2, thus maintaining its bipotentiality. Despite the marked phenotypic differences, the TALL-103/2 and TALL-103/3 cell lines show the same karyotypes with multiple abnormalities present in the primary malignant clone and have identical rearrangements of the TCR-gamma and -delta loci, thus confirming their derivation from a common precursor cell. Together, these findings indicate that the phenotype of immature T-ALL cells can be drastically modified by the presence of specific hemopoietic growth factors in the environment, leading to either lymphoid or myeloid lineage commitment while leaving their karyotype and genotype intact. ",3 14,"Cerebrospinal fluid changes after 48 hours of effective therapy for Hemophilus influenzae type B meningitis. Interval cerebrospinal fluid (CSF) analysis is often performed to assess efficacy of treatment for bacterial meningitis. The authors reviewed 101 cases of pediatric bacterial meningitis resulting from Hemophilus influenzae type b in which analysis of CSF occurred on admission and between 48 and 72 hours after initiation of parenteral antibiotic therapy; of these, only one patient had a positive repeat CSF culture. Of the 100 cases with sterile CSF on repeat culture, there was no instance of recrudescence of infection during hospitalization. The following characterized the interval changes in CSF profile of this group: 100 (100%) with persistence of pleocytosis; 14 (14%) with differential cell count conversion from polymorphonuclear neutrophil leukocyte (PMN) predominance to relative lymphocytosis; 96 of 98 (98%) with initial positive Gram-stained smear with negative results for organisms; 53 of 75 (71%) with normalization of initial hypoglycorrhachia; and 10 of 94 (11%) with normalization of initial abnormally elevated protein levels. The differences in mean values of CSF total white blood cell counts, percentage PMNs, and glucose and protein concentrations on presentation and between 48-72 hours of therapy were highly significant (P less than 0.0001). After 48 hours of effective antibiotic therapy for H. influenzae type b meningitis, CSF pleocytosis and abnormally elevated protein concentration are usually preserved, whereas hypoglycorrhachia usually resolves; it is not uncommon for the differential cell count to convert from a PMN predominance to a relative lymphocytosis. Significant alteration in all CSF parameters associated with H. influenzae type b meningitis can occur after 48 hours of effective parenteral antibiotic therapy. ",0 2160,"Impaired thermoregulation and thyroid function in iron-deficiency anemia. Ten women with iron-deficiency anemia, 8 with depleted iron stores (nonanemic), and 12 control women, all of similar body fatness, were exposed to a 28 degrees C water bath to test the hypothesis that iron-deficiency anemia impairs thermoregulatory performance. The anemic women had lower rectal temperatures than did control women (36.0 +/- 0.2 vs 36.2 +/- 0.1 degree C, respectively, P = 0.001) and a lower rate of oxygen consumption (5.28 +/- 0.26 vs 5.99 +/- 0.29 mL.min-1.kg body wt-1, respectively, P = 0.04) at 100 min of cold exposure. Plasma thyroxine and triiodothyronine concentrations were significantly (P less than 0.002) lower in anemic than in control women at baseline and during cold exposure. Responses of iron-depleted subjects were similar to those of control subjects. Iron supplementation corrected the anemia, significantly (P = 0.03) improved rectal temperature at 100 min, and partially normalized plasma thyroid hormone concentrations. Plasma catecholamines were unaffected by iron status. This experiment demonstrates a functional consequence of iron-deficiency anemia in the balance of heat production and loss and suggests that thyroid-hormone metabolism may be responsible. ",14 2295,"Lymphocyte chemoattractants in psoriasis and normal skin. The local production of lymphocyte attractants may influence both physiologic lymphocyte trafficking in the skin as well as the infiltration of these cells in pathologic states. Recent evidence for the production of acidic lipid lymphocyte chemoattractants, particularly 12[R]-hydroxyeicosatetraenoic acid, in psoriatic lesions is reviewed. Water extractable lymphocyte attractant activity may also be recovered from both normal skin samples and psoriatic lesional stratum corneum, and may be important in the pathophysiology of lymphocyte trafficking. Less than 10 kD activity from normal skin has undergone the most detailed characterization. This has led to the isolation of a novel, as yet unidentified compound from normal skin, which we have termed ""plasma-associated lymphocyte chemoattractant"" (PALC). ",16 346,"Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy. ",3 2692,"Recognition of a B cell lymphoma by anti-idiotypic T cells. Idiotypic IgM derived from a B cell lymphoma can act as a tumor-associated Ag, in that immunization with this purified protein generates an anti-idiotypic immune response that specifically suppresses tumor development. Spleens of immune mice contain T cells that proliferate in response to idiotypic IgM. However, idiotypic Ag is presented to the T cells most efficiently in its natural form at the surface of the lymphoma cells, than as soluble IgM plus presenting cells. Variant tumors that display either little or no idiotypic IgM at the cell surface, but which are otherwise indistinguishable from parental tumor, induce a weak response or fail to stimulate the T cells, respectively. Anti-idiotypic lines and clones have been derived from the splenic T cells by growth in the presence of irradiated tumor cells. Phenotypic analysis revealed that cells from both lines and clones express CD3 and CD4 Ag, but not CD8. Recognition of tumor Id, which required no added presenting cells, was inhibited by antibody against MHC class II Ag, and variably by anti-CD4. Proliferative responses were inhibited by anti-idiotypic antibodies, but also by antibodies against the constant region of the mu H chain, indicating that perturbation of the surface IgM abrogates availability of idiotypic determinants to the T cells. ",19 328,"Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype. We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high. ",3 2018,"Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats. The myocardium contains collagen matrix that is a major determinant of its architecture, structural integrity, and mechanical properties. This fibrillar matrix consists primarily of type I and type III collagens having epimysial, perimysial, and endomysial components. The present study shows the alteration of collagen phenotypes during the evolution of hypertensive hypertrophy. Therapy with captopril, an angiotensin-converting enzyme inhibitor that regresses cardiac hypertrophy, not only reduces the total amount of collagen but reverses the altered distribution of type I and type III collagen. In normotensive rats, captopril did not significantly reduce collagen content or alter the ratio of type I to type III collagen. ",13 2841,"Diagnostic peritoneal lavage: accuracy in predicting necessary laparotomy following blunt and penetrating trauma. The purpose of this study was to evaluate the ability of diagnostic peritoneal lavage (DPL) to predict intra-abdominal injuries that required surgical repair. To do this, we retrospectively reviewed 944 patients with blunt and penetrating abdominal trauma who underwent 975 DPLs. Initial DPL in 608 patients sustaining blunt trauma had a sensitivity of 87%, a specificity of 97%, an accuracy of 95%, a positive predictive value (PPV) of 85%, and a negative predictive value (NPV) of 97%. Initial DPL in 336 patients with penetrating trauma had a sensitivity of 87%, a specificity of 89%, an accuracy of 89%, a PPV of 75%, and a NPV of 95%. When utilizing final lavage results on the 944 patients, DPL had a sensitivity of 91%, a specificity of 94%, an accuracy of 93%, a PPV of 80%, and a NPV of 98% in predicting intra-abdominal injury requiring surgical repair. ",20 880,"Confluence of pulmonary veins simulating a pulmonary mass. Confluence of the pulmonary veins commonly appears on the frontal view of the chest and generally is easily recognized as such. On plain film tomography, computerized tomography, and pulmonary angiography, the anatomy of convergence of pulmonary veins prior to common entry into the left atrium is clearly displayed. In this report, attention is called to the occasional appearance of confluence of the pulmonary veins on the lateral view of the chest as a clearly circumscribed round opacity mimicking a lung or mediastinal mass. ",7 320,"Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours. A multiparameter flow cytometric assay for the simultaneous study of tumour associated antigens (TAA) and DNA in fresh solid tumours was devised. Cell suspensions were prepared by disaggregating unfixed solid tumour samples mechanically over a stainless steel mesh. Indirect immunofluorescence was used to identify the TAA, and DNA was stained with propidium iodide. Cell morphology was well preserved, cell clumping was negligible, and high quality indirect immunofluorescence quality indirect immunofluorescence and DNA staining were obtained. The technique is simple, rapid, and reproducible. Multiparameter assays can be developed to study prognostic indicators such as membrane oncoproteins, receptors, and multidrug resistance in solid tumours. With a suitable panel of antibodies the technique might become an aid in the differential diagnosis and biochemical diagnosis of some solid tumours. ",3 1862,"Embolization of a giant renal arterial aneurysm. A 49-year-old man presented with right flank pain. Angiography revealed a giant right renal arterial aneurysm. Giant renal arterial aneurysms are typically treated by nephrectomy. In this patient the aneurysm was embolized successfully with multiple Gianturco-Wallace coils and polyvinyl alcohol. This case indicates that embolization may be a reasonable alternative to nephrectomy. ",13 783,"Intracorporeal biliary lithotripsy. Most bile duct calculi can be removed with standard percutaneous or endoscopic techniques. Very large stones are the most common cause for failure. Intracorporeal lithotripsy, and EHL in particular, can be used safely in either the biliary tree or gallbladder to fragment these large stones and allow percutaneous removal or passage. Intracorporeal EHL requires direct vision to prevent damage to the bile duct mucosa. Intracorporeal laser lithotripsy may offer some safety advantages, but the laser requires much more expensive equipment than intracorporeal EHL. Additional studies are needed to determine the technique that is better in each circumstance. ",5 2571,"Platelet activating factor-induced clinical and histopathologic responses in atopic skin and their modification by the platelet activating factor antagonist BN52063. The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF-acether but had little effect on cellular recruitment at the site of injection. ",19 2191,"Value of transesophageal echocardiography during repair of congenital heart defects. Two-dimensional transesophageal color Doppler echocardiography was employed intraoperatively in 30 children undergoing repair of a variety of simple and complex cardiac malformations. There were 16 female and 14 male patients, with a mean age of 9 +/- 3 years (range, 4 to 13 years) and a mean weight of 31 +/- 9 kg (range, 16 to 50 kg), 16 children weighing less than 30 kg. A standard, commercially available transesophageal echocardiography probe (5 MHz, 64 elements) was used in all patients without complications. Transesophageal echocardiography proved helpful in selecting the surgical approach, in assessing the adequacy of surgical repair, in detecting residual intracardiac shunts, and in allowing uninterrupted monitoring of ventricular performance throughout the procedure. Our initial experience suggests that transesophageal echocardiography is a valuable tool to be used in children with congenital cardiac malformations, particularly in those requiring complex intracardiac procedures. The amount of information obtained by the surgeon should favor the routine use of transesophageal echocardiography during open heart procedures and stimulate the development of probes to be safely used even in infants and newborns. ",15 273,"Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow. Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L-phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment. ",3 1522,"Home monitoring of gonadotropin ovulation induction using the Ovarian Monitor. The safe use of gonadotropins relies on close hormonal and/or ultrasound monitoring to assess the response to treatment, requiring multiple hospital visits. Home monitoring with the Ovarian Monitor (St. Michael Research Foundation, Macleod, Victoria, Australia) minimizes hospital visits and overcomes many of the logistic difficulties associated with gonadotropin use. It utilizes a system of homogenous enzyme immunoassay using lysozyme conjugates to measure quantitatively either urinary estrone-3 or pregnanediol-3-glucuronide. Results obtained by 24 patients in 57 cycles using the Ovarian Monitor at home correlate closely with results obtained in the laboratory (estrone-3-glucuronide r = 0.955; pregnanediol-3-glucuronide r = 0.958). Cycle outcomes (ovulation, 74%/cycle; clinical pregnancy, 30%/cycle; multiple pregnancy, 13%/pregnancy; hyperstimulation, 11%/cycle) are no different from those achieved in laboratory-monitored patients. Home monitoring can be as safe and effective as laboratory monitoring, offers significant social benefits, and improves access to this form of therapy. ",12 1289,"Glaucoma secondary to epithelial downgrowth and 5-fluorouracil. Since epithelial downgrowth involves an actively proliferating intraocular tissue, it is possible that the antimetabolite 5-fluorouracil may inhibit it. We report a case of secondary glaucoma caused by epithelial downgrowth in which filtration surgery was performed with adjunctive use of subconjunctival 5-fluorouracil. On cessation of the injections, the retrocorneal membrane grew rapidly to involve the entire posterior cornea. The eye eventually became blind and painful and was enucleated. The use of 5-fluorouracil given in the usual manner appears to have been a failure. ",10 1769,"Evidence for decreased coronary flow reserve in viable postischemic myocardium. To try to unravel the complexity and heterogeneity of the ""no-reflow"" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool. ",13 614,"Studies of the porcine intestinal calcitriol receptor in pseudo-vitamin D deficiency rickets type I. 1. Calcitriol (1,25-dihydroxyvitamin D3) concentrations in plasma of humans and pigs with pseudo-vitamin D deficiency rickets type I (PVDRI) have been reported to be significantly lower than in normal subjects and animals. Sometimes, however, calcitriol concentrations are relatively high in these subjects and animals (50-80 pmol/l) and nevertheless clinical symptoms of rickets develop. We have studied whether or not the development of rachitic lesions in piglets with PVDRI is due to altered binding properties of the intestinal calcitriol receptor in addition to the defective renal production of calcitriol. PVDRI piglets with clinical and biochemical symptoms of rickets (hypocalcaemia, increased activity of alkaline phosphatase) and with calcitriol concentrations in plasma of 83.7 +/- 4.2 pmol/l (n = 7) were used. They were compared with unaffected piglets with normal calcitriol concentrations (178.0 +/- 17.7 pmol/l, n = 9). 2. The equilibrium dissociation constant (Kd) of the receptor in the PVDRI piglets (0.31 +/- 0.05 nmol/l) and in control piglets (0.33 +/- 0.05 nmol/l) and the maximum binding capacity (Bmax.) (674 +/- 103 and 719 +/- 122 fmol/mg of protein, respectively) were not different (n = 9). 3. The association rate constant (kass) at 4 degrees C [0.15 x 10(7) and 0.24 x 10(7) (mol/l)-1 min-1] and the dissociation rate constant (kdiss) (0.40 x 10(-3) and 0.48 x 10(-3) min-1; half-life of dissociation = 24.1 and 28.9 h, respectively) were also not different between diseased and control piglets. ",4 3209,"Postoperative hypoxemia after nonabdominal surgery: a frequent event not caused by nitrous oxide. We tested whether anesthesia that includes nitrous oxide (N2O) results in the development of intraoperative and postoperative pulmonary complications, including hypoxemia. We also tested whether aging contributes to the development of such complications, particularly when anesthesia includes N2O. We randomly allocated patients having total hip replacements, carotid endarterectomies, or transsphenoidal hypophysectomies (total n = 270) to an anesthetic regimen with and without N2O (stratified within surgical group). A heat-and-moisture exchanger was included in the anesthetic circuit of all patients. Patients were monitored perioperatively and for 1 wk after surgery using intermittent and continuous pulse oximetry to determine oxyhemoglobin saturation. Intraoperatively, mean oxygen (O2) saturations were lower in patients given N2O, particularly older patients. Hypoxemia (O2 saturation less than 86%) developed in five patients receiving N2O and in one receiving O2. This difference was not significant. Administration of N2O did not decrease postoperative O2 saturation, nor did it alter the incidence of postoperative hypoxemia, cough, or sputum production. ",22 3249,"The efficacy of methylprednisolone in reducing flap edema. It has been suggested that systemic steroids reduce postoperative flap edema. This has been poorly documented by several reports based on subjective clinical observations. In an effort to provide quantitative data on methylprednisolone and edema, a flap edema model in the rat was developed based on the inferior epigastric vessels. Significant edema developed after 48 hours. Differing intraoperative doses of methylprednisolone were studied, producing a dose-response curve. A single low dose of intraoperative steroid is effective in reducing flap edema; previously recommended doses are probably excessive. ",22 2251,"Contact dermatitis from acrylate and methacrylate compounds in Lowicryl embedding media for electron microscopy. This report is about occupational contact dermatitis found in 3 out of 6 workers of a chemistry laboratory using Lowicryl embedding media, which contain (meth)acrylate monomer mixtures of known composition. The notation (meth)acrylates is used to refer to both acrylates and methacrylates. (Meth)acrylate monomers will polymerize in the absence of oxygen when induced by metal ions, peroxides, heat or ultraviolet light. The monomers are of low viscosity and remain in the liquid state at temperatures far below 0 degree C. The volatile compounds, some of which exhibit a most pungent odour, have a tendency to penetrate all tissue and to permeate into the finest fissures, a property which makes them suitable as sealants, glues, embedding material, etc. This and their toxicity may represent a danger to the health of individuals who need to work with them, especially if no precautions are taken. We show with patch testing that one patient reacted strongly to the compound 2-hydroxyethyl acrylate at the dilutions tested (0.5 and 1% v/v), but not at all to 10 other (meth)acrylates. In the same test, 3 volunteer controls were negative to 2-hydroxyethyl acrylate. We demonstrate that at maximum working concentration, 2-hydroxyethyl acrylate penetrates both latex and vinyl gloves and elicits irritant/allergic reactions on the patient and irritant reactions on a control. Finally, we discuss the necessary protective measures. ",16 2478,"Multigenic basis for type I diabetes. Association of HRAS1 polymorphism with HLA-DR3, DQw2/DR4, DQw8. We analyzed extended haplotypes composed of DNA loci on the short arm of chromosome 11 for segregation with insulin-dependent (type I) diabetes mellitus. The markers for these loci are tyrosine hydroxylase, insulin, and c-Ha-ras-1 proto-oncogene (HRAS1). We report, in a study of 27 families, that a specific haplotype (H), containing a 3-kilobase (kb) HRAS1-Taq I DNA polymorphism, segregated differentially in diabetic and nondiabetic siblings (P = 0.005). A parallel population study showed that the 3-kb HRAS1-Taq I polymorphism is increased in frequency in type I patients having two strong HLA-susceptibility haplotypes compared with other type I patients or healthy control blood donors (P less than 0.010 and P less than 0.025, respectively). The polymorphic variable, enhancer, and promoter regions flanking the human insulin gene on the H haplotype were not associated with type I diabetes. These results indicate that the HRAS1 locus or genes in linkage disequilibrium with this locus are involved in the pathogenesis of HLA-DR3/4 type I diabetes mellitus. ",17 514,"Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects. ",3 972,"Pentoxifylline attenuates edema formation in proteolytic enzyme-induced lung injury. Ex vivo canine lung lobes were exposed to a pancreatic proteolytic enzyme (chymotrypsin) alone or chymotrypsin after pretreatment with a continuous infusion with pentoxifylline. The lobes exposed to chymotrypsin gained 133 g, while the pentoxifylline-treated lobes gained only 65 g (p less than .05) over the 3-h experimental period. These results suggest that pentoxifylline significantly attenuates the lung weight gain associated with chymotrypsin. ",7 1709,"Intraoperative coronary excimer laser angioplasty: preliminary clinical experience. Diffuse coronary artery atherosclerosis is generally recognized as a deterrent to successful revascularization if it cannot be adequately treated. Mechanical endarterectomy can be useful, but it is not the optimal solution owing to the associated higher incidences of perioperative infarction and mortality. The use of laser energy as an endarterectomy tool appears promising. To investigate the application of excimer laser radiation to intraoperative coronary artery endarterectomy, 15 stenotic lesions in 13 patients were treated with excimer irradiation during coronary artery bypass grafting. Eleven (73%) of the lesions were enlarged by the excimer probe (6 of the successes were in calcified lesions). The 4 arteries not enlarged by the excimer laser all demonstrated calcified lesions. There were 3 perforations and 2 dissections, all but 1 in heavily calcified arteries. The results of this phase 1 safety and efficacy study indicate that excimer irradiation can recanalize most arteries, including total and subtotal occlusions and some calcified lesions. Further evaluation with better delivery systems is needed to determine whether the perforation rate can be reduced. ",13 1376,"The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats. It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis. ",11 3,"Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine-resistant septic shock. The hemodynamic effects of epinephrine were prospectively studied in 13 patients with septic shock who remained hypotensive after both fluid loading and dopamine. Hemodynamic measurements were performed before and one hour after the start of epinephrine infusion. Systolic, diastolic, and mean arterial pressure increased in all patients (p less than 0.01). Cardiac index and systemic vascular resistance increased by 34 and 32 percent, respectively (p less than 0.05), but heart rate and pulmonary vascular resistance remained unchanged. There was a concomitant increase in oxygen delivery (p less than 0.01) and oxygen consumption (p less than 0.05), the magnitude of the latter being related to baseline lactacidemia (p less than 0.01). In view of the generally recognized physiologic goals of septic shock management, we conclude that epinephrine could be an appropriate alternative where fluid loading and dopamine have failed. ",0 2098,"Bioenergetic recovery processes of injured myocardium. We employed cervically transplanted nonworking myocardium to simulate the condition of a heart supported by a ventricular assist device, and to investigate the bioenergetic recovery processes of injured myocardium with 31P nuclear magnetic resonance (NMR) techniques. A heterotopic graft was placed in the cervical portion of a recipient rat. One week later, a control 31P NMR spectrum was obtained from the graft. On the same day, the aorta of the graft was clamped for 30 minutes at room temperature. After this procedure, 31P NMR measurements of the graft were performed for 1 week. The phosphocreatine (PCr)/Inorganic phosphate (Pi) ratio, and beta-phosphate from adenosine triphosphate (beta-ATP)/Pi ratio on the first and second day after injury were significantly lower than control (p less than 0.05). However, these ratios recovered to a significant extent on the third and fourth day. These results suggest that 3 or 4 days are required for bioenergetic recovery of reversibly injured myocardium, even under nonworking conditions. ",13 1938,"Comparison of blood flow assessment between laser Doppler velocimetry and the hydrogen gas clearance method in ischemic intestine in dogs. Blood flow of the colon and the ileum was measured before and after intestinal devascularization by laser Doppler velocimetry and the hydrogen gas clearance technique in 10 dogs in order to evaluate the clinical usefulness of laser Doppler velocimetry. The submucosal blood flow of the colon and the ileum measured by the hydrogen gas clearance method was significantly decreased, as was the subserosal blood flow of both sites measured by laser Doppler velocimetry. There was a linear relationship between the flow values using the two methods both in the colon (r = 0.7192, p less than 0.001) and in the ileum (r = 0.7646, p less than 0.001). These data suggested laser Doppler velocimetry may be a useful method to assess the degree of intestinal ischemia because of its noninvasiveness and good correlation with submucosal blood flow by the hydrogen gas clearance technique. ",13 170,"Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy. The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy. ",3 2602,"A randomized comparison of methotrexate dose and the addition of bleomycin to CHOP therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas. Cancer and Leukemia Group B study 7851. In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%). ",19 350,"Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody. The safety and diagnostic accuracy of immunoscintigraphy with the indium-111-labeled monoclonal antibody OV-TL 3 F(ab')2(111In-OV-TL 3 F(ab')2) for diagnosis and follow-up of ovarian cancer was prospectively studied in 31 patients. Planar and SPECT scintigraphy were performed up to 4 days after i.v. injection of 140 MBq 111In-OV-TL 3 F(ab')2. Surgical evaluation was possible in 22 out of 31 patients. Imaging results were compared with X-ray computed tomography, ultrasound, and CA 125 serum level using the histologically confirmed surgical findings as a ""gold standard."" Apart from a transient rash observed in two patients, no other immediate or delayed adverse reactions were observed. Within the surgically evaluated group, ovarian cancer lesions were detected in 16 out of 17 patients (94%). Of 45 distinct tumor deposits found at operation, 67% were detected and localized with immunoscintigraphy while X-ray computed tomography and ultrasound visualized 53% and 23%, respectively. ",3 1624,"Intracoronary adenosine administration during reperfusion following 3 hours of ischemia: effects on infarct size, ventricular function, and regional myocardial blood flow. Previous studies have demonstrated that adenosine significantly enhances myocardial salvage after 90 minutes of regional ischemia. To determine its effect after prolonged ischemia, closed-chest dogs underwent 3 hours of left anterior descending artery occlusion followed by 72 hours of reperfusion. Intracoronary adenosine (3.75 mg/min; at 1.5 ml/min:total volume = 90 ml; n = 10) or an equivalent volume of saline (1.5 ml/min: total volume = 90 ml; n = 9) was infused into the left main coronary artery during the first 60 minutes of reperfusion. Regional myocardial blood flow was assessed serially with microspheres and regional ventricular function was assessed by contrast ventriculography. Infarct size was determined histologically. Light and electron microscopy were utilized to assess neutrophil infiltration and microvascular injury. Adenosine failed to reduce infarct size expressed as a percentage of the area at risk (38.0 +/- 4.9% versus 34.8 +/- 4.6%; p = NS) or to improve regional ventricular function as measured by the radial shortening method (3.2 +/- 1.8% versus 2.2 +/- 3.1%; p = NS) at 72 hours after reperfusion. Vasodilatory effects were not observed in the endo- and midmyocardial regions of the ischemic zone during adenosine administration. This was associated with a similar extent of capillary endothelial changes and neutrophil infiltration in both adenosine-treated and saline control groups. These results suggest that severe functional abnormalities are present in the vasculature after 3 hours of ischemia and that adenosine therapy is ineffective in enhancing myocardial salvage. ",13 149,"Variations in malaria transmission rates are not related to anopheline survivorship per feeding cycle. Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village. Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year. However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly. Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area. Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period. However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea. ",2 2404,"Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass. We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age-matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/- 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction. ",17 1845,"Effects of calcium channel blockers on coronary vasoconstriction induced by endothelin-1 in closed chest pigs. The purpose of this study was to determine the effects of endothelin-1 on the coronary vascular bed of closed chest pigs. Endothelin-1 (3 to 30 pmol/kg body weight) was selectively administered into the left anterior descending coronary artery. Coronary blood flow and epicardial vessel diameter were measured by quantitative arteriography. Arterial pressure increased after a 30 pmol/kg dose and heart rate was not changed. Coronary blood flow and vessel diameter of the left anterior descending artery significantly decreased by 74% and 32%, respectively (p less than 0.01 versus control) after the 30 pmol/kg dose, whereas these variables modestly decreased in the left circumflex artery. Endothelin-1 in doses of 10 to 30 pmol/kg produced electrocardiographic ST segment elevation associated with decreased oxygen saturation of coronary sinus venous blood. Endothelin-induced coronary vasoconstriction was significantly inhibited after treatment with intravenous diltiazem (0.2 mg/kg, n = 6) or nifedipine (0.1 mg/kg, n = 5), but not after vehicle administration (n = 4). This study demonstrates that intracoronary administration of endothelin-1 causes significant myocardial ischemia through coronary vasoconstriction, which is inhibited by a calcium channel blocker. The data suggest that calcium influx into the smooth muscle cells appears to be involved at least in part in the mechanism of endothelin-induced coronary vasoconstriction in vivo. ",13 380,"Overall mortality and cancer mortality around French nuclear sites Higher than expected mortality from leukaemia has been observed in the population under age 25 living around Sellafield and Dounreay, nuclear reprocessing plants in the United Kingdom. We report the results of a similar study for the population residing around nuclear sites in France. The number of leukaemia deaths was 58, comparable to the 62 in control areas, and slightly less than the 67 expected from national mortality statistics. Twelve deaths due to Hodgkin's disease were observed around nuclear sites; this is about twice the number of Hodgkin's deaths observed in control areas and twice the number expected from national mortality statistics. This observation must, however, be interpreted in light of the fact that several causes of deaths were studied, increasing the play of chance. ",3 696,"Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity. Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease. ",5 347,"Drug-induced DNA damage and tumor chemosensitivity. Cytotoxic drugs act principally by damaging tumor-cell DNA. Quantitative analysis of this interaction provides a basis for understanding the biology of therapeutic cell kill as well as a rational strategy for optimizing and predicting tumor response. Recent advances have made it possible to correlate assayed DNA lesions with cytotoxicity in tumor cell lines, in animal models, and in patients with malignant disease. In addition, many of the complex interrelationships between DNA damage, DNA repair, and alterations of gene expression in response to DNA damage have been defined. Techniques for modulating DNA damage and cytotoxicity using schedule-specific cytotoxic combinations, DNA repair inhibitors, cell-cycle manipulations, and adjunctive noncytotoxic drug therapy are being developed, and critical therapeutic targets have been identified within tumor-cell subpopulations and genomic DNA alike. Most importantly, methods for predicting clinical response to cytotoxic therapy using both in vitro markers of tumor-cell sensitivity and in vivo measurements of drug-induced DNA damage are now becoming a reality. These advances can be expected to provide a strong foundation for the development of innovative cytotoxic drug strategies over the next decade. ",3 297,"Medroxyprogesterone acetate lowers plasma corticotropin and cortisol but does not suppress anterior pituitary responsiveness to human corticotropin releasing factor. The endocrine action of medroxyprogesterone acetate (MPA) has been claimed to be of a glucocorticoid-like nature. Upon clinical observation, MPA has been shown to improve life quality and overall well-being in patients with advanced breast cancer, renal carcinoma, prostatic carcinoma, and uterine adenocarcinoma. The authors have evaluated MPA endocrine action by the administration of human corticotropin releasing factor (hCRF) in a 90-minute assay in 15 patients with advanced breast cancer or renal cell carcinoma both, before the initiation of oral high-dose MPA treatment (1000 mg MPA) as well as after at least 10 days of therapy. The curves for corticotropin, beta-endorphin, and cortisol responses to hCRF of tumor patients who were tested before the initiation of MPA treatment were parallel to the curves of a healthy control group of probands tested under equal conditions, although at significantly higher respective hormone levels. In patients with malignant disorders assayed after MPA administration, both basal and peak hormone levels were found to be comparable with values obtained in healthy controls. In conclusion, MPA appeared to act at a suprapituitary level since pituitary responsiveness to hCRF was preserved under MPA treatment. Moreover, it appeared that MPA brought the hormonal stress state found in patients with malignant tumors back to normal. ",3 2113,"Buerger's colour. Cyanosis of the hands and feet in Buerger's disease is known as 'Buerger's colour'. This characteristic skin colour is produced by the subpapillary venous plexus. The reactions of the subpapillary venous plexus in patients with Buerger's disease were observed by analysing the fractional blood volume of tissue using a visible light reflective spectrophotometer. Capillary morphology was investigated using an intravital video-microscopic system. Twenty-seven subjects, comprising 13 normals and 14 patients with Buerger's disease, were studied. In the nailbeds of patients with Buerger's disease, an increase in the number of loops, cyanotic colour change and dilatation were observed. In this condition there was incompetence of venular tonus and regurgitation at venular valves. Buerger's colour is probably due to excessive congestion of venous blood in the subpapillary venous plexus which is produced by these mechanisms. ",13 877,"Sialolithiasis: case studies and review. Three cases of sialolithiasis are presented, each representative of acute and chronic presentations of this problem. The evaluation and treatment of salivary gland and duct stones are outlined. The primary axiom is, ""Treat the gland, not the stone,"" and the essential aspects of emergency medical management are antibiotics, sialogogues, warm compresses, mechanical stimulation, and appropriate referral to an otolaryngologist. ",6 70,"Day care characteristics associated with Haemophilus influenzae disease. Haemophilus influenzae Study Group. To identify characteristics of day care facilities associated with H. influenzae disease, we compared 92 licensed facilities in which a case of H. influenzae disease had occurred with randomly selected facilities at which no cases occurred. Matched univariate analysis showed that personnel at facilities where H. influenzae disease occurred were more likely than those at control facilities to use towels or handkerchiefs to wipe children's noses, admit children who were not toilet trained or had diarrhea (""liberal fecal policy""), had a narrower age range, were more likely than control facilities to be for-profit and less likely to use volunteers. In a multivariate model that adjusted for age range, profit status and liberal fecal policy, towel or handkerchief use (OR 5.5, 95% CI: 1.1, 30) was the only variable independently associated with case facilities. This is the first association of a specific day care practice with H. influenzae disease. ",0 2293,"Psoriasis vulgaris: a genetic approach. Evidence for a genetic contribution in psoriasis comes from direct examination of a large segment of the population in an isolated island environment, epidemiologic and questionnaire studies presented to psoriatic patients, twin studies collected from the literature and from twin registries, and splitsibship analysis. The concordance of psoriasis in monozygotic twins was 65-72%, whereas psoriasis in dizygotic twins was 15-30%. Determination of concordance in older twin pairs from a national twin registry in Denmark revealed nearly 90-100% heritability. In order to link psoriasis with known markers within the human genome, serologic studies have been carried out with a variety of blood group and polymorphic protein antigens. A weak association with the MNS and Lewis Blood Groups Systems (relative risk, 3.5) has been identified. Stronger associations with class I B locus and class II D locus genes (relative risk, 8-12) have also been determined by studies of the human lymphocyte-antigen system. Finally, a strong association with HLA Cw6 has been determined; this marker is thought to be in linkage disequilibrium with B and D locus genes previously associated with psoriasis. The relative risk of developing psoriasis in HLA Cw6 positive individuals is about 24. A few large kindred have been reported in the dermatology literature. These support the hypothesis of autosomal dominant inheritance with penetrance of approximately 60%. In cooperation with The National Psoriasis Foundation, we have now identified over 90 families with psoriasis in three generations. We have begun the process of ascertainment, the construction of family trees, and the collection of leukocyte DNA for linkage analysis with established restriction fragment polymorphisms (RFLP). Our initial assessment is being directed to four RFLP that span approximately 30 centiMorgans of the short arm of human chromosome 6. Although karyotyping is uncommonly done in patients because of psoriasis, we now seek evidence of translocations of chromosome 6 in association with psoriasis. ",16 1124,"Mechanism of stroke in patients taking aspirin. During a 1-year period, we prospectively studied the mechanism and severity of stroke in 47 patients sustaining a cerebral infarction while taking aspirin. The mechanism of stroke was undetermined in 12 patients (26%). In the remaining 35 patients, we identified 39 potential mechanisms: large-artery atherosclerosis (19 patients, 40%), cardioembolism (15 patients, 32%), and small-vessel occlusive disease (5 patients, 11%). Of 11 patients with carotid atherosclerosis and stroke, 9 (82%) had greater than 90% carotid stenosis or occlusion; of 12 patients with stroke of undetermined mechanism, 10 (83%) had previous stroke, of which 8 were also of undetermined mechanisms. Disability after stroke was moderate or severe in 27 patients (57%). These data suggest that (1) stroke in patients taking aspirin has a variety of etiologies and frequently causes moderate or severe disability; (2) patients with carotid disease failing aspirin often have high-grade carotid stenosis or occlusion; (3) stroke of undetermined mechanism may recur more frequently than other stroke subtypes in patients taking aspirin. ",9 3007,"Effects of stress on gastric mucosal prostaglandin generation in intact, adrenalectomized, and sham-operated rats. To study the effects of (a) cold restraint stress and (b) adrenalectomy in association with cold restraint stress on gastric mucosal ulceration and prostaglandin generation, we performed two experiments. In the first, 40 rats were divided into four groups of 10 rats each: (a) unstressed and (b) stressed for 0.5 h, (c) stressed for 2 h, and (d) stressed for 4 h. In the second experiment, another 80 rats were divided into four groups of 20 rats each: (a) adrenalectomy plus cold restraint stress for 2 h, (b) adrenalectomy plus no stress, (c) sham operated plus 2 h of stress, and (d) sham operated plus no stress. In both experiments we recorded an ulcer index and measured mucosal generation of prostaglandin E2 (PGE2) and prostaglandin I2 (6-keto-PGF1a). In conclusion: (a) Cold restraint stress is associated with a time-dependent decrease in gastric mucosal PGE2 generation, but no change in 6-keto-PGF1a generation, and an increase in mucosal injury that is maximal by 2 h. (b) Adrenalectomy augments the effects of stress on mucosal injury but has no effect on prostaglandin generation; thus, the ulcerogenic effect of adrenalectomy appears to be independent of an effect on prostaglandin generation. ",22 1995,"Effects of renin inhibition in systemic hypertension. The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension. ",13 615,"Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. The op/op variant of murine osteopetrosis is a recessive mutation characterized by impaired bone resorption due to lack of osteoclasts. Cultured osteoblasts and fibroblasts from this mutant do not secrete M-CSF activity and resident macrophages are absent in bone marrow. This failure has been related to a mutation within the M-CSF coding region. We report now that the administration of recombinant human M-CSF (rhM-CSF) corrects in vivo the impaired bone resorption in this animal. The treatment restores the bone marrow cavity virtually absent in the op/op animal and induces the appearance of resorbing osteoclasts and of resident bone marrow macrophages. This proves that the deficiency of M-CSF is the cause of the op/op bone disorder and that this cytokine is directly or indirectly necessary for physiological osteoclastogenesis, the resulting bone resorption and for the establishment of bone marrow hemopoiesis. ",4 444,"Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic resonance imaging. Elective neck dissection in patients with head and neck cancer continues to be controversial. The management of these patients would be greatly facilitated by improvements in predicting cervical metastases. Recent investigations have suggested that computed tomography and magnetic resonance imaging are more sensitive in detecting cervical metastases than physical examination. The Department of Otolaryngology at the Ohio State University Hospitals, Columbus, undertook a prospective study to compare the preoperative sensitivities of physical examination, computed tomography, and magnetic resonance imaging with pathologic findings in 27 patients undergoing neck dissections for head and neck cancer. The results indicate that computed tomography and magnetic resonance imaging were more sensitive (84% and 92%, respectively) than physical examination (75%), although the results did not achieve statistical significance. The sensitivity of combined computed tomography and magnetic resonance imaging was 90%. ",3 2256,"Localized hyperhidrosis in pretibial myxedema. Two cases of spontaneous hyperhidrosis limited to pretibial myxedema lesions were studied. Quantitative measurements of stimulated eccrine sweat were made after the intradermal injection of methacholine. The sweat rate was two to four times greater in the lesional skin than in perilesional skin. Eccrine secretory glands in excisional biopsy specimens from the pretibial lesions were significantly larger than those in perilesional skin. To our knowledge, hyperhidrosis localized to areas of pretibial myxedema has not been reported. ",16 2469,"Reduced beta-cell glucose transporter in new onset diabetic BB rats. Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transporter of beta-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT-2-positive to insulin-positive beta-cells was only 0.48 +/- 0.06, compared to 0.91 +/- 0.02 in age-matched nondiabetic diabetes-resistant controls (P less than 0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85 +/- 0.02, also less than the controls (P less than 0.05). Protein A-gold labeling of GLUT-2 in beta-cells of day 1 diabetic rats revealed 2.17 +/- 0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.91 +/- 0.14 in controls (P less than 0.001) and 2.87 +/- 0.24 in the nondiabetic diabetes-prone rats (P less than 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes. ",17 775,"Increased cholecystectomy rates in Saudi Arabia Gallstones have become increasingly prevalent in Saudi Arabia, where cholecystectomy is now one of the commonest major abdominal operations. 2854 people underwent cholecystectomy in the 14 hospitals of the country's Eastern Province in the years 1977 to 1986. During this period the overall frequency of cholecystectomy increased by 978%, a finding not explained by the 67% increase in population or the 87% increase in other operations. Simultaneously, the average daily individual consumption of total calories, fat, and sugar increased by 81%, 197%, and 164%, respectively, and consumption of high-fibre grain fell by 75%. This striking increase in the frequency of cholecystectomy, which presumably reflects the incidence of gallstones, cannot be explained by demographic changes and seems more closely linked to the concomitant changes in dietary habits. ",5 3111,"Measurement of resistance versus flow in assessing efficiency of aortocoronary bypass grafts. Measurement of flow in saphenous bypass grafts with an electromagnetic flowmeter is complicated and poorly reproducible. Since coronary flow is largely dependent on variable factors the stable value of resistance seems more appropriate for comparison. A simple method has been developed for intraoperative measurement of resistance in the respective coronary bed. Pressure is recorded in the saphenous graft by an electromanometer during continuous flushing with known amounts of blood, and resistance is calculated instantaneously. The procedure is very simple and takes less than one minute. The quality of the saphenous vein itself can be assessed simultaneously by the same method. Resistances were measured during coronary surgery in over 500 saphenous grafts. The results were highly reproducible and comparable. Excellent flows can be expected if resistance is below 200 Peripheral Resistance Units (PRU); if this is over 800 PRU flow is very poor. ",22 2084,"In vitro and in vivo evaluation of intraluminal ultrasound in normal and atherosclerotic arteries. This study evaluated the dimensional and morphologic precision of arterial images obtained using intraluminal rotating A-scan ultrasound catheters [5.0F (30 mHz) and 8.0F (20 mHz)]. Dimensions of in vitro ultrasound images from human arteries (eight normal and nine arteriosclerotic) were compared with those from histologic sections of the vessels. In addition, in vivo ultrasound studies (23 normal and 22 arteriosclerotic) of canine femoral arteries were compared with luminal dimensions obtained from angiograms of the vessels. The correlation of in vitro ultrasound images to luminal diameters (n = 22, r = 0.96), adventitial diameters (n = 19, r = 0.83), and wall thickness (n = 19, r = 0.68) in normal human vessels was significant (p less than 0.05). In vitro measurements of images and histologic specimens from human atherosclerotic arteries also correlated significantly (p less than 0.05) with luminal diameters (n = 27, r = 0.91), adventitial diameters (n = 24, r = 0.60), and wall thickness (n = 24, r = 0.62). Morphologically, in vitro images of the wall of normal human arteries had a concentric laminated appearance and atherosclerotic vessels had patchy echodense and echolucent areas. In vivo studies showed significant correlation of diameters for both normal (n = 16, r = 0.91, p less than 0.05) and arteriosclerotic (n = 16, r = 0.57, p less than 0.05) canine arteries compared with luminal dimensions measured from uniplanar angiograms. We conclude that rotating A-scan intraluminal ultrasound accurately defines both normal and atherosclerotic arterial wall morphology and dimensions. This technology may be valuable for intravascular guidance of angioplasty devices by identifying the location and consistency of lesions. ",13 2288,"The role of antihistamines in atopic dermatitis. Although several lines of evidence support a role for histamine in the pathogenesis of atopic dermatitis, antihistamines have generally offered only marginal therapeutic benefit. The efficacy of the classic antihistamines has been severely limited by sedative effects, demonstrating the need for improved, nonsedating agents. Multifunctional antihistamines, or third-generation ""antiallergic"" drugs, appear to offer a variety of advantages beyond their ability to inhibit histamine release, such as inhibition of mediator release and interference with eosinophil migration. Double-blind studies of high-dose regimens are needed to help clarify the therapeutic efficacy of these antiallergic drugs. ",16 576,"Soft-tissue tumor with abnormal amianthoid collagen fibers. Electron microscopic examination of a solitary soft-tissue tumor from the face demonstrated large areas with abnormal amianthoid collagen fibers in the neoplasm. The lesion was classified as a benign neoplasm of myofibroblasts and tentatively named a myofibroblastoma. The significance of the amianthoid collagen fibers is unknown. Normal native collagen fibers were found in some parts of the neoplasm. ",3 1486,"Sodium lauryl sulfate-induced irritant contact dermatitis in vulvar and forearm skin of premenopausal and postmenopausal women. Reactivity of the skin of the forearm and labia majora to three concentrations (2%, 3%, 5%) of sodium lauryl sulfate was studied in 20 healthy women, 10 premenopausal and 10 postmenopausal. Patches with the irritant were applied on day 0 for 24 hours. Skin changes were monitored by visual scoring and by the measurement of transepidermal water loss and capacitance as indicators of stratum corneum hydration on days 2, 3, 7, and 10. In forearm skin, irritant dermatitis developed in the majority of subjects as indicated by visual scoring and increase of transepidermal water loss. These changes were not significantly dependent on the concentration of sodium lauryl sulfate. In labia majora skin, irritant dermatitis developed in 50% of the women as determined by visual scoring; however, because of the pigmentation, visual scoring readings were less reliable in labia majora skin. Transepidermal water loss did not increase, but a significant and immediate decrease in capacitance was noted in labia majora skin. In forearm skin, postmenopausal women reacted less frequently and more slowly to sodium lauryl sulfate than premenopausal women whereas no age-related differences were observed in reaction of the vulvar skin. It is concluded that labia majora skin is not more reactive to sodium lauryl sulfate than forearm skin and that capacitance is more sensitive than transepidermal water loss in monitoring vulvar irritant dermatitis. Age-related differences in irritant reaction are apparent in the forearm, but not the vulva. ",12 3016,"Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis. The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right. ",22 510,"Haemangiosarcoma of the maxillary antrum. Angiosarcomas are extremely rare in the head and neck and the histological diagnosis is often difficult. We present a case of a haemangiosarcoma of the maxillary antrum in a 33 year old male. The histological diagnosis and subsequent management are discussed. ",3 141,"Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria. Resurgence of falciparum malaria occurred in the Central Highlands of Madagascar in the 1980s and the disease is currently hyperendemic. We determined the humoral and cellular responses to synthetic peptides reproducing the repeat sequences of 2 major Plasmodium falciparum antigens: the Pf155/RESA and the circumsporozoite (CS) protein. Blood samples from 83 subjects living in a rural community near Antananarivo were obtained at the beginning and the end of the transmission season. At enrollment, 40 subjects presenting with and 43 without blood parasites had similar T cell proliferative response and antibody level to all antigens tested. However, P. falciparum-infected individuals exhibited a decrease in the absolute number of T lymphocytes, due to a diminished number of CD8+ and natural killer lymphocytes. The number of CD4+ cells was similar in both groups. In the overall population, 45% of subjects had a T cell response to at least 1 RESA peptide (29-35% responding to a given peptide) and 35% to the CS protein peptide. Thirty-two percent of the donors presented with RESA antibodies and 23% had CS protein antibodies. After 20 weeks, at the end of the transmission season, cellular proliferative responses to all antigens markedly decreased as evidenced by a decrease of both the number of responders and mean stimulation indexes. Humoral response to RESA, as detected by erythrocyte membrane immunofluorescence (number of responders and mean antibody titers) markedly increased. Humoral responses to the CS protein and RESA peptides were similar. ",2 838,"Antibiotic use among children in an urban Brazilian slum: a risk factor for diarrhea? [published erratum appears in Am J Public Health 1991 Apr;81(4):417] Among a cohort of children in a poor urban setting in Brazil, the relative risk for the occurrence of a new episode of diarrhea in the two weeks following antibiotic use vs all other weeks was 1.44 (95% confidence interval (CI) = 1.33, 2.45). Among children ever [corrected] exposed to antibiotics, the odds ratio was 1.34 (95% CI = 0.84, 2.16) after stratifying by individual child and controlling for previous diarrhea. Further research is needed to confirm whether antibiotics are a risk factor for diarrhea in such settings. ",5 1106,"Systems analysis of cerebrovascular pressure transmission: an observational study in head-injured patients. In an observational study in head-injured patients, cerebrovascular pressure transmission was investigated using a systems analysis approach whereby the blood pressure (BP) waveform was used as a measure of an input stimulus to the cerebrovascular bed (CVB) and the intracranial pressure (ICP) waveform as the response to that stimulus. The transfer function is a measure of how much pressure is transmitted through the CVB at a given frequency and is calculated using Fourier analysis of the pressure waveforms. The transfer function allows quantification of the pressure transmission performance of the CVB, thus providing a basis for comparison between normal and abnormal function. Fifteen hundred samples of ICP and BP waveforms were collected from 30 head-injured patients via microcomputer. Off-line spectral analysis of the waveform database revealed four main classes of transfer function: those with an overall flat transfer function (curve type 1); those with an elevated low-frequency response (curve type 2); those with an elevated high-frequency response (curve type 3); and those exhibiting both an elevated low- and high-frequency response (curve type 4). Curve types 2 and 4 were most often associated with raised ICP (greater than 20 mm Hg), whereas curve types 1 and 3 were most often affiliated with ICP less than 15 mm Hg. Studies of this type may provide insight into the pathophysiology of the CVB and ultimately aid in the prediction and treatment of raised ICP. ",9 1184,"Pharmacologic treatment of noncognitive behavioral disturbances in elderly demented patients. Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week randomized, double-blind comparison trial of haloperidol, oxazepam, and diphenhydramine to test the efficacy of these agents in the treatment of clinically significant behavioral disturbances in patients with dementia. All three agents demonstrated modest but significant efficacy as measured by clinician ratings of agitated behavior and activities of daily living. The absolute magnitude of improvement was greater for haloperidol and diphenhydramine than for oxazepam, but differences among groups did not approach statistical significance. Frequencies of acute adverse events during the trial were similar across the drug treatment groups. Although these drugs may differ in terms of long-term safety and efficacy, they appear to be equivalent for short-term management of agitated behavior in severely demented patients. ",9 2866,"The MAC scale in a normal population: the meaning of ""false positives"". The MAC scale has been very successful in identifying alcoholics and, in studies of clinical populations, is often considered a test for predisposition to alcoholism. MacAndrew, however, holds that the MAC scale assesses a more general personality trait characterized by sociability, boldness, rebelliousness and pleasure seeking. The present study examines the distribution of MAC scale scores in a normal population and tests for correlates of high MAC scores other than alcohol-related problems (e.g., arrest history). The sample consisted of 1,117 men, participants in the Normative Aging Study (mean age = 61.6). As expected, heavier drinkers and problem drinkers reported significantly higher MAC scale scores than did lighter and nonproblem drinkers. However, arrestees without drinking problems had MAC scale scores nearly identical to those of problem drinkers without arrest histories (23.19 and 23.42, respectively). Further, 36% of the sample without problem drinking or arrest histories had MAC scale scores of 24 or above, the clinical indicator of alcoholism, and more than 32% of these had scores above 27. In the entire sample, of the 152 men who had MAC scores above 27, 71% had no problems, either with arrest or drinking. Results are interpreted as supporting MacAndrew's interpretation of the meaning of the MAC scale as a general personality measure rather than a specific alcoholism instrument. ",20 2534,"A review of iodine toxicity reports. This article summarizes case reports, population studies, and experimental studies from the literature concerning adverse effects of exposure to iodine from the mid-1880s to 1988. Exposure to excessive iodine through foods, dietary supplements, topical medications, and/or iodinated contrast media has resulted in thyroiditis, goiter, hypothyroidism, hyperthyroidism, sensitivity reactions, or acute responses for some individuals. Reports of maternal iodine exposure during pregnancy or lactation affecting newborn or nursing infants are cited. Susceptibility to excess iodine is discussed as well as the relationship between dose and response. It is concluded that some individuals can tolerate very high levels of iodine with no apparent side effects and that iodine intakes less than or equal to 1.000 mg/day are probably safe for the majority of the population, but may cause adverse effects in some individuals. Determination of maximum tolerable levels of iodine intake will require human experimental studies at levels between 0.150 and 1.000 mg/day for normal subjects, subjects with autonomous thyroid tissue, and iodine-sensitive subjects. ",18 3030,"Reversal of colchicine-induced mitotic arrest in Chinese hamster cells with a colchicine-specific monoclonal antibody. The ability of a high-affinity colchicine-binding monoclonal antibody to reverse the effects of colchicine on Chinese hamster ovary cells was investigated. Using flow cytometry, a complete mitotic blockade was demonstrated after 16 hours with 2.5 x 10(-7) mol/l (molar) colchicine. Colchicine-induced changes were reversible when equimolar antibody was added simultaneously with or up to 6 hours after colchicine. With further delay in addition of antibody, a progressive irreversible increase in mitotic blockade and increase in mean cell size was observed. Prolonged colchicine exposure, without antibody reversal, led to polyploidy and structural chromosome breakage. Early antibody reversal restored cells to the diploid state, whereas delayed reversal resulted in a time-dependent increase in polyploidy. Colchicine-induced polyploidy and chromosomal aberrations may be the basis for both colchicine toxicity and the time-dependent increase in irreversibility of colchicine effects. ",22 2373,"Increased preproinsulin mRNA in pancreatic islets incubated with islet cell-stimulating antibodies from serums of type I diabetic patients. We recently described autoantibodies that stimulate the release of insulin from pancreatic beta-cells both in vitro and in vivo. The aim of this study was to establish whether islet cell-stimulating antibodies (ICSTAs) also increase islet cell preproinsulin mRNA content. Wistar rat islets, isolated by collagenase digestion, were exposed to 2.7 and 11.1 mM glucose. Insulin release increased 10-fold in response to the higher glucose concentration, and dot-blot analysis of islet mRNA with a rat preproinsulin cDNA probe showed a concomitant increase in mRNA levels. The globulin fractions of four test serums, three from patients with type I (insulin-dependent) diabetes and one from a patient with the insulin autoimmune syndrome, showed clear (5- to 8-fold) stimulation of insulin release. The nonglobulin fractions of these serums and both fractions of three control serums failed to stimulate secretion of insulin. The insulin mRNA content of islets incubated with the ICSTA globulin fractions was greatly increased compared with levels observed in islets treated with control serum globulin fractions. We conclude that ICSTAs not only can stimulate the release of insulin but also increase the preproinsulin mRNA content of islet cells. ",17 533,"Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity. ",3 2906,"Skiing and snowboarding injuries. When schussing is a pain. Downhill and cross-country skiing and snowboarding are growing rapidly in popularity. With the ever-increasing number of participants, physicians must be prepared to deal with the injuries specific to these sports. More important, physicians need to use epidemiologic data to advise patients of methods to minimize the risk of injury as they participate in these healthy and vigorous winter sports. ",20 258,"Serologic determinants of survival in patients with squamous cell carcinoma of the head and neck. Specific circulating serum proteins may reflect unique properties governing the growth and progression of head and neck cancers. One hundred three previously untreated patients with squamous cell carcinoma of the head and neck were prospectively evaluated for serum IgA, IgG, and IgM and C1q-binding macromolecules. Immunoglobulins were assessed by the immunoturbidimetric technique. C1q-binding macromolecules (C1qBM) were measured utilizing the iodine-125 assay of Zubler et al (J Immunol 1976; 116: 232-5). Neither the level of serum immunoglobulins nor C1qBM values were correlated with the primary site, AJC (American Joint Committee on Cancer) stage of disease, or size of primary lesion. Likewise, comparison of serum IgA with C1qBM values demonstrated that these laboratory parameters were independent variables (r = 0.15 by Pearson linear regression). Univariate statistical analysis, utilizing the Cox proportional hazard model, showed serum IgA and C1qBM values to each contribute significantly to the ability to predict survival in patients with advanced squamous cell carcinoma of the head and neck (p = 0.01 and 0.003, respectively). Furthermore, multivariate analysis reveals that both C1qBM and serum IgA levels contribute significantly to the hazards model beyond staging in predicting survival (p less than 0.001). Predictive results were most apparent in patients with stage IV disease and related to the probability of both regional and distant metastatic recurrences. Conversely, serologic analysis provided no information in patients who were staged early. These results support pretreatment multiparametric serologic analysis of patients with squamous cell carcinoma of the head and neck. ",3 3252,"Obstructive jaundice: use of expandable metal endoprosthesis for biliary drainage. Work in progress. Expandable metal endoprostheses were implanted transhepatically in 61 patients with obstructive jaundice. Fifty-three patients had malignant and eight had benign obstructions. Because of the small diameter of the compressed stent (7 F), primary implantation of the stent without a previous catheter drainage was preferred. Postprocedural complications occurred in three patients (5%) (biliary pleuritis, peritonitis, hepatic artery aneurysm). The 30-day mortality rate was 8.2%. Reocclusions were observed in six of the patients with malignant obstructions (11%) (observation period, 1-10 months; mean, 4.5 months) and in two of the patients with benign stenoses (25%) (observation period, 3-21 months; mean, 9 months). The higher reocclusion rate of benign obstructions must be interpreted with care because of the small number of patients. From their preliminary experience, the authors conclude that expandable metal endoprostheses offer patency rates equal to those of plastic stents. The implantation trauma is reduced due to the small 7-F introducing catheter system. ",22 832,"High-fat semielemental diet in the treatment of protracted diarrhea of infancy. The capacity for greater fat absorption relative to carbohydrate absorption in protracted diarrhea of infancy was studied in a developed and a developing country (Buffalo, NY, and Bangkok, Thailand). Fifty patients with protracted diarrhea in the first year of life (defined as liquid stools of more than 20 mL/kg per day with more than a 14-day duration) were randomly assigned to receive either a standard semielemental diet (Pregestimil) or a high-fat semielemental diet that contained 40% more fat. The increased fat was largely in the form of medium-chain triglycerides, with the new diet providing 60% of the fat as medium-chain triglycerides compared with 40% in the standard diet. Tolerance to both diets was good in both studies. Both groups showed adequate weight gain and an improvement in anthropometric and biochemical parameters. The patients receiving the high-fat diet showed no initial weight loss, however, and their weight gain was initiated earlier. Cumulative weight gain was also higher in the group receiving the high-fat semielemental diet. Fecal fat analyses were performed after 1 week of therapy. There was no difference observed in the coefficient of fat absorption between the groups receiving the two formulas, indicating that infants with protracted diarrhea may be able to tolerate a higher fat intake than is normally provided. As carbohydrate intolerance is known to be a complicating factor when using semielemental enteral feeds for infants with protracted diarrhea, a higher-fat semielemental diet may be the most appropriate way to provide adequate caloric intake. ",5 1964,"Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study In the Whitehall study, 18,388 subjects aged 40-64 years completed a questionnaire on intermittent claudication. Of these subjects, 0.8% (147) and 1% (175) were deemed to have probable intermittent claudication and possible intermittent claudication, respectively. Within the 17-year follow-up period, 38% and 40% of the probable and possible cases, respectively, died. Compared with subjects without claudication, the probable cases suffered increased mortality rates due to coronary heart disease and cerebrovascular disease, but the mortality rate due to noncardiovascular causes was not increased. Possible cases demonstrated increased mortality rates due to cardiovascular and noncardiovascular causes. This difference in mortality pattern may be due to chance. Possible and probable cases still showed increased cardiovascular and all-cause mortality rates after adjusting for coronary risk factors (cardiac ischemia at baseline, systolic blood pressure, plasma cholesterol concentration, smoking behavior, employment grade, and degree of glucose intolerance). Intermittent claudication is independently related to increased mortality rates. It is not a rare condition, and simple questionnaires exist for its detection. The latter can be usefully incorporated in cardiovascular risk assessment and screening programs. ",13 2691,"Serologic, biologic, and western blot analysis of a T suppressor factor with specificity for the hapten 4-hydroxy-3-nitrophenyl acetyl derived from serum-free medium. A T cell hybridoma producing a T suppressor factor (TsF) with specificity for the hapten nitrophenyl was converted to long term growth in serum-free medium and its product tested by serology, bioactivity, and Western blot analysis. Results indicated that Ag-specific suppressive activity was present in serum-free medium and this TsF could exhibit the characteristics ascribed to it by various groups: it could bind nominal Ag with specificity, it was bound by anti-TsF mAb, and it could mediate Ag-specific suppression both in vivo and in vitro. Western blot and SDS-PAGE analysis of this purified TsF revealed a 43-kDa single chain protein. ",19 1243,"Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery. The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease. ",9 1302,"Treatment of idiopathic testicular failure with high-dose testosterone undecanoate: a double-blind pilot study. The effect of high-dose (240 mg/d) intake of testosterone (T) undecanoate was studied for sperm characteristics, function of the accessory sex glands, and hormonal parameters of men with idiopathic oligozoospermia, asthenozoospermia, or teratozoospermia using a two-phase protocol including a 3-month double-blind period followed by a 3-month open phase. Increased sperm viability and semen content of adenosine triphosphate were either not reproducible after patients on placebo were switched over to T undecanoate or did not reach statistical significance, whereas no changes were detected in other sperm characteristics and the accessory sex glands. Intake of T undecanoate significantly increased the concentration of 5-alpha-dihydrotestosterone (DHT) and the ratio of DHT over T in peripheral blood, suppressed the luteinizing hormone concentration, and tended to decrease serum follicle-stimulating hormone concentration. It is concluded that high-dose T undecanoate is not effective in the treatment of men with infertility with idiopathic testicular failure. ",11 2886,"Overcoming potential pitfalls in the use of Medicare data for epidemiologic research. We used Medicare data bases and US Census data to address two questions critical to the use of Medicare files for epidemiologic research. First, we examined the degree to which the population enrolled in the Medicare program is similar to the elderly resident population of the United States, as estimated by the US Census. We found small differences in the total population estimates but substantial differences by age and race. Second, we found that among Medicare enrollees, physician claims identify a small proportion of hip fracture cases which are not documented in the hospital discharge files. This proportion varies by age, region, and state within the United States. Calculation of rates based on Medicare hospital discharge data, and probably other hospital discharge data sets as well, must take these limitations into account. Use of all available Medicare data files can overcome these limitations. ",20 1438,"Suppression of immunoglobulin and interleukin-6 production from peripheral blood mononuclear cells by dialysis membranes. The influence of dialysis membranes on immunoglobulin and interleukin-6 production was estimated in vitro. Peripheral blood mononuclear cells from 11 patients undergoing hemodialysis were incubated for 7 days on Cuprophan, Hemophan, and polyacrylonitrile flat sheet membranes. IgG, IgA, IgM, and IL-6 were assayed in the supernatants with the aid of enzyme-linked immunosorbent assay (ELISA) techniques. Pokeweed mitogen-stimulated IgG production declined significantly from 319 +/- 40 ng/ml on polystyrole to 162 +/- 26 ng/ml on Cuprophan; 135 +/- 25 ng/ml on Hemophan; and 109 +/- 20 ng/ml on polyacrylonitrile. A similar pattern was observed for IgA and IgM production. IL-6 production was significantly reduced in the presence of Cuprophan (151 +/- 45 pg/ml), Hemophan (167 +/- 6 pg/ml), and polyacrylonitrile (108 +/- 33 pg/ml) when compared with polystyrole (724 +/- 34 pg/ml). It was concluded that the long-term exposure of mononuclear cells to artificial surfaces during dialysis may contribute to the impaired humoral response observed in dialysis patients. This effect may be due to a decline in B cell stimulation by monocytes, a possibility suggested by the reduction in monocytic IL-6 production. ",11 2275,"The inhibition of NK cell function by azathioprine during the treatment of patients with rheumatoid arthritis. Treatment with azathioprine of patients with rheumatoid arthritis leads to a dramatic reduction in the 4 h NK cytotoxicity against K562 cells. The 24 h cytotoxicity against K562 and U937 cells, however, remains intact. The generation of cell-free supernatant cytotoxic factor(s) after incubating non-adherent mononuclear cells with U937 cells for 24 h is similar in the azathioprine patients and the controls. A large part of this supernatant cytotoxicity is due to tumour necrosis factor alpha which can be inhibited by a specific monoclonal antibody. The mechanism of the reduced 4 h NK cytotoxicity remains unknown but is probably not related to the anti-inflammatory properties of azathioprine. ",16 1975,"Body surface mapping of high-frequency components in the terminal portion during QRS complex for the prediction of ventricular tachycardia in patients with previous myocardial infarction. To study the clinical significance of terminal QRS high-frequency components for the prediction of ventricular tachycardia, an 87-lead body surface signal-averaged mapping was performed in 21 healthy subjects (control) and in 41 patients with previous myocardial infarction (anterior, 20; inferior, 21). Mapping data were analyzed and averaged (129.7 +/- 26.5 beats) for 160 seconds, and the signal-averaged beat was filtered with a bidirectional bandwidth (80-250 Hz) digital filter. J-point was determined from the 87-lead RMS voltage of nonfiltered QRS. For each lead, we calculated the sum of the absolute value of filtered QRS from 20 msec ahead of the J-point to the J-point (A-20). The body surface distribution of A-20 was expressed as A-20 map. The maxima in A-20 maps were mainly located on the upper sternal region in healthy subjects, on the left anterior chest in patients with previous anterior myocardial infarction, and on the central anterior chest in patients with previous inferior myocardial infarction. In the patients in both the group with anterior myocardial infarction and the group with inferior myocardial infarction, the value of maximum was significantly greater than in the subjects in the control group (0.181 +/- 0.086 and 0.138 +/- 0.048, respectively, vs. 0.075 +/- 0.031 mV.msec; p less than 0.01). In patients with myocardial infarction (n = 41), the value of maximum was significantly greater with ventricular tachycardia (n = 11) than without ventricular tachycardia (n = 30) (0.240 +/- 0.076 vs. 0.130 +/- 0.043 mV.msec; p less than 0.01). ",13 348,"Motility factor produced by malignant glioma cells: role in tumor invasion. To better understand the cellular mechanism of tumor invasion, the production of a cell motility-stimulating factor by malignant glioma cells was studied in vitro. Serum-free conditioned media from cultures of rat C6 and human T98G cell lines contained a factor that stimulated the locomotion of the producer cells. This factor was termed the ""glioma-derived motility factor."" The glioma-derived motility factor is a heat-labile protein with a molecular weight greater than 10 kD and has relative stability to acid. The factor showed not only chemotactic activity but also chemokinetic (stimulated random locomotion) activity in the two types of glioma cells studied. Although glioma-derived motility factors in conditioned media obtained from two different cell origins are likely to be the same, chemokinetic migration of T98G cells to their conditioned medium was much stronger than that of C6 cells to theirs. Coincubation of cells with cytochalasin B, which disrupts the assembly of cellular actin microfilaments, almost completely inhibited the cell migration stimulated by glioma-derived motility factor. Cytochalasin B also induced marked alterations in cell morphology, including cell retraction and arborization, while the drug did not affect cell attachment to culture dishes. These results indicate that glioma cells produce a motility factor which may play a role particularly when tumor cells are detached and migrate away from the original tumor mass, thus promoting tumor invasion. Also, glioma cell migration stimulated by the motility factor requires the normal organization of cytoskeletons such as actin microfilaments. ",3 1667,"Results of percutaneous transluminal coronary angioplasty in patients greater than or equal to 65 years of age (from the 1985 to 1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry). The 1985 to 1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry series of 1,801 initial procedures included 486 patients age greater than or equal to 65 years (elderly). In comparison to younger patients, a greater proportion of elderly patients were women and had unstable angina. Elderly patients had more history of hypertension and more history of congestive heart failure. Although the elderly had more extensive vessel disease, the numbers of lesions and vessels attempted with PTCA were similar in the older and younger cohorts. Angiographic success rates were similar for all age groups. Although complication rates in the catheterization laboratory did not differ, patients greater than or equal to 65 years were much more likely to require emergency coronary artery bypass graft surgery (CABG) (5.4 vs 2.8%, p less than 0.05) or elective CABG (3.9 vs 1.6%, p less than 0.01). The in-hospital death rate was considerably higher among the elderly (3.1 vs 0.2%, p less than 0.01). At 2-year follow-up, symptomatic status and cumulative rates of myocardial infarction, CABG and repeat PTCA were similar for elderly and younger patients. The death rate after 2 years was higher among elderly patients (8.8% of patients greater than or equal to 65 years vs 2.9% of patients less than 65 years, p less than 0.01). When the relative risk of death for the elderly was adjusted for factors more prevalent among those greater than or equal to 65 years (history of congestive heart failure, multivessel disease, unstable angina, history of hypertension and female gender), the relative risk remained significant but was substantially reduced (from 3.3 to 2.4). ",13 1544,"Interobserver variation in histopathological grading of cervical dysplasia. In order to assess the variability among histopathologists in grading cervical dysplasia, four experienced histopathologists examined the same set of 106 biopsy specimens and assigned them to one of five diagnostic categories. These were: no dysplasia, mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ. The histopathologists did not discuss the grading criteria beforehand. There was considerable disagreement among the pathologists: unweighted group kappa 0.28, weighted group kappa 0.56. It appeared that all grades of dysplasia were equally difficult to distinguish from adjacent categories. Various explanations for this interobserver variation are put forward. ",12 2290,"Arthritis and mast cell activation. The significance of the mast cell in the pathogenesis of rheumatic diseases continues to receive attention. Increased numbers of mast cells are found in the synovial tissue and fluid of patients with inflammatory arthritides, and these mast cells can be activated by many of the substances found in inflammatory synovial fluid. This activation results in the release of mediators that are capable of amplifying the inflammatory process within the joint space. Recent research has shown that mast cells also produce a variety of cytokines and hematopoietic growth factors that may have paracrine and autocrine functions that are important to the development of the inflammatory cell infiltrate. Increased numbers of mast cells are also found in many fibrotic conditions, including scleroderma. These mast cells, directly or through mediator generation, affect the function of endothelial cells, fibroblasts, and growth factors important to the proliferation and function of these cells. A clearer understanding of mast cell involvement in the inflammatory arthritides and fibrotic processes should lead to new therapeutic strategies. ",16 1976,"Area-at-risk determination by technetium-99m-hexakis-2-methoxyisobutyl isonitrile in experimental reperfused myocardial infarction In a canine model of reperfused myocardial infarction, we tested the hypothesis that after reperfusion, technetium-99m-hexakis-2-methoxyisobutyl isonitrile (Tc-MIBI) tomographic imaging still reflects occlusion blood flow when the tracer is injected before reperfusion. Nine anesthetized dogs underwent 2 hours of coronary occlusion followed by 3 hours of reperfusion ending by being killed. Reference coronary blood flow was determined by radioactive microspheres injected during occlusion and after reperfusion. Biopsies in normal and ischemic myocardium and single photon emission computed tomography were obtained during occlusion and after reperfusion. Circumferential profiles were applied to axial slices divided into 5-degree sectors. The sectors were divided into 3 groups selected on the occlusion acquisition (normal, mildly reduced, and severely reduced) and compared with the postreperfusion acquisition. Tissular Tc-MIBI kinetics was assessed both by Tc-MIBI time-activity curves of normal and ischemic tissue obtained by biopsy and by the relative gradient between normal, ischemic, and necrotic postmortem tissue samples. In biopsy samples, Tc-MIBI content remained unchanged during occlusion and after reperfusion in normal as well as in ischemic tissue (4,662 +/- 2,237 counts/min/mg vs. 4,599 +/- 1,577 counts/min/mg in normal tissue, NS; 941 +/- 903 counts/min/mg vs. 1,087 +/- 721 counts/min/mg in ischemic tissue, NS). In postmortem tissue samples, there was a good correlation between occlusion microsphere blood flow and Tc-MIBI activity (r = 0.91). In the necrotic samples, mean normalized Tc-MIBI activity (10 +/- 17%) was slightly higher than the normalized microsphere blood flow (3 +/- 3%, p less than 0.001) but markedly lower than the normalized microsphere reperfusion blood flow (63 +/- 31%, p less than 0.001). Comparing the single photon emission computed tomographic acquisitions before and after reperfusion, Tc-MIBI activity remained unchanged in normal as well as in mildly reduced or severely reduced segments. Thus, our data are consistent with the hypothesis that Tc-MIBI traces blood flow, does not redistribute significantly despite reperfusion, and can be used for imaging the area at risk. ",13 2452,"Urinary organic acid excretion during feeding of medium-chain or long-chain triglyceride diets in patients with non-insulin-dependent diabetes mellitus. Medium-chain triglycerides (MCTs) are absorbed and metabolized differently from long-chain triglycerides (LCTs). Recent data indicate that MCTs may be useful as a dietary substitute in a variety of clinical disorders. The current studies were undertaken to characterize urinary organic acid excretion in patients with non-insulin-dependent diabetes mellitus during 4 d of an LCT or MCT diet. Urinary excretion of the dicarboxylic acids adipic, suberic, and 3-hydroxysebacic and the (omega-1) hydroxylation products 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, was increased during MCT feeding as compared with LCT feeding. Urinary suberic and 7-hydroxyoctanoic acid excretions were increased 55- and 30-fold, respectively, during the MCT-substituted diet. Urinary organic acid profiles provide information on the fate of lipids during MCT feeding and may also be useful in assessing complicance during clinical trials employing MCT-substituted diets. ",17 2411,"Natural history of beta-cell dysfunction in NIDDM. Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and beta-cell dysfunction. This review focuses on the beta-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The beta-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of beta-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory beta-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (so-called glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that beta-cell function in NIDDM can be maximized by achieving the best metabolic control possible. ",17 1283,"Ocular movements in essential blepharospasm. In essential blepharospasm histopathologic and electrophysiologic evidence supports the existence of lesions in proximity to brainstem nuclei controlling ocular movements. We studied horizontal ocular movements in eight patients who had been treated previously with surgery or botulinum toxin injection to control essential blepharospasm (mean age, 58 years) and compared these with seven control subjects who did not have blepharospasm (mean age, 68 years). We examined fixation stability, saccades, the vestibulo-ocular reflex, visual enhancement and suppression of the vestibulo-ocular reflex, optokinetic nystagmus, and pursuit by using digitally sampled, direct current electro-oculography. Patients with blepharospasm exhibited no ocular movement abnormalities. Since quantitative aspects of ocular movements are sensitive to nonspecific brainstem lesions, the absence of abnormal ocular movements suggests that the lesion in blepharospasm is specifically limited to neurons regulating the facial muscles. ",10 1152,"Loss of consciousness after emergence from anaesthesia. A case of suspected micturition syncope. A case of postanaesthesia micturition syncope with respiratory arrest is described. If syncope occurs, the temporary myocardial ischaemia and cerebral hypoperfusion may increase anaesthetic risk in the marginally compensated patient. The loss of airway protection during the syncopal period is also a cause of concern. We recommend the use of an indwelling bladder catheter during any prolonged surgical procedure. ",9 640,"The operative treatment of progressive early onset scoliosis. A preliminary report. Thirteen patients with progressive early onset scoliosis have been managed operatively in an attempt to achieve correction without bracing and to allow the spine to grow. All had posterior segmental spinal instrumentation (SSI) without fusion and 9 of 13 had anterior apical growth arrest as a separate additional procedure. At 2-year follow-up, curve correction averaged 46%. Patients who had anterior apical growth arrest and SSI without fusion had less curve deterioration than those who had SSI alone. New methods are described for 1) measuring growth of the instrumented segment of the spine and 2) calculating the predicted growth of the instrumented segment. Eight of the 13 had more than 50% of predicted growth, three had 30-50% of predicted growth, and two had less than 30% of predicted growth. Operative treatment has been successful in the short term in all but the most malignant form of infantile idiopathic scoliosis. ",4 1296,"A new ophthalmic microtrephine. We present a new instrument designed to facilitate the microtrephination of tissues required in various ophthalmic procedures. This microtrephine is a 21-gauge stainless steel tube, 0.81 mm in diameter and 16 mm long, with a sharpened cutting end and a plastic finger-grip area to facilitate micro-rotation. A standard plastic luer hub allows the trephine to be used with a syringe, either a standard type or one with a spring-assisted plunger. Scar tissue, biopsy specimens, or abnormal inflammatory fluids can be suctioned into the syringe for subsequent pathologic examination. ",10 2415,"Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. It has been postulated that the etiology of the complications of diabetes involves oxidative stress, perhaps as a result of hyperglycemia. Consistent with this hypothesis, it has been shown that glucose, under physiological conditions, produces oxidants that possess reactivity similar to the hydroxyl free radical. These oxidants hydroxylate benzoic acid, fragment protein, and induce peroxidation in phosphatidylcholine liposomes and low-density lipoprotein (LDL) when LDL is incubated with hyperglycemic levels of glucose in vitro. These reactions are accelerated by transition metals and inhibited by a metal-chelating agent. The atherosclerotic potential of LDL in diabetes mellitus is often discussed in terms of protein glycosylation, which may affect cellular interactions. Our studies demonstrate, however, that peroxidative reactions also accompany LDL glycosylation in vitro. Peroxidative modification of LDL has also been implicated in LDL atherogenicity. Our studies indicate that glycosylation and peroxidation occur concomitantly in LDL modified by glucose in vitro and may both contribute to the behavioral changes of this lipoprotein. ",17 1805,"Bronchial hyperreactivity in patients with mitral valve disease. To elicit the mechanism of bronchial hyperreactivity (BHR) in chronic heart failure (CHF), a methacholine inhalation test, pulmonary function test, and cardiac catheterization were performed in 19 patients with mitral valve disease (MVD), and the change of severity of BHR before and after mitral valve replacement (MVR) was also examined in seven of 19 patients with MVD. Sixteen of 19 patients with MVD showed significant increase in respiratory resistance in methacholine inhalation test, while all normal subjects did not. The maximal expiratory flow at 25 percent of vital capacity (Vmax25), a parameter of small airway disease, correlated significantly with log cumulative dose producing a 35 percent decrease in respiratory conductance (PD35Grs) (r = 0.536) and the duration of symptoms (r = -0.682). There was a significant correlation between log PD35Grs and mean pulmonary artery wedge pressure (r = -0.466). After MVR, log PD35Grs was significantly improved in all seven operated-on patients, although six patients retained BHR. We conclude that patients with long-term MVD have marked BHR and that BHR in long-term MVD is related to peripheral airway narrowing with organic remodeling, which was not ameliorated with MVR procedure, in addition to pulmonary congestion. ",13 3033,"Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs. The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 (""hyperoxia"") or with an hypoxic gas mixture (""hypoxia"": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related. ",22 1272,"Effect of local anesthesia and ocular massage on central corneal curvature. Using a standard Javal keratometer, we obtained central corneal curvature measurements in 19 patients before and after the administration of local anesthesia. We noted flattening of mean average keratometry which approached statistical significance, along with an increase in overall astigmatism. Decreased intraocular pressure was not found to be a factor. ",10 2261,"Itraconazole in the treatment of tinea capitis. Fifty patients with tinea capitis were treated with itraconazole, 25 to 100 mg/day, for 20 to 73 days in six countries. Forty-seven patients (94%) responded clinically (healed or markedly improved) to therapy, of which 38 patients (76%) completely healed and 9 patients (18%) markedly improved. Three patients (6%) failed therapy. Forty-two patients were assessable for mycologic examination; 38 patients (93%) converted mycologically to negative and 4 patients (7%) remained positive for organisms. In one group of 20 patients treated for 30 days, 6 patients were clinically and mycologically healed. By the 2-week follow-up visit 9 additional patients were healed, and 4 weeks after treatment all 20 patients were both clinically and mycologically healed. The primary organisms reported were Microsporum canis and Trichophyton tonsurans. Only one patient reported a possible side effect (tired legs). Laboratory values were all within normal limits, except for one patient who had a transient and slight increase in serum transaminase level. Low-dose itraconazole appears to be safe and effective in the treatment of tinea capitis. ",16 1986,"Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group Investigators in eight communities collected aortas, right coronary arteries, blood, and associated information from 390 males, 15 to 34 years of age, who died of violent causes. Pathologists at central laboratories graded the arteries for atherosclerotic lesions, and serum lipoprotein cholesterol and thiocyanate concentrations were measured. The percentage of intimal surface involved with atherosclerotic lesions in both the aorta and the right coronary artery was positively associated with serum very low-density lipoprotein + low-density lipoprotein cholesterol concentration and negatively associated with serum high-density lipoprotein cholesterol concentration. The serum thiocyanate concentration, a marker for smoking, was strongly associated with prevalence of raised lesions, particularly in the abdominal aorta. The effect of smoking was not explained by lipoprotein levels. Blacks had more extensive total surface involvement of the aorta after adjustment for lipoprotein cholesterol levels and smoking. These associations indicate that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults. ",13 2928,"Discharge videotaping: a means of augmenting occupational and physical therapy. Regional burn centers commonly receive patients from medical facilities that are geographically distant. Logistic problems that may hamper follow-up care in the burn center can lead to a decrease in function as a result of contractures and hypertrophic scar formation. Inexperience on the part of therapists at community facilities serves to intensify this problem. Discharge videotaping, with respect to physical and occupational therapy programs, is a means of documenting range of motion at the time of discharge and providing visual documentation of the therapy program to be followed on an outpatient basis. The video tapes are forwarded to the outlying community hospital's therapy department in order to accomplish these goals. ",20 1955,"New technique for the arterial switch operation in difficult situations. The technique described here, a modification of the Aubert operation, avoids coronary reimplantation and also eliminates the need to use artificial material to transfer coronary circulation. ",13 1306,"Experimental treatment of benign prostatic hyperplasia with transurethral balloon dilation of the prostate: preliminary study in 73 humans. A prospective noncontrolled study of the safety and potential efficacy of transurethral balloon catheter dilation of the prostate (TUDP) in the treatment of benign prostatic hyperplasia (BPH) was performed in 73 subjects with moderate to severe symptoms and signs of prostatism who were selected on the basis of a quantitative symptom score (SS), uroflowmetry measurements, and residual urine volume. Seven patients had urinary retention. Mean age was 69.6 years (range, 59-95 years). TUDP was successfully accomplished in 70 patients (96%). There were no significant complications. Mean follow-up was 16.2 months (range, 6-36 months). Forty-six patients (66%) showed improved SS at the most recent follow-up. In 24 patients (34%) SS was unimproved, necessitating prostatectomy in 17 subjects (24%). Reduction in mean residual urine volume was not statistically significant. Only 38% of patients with median lobe enlargement showed improvement in SS, compared with 74% for the others. The authors conclude that TUDP is safe and shows promising effectiveness and that the ultimate demonstration of effectiveness requires a controlled clinical trial. ",11 2933,"Recovery of morphine from a controlled-release preparation. A source of opioid abuse. MS-Contin (Purdue-Fredrick, Norwalk, CT) is a controlled-release preparation of morphine sulfate that has demonstrated efficacy in the management of chronic cancer pain problems. It has recently come to the attention of the authors that MS-Contin represents a potential source of opioid abuse through the extraction and intravenous injection of the morphine from this preparation. The authors describe a simple aqueous extraction method that was used to quantitatively determine the extent to which morphine could be obtained from MS-Contin tablets. ",20 2838,"Facial trauma in women resulting from violence by men. In a 2 1/2-year period, 546 women with facial injuries were treated. In 8.2%, the injury was related to some form of violence exerted by a man. In cases where the individual was known, it was usually the husband or boyfriend (almost 67%). The assault consisted of a beating with the hands in over 70% of the cases. Fracture of the mandible was the most common injury. There were also 62 cases of home accidents. ",20 234,"Uneventful delivery following series of successive treatments for virilized Cushing syndrome due to adrenocortical carcinoma. A twenty-one-year-old virilized woman with Cushing syndrome due to a huge adrenocortical carcinoma was successively treated with trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor), subsequent adrenalectomy, and postoperative cis-platinum. Clinical or biochemical abnormalities peculiar to Cushing syndrome gradually subsided, and three and one-half years after the adrenal surgery, the patient delivered a normal female infant. This study points out some of the clinical and biochemical responses of each treatment. ",3 2210,"Elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein after multifetal pregnancy reduction. Forty patients underwent fetal reduction at approximately 12 weeks' gestation for multiple pregnancy. Twenty-two had maternal serum alpha-fetoprotein (MSAFP) determinations and all but one was elevated, with a mean value of 9.41 multiples of the median (MOM). A total of 53 amniotic fluid specimens were evaluated for AFP; 25% were elevated above 2.0 MOM and one sample was positive for acetylcholinesterase. None of these elevations were associated with a neural tube defect, although two neural tube defects were detected by other means. Routine MSAFP is not recommended for patients with multifetal pregnancy reduction. ",15 310,"Diagnosis of metastatic lesions to the stomach by salvage cytology. A report of three cases. Secondary neoplasms of the stomach are rare and are often clinical and diagnostic problems. Three patients with bleeding ""volcano-like"" ulcers were diagnosed by combined endoscopic ""salvage"" cytology and surgical biopsy as having metastatic submucosal lesions from hematologic spread. The combination of endoscopic appearance, clinical findings, and tissue and cytologic examination can lead to the correct diagnosis. The results from these cases support the utility of this cytologic technique in combination with biopsy in this clinical setting. ",3 1290,"Use of a symblepharon ring for treatment of over-filtration and leaking blebs after glaucoma filtration surgery. We report the use of a symblepharon ring in the treatment of seven cases of flat anterior chamber (six cases of total iridocorneal touch, and one of corneallens touch) secondary to overfiltration or to bleb leak. In all cases, the anterior chamber reformed within 24 hours after the symblepharon ring was used. Advantages of using the ring are: (a) it permits testing of visual acuity, tonometry, and intraocular examination without removing it; (b) it does not require suturing to the conjunctiva; (c) it does not disturb the corneal epithelium; (d) it may be available at institutions lacking other shells; and (e) it is cost-effective. ",10 172,"A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies. Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies. ",3 3048,"Massive splenomegaly. Superior results with a combined endovascular and operative approach. Splenectomy for massive splenomegaly (drained splenic weight, greater than 1000 g) has an uncommonly high morbidity and mortality because of technical challenges and problems of hemostasis. In a group of 10 patients with massive splenomegaly due to myeloproliferative disorders (average splenic weight, 4193 g), we developed a management algorithm based on preoperative angiographic embolization of the splenic artery. Average operating time was 1.7 hours (range, 1 to 2.5 hours). Average blood loss was 528 mL; six of the 10 patients had blood loss less than 250 mL. There were four minor complications and one major complication (gastric ulcer requiring reoperation). There were no deaths in the perioperative period, and no patients required reoperation for hemorrhage. ",22 723,"Biliary lithotripsy: in vitro analysis of gallstone fragmentation for equivalent stone volumes. The relationship between gallstone fragmentation during extracorporeal shock wave lithotripsy (ESWL) and gallstone volume is poorly understood. Clinical results of ESWL show that the highest stone-free rate at 6 months occurs with radiolucent single gallstones 20 mm or less in diameter. In an in vitro study, individual gallstones from cholecystectomy specimens were divided by size and composition into nine single- and nine multiple-stone groups; the stones were then paired on the basis of similar volume. ESWL was performed in a phantom and the size of the largest fragment was measured at 500, 1,000, and 1,500 shock waves. At 1,500 shock waves, sandlike particles were present in six of nine single stones versus two of nine multiple stone groups; the mean size of the largest fragment at 1,500 shock waves was 2.1 mm (single) and 4.4 mm (multiple) in diameter. When corrected for volume, the authors' data suggest that single stones are more easily broken into fragments smaller than 5 mm in diameter than multiple gallstones. The implication, especially when spark-gap technology is used, is that more shock wave energy (ie, an increased number of shock waves at a higher kilovoltage) will be necessary to achieve the same results when treating patients with multiple stones versus a single gallstone with a similar stone volume. ",5 3089,"Effects of intravenous immunoglobulin on hemorrhage-induced alterations in plasma cell repertoires. Hemorrhage produces decreases in serum immunoglobulin (Ig) levels and alterations in the number and frequency of B cells producing antibodies against bacterial antigens. These abnormalities in immune response may contribute to the increased susceptibility to infection after injury and hemorrhage. To examine the relationship between serum Ig levels and bacterial antigen-specific plasma cell numbers and frequencies after blood loss, we treated hemorrhaged mice with intravenous Ig (IVIG). Hemorrhaged mice given IVIG had increased total numbers of splenic plasma cells compared with normal or hemorrhaged, untreated mice. Immunization with the bacterial polysaccharide antigen levan immediately after hemorrhage resulted in approximately 60% fewer levan-specific splenic plasma cells than those seen in normal unhemorrhaged mice. Treatment of hemorrhaged mice with IVIG did not correct the decrease in levan-specific plasma cells. These results demonstrate that hemorrhage-induced alterations in the numbers and frequencies of bacterial antigen-specific B cells are not related to changes in serum Ig levels and cannot be corrected through administration of IVIG. ",22 637,"1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex. ",4 2158,"Evaluation of the manual hexadimethrine bromide (Polybrene) technique in the investigation of autoimmune hemolytic anemia. The use of the direct manual hexadimethrine bromide (Polybrene) test (DPT) in the investigation of patients for autoimmune hemolytic anemia (AIHA) was evaluated. Seventy-nine blood samples from 68 patients were tested. A direct antiglobulin test (DAT) using monospecific reagents and the DPT were performed, and a concentrated ether eluate was tested. The DAT was positive in 62 (78%) of 79 patients and negative in 17 (22%). There is a good correlation among DAT, eluate, and DPT in demonstrating the presence of immunoglobulin on the red cell surface. In contrast, the DPT does not detect C3d and is often negative in cases of AIHA in which C3d alone is demonstrated by the DAT. In DAT-negative cases, DPT results correlated with reactive eluates. However, in four cases of steroid-responsive, DAT-negative hemolytic anemia, the DPT supported the diagnosis of AIHA when the eluate did not react. The DPT is a useful additional screening test for the investigation of AIHA, but it is not recommended as a replacement for either eluate testing or the DAT. ",14 2340,"Clinical and laboratory effects of prolonged therapy with sulfasalazine, gold or penicillamine: the effects of disease duration on treatment response. Serial observations for up to 5 years of clinical score (a subjective global assessment), serum C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were analyzed in 3 groups of patients with active rheumatoid arthritis (RA) requiring treatment with a second line drug. The groups comprised 315 patients (243 women, 72 men) who had sulfasalazine (SAS); 203 patients (141 women, 62 men) who had sodium aurothiomalate (gold) and 163 patients (131 women, 32 men) who had penicillamine. The groups matched in most respects but the gold group had a smaller proportion of women, a shorter median disease duration and a higher median CRP than the remaining 2 groups. The penicillamine group contained a higher proportion of seropositive patients. In each group there were significant improvements in clinical score, CRP and ESR for all time points from 6 to 30 months; these improvements were maintained for longer (up to 60 months for SAS) in the SAS and gold groups but the differences between the drugs after 30 months were probably a consequence of falling number of patients, not differing drug potencies. The mean ESR and CRP levels fell to about 30 mm/h and 20-30 mg/l, respectively. Response was defined as (1) treatment duration greater than 6 months, (2) clinical score improvement greater than 4 by 6 months, (3) ESR fall to less than 30 mm/h by 6 months. By these criteria 142 of 681 patients (20.9%) responded; the response rates were SAS 20.3%, gold 24.1%, penicillamine 17.8%. ",16 1235,"Alkalinisation of prilocaine for intravenous regional anaesthesia. Suitability for clinical use. Eighty unpremedicated patients undergoing day-case hand surgery under intravenous regional anaesthesia were randomly allocated to receive, in a double-blind study, either 40 ml 0.75% prilocaine hydrochloride, with 5 ml 8.4% sodium bicarbonate or 5 ml 0.9% saline. The alkalinised group had significantly less pain on injection (p = 0.0045), during surgery (p = 0.0074) and 5 minutes after the tourniquet was deflated (p = 0.0027). The time elapsed between insertion of the block and commencement of surgery was not affected. ",9 2768,"Identification of the driver in an automobile collision. We report on a three-occupant automobile collision in which one of the two survivors claimed that the deceased had operated the vehicle. We attempted to identify the driver. The left face and neck of the deceased appeared to have struck the vehicle's interior. The survivors were slightly injured on the right side of their faces. In Japan, the passenger side is on the left, and in this case, the right side of the vehicle had been damaged. By comparing the injuries of the deceased and the survivors in relation to the vehicle damages, we concluded that the deceased occupant had probably been a passenger, not the driver. ",20 695,"Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity. Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease. ",5 2549,"Hyperinsulinemia increases the amount of GLUT4 mRNA in white adipose tissue and decreases that of muscles: a clue for increased fat depot and insulin resistance. To mimick a state of hyperinsulinemia, normal rats were infused with insulin for 4 days via minipumps, and compared to saline infused rats. At the end of the experimental period, the abundance of mRNA was increased in white adipose tissue (WAT) and decreased in muscles of ""insulinized"" rats compared to controls. These findings were accompanied, in all tissues considered, except the diaphragm, by parallel changes in the amount of the glucose transporter protein and by parallel changes in the in vivo glucose utilization index. Hyperinsulinemia is thus a driving force in stimulating adipose tissue metabolic activity, while bringing about incipient muscle insulin resistance. ",18 1107,"Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. An increase in extracellular K+ concentration ([K+]c) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]c increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]c, the extracellular concentration of glutamate ([Glu]c) was measured along with [K+]c. The results indicate that a relatively specific increase in [Glu]c (as compared with other amino acids) was induced concomitantly with the increase in [K+]c. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]c. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury. ",9 1349,"Protein differences between normal and oligospermic human sperm demonstrated by two-dimensional gel electrophoresis. Protein expression by sperm obtained from men with normal semen analysis and men with oligospermia were evaluated by two-dimensional gel electrophoresis. Proteins were solubilized in a 9.5 M urea/2% Nonidet-P40 (LKB, Bromma, Sweden) lysis buffer and underwent second dimension separation on 10 to 16% polyacrylamide gradient gels. A set of 36 invariant proteins was identified in all normospermic samples, whereas 8 of 10 evaluable oligospermic samples lacked 1 or more of the invariant proteins. Proteins absent in oligospermic samples may be critical to normal sperm function and may serve as markers for infertility. ",11 1700,"Experimental and clinical percutaneous angioscopy experience with dynamic angioplasty. The authors have used ultrathin angioscopes with high optical resolution to assess the effects of dynamic angioplasty in vitro and in vivo. Experimentally, angioscopy was used to study the effects of the 5F ""Kensey"" catheter in ""normal"" porcine coronary arteries (NPCA) and postmortem human coronary arteries (PMHCA). In NPCA, the catheter keeps a coaxial position. Intimal flaps (IFs) were seen in 21/23 NPCAs. They occurred with all cam rotation speeds and were usually single and small (less than 25% of lumen). Perforations in patent arteries were rare (1/23). However, when the catheter was forced against the wall by passing through a narrowing of 5F diameter (made by a band ligature), perforations were more common at higher cam speeds. The epicardium remained intact in two thirds of perforations. Angioscopy visualized perforations in only 10% of cases (1/10), the common sign being that of large and multiple intimal flaps, which were often obstructive (5/10). In PMHCAs, angioscopy was more sensitive than angiography in detecting atheromatous lesions. The authors were able to give a better assessment of the effect of dynamic angioplasty on treated lesions, including the demonstration of intimal flaps that were not visible on angiography. In vivo, they have performed percutaneous angioscopy before and after dynamic angioplasty using 8 French Kensey catheters. Angioscopy revealed features that were not shown angiographically. ",13 1119,"AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation. We elicited motor evoked potentials (MEPs) using transcortical magnetic stimulation in 150 control subjects aged 14 to 85 years and 275 patients with a variety of diseases. There were no significant side effects. Cortex-to-target muscle latencies measured 20.2 +/- 1.6 ms (thenar), 14.2 +/- 1.7 ms (extensor digitorum communis), 9.4 +/- 1.7 ms (biceps), and 27.2 +/- 2.9 ms (tibialis anterior). Central motor delay between the cortex and the C-7 and L-5 measured 6.7 +/- 1.2 ms and 13.1 +/- 3.8 ms, respectively. Mean spinal cord motor conduction velocity measured 65.4 m/s. MEP amplitude expressed as a percentage of the maximum M wave was never less than 20% of the M wave. A value of less than 10% is considered abnormal. MEP latency increases linearly with age and central motor delay is longer in older subjects. Compound muscle action potentials and absolute MEP amplitudes decreased linearly with age. In multiple sclerosis (MS), MEP latency and central delay were often very prolonged. The MEP was more sensitive than the SEP in MS. In amyotrophic lateral sclerosis, MEP latencies were only modestly prolonged; the characteristic abnormality was reduced amplitude. When pseudobulbar features predominated MEPs were often absent. The MEP was of normal latency in Parkinson's disease, but age-related amplitude was often increased. MEP latency and amplitude were normal in Huntington's disease. Abnormal MEPs persisted several months after stroke despite good functional recovery. The MEP could be used to advantage to demonstrate proximal conduction slowing and block in demyelinating neuropathies. In plexopathy, ability to elicit an MEP several days after onset of paresis was good evidence of neuronal continuity in motor fibers. ",9 1138,"Embolic stroke after smoking ""crack"" cocaine. A 39-year-old woman had an embolic upper division middle cerebral artery branch occlusion 3 hours after smoking the free base of cocaine (""crack""). Radionuclide ventriculography demonstrated cardiomyopathy, and echocardiography documented a left atrial thrombus. This case demonstrates that embolism is one mechanism of ischemic stroke after cocaine use, and that cardiomyopathy, possibly cocaine induced, may be the source of embolus. A cardiac source of embolus should be sought in patients with cocaine-associated cerebral infarction. ",9 2447,"Therapy for hypercholesterolemia. For most patients, hypercholesterolemia can be effectively lowered with drug therapy but only after several issues have been considered. First, drug therapy should never be considered without adequate dietary intervention. Dietary therapy may be effective for many patients with mild to moderate elevations in cholesterol. None of the drugs used to treat lipid disorders are benign agents. There is still debate about the interpretations of recent studies, the ability to generalize from studies to the whole population, and the cost effectiveness of drug treatment. Within the framework of the AHA and NCEP guidelines, an individualized approach to therapy is prudent. This should be initiated with maximal patient education because drug therapy will be maintained for the long-term or for life. The LDL and HDL levels, age, sex, other CHD risk factors, cost of treatment, patient awareness, and motivation must all be assessed when making treatment decisions. When drug therapy is considered for patients with isolated hypercholesterolemia, bile acid sequestrants are the drugs of choice. ",17 681,"Outpatient health care utilization of patients with inflammatory bowel disease. On the basis of the normal life expectancy of inflammatory bowel disease patients, the early onset of their disease, and the variety of symptoms, inflammatory bowel disease patients were anticipated to be frequent users of outpatients services. This study assesses (1) the characteristics, (2) outpatient health care utilization, and (3) the degree of satisfaction with health care of inflammatory bowel disease patients compared to patients with other gastrointestinal disease. The study method was a secondary analysis of data collected on 395 patients attending the University of Calgary Gastroenterology Outpatient Clinic in 1988. Inflammatory bowel disease patients were significantly younger (P less than 0.001) and better educated (P less than 0.05) than other patients. During the past year inflammatory bowel disease patients consulted significantly more often with their gastroenterologist (P less than 0.001) and spent more time in hospital (P less than 0.05) than other patients. Inflammatory bowel disease patients also consulted more frequently with herbalists and naturopaths. Lastly, inflammatory bowel disease patients were as satisfied with the health care they received as other patients. These results provide information useful for health care planners as well as for those dealing directly with inflammatory bowel disease patients. ",5 2383,"Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus. Many abnormalities in collagen have been reported in insulin-dependent diabetes mellitus, some or all of which have been attributed to increased cross-linking. Although recent work has focused on the role of glucose-derived collagen cross-links in the pathogenesis of diabetic complications, relatively few studies have investigated the role of lysyl oxidase-dependent (LOX) cross-links. In the present study, LOX cross-links and nonenzymatic glycosylation were quantified in skin collagen from diabetic subjects. There was an increase in the difunctional cross-link dihydroxylysinonorleucine (DHLNL) as well as in one of its trifunctional maturation products, hydroxypyridinium. All other LOX crosslinks were normal. Nonenzymatic glycosylation was increased in diabetic skin collagen, and this increase was correlated with increases in DHLNL (P less than 0.001). The biochemical results were examined for correlations with clinical data from the same subjects. Increases in DHLNL content were associated with duration of diabetes (P less than 0.003), glycohemoglobin levels (P less than 0.001), hand contractures (P less than 0.05), skin changes (P less than 0.005), and microalbuminuria (P less than 0.01). In nondiabetic subjects age was not correlated with collagen cross-link content with the exception that his-HLNL increased with age (r = 0.79, P less than 0.02). In diabetic subjects, PA levels decreased with age (r = 0.51, P less than 0.02). With increased duration of diabetes, DHLNL content was increased (r = 0.55, P less than 0.003) and OHP was increased (r = 0.59, P less than 0.01), whereas PA levels were decreased (r = -0.48, P less than 0.04). Nonenzymatic glycosylation of collagen was also increased with increased duration of diabetes (hex-lys, r = 0.47, P less than 0.02; hex-hyl, r = 0.39, P less than 0.05). We conclude that: (a) lysyl oxidase-dependent cross-linking is increased in skin collagen in diabetes and (b) that these changes in skin collagen are correlated with duration of diabetes, glycemic control, and long-term complications. ",17 1164,"Syncope and presyncope associated with probable adverse drug reactions. The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications. ",9 2975,"A rat femoral artery model for vasospasm. A new animal model for vasospasm using rat femoral artery has been developed. Whole blood, washed erythrocytes, or leukocytes in platelet-rich plasma were selectively applied to the adventitial surface of the femoral artery for 7 days in 15 rats, after which the vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. As compared with matched control arteries, there was a prominent reduction in luminal cross-sectional area after 7 days in vessels exposed to whole blood or washed erythrocytes, but not in those exposed to leukocytes in platelet-rich plasma. In arteries with luminal narrowing, light and transmission electron microscopy demonstrated marked morphological changes throughout the vessel wall similar to those seen in cerebral vasospasm after subarachnoid hemorrhage. Immunohistochemistry disclosed a prominent loss of immunoreactive actin in smooth muscle cells of arteries exposed to whole blood or erythrocytes. To assess the time course of arterial narrowing in this model, whole blood was selectively applied to the adventitial surface of femoral arteries in 23 rats for periods from 2 to 20 days. As compared with control arteries, arterial narrowing was variably present at 2 days, progressively increased by 5 days, was maximal at 7 to 10 days, and returned to near control levels by 20 days. The presence and severity of ultrastructural changes in vessel wall corresponded to the degree of arterial narrowing over time. These results suggest that chronic narrowing in rat femoral artery exposed to periadventitial blood is analogous to that observed in cerebral arterial vasospasm after subarachnoid hemorrhage. This new model represents a simple and reliable means to investigate pathogenic mechanisms and potential therapies for vasospasm. ",21 2384,"Chylomicron remnant clearance from the plasma is normal in familial hypercholesterolemic homozygotes with defined receptor defects. The retinyl palmitate fat tolerance test was used to measure chylomicron remnant clearance in 10 normal subjects (apolipoprotein E [apo E] isotypes 3 or 4 only), 6 normolipidemic apo E2/2 homozygotes and 5 familial hypercholesterolemic homozygotes. Skin fibroblasts with fully upregulated LDL receptors from the latter subjects degraded rabbit 125I-beta VLDL in vitro at rates ranging from less than 10-48% of normal. Experiments in vivo revealed no significant differences between the normal and homozygous familial hypercholesterolemic (FHH) subjects in chylomicron remnant clearance assessed on the basis of ""areas under the curves"" for retinyl palmitate levels present in post-prandial serum, chylomicron remnants (Sf. less than 1,000), or chylomicrons (Sf. greater than 1,000). Remnant clearance was greatly decreased at all times in the apo E2/2 homozygotes, indicative of an important degree of flux control exerted by a receptor-mediated step involving apo E as ligand. The absence of any excess remnant accumulation in FHH subjects with varying ""impairment"" of LDL receptor-mediated degradation of apo E-containing lipoproteins, permits the conclusion that chylomicron remnants are initially cleared from the plasma by apo E-recognizing receptors which are genetically distinct from LDL receptors. ",17 2682,"Diagnosis of mold allergy by RAST and skin prick testing. Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum. ",19 1337,"In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth. Nine human-derived cancer and non-cancer continuous cell lines were employed to evaluate the relative in vitro activity of the pollen extract, Cernitin T-60. Responses of the cell lines to the drug were assessed by measuring growth and cell survival as determined by cell count. The results demonstrated that of the 9 continuous cell lines tested, only those derived from the human prostate were growth inhibited by the pollen extract, whereas the non-prostate derived cells exhibited variable degrees of resistance to the T-60. The selectivity of the drug for the prostate cell lines was even more pronounced in the hormone-independent models, suggesting that there might be a place for the pollen extract in the control of abnormal growth in hormone-insensitive cells. ",11 1136,"Correlation of clinical and computed tomographic findings in stroke patients. We evaluated the correlation between clinical features and computed tomographic findings in a prospective study of 1,191 consecutive patients with acute cerebrovascular disease seen during 1 year. In the 386 patients in whom symptoms and signs initially suggested a cerebrovascular disorder, computed tomography revealed a relevant lesion in 154 (hemorrhagic in 52 [33.8%], ischemic in 102 [66.2%]) and a significant nonstroke abnormality in 14 (3.1%). Among the remaining 805 patients with symptoms and signs suggesting some central nervous system disorder other than stroke, computed tomography revealed a cerebrovascular lesion in 38 (4.7%); 35 of these lesions were ischemic. The computed tomographic findings was compatible with the final clinical diagnosis in 192 (84.2%) of the 228 patients with lesions. In the entire sample of 1,191 patients, a cerebrovascular disorder would have been missed in 38 (3.2%) without computed tomography. On the other hand, computed tomography failed to visualize a cerebrovascular lesion in 40 patients in whom such a lesion was clinically obvious. Our results emphasize that both careful neurologic assessment and a policy of early computed tomography are of crucial importance in the diagnosis of stroke and for therapeutic considerations. ",9 670,"Prerandomization: an alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee. Possibly the greatest threat to the success of a randomized clinical trial is the inability to recruit an adequate number of subjects. Concern that the randomized clinical trial will adversely affect the physician-patient relationship is the most common reason for physicians' reluctance to enroll patients in such trials. We report a modification of a prerandomized design, first described by Zelen, which was implemented in a randomized clinical trial of arthroscopy for patients who had osteoarthrosis of the knee. The method was associated with a sixfold increase in the rate of accrual of patients as compared with the use of a classic randomization trial. We propose the design as a potential solution to the problem of recruitment of subjects, particularly for clinical studies. ",4 318,"Growth of cultured human cerebral meningiomas is inhibited by dopaminergic agents. Presence of high affinity dopamine-D1 receptors. We have found that microM concentrations of the dopamine agonist bromocriptine significantly decrease the proliferation rate of human meningioma cells in culture (25-56% inhibition). This effect was also seen with direct application of dopamine, as well as the dopamine-D1 agonist (+)-SKF-38393 (both applied in microM concentrations) to meningioma cell cultures. Receptor studies with the dopamine-D1 ligand (125I)SCH-23982 (dopamine-D1 antagonist) indicated that dopamine-D1 binding sites were present in the membranes of meningioma tissue. The mean dissociation constant (Kd) was 325 ( +/- 74.5 SEM) pM and the receptor density (Bmax) was 25.4 ( +/- 1.5 SEM) fmol/mg pellet protein in 5 human meningiomas. The pharmacological specificity was proven by (+)-SKF-38393, ( +/-SKF-83566 or (+)-butaclamol and their inactive isomers (-)-SKF-38393 and (-)-butaclamol in a 1000 fold excess. These results provide evidence that human meningiomas possess high affinity dopamine-D1 receptors and that dopamine agonists have an antiproliferative effect on these tumors in culture. We conclude that the proliferation of cerebral meningiomas may be under dopaminergic control and that dopamine agonists may have a role in the medical treatment of patients with meningiomas. ",3 2728,"Is the incubation period of AIDS lengthening? Data from a cohort study of 1,637 homosexual men in Los Angeles are used to estimate the distribution of times from HIV infection to AIDS, and to detect any changes in the distribution. We find weak, but not statistically significant, evidence that the incubation period is lengthening. When the incubation period distribution is assumed not to have changed, we estimate that the proportion developing AIDS within 6 years of HIV infection is 27%, with a 95% confidence interval of (23%, 31%). However, if we assume that the incubation period distribution began to change in July 1987, then we estimate that for individuals infected in the first half of 1979, 28% develop AIDS within 6 years, and for those infected in the first half of 1983, 25% develop AIDS in 6 years. Four different hypotheses are suggested for a lengthening of the incubation period; these are a treatment hypothesis, a cofactor hypothesis, a better health care hypothesis, and a changing virus and disease hypothesis. The statistical method used is semiparametric modeling of the joint distribution of the date of infection and the incubation period for the participants in the study. These methods, although computationally intensive, are an attractive way of analyzing data from a prevalent cohort because only minimal parametric assumptions are made. ",19 868,"Secondary correction of the unilateral cleft lip nose using a conchal composite graft. The secondary deformity of the unilateral cleft lip nose has many components. One is the dorsal dislocation of the lateral crus of the alar cartilage. We used a conchal composite graft positioned between the piriform aperture and the lateral crus and the upper lateral cartilage to correct this dislocation in nine patients. We believe that this graft is effective because it elevates the lateral crus of the alar cartilage off the depressed piriform aperture. This technique is very simple to perform, and it is easy to achieve nasal symmetry. Our results have been quite satisfactory, with no recurrence of dorsal dislocation. The donor site was covered by a subcutaneous pedicled flap from the cephaloauricular sulcus, leaving an inconspicuous deformity. ",6 1346,"The interaction of parameters of male and female fertility in couples with previously unexplained infertility. A prospective study was undertaken of the relationship between semen variables, serial endocrine and follicular ultrasound measurements in one complete menstrual cycle, and the treatment-independent chance of conception for couples who were referred with unexplained infertility. For the 91 couples studied, the mean length of infertility was 70 months. A 100% follow-up rate was achieved. When a stepwise analysis was performed examining semen variables and ultrasonographic and endocrine variables, the mean ratio of salivary progesterone/plasma estradiol between days +1 and +3, with respect to the luteinizing hormone surge and the Grade 2 motile sperm density, were the only variables that achieved the 5% level of significance. There was a highly significant relationship between the product of these two variables and the chance of conception. This study clearly demonstrates an interaction between parameters of male and female fertility. ",11 1631,"Left ventricular mass regression after aortic valve replacement measured by ultrafast computed tomography. Left ventricular mass and function were measured using ultrafast computed tomography, and were correlated with clinical status in 17 patients with aortic stenosis and/or insufficiency undergoing aortic valve replacement or balloon valvuloplasty. Wall mass was 159 +/- 38 gm/m2 initially, decreased 25% to 116 +/- 29 gm/m2 at 4 month (p less than 0.001), and decreased a total of 34% to 105 +/- 33 gm/m2 at 8 months after valve repair. By 8 months not only was the mean wall mass within the normal range, but only three patients retained abnormal hypertrophy. Ejection fraction increased 8% (p = 0.06). Clinical function improved in all patients, with only three patients remaining outside of New York Heart Association functional class 1 at 8 months. Regression of ventricular mass into the normal range correlated with attainment of class 1 functional status (p less than 0.02), despite a lack of increase of ejection fraction. The single patient followed for 8 months after valvuloplasty had minor wall mass regression and minor clinical improvement. ",13 2114,"Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery. A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs. ",13 3223,"Blood conservation in cardiac surgery. We reviewed current blood conservation techniques and their use in cardiac surgery. Avoidance of aspirin preoperatively is an important blood conservation measure. Patients scheduled for an elective operation should participate in autologous predonation programs. With careful monitoring, patients with major coronary artery disease can safely donate blood preoperatively. Intraoperative processing of blood withdrawn before cardiopulmonary bypass provides autologous platelet-rich plasma for infusion after reversal of heparin sodium. Blood collected from the field during operation and blood remaining in the oxygenator after bypass can also be processed to yield washed and concentrated red blood cells for reinfusion. Randomized, prospective studies document that postoperative autotransfusion is both safe and effective in reducing homologous blood use. Aprotinin reduces plasma protein activation and platelet damage during bypass. The integration of available blood conservation techniques into a comprehensive program combined with careful consideration of the indications for transfusion may allow more patients to avoid transfusion entirely. ",22 2458,"Self-reported weight and height. The error in self-reported weight and height compared with measured weight and height was evaluated in a nationally representative sample of 11,284 adults aged 20-74 y from the second National Health and Nutrition Examination Survey of 1976-1980. Although weight and height were reported, on the average, with small errors, self-reported weight and height are unreliable in important population subgroups. Errors in self-reporting weight were directly related to a person's overweight status--bias and unreliability in self-report increased directly with the magnitude of overweight. Errors in self-reported weight were greater in overweight females than in overweight males. Race, age, and end-digit preference were ancillary predictors of reporting error in weight. Errors in self-reporting height were related to a person's age--bias and unreliability in self-reporting increased directly with age after age 45 y. Overweight status was also a predictor of reporting error in height. ",17 2472,"Use of cholesterol measurements in childhood for the prediction of adult hypercholesterolemia. The Muscatine Study This article describes the validity and utility of screening tests for total cholesterol levels in school-age children to predict those who, when adults, will have cholesterol levels that the National Cholesterol Education Program suggests need continuing surveillance and intervention. Two thousand three hundred sixty-seven children aged 8 to 18 years were examined on several occasions and were followed up to ages 20 to 30 years. Of children with cholesterol concentrations exceeding the 75th percentile on two occasions, 75% of girls and 56% of boys would not qualify for intervention as adults by the National Cholesterol Education Program criteria. Of children with cholesterol levels exceeding the 90th percentile on two occasions, 57% of girls and 30% of boys would not qualify for intervention as adults. Because the efficacy, safety, acceptability, and cost of treatment for high cholesterol concentrations in childhood is evolving, the need for universal screening of childhood cholesterol levels must be considered carefully in view of the number of children with high levels of cholesterol who, as adults, do not meet the criteria for intervention suggested by the National Cholesterol Education Program. ",17 300,"Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Intraoperative pathologic examination with frozen section (FS) was performed on 504 specimens of thyroid tissue obtained from 457 patients over a period of 9 years. After examination of permanent sections (PS) a malignant neoplasm was diagnosed in 57 specimens (11.3%); 50 (87%) of these were primary thyroid carcinoma, four (8%) metastatic carcinoma, and three (5%) malignant lymphoma. The FS diagnosis was ""benign"" in 448 (88.9%), ""malignant"" in (30) 5.9%, and ""deferred"" in 26 (5.2%). The sensitivity of FS diagnosis of malignancy was 53% and the specificity and positive predictive value 100%. The negative predictive value was 97.8% and overall accuracy 97.9%. The PS disclosed a malignant neoplasm in 62% of specimens in which FS diagnosis was ""deferred."" Sixty-eight percent of papillary carcinomas, 87% of undifferentiated carcinomas, and a single case of medullary carcinoma were diagnosed with FS examination. A FS diagnosis of malignancy was not made in any of the ten specimens containing follicular carcinoma; in all ten the neoplasms were well-differentiated and eight were encapsulated and minimally invasive. The inability to diagnose follicular carcinoma intraoperatively with FS is the most significant factor accounting for the relatively low sensitivity of FS diagnosis of malignant thyroid neoplasms. ",3 1597,"Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. Magnesium abnormalities are common in patients with congestive heart failure but the clinical and prognostic significance of an abnormal serum magnesium concentration in this disorder has not been investigated. Therefore, the relation between serum magnesium concentration and the clinical characteristics and long-term outcome of 199 patients with chronic heart failure was evaluated. The serum magnesium concentration was less than 1.6 mEq/liter in 38 patients (19%), within the normal range in 134 patients (67%) and greater than 2.1 mEq/liter in 27 patients (14%). Patients with hypomagnesemia had more frequent ventricular premature complexes and episodes of ventricular tachycardia than did patients with a normal serum magnesium concentration (p less than 0.05). Even though the two groups were similar with respect to severity of heart failure and neurohormonal variables, patients with a low serum magnesium concentration had a significantly worse prognosis during long-term follow-up (45% versus 71% 1 year survival, p less than 0.05). Patients with hypermagnesemia had more severe symptoms, greater neurohormonal activation and worse renal function than did patients with a normal serum magnesium concentration but tended to have fewer ventricular arrhythmias. Hypermagnesemic patients had a worse prognosis than did those with a normal magnesium concentration (37% versus 71% 1 year survival, p less than 0.05). In conclusion, the measurement of serum magnesium concentration provides important clinical and prognostic information in patients with chronic heart failure. ",13 106,"Tuberculous meningitis. Short course of chemotherapy. In March 1986, we began a 6-month short course trial of therapy for tuberculous meningitis, in which 28 patients were analyzed. The diagnosis was based on the following cerebrospinal fluid test results: in 53.5% of the cases, Mycobacterium tuberculosis was identified by direct smear; in 57%, culture in Lowenstein-Jensen medium was positive; in 83.3%, the detection of anti-bacille Calmette-Guerin (BCG) antibodies by enzyme-linked immunosorbent assay was positive; and in 74%, the dosification of adenosine deaminase activity was positive. In addition, in 21.4% of the cases, the diagnosis was established by means of autopsy findings. Moreover, the diagnosis was supported by bacteriological analyses from another tissue or body fluids. Despite the administration of an antituberculous therapy, 32.4% of the patients died: all of the decreased had reached the last stage of the disease by the beginning of treatment. Sixteen percent of the patients who survived after more than 18 months of follow-up after therapy had ended suffered neurological sequelae. With the 6-month therapeutic regimen, the morbidity/mortality is similar to that found in the longer-course therapies. The latter regimen is therefore thought to be a good and acceptable therapeutic option for the treatment of tuberculous meningitis. ",0 3069,"Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF. ",22 1042,"Semantic deterioration in Alzheimer's: the patterns to expect. Differentiating language changes between the normal aged and those in the early stages of dementia is never simple. Knowing the differences and what to expect can aid in making this diagnosis. ",9 2673,"Seroprevalence of HIV-2 infection in Greece (Crete). The seroprevalence of HIV-2 was evaluated in 20,407 consecutive normal blood donors, 100 homo- and/or bisexuals, and 7,020 heterosexuals presenting for an HIV test using an EIA test. Sixty-seven sera were revealed to be repeatedly positive. Analysis by Western blot confirmed the infection in four cases, an indeterminate (antibodies against only the gag-encoded proteins) pattern was revealed in 25 cases, whereas 38 sera were negative. Three of the four HIV-2-positive sera also reacted with two distinct, but close, synthetic peptides homologous to viral gp36. The fourth serum, which did not display antibodies against gp36 on Western blot, did not react with gp36-derived synthetic peptides. None of these sera reacted with native HIV-1 antigens or synthetic peptides homologous to gp41. Sera with an indeterminate HIV-2 Western blot did not react with gp36-derived synthetic peptides. Although 10 of them also displayed an indeterminate HIV-1 Western blot, no serum sample reacted with two gp41-derived synthetic peptides or proved to be positive when they tested for p24 antigen. One bisexual and one heterosexual HIV-2 positive subject reported sexual contacts with West Africans, whereas two other heterosexuals had had multiple sexual partners from different countries. ",19 2323,"The protective effect of the oral contraceptive pill on rheumatoid arthritis: an overview of the analytic epidemiological studies using meta-analysis. The oral contraceptive pill (OCP) has been implicated as having a protective effect on the development of rheumatoid arthritis (RA). The results of 12 studies have now been reported and produced differing results and conclusions. Because of the discrepancy in results and the importance of the issue we undertook a review of the studies and performed a meta-analysis. In all, 9 independent studies satisfied the criteria for selection, 6 case-control design and 3 longitudinal. Using standard meta-analysis techniques, the overall pooled odds ratio for all the studies was 0.68 for the crude results (95% CI 0.58-0.78) and 0.73 for the adjusted results (95% CI 0.61-0.85). The graphical odd-man-out method produced a 94% interval of 0.70-0.72. The pooled odds ratio of the case-control studies was lower than for the longitudinal studies. However, subdividing studies by the type of case source produced a pooled odds ratio for studies using hospital-based cases of 0.49 (95% CI 0.39-0.63) which was considerably less than that of studies using population-based cases: 0.95 (0.78-1.16). This difference was unlikely to have explained by bias due to selection of controls. We suggest that OCP use may not have a ""protective effect"" on the development of RA but may prevent the progression to severe disease by modifying the disease process. ",16 2771,"Plasma noradrenaline, platelet alpha 2-adrenoceptors, and functional scores during ethanol withdrawal. Plasma noradrenaline and platelet alpha 2-adrenoceptor density (sites/cell using 3H-rauwolscine with and without phentolamine) were correlated with withdrawal score in 23 hospitalized patients undergoing ethanol withdrawal. Control groups for plasma noradrenaline were 25 patients admitted to hospital for elective gastroscopy and 12 laboratory workers accustomed to venipuncture. Controls for platelet alpha 2-adrenoceptor measurements were a separate group of 31 normal subjects with a mean age close to that of the patients' withdrawing from ethanol. Plasma noradrenaline was significantly higher in the patients undergoing ethanol withdrawal than in patients admitted to hospital for elective endoscopy. Twelve laboratory controls had plasma noradrenaline levels significantly lower than either patient group. A significant though poor statistical correlation existed between ethanol withdrawal score and simultaneously determined plasma noradrenaline level. Platelet alpha 2-adrenoceptor sites/cell were reduced in ethanol withdrawal compared with the normal controls. Platelet alpha 2-adrenoceptor sites/cell increased over the first 24 hr of ethanol withdrawal but remained significantly lower than control values. The change in platelet adrenoceptors was accompanied by a fall in mean plasma noradrenaline. Thus, the stress of hospital admission itself is associated with an increase in plasma noradrenaline, but ethanol withdrawal enhances this increase, which is accompanied by and probably causes a reduction in platelet alpha 2-adrenoceptor numbers. These changes begin to return towards normal within 24 hr as the withdrawal reaction subsides. ",20 1018,"Evaluation of neonatal subglottic stenosis: a 3-year prospective study. Subglottic stenosis is the most common cause of chronic airway obstruction. It results in prolonged tracheal cannulation of infants and children. Following the widespread adoption over the past 20 years of prolonged intubation for respiratory support in neonates, the incidence of acquired subglottic stenosis increased dramatically. On January 1, 1987, we began a 3-year prospective study to delineate potential etiologic factors involved in the development of subglottic stenosis in neonates. The present study analyzes data from 289 infants. Relationships between birth weight, gestational age, endotracheal tube size, duration of intubation and ventilation, number and difficulty of intubations, and the subsequent need for medical and surgical therapy are discussed. Whole organ larynges from autopsy specimens provide histological correlation. ",8 1351,"Studies on requirements for trackpoints in CellSoft automated semen analysis. The CellSoft (CRYO Resources, Ltd., New York, NY) system for computer-assisted sperm analysis was evaluated as to the appropriate settings for trackpoints. Fifty-eight human spermatozoa exhibiting complex swimming modes were chosen for analysis at room temperature. The accumulated measures for curvilinear velocity, linearity, mean and maximum amplitude of lateral head displacement, and beat cross frequency were determined over a range of trackpoints from 2 to 37. Stable measures (within the 95% confidence interval at 37 frames) were observed at 4 frames for curvilinear velocity and at 20 frames for linearity. The corresponding figure for mean amplitude of lateral head displacement and beat cross frequency was 8 frames. We conclude that the frame requirements concerning measures for curvilinear velocity/linearity and mean amplitude of lateral head displacement/beat cross frequency should be 20 and 8, respectively. Thus, 20 consecutive frames to analyze will suffice. ",11 2431,"Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. Two hundred and nineteen second generation Japanese-American men were classified with a 75-g oral glucose tolerance test: 77 with normal glucose tolerance, 74 with impaired glucose tolerance (IGT), and 68 with noninsulin-dependent diabetes mellitus (NIDDM). The peak insulin response to the oral glucose load was progressively delayed with each of the 3 glucose tolerance categories. A similar finding was observed with the peak C-peptide response to oral glucose, except for the absence of distinction between IGT and NIDDM. Variables measuring the initial rate of insulin or C-peptide secretion (0-30 min) after oral glucose also demonstrated a progressive diminution with increasing glucose intolerance. The relative incremental insulin response at 30 min and the relative incremental C-peptide response at 30 min were highly correlated with the fasting glucose levels (r = -0.61 and r = -0.62; P less than 0.0001, respectively). Variables measuring the 0-30 min secretory response had high variances, whereas the variance for fasting glucose was low. Twelve men who were initially classified as IGT subsequently developed NIDDM. These 12 men had significantly higher fasting glucose levels at baseline than the remaining men who did not develop diabetes, but the 30 min secretory parameters after oral glucose, although lower in those who subsequently developed diabetes, were not significantly different at baseline. However, if fasting glucose is used as a surrogate measure of secretory response, these 12 men appear to have had an impairment of oral glucose-stimulated insulin secretion antedating the development of NIDDM. The inability of the secretory parameters to detect the abnormality may be due to a type II statistical error, which may be resolved by a larger sample size. ",17 1285,"Contact transscleral laser cyclocoagulation in glaucoma. A new way to treat glaucoma by laser coagulation of the ciliary body was developed. The laser beam is channeled to the eye through the fiberoptic system. The tip of the fiberoptic probe is placed in direct contact with the surface of the eye to be treated. The technical equipment developed for contact transscleral laser cyclocoagulation is simple, practical, and easy to use. The method was investigated experimentally (on animals and on human eyes to be enucleated) and tried in clinical practice. Only patients facing glaucoma surgery (on whom all other methods of conservative therapy failed) were selected for this kind of treatment. The immediate hypotensive effect was approximately 13 mmHg during the first 24 hours; then there was a gradual elevation of the tension, reducing the initial effect on average by 30%. This method has definite advantages over surgical cyclocoagulation as far as safety and simplicity are concerned. The use of contact fiberoptic systems may open up new possibilities in other fields of laser treatment of glaucoma, including techniques to channel the laser beam to the structures of the anterior chamber angle. ",10 1158,"Clarifying confusion: the confusion assessment method. A new method for detection of delirium OBJECTIVE: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk settings. DESIGN: Prospective validation study. SETTING: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). PATIENTS: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. MEASUREMENTS AND MAIN RESULTS: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). CONCLUSIONS: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium. ",9 1095,"Clinical characteristics of migraine and episodic tension-type headache in relation to old and new diagnostic criteria. Eighty-one patients were diagnosed as having migraine, tension headache or both according to previously used criteria. Then we performed a standardized interview to determine the frequency and severity of headache characteristics used in the new operational diagnostic criteria of the International Headache Society (IHS). In every patient the original diagnosis fulfilled also the IHS criteria, but in 9 patients the criteria were only fulfilled in half or less of the attacks, and applying the IHS criteria they also achieved an additional diagnosis. In one patient these attacks did not fulfill the pain criteria and in 8 (4 migraine, 4 tension headache) they did not fulfill the criteria for accompanying symptoms. Overall the IHS criteria are sensitive and specific, but they may possibly be improved with regard to accompanying symptoms. The present study suggests that recording of frequency and graded severity of characteristics using a headache diary may further improve the distinction between the different types of headache. ",9 1491,"Midtrimester tubal pregnancy with markedly elevated maternal serum alpha-fetoprotein. A case report. Elevated maternal serum alpha-fetoprotein levels have been reported to occur in a variety of pathologic conditions, including early tubal pregnancy. In this case, markedly elevated maternal serum alpha-fetoprotein was associated with a midtrimester tubal pregnancy. The breakdown of the normal fetomaternal circulatory barrier, allowing the transplacental exchange of alpha-fetoprotein, was the likely etiology of the elevation. ",12 2410,"Role of insulin in management of surgical patients with diabetes mellitus. Because surgery is a likely event during the lifetime of patients with diabetes, health-care team members need to be aware of the metabolic problems that may occur during the perioperative period. Surgery, especially in the presence of general anesthesia, will produce a diabetogenic response. This is generally due to an elevation of counterregulatory hormones, although endogenous insulin is also suppressed. The excessive lipolysis and ketogenesis that can occur during surgery can have particularly deleterious effects for patients with diabetes. Thus, sufficient insulin must be provided during this period to suppress these catabolic processes. The major controversy regarding surgery and diabetes concerns the route of insulin administration. This article reviews the various treatment options for patients with insulin-dependent and non-insulin-dependent diabetes mellitus, with particular emphasis on the role of insulin. Special situations, e.g., outpatient surgery, coronary artery bypass, and emergency surgery, are also discussed. ",17 2560,"Total hip and knee arthroplasty in juvenile rheumatoid arthritis. Total hip or knee arthroplasty is indicated in patients with juvenile rheumatoid arthritis when there is marked functional impairment and/or severe disabling pain from advanced structural hip or knee joint involvement. Relief of pain and dramatic improvement in function can be achieved in most patients. When both the hip and knee are involved, hip arthroplasty should probably be done first. Regional anesthesia is preferable. Careful preoperative planning is essential because custom prostheses are often required. Small bone size, osteoporosis, and soft-tissue contractures make the surgery technically demanding. Skeletal immaturity is not an absolute contraindication to surgery. Component loosening is the most frequent late complication in hip arthroplasty. It is less common in condylar metal-to-plastic knee arthroplasty in which patellar complications predominate. Cementless arthroplasty has an evolving role in the patient with juvenile rheumatoid arthritis and, to date, is more often used in the hip than in the knee. ",19 712,"Current concepts of cholesterol transport and crystal formation in human bile. The presence of vesicles in human bile probably accounts almost entirely for the frequently observed, but hitherto unexplained, phenomenon of metastable cholesterol supersaturation. This, in turn, largely explains the prolonged stability of cholesterol solubilized in supersaturated human bile. Under certain overall compositional conditions for a supersaturated native bile, the vesicular phase in its contribution to total cholesterol transport also becomes supersaturated in cholesterol. Because of this, the vesicles also become unstable, leading to formation of cholesterol crystals. A simple but common example of one factor affecting composition in this way is concentration of total solutes, especially the biliary lipids. Conversely, dilution of bile (e.g., hepatic bile) markedly reduces the cholesterol saturation level in biliary vesicles. The result is that such vesicles become much more stable. Under these conditions, cholesterol crystal formation becomes unlikely and rarely, if ever, occurs. ",5 1421,"Income and survival in chronic dialysis patients. The relationship between income and survival rates for chronic dialysis patients in Michigan was examined. To evaluate the relative risk (RR) of dying, by income, a Cox survival regression model was used to adjust for age, race (black versus white), gender, dialytic treatment modality, year of first end-stage renal disease (ESRD) therapy, and primary cause of ESRD. The average household income reported from census data for the ZIP Code of residence for each patient was analyzed as a socioeconomic indicator. Treatment modality on day 120 of ESRD was classified as either center hemodialysis (HD) or CAPD. All new patients, aged 20-59 and registered at the Michigan Kidney Registry between 1/1/80 and 12/31/87 were included in the study. Patients were followed from day 180 of ESRD until death, censoring at transplant, or 12/31/87. The adjusted relative risk of dying decreased for black patients by 3.3% per $1,000 increase in income (p less than 0.01), while the trend by income for white patients was negligible (p greater than 0.10). The difference in trends for the two groups was statistically significant (p less than 0.01). This is a surprising result, since white patients have higher death rates, overall, than do black patients, particularly among subgroups with diabetes and hypertension whose RR was 1.77 and 1.82, respectively. Poor socioeconomic status of the area of residence has a strongly negative effect on survival for black patients, but not for white patients. The reasons for the relationship of death rates with income, especially for black patients, need to be examined in greater detail. ",11 3263,"Effect of chemodenervation on the cerebral vascular and microvascular response to hypoxia. This study evaluated the effect of bilateral carotid chemodenervation on the cerebrovascular response to hypoxia in conscious rats. Cerebral blood flow was measured using 4-iodo[N-methyl-14C]antipyrine, and the total and perfused microvasculature was studied by injection of fluorescein isothiocyanate dextran and alkaline phosphatase staining. To maintain constant PCO2, hypoxia was achieved in chemoreceptor-intact rats by the use of 4% CO2-8% O2-88% N2 and in chemodenervated rats by the administration of 8% O2-92% N2. Blood gas and hemodynamic parameters were similar in the two groups of rats. Chemodenervation had no significant effect on either resting blood flow or the perfused microvasculature during normoxia. A significant increase in cerebral blood flow (from 71 +/- 3 to 138 +/- 9 ml/min/100 g in control and from 91 +/- 5 to 127 +/- 7 ml/min/100 g in chemodenervated rats) and in the percent of cerebral arterioles and capillaries perfused occurred in both hypoxic control and chemodenervated rats. In chemoreceptor-intact rats, the greatest increase in blood flow and in perfused microvasculature occurred in caudal structures (medulla and pons) in comparison with rostral structures (cortex, thalamus, and hypothalamus). In chemodenervated rats, a similar increase in blood flow and perfused microvasculature occurred in all brain regions, with no regional differences. Thus, chemodenervation did not affect the overall cerebral blood flow or the microvascular response to hypoxia; however, rostral-to-caudal regional differences in the hypoxic response were lost after chemodenervation. ",22 2069,"Delayed detection of coarctation in infancy: implications for timing of newborn follow-up. During a recent 5-year period, 74 patients younger than 6 months of age were diagnosed with coarctation of the aorta. Coarctation was correctly diagnosed in only 22% of patients prior to referral despite readily apparent femoral pulse abnormalities in 86%. Infants whose symptoms were detected between 5 and 14 days of age were significantly more ill than infants outside this age range and had a high mortality rate (25%). The number of associated cardiac defects was not related to the severity of clinical illness in this group, suggesting that closure of the ductus arteriosus is the primary determinate of disease severity. Observations in two patients suggested that a detectable pulse discrepancy occurs between 3 and 5 days postnatally. Upper extremity hypertension was found commonly in infants after 5 days of age despite the presence of congestive heart failure. Earlier detection of coarctation in the newborn requires a diligent cardiovascular and peripheral pulse examination between 3 and 7 days of life, upper extremity and lower extremity blood pressure measurement, and a high index of suspicion. ",13 110,"Low gastric acid as a risk factor for cholera transmission: application of a new non-invasive gastric acid field test. Although gastric acid is thought to be an important host defense against certain enteric infections, field studies of the role of gastric acid in preventing enteric infections have been hampered by the lack of a suitable non-invasive test. Because low gastric acid output (GAO) is an established risk factor for cholera, we assessed after validation, whether a new non-invasive test which estimates GAO by measuring breath hydrogen excess after ingestion of magnesium and a stimulant of gastric acid secretion, could discriminate between persons at high and at low risk of developing cholera. Fifteen age-matched pairs, participants in the field trial of two oral cholera vaccines in rural Bangladesh, were tested. In each pair the ""case"" was a person who had recovered from severe cholera at least 6 months before testing and the ""control"" was a person who resided in the home of a cholera patient but remained uninfected. The stimulated breath hydrogen was higher in controls (median hydrogen excess = 369 mumol/80 min) than in cases (median hydrogen excess = 150 mumol/80 min) (p less than 0.05) and was higher in controls in 12 out of 15 pairs. The results, which are consistent with past invasive assessments of the association between hypochlorhydria and cholera, suggest that this non-invasive test may be useful in evaluating GAO in epidemiological field studies. ",0 473,"Correlation between hyperthermoradiosensitivity and clinical effect in carcinoma of the esophagus. The correlation between hyperthermoradiosensitivity evaluated by an in vitro succinate dehydrogenase inhibition (SDI) test and the histopathologic effects of hyperthermochemoradiotherapy (HCR therapy) were investigated in 43 patients with carcinoma of the esophagus. The succinate dehydrogenase (SD) activity of tissue fragments taken at biopsy was assayed after exposure to heat (43 degrees C.) and radiation (6 grays) was done. The sensitivity to radiation plus heat treatment was estimated by the percentage of SD activity of the treated cells, compared with that of the control cells. The 43 patients were divided into three groups according to the degree of SD activity after exposure to radiation plus heat treatment. The SD activity was less than 50 per cent in group 1 (highly sensitive), between 50 and 70 per cent in group 2 (moderately sensitive), more than 70 per cent in group 3 (less sensitive). Eighteen of 20 in group 1, 11 of 17 in group 2 and two of six in group 3 were classified as being histopathologically ""effective"" for HCR therapy. The two year survival rate for groups 1, 2 and 3 were 55.5, 34.9 and zero per cent, respectively, while there were no statistical differences with regard to prognostic factors. These data suggest that in vitro activities of SD correlate well with the clinical effectiveness of HCR therapy. Therefore, it is recommended that a SD inhibition test be included among the guidelines for clinical management. ",3 440,"The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases. ",3 1753,"Haemorheological changes in patients with retinal vein occlusion after isovolaemic haemodilution. In 83 patients with central retinal vein occlusion and branch vein occlusion we measured the haematocrit (HCT), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF) and apparent whole blood viscosity (WBV). A control group (n = 41) was matched for sex, age, and cardiovascular risk factors. Measurements were performed before and after treatment with isovolaemic haemodilution (IHD). We found no significant differences between patients with retinal vein occlusion (RVO) and control subjects in haematocrit, plasma viscosity, red cell aggregation, and red cell filterability and no increased whole blood viscosity in the patient group. Patients with ischaemic retinal vein occlusion and non-ischaemic retinal vein occlusion did not show different haemorheological parameters either. After treatment with haemodilution, only the haematocrit and whole blood viscosity were significantly decreased, and there were no changes in plasma viscosity, red cell aggregation or red cell filterability. ",13 2956,"Lead. This article reviews historical and current uses of lead and sources of absorbed lead, such as water, lead-based paint, cookware, and bullet wounds. The means of absorption, collection of specimens, quantification methods, and effects of lead toxicity are discussed. ",20 237,"Bcr/abl recombinant DNA analysis versus karyotype in the diagnosis and therapeutic monitoring of chronic myeloid leukemia. Karyotype and bcr/abl recombinant DNA analyses are two means of detecting the chromosomal aberration in chronic myeloid leukemia. The authors compared these two methods in a retrospective study of 36 patients with CML in which they found the bcr/abl DNA recombinant event in 100% (29 of 29) of those patients who had the Philadelphia chromosome. To achieve this sensitivity, a battery of two bcr probes and three restriction enzymes is necessary. The authors propose a sequential algorithm for efficient use of these probes and enzymes. In 76% of the patients, bcr/abl rearrangement can be detected with a Bgl II digest and a 3' commercial probe. An additional 21% of patients can be detected by a second assay in which the same membrane is rehybridized to a 3' and 5' combination bcr probe. One patient (3%) required an additional restriction enzyme digest with BamH I to detect the recombinant event by the same 3' probe. Karyotype analysis is used to determine cytogenetic remission in patients with CML under therapy. The authors studied the use of DNA analysis by the Southern blot technique to detect a decrease in the relative number of leukemic cells. By dilution studies and densitometric scanning of autoradiographs, the authors were able to detect a 15% decrease in the relative number of cells having the bcr/abl recombinant event. The authors report the preliminary results of three patients in whom they compared the karyotype and recombinant DNA analysis at multiple time points in their clinical course. In conclusion, the bcr/abl recombinant DNA analysis is superior to karyotype for the diagnosis of CML and can be used for monitoring treated patients. ",3 2781,"Alterations in splanchnic blood flow following chronic ethanol exposure. The purpose of these experiments was to determine whether or not tolerance develops to the effect of 3.0 g/kg ethanol on total and regional splanchnic blood flow in male Wistar rats. The animals were given the Lieber-DeCarli liquid diet containing ethanol for 10 days; ethanol-fed animals were withdrawn 24 hr prior to experiments. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique after an intraperitoneal injection of 3.0 g/kg of ethanol. Acute ethanol administration produced early nonsustained increases in portal vein blood flow in animals fed ethanol for 10 days and withdrawn for 24 hr and in control animals. However, after chronic exposure to ethanol, the pattern of increase in blood flow in response to ethanol in the splanchnic organs was different between the ethanol-fed and control groups. Increases in portal vein flow in control groups were due to concomitant increases in small intestinal, colonic, and cecal blood flow while the increase in the ethanol-fed group was due to a rise in small intestinal and stomach blood flow. The increase in stomach blood flow that occurred in the animals treated chronically with ethanol may be viewed as a conditioned response to ethanol, since this was not found in the control group. These results, demonstrate that the pattern of increase in blood flow in the splanchnic organs produced by an acute dose of ethanol depends on the animal's previous exposure to ethanol. ",20 2315,"Dermatitis herpetiformis bodies. Ultrastructural study on the skin of patients using direct preembedding immunogold labeling. Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin. ",16 1797,"Prolonged cardiac preservation. Evaluation of the University of Wisconsin preservation solution by comparison with the St. Thomas' Hospital cardioplegic solutions in the rat. The University of Wisconsin solution differs from other types of solutions used for organ preservation because it contains high-energy phosphate precursors (adenosine and phosphate), impermeants (lactobionate and raffinose), an oncotic agent (pentafraction), and antioxidants (allopurinol and glutathione). These components have the potential to enhance the preservation of ATP, reduce intracellular and extracellular edema, and attenuate free-radical-mediated injury. The University of Wisconsin solution has been demonstrated to enhance and extend the preservation of the liver, pancreas, and kidney, but its potential role in the heart remains unproven. We have evaluated the University of Wisconsin solution (Du Pont) by comparing it with the St. Thomas' Hospital cardioplegic solutions No. 1 and No. 2 (Plegisol), which are used in Europe and the United States for routine cardiac surgery and transplantation. For each solution, 10 isolated working rat hearts were arrested by 10 ml of the solution (at 4 degrees C) and then maintained immersed in the same solution for 4 hours at 4 degrees C. Mean recovery of functional indexes (expressed as a percentage of their preischemic control values) after use of the University of Wisconsin solution were as follows: peak aortic pressure, 90.6 +/- 1.0; dP/dt, 71.5 +/- 5.5; aortic flow, 81.6 +/- 4.7; coronary flow, 87.5 +/- 3.5; and cardiac output, 82.6 +/- 3.5. In contrast, the mean recoveries after St. Thomas' Hospital solution No. 1 were as follows: peak aortic pressure, 82.8 +/- 1.3; dP/dt, 49.7 +/- 3.0; aortic flow, 58.4 +/- 5.3; coronary flow, 79.6 +/- 5.9; and cardiac output, 63.0 +/- 4.9. In contrast still, mean recoveries after St. Thomas' Hospital solution No. 2 were as follows: peak aortic pressure, 83.1 +/- 1.2; dP/dt, 40.7 +/- 6.1; aortic flow, 37.0 +/- 5.1; coronary flow, 65.8 +/- 3.6; and cardiac output, 43.1 +/- 5.6. The recovery of all indexes were significantly superior (p less than 0.005) after preservation with University of Wisconsin solution compared with either of the St. Thomas' Hospital solutions. ",13 1991,"Medical management of congestive heart failure. The syndrome of congestive heart failure can result from a variety of cardiac disorders of which left ventricular dysfunction is the most common. The clinical presentation is determined by the interaction between cardiac dysfunction and a series of compensatory mechanisms that are activated throughout the body. Therapy for this disorder is best approached through an understanding of this complex relationship and an appreciation for the influence of preload, afterload, and contractility on cardiac performance. Recent important advances in therapy include the use of combined diuretic therapy, a better understanding of the value of the digitalis glycosides, and evidence that angiotensin-converting enzyme (ACE) inhibitors can relieve symptoms and prolong life. More intensive therapy earlier in the course of congestive heart failure appears to have some clinical benefit. The use of ACE inhibitors during this phase may delay progression of the underlying left ventricular dysfunction. Future therapy will be influenced by the results of ongoing trials that are testing both new agents and expanded indications for drugs that are currently available. ",13 2387,"Beneficial effects of fetal liver tissue on fetal pancreatic transplantation. Recently, composite grafts of hepatocytes and islets have been shown to improve the survival of hepatocytes. The possibility of a reciprocal effect of hepatocytes on islet function was investigated. Diabetic Lewis rats were isografted with (1) fetal pancreas and fetal liver (FP/FL), (2) fetal pancreas alone (FP), and (3) fetal pancreas and fetal spleen (FP/FS). Grafts were transplanted to the small bowel subserosa. All (6/6) FP/FL recipients were cured (glucose less than 250 mg/dl for greater than 30 days), whereas only 72% (13/18) of FP alone and 60% (3/5) of FP/FS recipients were cured. The amount of time to normoglycemia for FP/FS recipients was less (26 +/- 15 days) compared with FP (50 +/- 29 days) or FP/FS recipients (71 +/- 40 days). Mean glucose levels at 6 weeks were 166 +/- 78 mg/dl, 237 +/- 97 mg/dl, and 355 +/- 81 mg/dl in cured FP/FL, FP, and FP/FS recipients, respectively. Glucose tolerance test results were not significantly different from those of nondiabetic control rats. In contrast to FP alone, FP/FL recipients had well-granulated hyperplastic islets and hepatocytes on histologic examination. When new isograft recipients were treated with cyclosporine, all FP recipients remained hyperglycemic; however, 75% (6/8) of FP/FL recipients were cured. In conclusion, FL in a composite graft with FP resulted in better engraftment, earlier isograft function, and protection from cyclosporine islet toxicity. ",17 2735,"A ten-year review of treatment of delayed union and nonunion with an implanted bone growth stimulator. A ten-year clinical and roentgenographic review was conducted on the patients in the original Australian multicenter trial that evaluated use of an implantable bone growth stimulator for delayed union and nonunion. Of the original 81 patients, 38 patients were located, seven patients had died from unrelated causes, and 36 were unlocatable. Of the 38 patients located, 37 patients (representing 38 fractures) participated in a detailed clinical review and had a roentgenographic assessment. All fractures had remained united, and normal bone remodeling had occurred. There were no adverse effects of the generator or cathode wire. Six patients initially reported as failures had healed after further surgical intervention. Thus, normal osteogenesis occurs in association with electrical stimulation using an implantable bone growth stimulator. This ten-year review supports the long-term safety and effectiveness of this technique in treating nonuniting fractures. ",20 1841,"Surgical treatment of endomyocardial fibrosis: a new approach. Endomyocardial fibrosis has been treated surgically for many years. For complete removal of fibrosis from both ventricles by the classic technique, each atrioventricular (AV) valve was removed and replaced with a prosthesis. Relapse of endomyocardial fibrosis has not been observed after surgical correction. Reoperations have been carried out because of complications of valve prostheses. A new surgical technique for removal of ventricular fibrous tissue with preservation of the mitral and tricuspid valves was used in nine consecutive patients with endomyocardial fibrosis. Initial results show a reduction of pulmonary hypertension, mean right and left atrial pressures and end-diastolic pressures in both ventricles. Tricuspid annuloplasty was performed in seven patients and mitral annuloplasty in five. No valve prosthesis was used. There was no death and New York Heart Association functional class improved from class III or IV in the preoperative period to class I or II in the postoperative period. These data suggest that resection of endocardial fibrous tissue can be indicated early in the clinical course and performed with preservation of the AV valves. ",13 2486,"Late-onset ornithine transcarbamylase deficiency in male patients [published erratum appears in J Pediatr 1991 Feb;118(2):326] We report on 21 male patients who presented after 28 days of age with ornithine transcarbamylase (OTC) deficiency, which we define as late-onset OTC deficiency. These patients appeared normal at birth, but irritability, vomiting, and lethargy, which were often episodic, later developed. The age at presentation ranged from 2 months to 44 years. Biochemical testing revealed hyperammonemia, hyperglutaminemia, hypocitrullinemia, increased urinary orotate excretion, and decreased liver OTC activity measured in vitro, which ranged from 0% to 15% of normal. Male patients who were older at presentation had a somewhat different pattern of presenting symptoms and were more likely to die. These data illustrate the phenotypic variability of OTC deficiency. Unexplained episodes of repetitive or protracted vomiting in association with progressive alterations in behavior or neurologic findings should suggest the diagnosis of a urea cycle defect (or another symptomatic inborn error of metabolism), regardless of the age or medical history of the patient. ",17 2575,"Molecular targets for AIDS therapy. The development of antiretroviral therapy against acquired immunodeficiency syndrome (AIDS) has been an intense research effort since the discovery of the causative agent, human immunodeficiency virus (HIV). A large array of drugs and biologic substances can inhibit HIV replication in vitro. Nucleoside analogs--particularly those belonging to the dideoxynucleoside family--can inhibit reverse transcriptase after anabolic phosphorylation. 3'-Azido-2',3'-dideoxythymidine (AZT) was the first such drug tested in individuals with AIDS, and considerable knowledge of structure-activity relations has emerged for this class of drugs. However, virtually every step in the replication of HIV could serve as a target for a new therapeutic intervention. In the future, non-nucleoside-type drugs will likely become more important in the experimental therapy of AIDS, and antiretroviral therapy will exert major effects against the morbidity and mortality caused by HIV. ",19 895,"Appropriate and inappropriate neuroendocrine products in pulmonary tumourlets. Pulmonary tumourlets are focal aggregates of neuroendocrine cells that occur in the periphery of the lung and may be associated with chronic inflammation and scarring. Six such lesions were seen in five lungs from a series of 35 pairs of lungs studied at necropsy. All were immunoreactive for neurone-specific enolase, protein gene product 9.5, and a range of neuroendocrine products. Of the peptides found in neuroendocrine cells in normal human lungs, gastrin releasing peptide was present in all tumourlets and calcitonin in all but one; none contained leucineenkephalin. Of a series of peptide and protein hormones not present in the neuroendocrine cells of healthy human lungs, growth hormone was present in all six tumourlets and adrenocorticotrophin in two. Identical patterns of peptide expression were displayed by neuroendocrine cells in the airway associated with the tumourlets in two cases. Such cells were increased in number and abnormally clustered. Aberrant expression of peptides might accompany the morphological changes in the pulmonary neuroendocrine cells seen in diseased lungs, their florid focal proliferation occasionally resulting in the formation of a tumourlet. ",7 630,"Psoriatic arthropathy of the temporomandibular joint. A case of psoriatic arthritis of both temporomandibular joints is described with a brief review of the literature and discussion on the management of this condition. To date, psoriatic arthritis has been successfully treated by conservative means. In the case reported, surgical replacement of the condyles became necessary to eliminate pain and restore function. ",4 1059,"Ubiquitin immunoreactivity in kuru plaques in Creutzfeldt-Jakob disease. Cerebellar kuru plaques in 2 cases of Creutzfeldt-Jakob disease were studied immunohistochemically. Similar to cerebellar senile plaques in Alzheimer's disease, many kuru plaques contained ubiquitin-positive, tau-negative small granular elements, presumably representing dystrophic neurites. Our results suggest that similar mechanisms are involved in neuritic changes in cerebellar plaques in Creutzfeldt-Jakob and Alzheimer's diseases despite differences of amyloid proteins in the plaques. ",9 736,"Surgical aspects of sclerosing cholangitis. Results in 178 patients. Of 178 patients with sclerosing cholangitis treated since 1950, 88 patients had associated inflammatory bowel disease, 72 had no such history, and 18 had iatrogenic injury or stone disease. A total of 233 biliary operations were performed, with a 75% rate of temporary improvement after initial operation. Subsequent operations resulted in a lower success rate and a higher mortality rate. Radiologic findings included predominant extrahepatic, intrahepatic, and diffuse disease in 29%, 28%, and 43% of patients, respectively; no survival differences were noted. Seventy-five of one hundred three deaths (73%) were related to liver failure, bleeding, or sepsis. Of 14 patients undergoing portosystemic shunt, 13 died of surgical complications or related disease. Orthotopic liver transplantation was performed in 16 patients and resulted in eight deaths, mainly in patients who had previously undergone extensive surgical treatment. No survival differences were seen between the patients with inflammatory bowel disease, those without the condition, or those who had colectomy. Surgical treatment in patients with sclerosing cholangitis should be minimized. Orthotopic liver transplantation should be offered as the treatment of choice for patients with portal hypertension, refractory cholangitis, advanced cirrhosis, or progressive liver failure. ",5 973,"Prototype volume-controlled resuscitator for neonates and infants. Twenty-five infants receiving assisted ventilation in an ICU were manually ventilated for 5-min periods using either a new prototype volume-controlled resuscitator (VCR) or a standard self-inflating resuscitator (SIR). Variables monitored during these 5-min periods included heart rate, respiratory rate, mean arterial pressure, mean airway pressure (Paw), end-tidal CO2 (PetCO2), pulse oximetry oxygen saturation, PaO2, and PaCO2. Significant differences in posttrial values for the following variables were: a) PetCO2 (31.2 +/- 9.1 vs. 25.6 +/- 8.2 torr, p less than .001); b) PaCO2 (38.0 +/- 4.9 vs. 33.2 +/- 6.7 torr, p less than .01); and c) pH (7.4 +/- 0.6 vs. 7.5 +/- 0.1, p less than .04) at comparable Paw (9.5 +/- 7.6 vs. 8.0 +/- 6.0, NS). Eighty-four percent (21/25) of infants in the VCR group had normal PaCO2 values (35 to 45 torr) while only 44% (11/25) in the SIR group achieved normocarbia (p less than .001). Measurements of the highest (Pmax) and lowest (Pmin) inspiratory pressure (cm H2O) in 15 patients demonstrated marked variation in Pmax with the SIR. Differences in Pmax (SIR minus VCR) were significant (10.8 +/- 3.7, p less than .02) but not in Pmin (0.5 +/- 3.5, NS). Our study demonstrates that ventilation with the VCR resulted in less hyperventilation with minimal pressure variability as compared with the SIR. Further studies in the neonate are warranted. ",7 1053,"Depression in dementia of the Alzheimer type and in multi-infarct dementia. The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia. ",9 1262,"Evaluation of visual fields by ophthalmologists and by OCTOSMART program. The introduction of Goldmann perimetry standardized measuring conditions as much as possible. In spite of this, it had been possible for the perimetrist to influence the results of perimeter measurements. The introduction of computer-controlled perimetry, however, has largely eliminated the influence of the investigator on perimetry results. Nevertheless, the interpretation of a perimetric result in the everyday clinical situation is still extensively subjectively coloured and is liable to vary, depending on the doctor carrying it out. The OCTOPUS Program G1 was introduced a few years ago and used above all for glaucoma. This program greatly simplified visual field assessment thanks to its visual field indices. The indices make it possible to compare visual field results with those of a normal population. The present introduction of the OCTOSMART program represents a further step forward. This program analyses measured visual fields with the aid of standardized, statistical criteria based on a large, normal value study. This analysis standardizes and thereby simplifies the interpretation of visual field results. This study compares the outcome of the OCTOSMART program with visual field interpretations by eye doctors. ",10 3092,"Measuring crackles. Crackles heard on auscultation can be represented graphically as a time-amplitude plot of the associated waveform. To assess the relative merits of several measures which might be considered for machine implementation in diagnostic instruments, we compared the reproducibility of those based on the initial voltage deflection which begins a crackle with those based on the largest deflection. The latter group showed less interobserver and less intraobserver variability when the same crackles were measured twice by each of two observers. Crackles from a teaching tape, categorized as fine and coarse, were used in this study. The ability of the various measures tested to distinguish between fine and coarse crackles on an individual basis was assessed and found to favor the measures based on the largest deflection. They showed an average of 9.96 percent incorrectly classified crackles, as opposed to 19.53 percent for the two measures based on the initial deflection. ",22 2904,"Unintended injuries in children: the French situation. The French situation with respect to mortality from unintentional injuries in children is far from satisfactory. International comparison is made difficult by statistical bias, but although excess injury mortality is decreasing in France, rates are higher than in most advanced European countries. Many regulations have been enacted during the past 30 years to reduce the economic and social burden of injuries, but political will is insufficient to establish a consolidated national program and enforcement of existing legislation is inadequate. Evaluation of preventive and educational programs is less than optimal; many attempts have not met basic methodologic requirements. The situation is improving, partly because of growing social concern. New regulations are in preparation, but solution of this major public health problem also demands behavioral change, which is much more difficult to effect than other measures. Greater commitment to research, proper evaluation of sound programs, and enforcement of existing law doubtless would reduce the excess morbidity and mortality resulting from unintended injuries to children. ",20 3167,"Postinduction repression of the beta-interferon gene is mediated through two positive regulatory domains. Virus induction of the human beta-interferon (beta-IFN) gene results in an increase in the rate of beta-IFN mRNA synthesis, followed by a rapid postinduction decrease. In this paper, we show that two beta-IFN promoter elements, positive regulatory domains I and II (PRDI and PRDII), which are required for virus induction of the beta-IFN gene are also required for the postinduction turnoff. Although protein synthesis is not necessary for activation, it is necessary for repression of these promoter elements. Examination of nuclear extracts from cells infected with virus reveals the presence of virus-inducible, cycloheximide-sensitive, DNA-binding activities that interact specifically with PRDI or PRDII. We propose that the postinduction repression of beta-IFN gene transcription involves virus-inducible repressors that either bind directly to the positive regulatory elements of the beta-IFN promoter or inactivate the positive regulatory factors bound to PRDI and PRDII. ",22 2264,"Basophil histamine release and airway response to mite allergen in atopic dermatitis. Twelve patients with atopic dermatitis (AD) were subjected to in vitro histamine release from peripheral blood leukocytes (basophils) and in vivo bronchial inhalation challenge using house dust mite (Dermatophagoides farinae) allergen. Not only seven patients with asthmatic history but also five patients without asthma responded to both the in vitro and the in vivo challenges. A significant correlation was observed between HR30 (a mite concentration producing a 30% release of total cellular histamine) and PC20 allergen (a mite concentration producing a 20% fall in FEV1). There was also a significant correlation between MHR (maximal histamine release) and the maximal fall in FEV1. The relationship held for both AD patients with asthma and without asthma. These results suggest that histamine release induced by the house dust mite allergen is a good in vitro test for predicting the bronchial response to this allergen. They also suggest that these tests are not disease specific, but are valuable in evaluating the degree of atopic state in a subject. ",16 2554,"Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong. The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan. ",19 2490,"Depletion of alcohol (hexanol) dehydrogenase activity in the epidermis and jejunal mucosa in Sjogren-Larsson syndrome. Using a histochemical technique, we have demonstrated a consistent deficiency of alcohol (hexanol) dehydrogenase activity within the epidermis and jejunal mucosa of patients with Sjogren-Larsson syndrome. Biochemical assay of the fatty alcohol: NAD oxidoreductase activity in cultured fibroblasts and leukocytes from these patients showed deficient activities compared with controls. The histochemical and biochemical results are complementary, and the simpler histochemical method can be used reliably for initial screening of patients with ichthyosis in whom a diagnosis of Sjogren-Larsson syndrome is suspected. ",17 1465,"A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone. Earlier we showed that because of the presence of functional progesterone receptors, lymphocytes of healthy pregnant women produced an immunomodulatory protein in the presence of progesterone, whereas those of nonpregnant persons did not. Progesterone-treated murine pregnancy lymphocytes release a similar factor. The present study reveals the biologic significance of this finding. Treatment of BALB/c mice that were 8 days pregnant with a progesterone receptor blocker (RU 486) resulted in 100% resorption of the fetuses. Simultaneous administration of the supernatant from progesterone-treated murine pregnancy spleen cells restored the resorption rate to the original 6% observed in untreated control animals. These data suggest that functional lymphocytic progesterone binding sites are needed for the maintenance of normal pregnancy. Because of the blockage of progesterone receptors and the consequent inability of the lymphocytes to produce the progesterone-induced blocking factor, abortion is initiated by immune factors. The fact that administration of the preformed blocking factor counteracted the effect of antiprogesterone treatment suggests that progesterone-mediated immunosuppression is needed for the maintenance of normal gestation. ",12 3005,"Problem solving in implant dentistry. Dental implants have become an accepted form of dental care, with reported functional 5-year success rates of 90% and higher. These impressive statistics include, but do not identify, the problems that may have been created by clinical ineptitude. Diagnostic acumen and preventive measures at each stage of the implant treatment can avoid many problems. Also, appropriate measures of timely recognition, rescue, and repair can often restore ailing implants and their prosthetic appliances to full function. ",22 15,"Streptococcus mitis sepsis in bone marrow transplant patients receiving oral antimicrobial prophylaxis. PURPOSE: Streptococcal infection has increasingly become a problem in neutropenic patients. We report on an outbreak of Streptococcus mitis sepsis in six bone marrow transplant patients receiving oral antimicrobial prophylaxis. PATIENTS AND METHODS: We performed an epidemiologic study of all patients in our bone marrow transplant program from 1986 to 1988. The hospital and microbiology records for all patients were reviewed. All bone marrow patients were treated according to specified protocols, including an oral prophylactic antimicrobial regimen that was changed in late 1987 from vancomycin/polymyxin/tobramycin to norfloxacin. Identification, susceptibility testing, and whole cell protein analysis of streptococcal isolates were performed at the Reference and Antimicrobial Investigations Laboratories at the Centers for Disease Control. RESULTS: We detected six cases of S. mitis sepsis among 21 patients undergoing bone marrow transplantation. No other concurrent pathogen was isolated from any patient at the time of the S. mitis bacteremia. Bacteremia developed within 72 hours of transplant in five of six patients and was associated with severe mucositis in four patients. An environmental study failed to reveal any common source for the outbreak, and whole cell protein analysis of all six S. mitis isolates revealed each to be distinct. Of 12 patients receiving oral vancomycin/polymyxin/tobramycin, one developed S. mitis bacteremia, versus five of nine patients receiving norfloxacin (p less than 0.03). CONCLUSION: We believe S. mitis bacteremia is a potential complication of bone marrow transplantation and is associated with antimicrobial prophylaxis with norfloxacin, especially in the setting of mucositis. ",0 2085,"Stunned myocardium during extracorporeal membrane oxygenation. The ""stunned myocardium"" is a syndrome of reversible myocardial dysfunction that may be mediated by oxygen-derived free radicals. This phenomenon has been seen in some neonates undergoing extracorporeal membrane oxygenation. We performed echocardiograms and measured creatine phosphokinase isoenzymes and lipid peroxide levels in 16 neonates before, during, and after extracorporeal membrane oxygenation. Infants who developed stunned myocardia by echocardiography did so shortly after initiation of bypass and exhibited concurrent elevations of the MB fraction of creatine phosphokinase. Lipid peroxide levels did not simultaneously rise. These data suggest that oxygen-derived free radicals may not cause the stunned myocardium seen in neonates undergoing extracorporeal membrane oxygenation. ",13 502,"Embryologic fusion planes and the spread of cutaneous carcinoma: a review and reassessment. It has long been held that embryologic fusion planes influence the spread of skin cancer. Embryologic fusion planes have been implicated in the depth of invasion, horizontal spread, and recurrence of cutaneous carcinoma. However, these structures have never been studied in detail. A review of the surgical literature reveals considerable confusion regarding the exact nature, location, and tumor interactions of these fusion planes. We review the gross and microscopic development of sites of embryologic fusion. We examine histologic sections through fusion sites in normally developed adult and fetal fresh cadaver specimens. Our studies, supported by our review of developmental anatomy, indicate that fusion planes do not persist as identifiable anatomic structures that would influence tumor spread. ",3 2968,"Pulmonary circulation and burns and trauma. The lung is a critical organ in victims of thermal injury or multiple trauma since the blood that drains injured organs circulates through the pulmonary circulation before passing through any other organ. The lung therefore will receive the first volley of cytotoxins released postinjury. In addition to being a target of injury, the lung may also contribute to the injury of systemic organs. This injury may be the result of a reduced delivery of oxygenated blood or the direct release of cytotoxins into the systemic circulation. The injury to the lung may be to the pulmonary microvasculature or the airway. The bronchial circulation responds to injury by a marked elevation in its blood flow and microvascular permeability. These latter effects may be important in mediating the changes which occur in the lung parenchyma. ",20 920,"Bronchial cartilage alterations in lung transplantation. Changes in the hyaline cartilage of the proximal bronchial tree were investigated in a group of combined heart-lung and double-lung recipients with and without OB. Ossification, calcification and fibrovascular ingrowth into the normally avascular hyaline bronchial cartilage were observed in almost all patients and were independent of small or large airway inflammation. Alterations in the integrity of hyaline cartilage have been produced by others in animals by ligation of the blood supply. Finding similar changes in airway cartilage of all transplanted lungs argues that there is relatively poor perfusion to the proximal air-conducting passage. Such a mechanism may contribute to the development of OB, bronchiectasis and a predilection for infections following pulmonary transplantation. ",7 1239,"Failure of nine-month phenobarbital administration to reverse amygdaloid-kindled seizure susceptibility in cats. Upon completion of left amygdaloid kindling, 4 cats underwent long-term phenobarbital administration during the subsequent 5- to 9-month rest period. Plasma phenobarbital levels were maintained above 15 to 20 micrograms/ml and were restimulated following plasma phenobarbital washout. Three cats served as nonmedicated controls. All 7 cats were subjected to repeated 6-hour sleep monitoring for observation of interictal discharges, which were observed most often in the immediate postictal period. Their frequency decreased gradually throughout the experiment in both the medicated and control animals, but they never completely disappeared except from the contralateral amygdala in 1 medicated animal. Upon primary site restimulation, all of the medicated animals responded with a generalized convulsion once the afterdischarge was induced. When these animals underwent secondary-site amygdaloid kindling, 3 showed a positive transfer effect. The findings suggest that although phenobarbital is a potent anticonvulsant, it has little effect on the acquired seizure susceptibility of previously amygdaloid kindled cats. ",9 1214,"Deteriorating ischemic stroke: risk factors and prognosis. To determine a risk profile of deterioration in cerebral infarction of less than 8 hours' duration, we studied prospectively a series of clinical and radiologic data in 98 patients. We evaluated the Canadian Neurological Scale Score and Barthel index during a follow-up period of 3 months. There was deterioration in the 1st 48 hours in 40.8% of the patients. High systolic blood pressure, elevated blood sugar concentration at admission, and carotid territory involvement were independently related with deterioration in the logistic regression analysis. Death occurred in 35% of the patients with deteriorating infarcts and in 8.6% of those with stable infarcts. At the end of the study, functional capacity was lower in those with deteriorating infarcts, but the 2 groups improved in parallel from the 4th day onward. ",9 499,"Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations. The site of the mutations is localized in codon 12 of K-ras gene. Such high incidence and localization of the ras gene mutations have not been observed in any other human malignancies. Polymerase chain reaction and direct sequencing method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small quantities of specimens obtained from needle biopsies and aspirate samples for pathological diagnosis. All the materials obtained from 12 patients with pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6 patients with chronic pancreatitis showed no mutations. In several cases using the mutations of K-ras gene as a marker, this analysis supplemented conventional pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The analysis of ras-gene mutations was useful for the clinical diagnosis of pancreatic adenocarcinoma. ",3 3003,"Blood loss reduced during hip arthroplasty by lumbar plexus block. We measured the blood loss during and after hip replacement in two groups of women, each consisting of 10 patients. In one group the lumbar plexus was infiltrated with bupivacaine, in the other it was not. The group in whom the plexus was blocked had significantly less blood loss. ",22 3013,"The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation. The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation. ",22 349,"Antigen related to cell proliferation in malignant gliomas recognized by a human monoclonal antibody. A human monoclonal antibody (CLN-IgG) was produced from a human-human hybridoma derived from lymphocytes of a patient with cervical carcinoma. The reactivities of this antibody with various human glioma tissues and cultured glioma cells and the characterization of the antigen recognized by CLN-IgG on malignant glioma cells were analyzed and reported. CLN-IgG reacted with various human glioma cells and glioma tissues, especially glioblastoma, but did not react with normal brain tissues or fetal brain tissues. A large amount of antigen recognized by CLN-IgG was expressed on cell membranes of undifferentiated glioma cells and of glioma cells at the G2/M tumor growth phase in cycling cells. Antigen recognized by CLN-IgG was detected in only one of seven samples of cyst fluid, and was not detected in 27 serum samples or 18 samples of cerebrospinal fluid from glioma patients. CLN-IgG exhibited antibody-dependent cell cytotoxicity against U-25 1 MG glioma cells and primary cultured cells of glioblastomas and anaplastic astrocytomas. These data suggest that the antigen recognized by CLN-IgG might be related to cell proliferation in malignant gliomas. Thus, CLN-IgG might be useful for immunotherapy or immunoimaging of malignant gliomas. ",3 89,"Accuracy in early prediction of prognosis of patients with septic shock by analysis of simple indices: prospective study. In 26 consecutive septic shock patients, we analyzed the clinical, hemodynamic, and metabolic data before and during volume infusion to test their circulatory reserve in response to fluid repletion. These patients were investigated to identify early variables that could predict outcome. There were 15 survivors (group A) and 11 nonsurvivors (group B). As a mean, group A patients were hemodynamically evaluated 2.3 h after onset of the sepsis syndrome, whereas group B patients underwent cardiac catheterization after a 12-h interval. At the initial evaluation, both groups demonstrated similarly decreased mean arterial pressure, mean heart rate, and mean cardiac filling pressure. Only group A patients evidenced elevated cardiac index (CI) (greater than 4 L/min.m2) associated with low systemic vascular resistance index (less than 7400 dyne.sec/cm5.m2), which is generally recognized as hyperdynamic cardiac state. However, none of the initial cardiovascular variables could serve as a predictor for survival. Fluid challenge increased left ventricular preload from 6 to 12.4 and from 7.8 to 12.7 mm Hg in group A and group B, respectively. The increases were associated with significant increases in CI from 4.4 to 6.9 and from 3 to 3.8 L/min.m2. However, at the end of fluid challenge, only group A patients exhibited normal cardiac response, as evidenced by the change in left ventricular stroke work index (LVSWI) for a given increase in the pulmonary capillary wedge pressure (WP) that was referred to as left cardiac preload. ",0 3188,"Patients at risk for cardiac death late after aortic valve replacement. A total of 100 patients aged 24 to 78 years were screened prospectively a mean of 71 months after aortic valve replacement for the presence of left ventricular hypertrophy (LVH) on the ECG (Estes scores greater than or equal to 5.0) and for repetitive ventricular premature beats VPBs greater than or equal to 2 couplets/24 hr) during 24-hour Holter monitoring. During the subsequent 41-month follow-up (range 10 to 50 months), the yearly cardiac mortality rate was 1.3% in patients with LVH, 2.9% in patients with VPBs, and 8.0% in patients with LVH plus VPBs but only 0.6% when none of these factors was present (p less than 0.05 chi 2 test). The patient groups did not differ with regard to age, time elapsed since operation, underlying valve lesion, and coronary artery disease. Both LVH and VPBs occurred more frequently in patients with left ventricular dysfunction. We conclude that after aortic valve replacement cardiac mortality is markedly increased in patients with LVH and repetitive VPBs, since they are noninvasive markers of left ventricular dysfunction. ",22 3154,"Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol. A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio. ",22 2193,"Longitudinal results after first-stage palliation for hypoplastic left heart syndrome. To evaluate the results of palliative surgery for hypoplastic left heart syndrome, we reviewed the records of 57 infants who underwent first-stage reconstruction at our institution between July 1983 and April 1989. Of the 57 infants, 12 (21%) are long-term survivors and 45 (79%) have died. Thirty-one infants died within the first 30 days after surgery. Twenty-six of the 31 early deaths occurred within the first 24 hours after surgery. Causes of early mortality were low cardiac output (23), sepsis (two), sudden death (two), pulmonary vein atresia (three), and cardiac transplant (one). Late death occurred in 14 infants due to sepsis (three), sudden death (four), and death at reoperation (seven - three after Fontan procedure, three after shunt replacement, and one after transplant). Of the 31 patients who survived more than 24 hours, the complications noted by echocardiography and confirmed by catheterization when reoperation was indicated were significant arch obstruction (13%), branch pulmonary artery stenosis (23%), small atrial septal defect (16%), inadequate shunt (26%), neoaortic regurgitation (13%), tricuspid regurgitation (13%), ventricular dysfunction (29%), thrombus (6%), and superior vena cava obstruction (3%). Of the 31 patients who survived more than 24 hours, 16 additional palliative surgical procedures were performed in eight patients. These procedures included arch reconstruction (four), additional shunt (four), Glenn shunt (three), atrial septectomy (two), coarctation balloon angioplasty (two), and pulmonary artery reconstruction and reshunting (one). Of the 12 long-term survivors, four have had a successful Fontan procedure, one has had a transplant, and seven are awaiting a second-stage procedure. Thus, 69% of all deaths occurred within the first 30 days of surgery, and 58% of all deaths occurred within the first 24 hours due to cardiovascular collapse. ",15 1937,"Fish oil supplementation in patients with stable claudication. Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients. ",13 1226,"Neonatal facial and cry responses to invasive and non-invasive procedures. Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures. ",9 1450,"Intracavernous injection of prostaglandin E1 in combination with papaverine: enhanced effectiveness in comparison with papaverine plus phentolamine and prostaglandin E1 alone. We compared the erectile response to intracavernous injection of a combination of papaverine and prostaglandin E1 with that of a combination of papaverine and phentolamine (49 patients), and prostaglandin E1 alone (38). The degree of erection achieved was significantly better with papaverine plus prostaglandin E1 than with papaverine plus phentolamine and the duration of erection was less, although the incidence of prolonged erections (greater than 5 hours) was similar with both combinations. Papaverine with prostaglandin E1 likewise resulted in a significantly better degree of erection than prostaglandin E1 alone (prolonged erections occurred only after the drug combination). All erections subsided spontaneously and none required medical intervention throughout the study. Pain was noted only after injection of prostaglandin E1. The incidence was clearly lower (7 of 38 versus 13 of 38) after the injection of only 5 micrograms. prostaglandin E1 in combination with papaverine (although the difference is not statistically significant). Subjectively, the side effects caused by the drug combination were described as much less dramatic by the patients than after prostaglandin E1 alone. The combination of papaverine and prostaglandin E1 shows a clearly synergistic effect and might suitably replace papaverine plus phentolamine or prostaglandin E1 alone in patients who do not respond well or suffer side effects after high single doses. ",11 3094,"Association of anterior ectopic anus and partial absence of levator musculature in a woman with impaired defecation. Report of a case. A 25-year-old nulliparous woman with adult onset constipation and slight anterior displacement of the anus underwent pelvic magnetic resonance imaging and was diagnosed with congenital hemiabsence of the levator ani sling. Impaired defecation was confirmed by anorectal function studies and defecography demonstrated an anterior rectocele, perineal descent at the upper limit of normal, and partial obstruction of defecation, which appeared related to the levator sling abnormality. To our knowledge, this combination of findings has not been previously described as a cause of adult onset constipation. ",22 1443,"Palmar keratoses in family members of individuals with bladder cancer. A total of 270 bladder cancer cases, 178 first-degree relatives and 127 spouses of the bladder cancer cases and 329 hospital controls were studied to evaluate the association between palmar keratoses, bladder cancer and environmental and genetic factors. Crude prevalences of keratoses in the 4 groups were 67, 54, 42 and 23%, respectively. Logistic regression models showed that bladder cancer patients had a raised risk of having palmar keratoses relative to hospital controls (odds ratio = 6.95; 95% CI: 4.77-10.12) whereas blood-relatives and spouses had significantly increased odds ratios only if the case in their family (or some other blood-relative) possessed keratoses. Among several environmental and behaviour factors, only cigarette smoking was significantly associated with increased risk (odds ratio = 2.32; 95% CI: 1.63-3.29). The data suggest a genetic component may influence the occurrence of palmar keratoses, but some unknown environmental agent appears to be causing the association between spouses. ",11 107,"Patterns of bacterial infection in calves implanted with artificial hearts. Device-related infection is one of the most serious potential consequences of total artificial heart (TAH) implantation. This complication must be addressed before the full potential benefit of these devices, especially fully implantable devices, can be realized. A review of research reports and clinical data was conducted to ascertain if similarities existed between the patterns of infection reported in human TAH recipients and those seen in the experimental animal models. Infection was reported in approximately 57% of the human TAH recipients and approximately 47% of the implanted animals. Implant periods ranged from 1-620 days for the humans, and 32-287 days for the animals. The spectrum of organisms isolated from both groups were similar, with a high proportion of infections caused by Pseudomonas aeruginosa and Staphylococcus epidermidis. In addition, numerous isolates of Enterobacter and Enterococci were obtained from the animals. Positive blood cultures have often been observed in animals within 2-4 weeks following implantation of the devices. The similarities noted in this review suggest that the calf may be an appropriate animal model in which to study the pathogenesis of TAH-related infection. ",0 3260,"Three-year outcomes for maintenance therapies in recurrent depression. We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a ""maintenance"" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication. ",22 1546,"Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation. To test the practicality of Doppler echocardiography to measure serial change, biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise, cold pressor stimulation, and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles, which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change, only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle, resolving flow area, and learning are variables that need greater emphasis. ",13 220,"Breast cancer during pregnancy and lactation. Breast cancer is the most frequently seen cancer in pregnancy and lactation, but the incidence is low, the disease being seen in approximately 0.03% of pregnancies. Only 1% to 2% of breast cancer overall is diagnosed during pregnancy or lactation. There is no evidence to implicate pregnancy or lactation in either the etiology or the progression of breast cancer. Careful breast examination early in the pregnancy is very important to find solid masses that require biopsy before breast engorgement hides them. Therapeutic options vary, depending on the stage of disease and the stage of the pregnancy. Operable disease in the first 6 to 7 months of the pregnancy should be treated by mastectomy, as irradiation is contraindicated. Late in the pregnancy, a lumpectomy and axillary dissection can be done, with irradiation being delayed until after delivery. General anesthesia is safe if the usual precautions are taken to compensate for the physiologic changes induced by pregnancy. Unfortunately, delay in diagnosis is common, and 70% to 89% of patients with operable primary lesions have positive axillary lymph nodes. Late stage appears to be the only reason for the generally worse prognosis in these patients, as stage for stage, they have a course similar to that of nonpregnant patients. Adjuvant chemotherapy can be considered late in the pregnancy but should usually be delayed until after delivery. In patients with locally advanced or metastatic cancer diagnosed early in the pregnancy, for whom both chemotherapy and radiation therapy would normally be recommended, consideration must be given to termination of the pregnancy. There is no evidence that termination of pregnancy improves the outlook for the patients, but it does permit standard aggressive therapy in advanced disease. ",3 1043,"Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide-induced acute liver failure. Functional changes of various neurotransmitter systems have been implicated in the pathogenesis of hepatic encephalopathy. In this study the role of brain monoaminergic neurotransmitter systems in hepatic encephalopathy was investigated in rats with thioacetamide-induced acute liver failure. Concentrations of serotonin, dopamine, noradrenaline and of their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylalanine (following inhibition of dihydroxyphenylalanine-decarboxylase), dihydroxyphenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenyl-glycol, were measured in the cerebral cortex, striatum and hippocampus by high performance liquid chromatography with electrochemical detection. In hepatic encephalopathy concentrations of 5-hydroxyindoleacetic acid were increased in all three brain areas (196%, 204% and 264% of saline-treated controls, p less than 0.01), and concentrations of serotonin were increased in the frontal cortex (121%, p less than 0.01). In the frontal cortex and hippocampus of encephalopathic rats dopamine levels were increased (157% and 289%, p less than 0.05), and levels of noradrenaline (53% and 46%, p less than 0.05) were decreased associated with increased 3-methoxy-4-hydroxyphenylglycol levels (173% and 206%, p less than 0.05). The extent of these changes correlated with the stage of hepatic encephalopathy. In hepatic encephalopathy dihydroxyphenylalanine accumulation was increased in the hippocampus and unchanged in the cerebral cortex. Dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid concentrations were unchanged in the striatum. The results of this study indicate that hepatic encephalopathy in thioacetamide-induced acute liver failure in rats is associated with neurochemical changes, suggesting an increased activity of the noradrenergic and serotoninergic neurotransmitter systems. ",9 1636,"Sensitivity of a set of myocardial infarction screening criteria in patients with anatomically documented single and multiple infarcts. A subset of 3 screening criteria (Q wave greater than or equal to 30 ms in lead aVF, any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV in lead V2, and R wave greater than or equal to 40 ms in V1) has been proposed to identify single nonacute myocardial infarcts. Cumulatively, these 3 criteria achieved 95% specificity, and 84 and 77% sensitivities for inferior and anterior myocardial infarcts, respectively, among patients identified by coronary angiography and left ventriculography. This study establishes the true sensitivities of the set of screening criteria in 71 patients with anatomically proven single myocardial infarcts and 32 patients with multiple myocardial infarcts. In the single inferior infarct group, the aVF criterion was 90% sensitive. The V2 criterion (any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV) was 67% sensitive in the single anterior infarct group. No single criterion proved sensitive in identifying a posterolateral infarct. The set of screening criteria performed just as well for multiple infarcts as it did for single infarcts, with a cumulative sensitivity of 72%. The overall sensitivity of the screening set in the 103 patients in all groups was 71%. ",13 755,"Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. This study was undertaken to determine whether routine use of a modified triple-lumen five French sphincter of Oddi manometry catheter would reduce the frequency and severity of post-manometry pancreatitis and pancreatic enzyme elevation. Seventy-six patients were alternately assigned to undergo sphincter of Oddi manometry (SOM) with a standard perfusion (infused group) catheter or the newly developed aspiration (aspirated group) catheter. After SOM, there were significantly more patients in the infused group with both amylase and lipase values elevated at least two times the upper limits of normal at 2 (p less than 0.001), 6 (p = 0.01), and 18 hours (p = 0.03) after the procedure. As compared with the standard perfusion system, the aspiration catheter was associated with a decreased frequency of clinical pancreatitis (23.5% vs. 3%, p = 0.01) reduced hospital stay (5 +/- 1.83 days, mean +/- SE, versus 1 day; p = 0.03) and milder pancreatitis. The aspiration manometry catheter should be considered for standard use for SOM, particularly if the pancreatic duct sphincter is being evaluated. ",5 2274,"Anaesthetic management of systemic mastocytosis. Systemic mastocytosis is an uncommon disorder of mast cell proliferation in connective tissues. Mast cell degranulation may occur on exposure to various stimuli and drugs. The release of histamine, heparin and vasoactive substances such as prostaglandin D2 may cause severe hypotension and other anaphylactoid manifestations. Anaesthetic management should include perioperative stabilization of mast cells and avoidance of the use of histamine-releasing drugs. Intradermal skin testing is useful in predicting the sensitivity to drugs that may be used during anaesthesia. We present a patient with systemic mastocytosis who underwent uneventful cholecystectomy. ",16 1067,"Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors? The entry characteristics of 1367 patients enrolled into the Extracranial/Intracranial Bypass Study were examined to determine if site differences in intracranial and extracranial arterial lesions among racial groups could be explained by differences in risk factors. Blacks were more often hypertensive, diabetic, or cigarette smokers, while whites had higher systolic blood pressure and hemoglobin values. Orientals had the lowest prevalence of vascular risk factors. Despite these differences in risk factors, multivariate analysis showed race to be an independent and strong predictor of the location of cerebrovascular lesions. To our knowledge, this study is unique in documenting risk factors prospectively and systematically in three racial groups simultaneously. Although generalization is limited by possible biases related to patient selection, the results affirm previous tentative conclusions about the role of race in determining the location of cerebrovascular disease. ",9 2023,"Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important. ",13 2512,"Tests of thyroid function: update in the diagnosis and management of thyroid disease. Current thyroid function tests give the clinician powerful tools for the accurate assessment of thyroid status in the majority of patients encountered. There are, however, a small number of clinical situations in which there appear to be inconsistencies in the interrelationship of the thyroid function tests and/or in which they are apparently inappropriate to the clinical status of the patient. In most instances, there is a rational explanation for these observed alterations. The application of this information should allow clinicians to further refine their diagnostic accuracy and thereby enable them to proceed with an appropriate therapeutic or management program. ",18 1722,"Critical care transportation medicine: new concepts in pretransport stabilization of the critically ill patient. Regionalization of health care for trauma has become commonplace, and the same concept for critically ill medical/surgical patients is developing. Recent evidence suggests that current stabilization measures used by transport teams can be inadequate for this critically ill patient population. In trauma, speed has been considered a necessity to get the patient to a facility which cannot be carried out to the field, eg, an operating room. For acute medical illnesses, critical care transport teams can bring intensive care technology to the patient. Accumulating evidence supports the premise that speed of transport is not as important as stabilization before transport, knowledge of hemodynamics during transport, and early use of critical care monitoring systems. Other reports identify the need for initial evaluation and stabilization of critically ill patients by physicians at the critical care level of expertise. Accordingly, critical care transportation teams have evolved, creating new notions of pretransport stabilization not applicable to previous transport systems. ",13 1484,"Comparative study of the changes in insulin-like growth factor-I, procollagen-III N-terminal extension peptide, bone Gla-protein, and bone mineral content in children with Turner's syndrome treated with recombinant growth hormone. Six girls (7-13 yr old) with Turner's syndrome and short stature were treated for 1 yr with recombinant human GH (0.15 U/kg.day, sc) and had sequential determinations of serum insulin-like growth factor-I (IGF-I), osteocalcin, and procollagen-III. Bone mineral content and density of the spine and radius were measured before treatment and at 90 and 360 days. Two girls received small doses of ethinyl estradiol (0.025 micrograms/kg) in addition to GH. Height velocity increased by 144% after 3 months of treatment. IGF-I was normal (0.75 +/- 0.20 kU/L) before treatment and increased by 90% on day 1 and by 290% on day 360. Procollagen-III was low before treatment; it peaked at 53.0 +/- 14.7 micrograms/L (260% above baseline) on day 30, then decreased to the normal range. Serum osteocalcin increased more slowly to reach a plateau on day 90 of 23.7 +/- 1.2 micrograms/L (46% above baseline). Before treatment, bone mineral content of the spine was 25% lower than that of children matched for bone age. Bone mineral contents of the peripheral and axial skeleton were increased by 10% and 17%, respectively, after 1 yr of treatment, an increase commensurate with that of bone age in the four patients who did not receive estrogen. On day 90, however, although radius mineral density was already increased by 3%, the mineral density of the lumbar spine was significantly decreased by 4%. We conclude that treatment with GH increases IGF-I, collagen turnover, osteoblastic function, and height velocity in Turner's syndrome. However, there is no catch-up of bone mineral content after 1 yr of treatment, and an early effect of GH is to decrease spine mineral density. ",12 1034,"Excitatory amino acids in the developing brain: ontogeny, plasticity, and excitotoxicity. Besides their role as neurotransmitters, excitatory amino acids (EAAs) in the developing brain are crucially involved in plasticity and excitotoxicity which are modified by their distinct ontogeny. Along with incomplete neuritogenesis and synaptogenesis, presynaptic markers of the EAA system are immature in the developing brain; however, postsynaptic EAA system activities, particularly of the N-methyl-D-aspartate and quisqualate receptors, are transiently enhanced early in life. This transient enhancement is presumably beneficial to the immature brain because physiologic activation of the EAA system plays a critical role in plasticity of early learning and morphogenesis. At the same time, this transient hypersensitivity renders the immature brain vulnerable to pathologic excitation of the EAA system (excitotoxicity) as observed during neonatal hypoxia-ischemia. ",9 1162,"Skin conductance and arousal in the newborn. We measured skin conductance continuously from the sole of a foot in babies of different conceptional ages before, during, and for 10 minutes after a 'heel prick' carried out for routine blood sampling. We studied 82 healthy babies whose gestational and postnatal ages ranged from 25-42 weeks, and 1-73 days. The median skin conductance level (preheel prick) in babies of 40-43 weeks' conceptional age was 0.6 microS (microsiemens) and differed significantly between awake babies (1.2 microS) and those who were asleep (0.5 microS). In contrast babies less than 40 weeks had a significantly lower median skin conductive level (0.3 microS) which was identical in awake and asleep babies. In response to the heel prick all babies became aroused and skin conductance rose sharply and immediately in 21 out of 22 (95%) babies 40-43 weeks' conceptional age, and in seven out of 23 (30%) babies 36-39 weeks. The median rise at one minute in babies of 40-43 weeks was significantly higher than those 36-39 weeks (2.7 microS compared with 0.5 microS). No babies less than 36 weeks had a change in their skin conductance after the heel prick. These results are consistent with the notion that 'emotional sweating' is a function of maturity and does not develop until 36 weeks' conceptional age. ",9 1009,"Sensorineural hearing loss in bullous myringitis. A prospective study of eighteen patients. Eighteen patients were seen over a period of 3 years. Twenty of their ears were diagnosed as having bullous myringitis. Pure tone audiograms and stapedial reflexes were performed within 48 h of referral. Six ears demonstrated sensorineural hearing loss, 7 ears mixed loss and 4 conductive loss. Recovery of sensorineural hearing loss complete in 8 out of 13 ears. Stapedial reflexes were elicited in 5 patients and all showed recruitment. The findings of this study confirms the fact that sensorineural hearing loss is more common in bullous myringitis than previously thought and that it is temporary in many cases. The stapedial reflex results suggest that the site of the lesion is in the cochlea. ",8 371,"Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women [published erratum appears in JAMA 1991 Apr 10;265(14):1828] We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk. ",3 2378,"Biochemical studies of RT6 alloantigens in BB/Wor and normal rats. Evidence for intact unexpressed RT6a structural gene in diabetes-prone BB rats. Lymphocytes bearing the T-lymphocyte differentiation antigen RT6 play an important immunoregulatory role in the development of autoimmune diabetes in BB rats. Immunofluorescence studies suggest that diabetes-prone (DP)- but not diabetes-resistant (DR)-BB rat lymphocytes fail to express RT6 antigen during ontogeny. Two alloantigenic forms of the molecule exist, i.e., RT6.1 and RT6.2; both are linked to cell membranes by a phosphatidylinositol (PI) linkage. In these studies, PI-phospholipase C (PLC) treatment of lymphocytes from BB and normal rats followed by immunoabsorption and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of released proteins with anti-RT6 allotype-specific monoclonal antibodies was performed. RT6.1 in several nondiabetic rat strains was found to consist of a family of nonglycosylated and variably glycosylated molecules: an N-Glycanase-resistant 24,000- to 26,000-Mr peptide and four N-Glycanase-sensitive peptides of 29,000, 31,000, 33,000, and 34,000 Mr. In contrast, RT6.2 was found to be a 24,000- to 26,000-Mr nonglycosylated polypeptide. The electrophoretic pattern of RT6.1 was observed to be the same when the antigen was extracted from W3/25+ (CD4+) versus W3/25- T lymphocytes or from resting versus mitogen-activated cells. A pattern of bands characteristic of the RT6.1 antigen found in normal rat strains was detected after PLC treatment or detergent solubilization of lymphocytes obtained from DR rats. In contrast, no evidence of either RT6 species was found after PLC or detergent treatment of comparable numbers of T lymphocytes from DP-BB rats. Interestingly, T lymphocytes from Wistar-Furth (RT6.2+) x DP (RT6-) F1 crosses were observed to coexpress both RT6.2 and RT6.1 molecules, with the electrophoretic pattern of RT6.1 being similar to that obtained in DR and other rat strains. This study provides biochemical evidence that DP rats may have an intact RT6a structural gene. ",17 2277,"Treatment of idiopathic guttate hypomelanosis with liquid nitrogen: light and electron microscopic studies. Idiopathic guttate hypomelanosis is a common skin disorder of unknown cause. Our studies have shown that significantly fewer dopa-positive melanocytes are in the white macules of idiopathic guttate hypomelanosis than in normal skin. By electron microscopy we observed that the melanocytes in the lesional skin were round and less dendritic with fewer melanosomes than in normal pigment cells. Lesions gently frozen with liquid nitrogen repigmented in 6 to 8 weeks. The number of dopa-positive melanocytes was significantly greater in the repigmented areas than in untreated lesions but less than in normal skin. ",16 1082,"An implantable neurocybernetic prosthesis system. The neurocybernetic prosthesis (Cyberonics, Inc.) is an implantable, multiprogrammable pulse generator that delivers constant current electrical signals to the vagus nerve for the purpose of reducing the frequency and/or severity of epileptic seizures. The device is implanted in a subcutaneous chest pocket just below the clavicle, similar to cardiac pacemaker placement. The stimulation signal is transmitted from the prosthesis to the vagus nerve through a stimulation lead. The prosthesis can be programmed using any IBM-compatible personal computer with programming software and a programming wand. The electrodes used in the first group of patients were found to break at an unacceptable rate. Design modifications appear to have resolved this problem. ",9 1638,"Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography. The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a ""subendocardial steal"" induced by dipyridamole. ",13 2132,"A specific in vitro bioassay for measuring erythropoietin levels in human serum and plasma. The accurate measurement of biologically active erythropoietin (Ep) in human serum and plasma using present in vivo and in vitro bioassays is difficult because of the presence of both inhibitors and non-Ep stimulators of erythropoiesis. We have developed a simple procedure to quantitatively purify Ep from serum and plasma for subsequent testing in the phenylhydrazine-treated mouse spleen cell assay. The method involves absorption of Ep to an immobilized high-affinity anti-Ep monoclonal antibody and acid elution of the antibody-bound material. After neutralization, the eluted EP is then tested directly in the in vitro bioassay without interference by other serum proteins. By using magnetic beads as a solid support for the antibody, washing and elution steps can be performed rapidly and efficiently. Recoveries of Ep after this procedure show very little sample-to-sample variation and are consistently between 45% and 55%, which is close to the maximum binding expected for the anti-Ep antibody. Coupled with the 7.4-fold concentration that this procedure affords, there is an overall increase in sensitivity of three- to fourfold, which makes this assay suitable for accurately measuring Ep levels in patients with below-average titers. Results with this magnetic bead assay indicate that accurate and reproducible estimates for Ep levels in the serum and plasma from healthy donors as well as from patients with hematologic disorders can be obtained. Titers of biologically active Ep in the sera from a group of patients with either leukemia or lymphoma were found to be elevated, and the values correlated well with titers of immunoreactive Ep measured in the Ep radioimmunoassay. Because of its specificity and high sensitivity, the magnetic bead assay is a valuable alternative to immunoassays for the measurement of elevated, normal, and even subnormal Ep levels in human serum and plasma. ",14 797,"A combined electromyographic and cineradiologic investigation in patients with defecation disorders. Records from 20 patients on whom defecography and electromyography were performed simultaneously because of defecation disorders were analyzed. According to the electromyographic investigation, the patients could be divided into three main groups: 1) normal sphincter reaction; 2) paradoxical sphincter reaction; and 3) combined reaction. Group A was characterized by a marked reduction of muscular activity during emptying and a pronounced closing reflex after emptying. This was followed by return of normal tonic activity. Patients in group B had no relaxation of the sphincters during emptying but a pronounced increased activity in the external sphincter and the puborectalis muscle. They also had severe emptying difficulties at defecography. No closing reflex was seen. In group C the electrical activity in the sphincters increased during moderate straining and when emptying was complete a clear closing reflex was seen. In this study, a dynamic visualization of the defecation together with a registration of electromyographic activity in the striated anal sphincters was performed. It was shown that patients with paradoxical sphincter reaction were lacking a closing reflex after emptying was complete. This has not been reported previously and is important evidence for the paradoxical defecation pattern. It was also shown that the patients with rectoceles had paradoxical sphincter reaction. ",5 1102,"Untying the gordian knot: the genetics of Tourette syndrome. A review of the current status of the genetics of Tourette syndrome is presented. Over the course of the 104 years since Gilles de la Tourette described the syndrome that bears his name, a body of carefully collected, described, and analyzed data has produced a model of the genetics that implicates a single dominant gene that is variably penetrant in males and females. Moreover, the locus of action of this gene is most likely in the dopaminergic system of the midbrain. A systematic search for this gene using recombinant DNA techniques is under way. ",9 1429,"Modulation of peritoneal macrophage antimicrobial activity by peritoneal dialysis fluid, Ca++, and 1,25(OH)2D3 in CAPD patients. Previous in vitro studies showed that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients. Twenty-four CAPD patients were evaluated in vivo (12 who had never had peritonitis, and 12 with an overall peritonitis incidence of more than one episode per 8 patient/months), for the effects of different peritoneal dialysis fluids (PDF) and Ca++ concentrations (1.25, 1.75, and 2.25 mmol/L) on PM0: cytoplasmic Ca++ concentration; superoxide generation; leukotriene B4 (LTB4) release; and bacterial killing for Staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PM0 Ca++ levels, superoxide and LTB4 generation, and bacterial killing such that, with 2.25 mmol/L of Ca++, these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca(++)-induced effects. On the other hand, with PDF Ca++ levels of 1,25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PM0 antibacterial function in CAPD patients, and may be useful in determining the prophylaxis and therapy of peritonitis. ",11 2174,"Elevated serum procollagen III aminopeptide levels in sarcoidosis. Procollagen III aminopeptide (P-III-P), a peptide released during the conversion of type III procollagen to type III collagen, is considered a potential marker of fibroblast activity in a variety of pulmonary and extrapulmonary diseases. The aim of the present article was to investigate the levels of P-III-P in serum samples (sP-III-P) from a large number of sarcoid patients, in particular looking at its relationship with other markers of disease activity and its presumed role as a marker of pulmonary fibrosis. sP-III-P has been radioimmunoassayed in an overall series of 57 patients and the levels were higher (19.18 +/- 9.17 ng/ml) than in 25 age- and sex-matched controls (11.32 +/- 2.15 ng/ml; p less than 0.001). The elevation was neither sex-related nor related to obvious liver sarcoid localization. Although sP-III-P levels were slightly higher in patients with stage II, there was no significant difference in patients with stage I or III. We found a positive relationship with serum angiotensin-converting enzyme (S-ACE) levels (p less than 0.04), but not with other markers of disease activity (67Ga uptake, bronchoalveolar lavage [BAL] lymphocyte percent, vital capacity, and lung diffusing capacity). The relationship with S-ACE was confirmed in a longitudinal follow-up study, where sP-III-P strictly paralleled the S-ACE behavior. Finally, the initial sP-III-P levels did not predict cases either with disease relapse or resistance to corticosteroid treatment. We conclude that, in our study, sP-III-P levels failed to characterize sarcoid patients with radiologic fibrotic pattern (stage III), and, in addition, were unable to predict which patients would have a poor prognosis. Rather, they reflect a metabolic activity of sarcoid granuloma cells. Thus, the usefulness of sP-III-P in the treatment of patients with sarcoid may be considered similar to that of S-ACE. ",14 2770,"The natural history of alcohol abuse: implications for definitions of alcohol use disorders Is the DSM-III-R category of alcohol abuse validly differentiated from the DSM-III-R category of alcohol dependence, or is abuse primarily a mild, prodromal condition that typically deteriorates into dependence? A 4-year longitudinal epidemiologic study of male drinkers provided data to answer this question. The study used identical questions at baseline and follow-up. At follow-up, 70% of the subjects who were initially classified as alcohol abusers were still abusers or were classified as remitted. This contrasted significantly with outcome in the subjects who initially reported alcohol dependence. Although additional research is needed, these results indicate that alcohol abuse often has a course distinct from that of alcohol dependence. ",20 1013,"Adenoid cystic carcinoma: a comparison between CT, MR and Gd MR imaging techniques. Nasopharyngeal carcinoma continues to be a difficult diagnostic problem in many patients. It is well known that amongst the many and varied manifestations of this disease, a unilateral middle ear effusion in an adult should be regarded with suspicion. Such a case in a 42-year-old patient is presented. In this case the benefit of Gadolinium enhanced magnetic resonance imaging over and above computerized tomography is demonstrated. ",8 1759,"Regression of infundibular pulmonary stenosis after successful balloon pulmonary valvuloplasty in adults. Between July 1985 and March 1988, 22 adult patients with congenital pulmonary stenosis underwent balloon pulmonary valvuloplasty. There were 10 males and 12 females aged 16-45 (average 25 +/- 9.9) years. All patients had additional mild to severe infundibular stenosis; 16 were restudied 6-36 (mean 12.6) months later by repeat catheterization. Student's t-test was used for comparison of data. Right ventricular (RV) systolic pressure before dilatation was 84-196 (mean 129 +/- 32.3) mm Hg, and the peak pulmonary gradient (PPG) was 60-176 (mean 111 +/- 33.2) mm Hg immediately after dilatation. The RV systolic pressure dropped to 32-140 (mean 59.2 +/- 27) (P less than 0.001); and PPG dropped to 10-113 (mean 37.8 +/- 26.4) (P less than 0.001), and the infundibular gradient ranged from 8 to 113 (mean 35.1 +/- 25.8) mm Hg. The infundibular diameter, before dilatation, ranged from 2 to 15 (mean 9.5 +/- 4) mm Hg. At repeat catheterization, the RV systolic pressure dropped further to 33-66 (mean 42.8 +/- 9.7) mm Hg and the PPG was reduced to 0-48 (mean 18.4 +/- 10.9) mm Hg (P less than 0.001). The infundibular gradient regressed to 0-34 (mean 15 +/- 8.8) mm Hg (P less than 0.001). The infundibular diameter increased to 8-25 (mean 15.8 +/- 5.4) (P less than 0.001). It is concluded that moderate to severe infundibular stenosis, in adults, can regress after successful pulmonary valvuloplasty. ",13 2669,"A novel X-linked combined immunodeficiency disease. A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders. ",19 1400,"Sodium loading treatment for amphotericin B-induced nephrotoxicity. The increased frequency and duration of antifungal treatment with amphotericin B in immunocompromised patients has stimulated a great deal of research into the mechanisms of its nephrotoxic effects and treatment modalities designed to attenuate these effects. A review of amphotericin B-induced nephrotoxicity, the underlying pathophysiologic mechanisms, and the role of salt loading as a means of minimizing renal impairment are described. Both animal and human studies regarding the efficacy of sodium loading are presented as well as a case report describing the use of salt supplementation over a prolonged course of therapy. ",11 3236,"Audiometric and subjective assessment of hearing handicap. This study compares self-perceived assessment of hearing handicap with audiometrically derived measures of hearing handicap in a sample of elderly persons. Subjects were evaluated by traditional audiometric tests, the Speech Perception in Noise test, and the Hearing Handicap Inventory for the Elderly, a self-assessment questionnaire. Hearing handicap was also calculated by the audiometrically derived American Academy of Otolaryngology (1979) method. Our results are consistent with other studies that indicate a low correspondence between audiometric measures of hearing handicap and self-assessment of hearing handicap. Furthermore, if the Hearing Handicap Inventory for the Elderly is considered the true measure of hearing handicap, our data indicate that the American Academy of Otolaryngology method tends to overestimate handicap among persons with no self-perceived hearing handicap and underestimates handicap among persons with significant self-perceived hearing handicap. ",22 962,"Glucocorticoids inhibit neurogenic plasma extravasation and prevent virus-potentiated extravasation in the rat trachea. Capsaicin increases the permeability of blood vessels in the rat tracheal mucosa through a mechanism involving the release of tachykinins from sensory nerves. This capsaicin-induced increase in vascular permeability is potentiated by viral infections of the respiratory tract. The present study was done to determine whether this ""neurogenic plasma extravasation"" can be inhibited by glucocorticoids, to learn the time course of this inhibition, and to determine whether glucocorticoids can prevent the potentiating effect of viral respiratory infections on neurogenic plasma extravasation. Groups of pathogen-free F344 rats were treated with dexamethasone for 2 or 8 h (4 mg/kg i.p.) or 48 or 120 h (0.5-4 mg/kg per d i.p.). Another group of rats was treated with dexamethasone for 120 h following the intranasal inoculation of Sendai virus. The magnitude of plasma extravasation produced by capsaicin or substance P was assessed after this treatment by using Monastral blue pigment and Evans blue dye as intravascular tracers. We found that dexamethasone reduced, in a dose-dependent fashion, the magnitude of plasma extravasation produced in the rat trachea by capsaicin and substance P. Significant inhibition was produced by a dose of dexamethasone as small as 0.5 mg/kg i.p. The effect of dexamethasone had a latency of several hours and reached a maximum after 2 d of treatment. Furthermore, dexamethasone prevented the potentiation of neurogenic plasma extravasation usually present after 5 d of Sendai virus respiratory infection. ",7 1690,"Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. We recently mapped the gene for ataxia-telangiectasia group A (ATA) to chromosome 11q22-23 by linkage analysis, using the genetic markers THY1 and pYNB3.12 (D11S144). The most likely order was cent-AT-S144-THY1. The present paper describes further mapping of the AT locus by means of a panel of 10 markers that span approximately 60 cM in the 11q22-23 region centered around S144 and THY1. Location scores indicate that three contiguous subsegments within the [S144-THY1] segment, as well as three contiguous segments telomeric to THY1, are each unlikely to contain the AT locus, while the more centromeric [STMY-S144] segment is most likely to contain the AT locus. These data, together with recent refinements in the linkage and physical maps of 11q22-23, place the AT locus at 11q23. ",13 1856,"Ultrasound-Doppler diagnosis of Budd-Chiari syndrome. We report a case of apparently idiopathic Budd-Chiari syndrome, diagnosed by ultrasound and Doppler sonography, in a patient with latent myeloproliferative disease. This case proves that Doppler sonography shows in the hepatic veins a flow pattern suggestive of partial thrombotic obstruction. Moreover, we suggest that the search for a latent myeloproliferative disorder, by means of the spontaneous erythroid colonies formation in culture of bone marrow or blood mononuclear cells, should be routinely included in the diagnostic evaluation of each case of hepatic vein thrombosis without other recognizable causes. ",13 550,"Ability of circular extrachromosomal DNA molecules to carry amplified MYCN proto-oncogenes in human neuroblastomas in vivo. Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification. ",3 746,"Alcoholic liver disease. Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease. ",5 1983,"Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l-cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action. ",13 180,"Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases. Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis. The DNA distribution patterns were grouped into three types, according to the proportion of aneuploid cell population. Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%), the same DNA distribution patterns were noted for both lesions. In 33 of these 36, DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node. Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions. This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01). Therefore, in primary lesions with a widely scattered DNA ploidy, the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes, particularly in cases of a differentiated carcinoma. Such observations may be pertinent in future designing of treatment protocols. ",3 3344,"Development and reversibility of T lymphocyte dysfunction in experimental obstructive jaundice This study evaluates the effect of experimental biliary obstruction by bile duct ligation (BDL) and biliary drainage on cell-mediated immunity in Wistar rats. Immune status has been assessed by a mitogen stimulation test of T lymphocytes with phytohaemagglutinin. Animals were followed for up to 35 days after BDL. Regression analysis showed a significant negative correlation between lymphocyte function and the period of jaundice (correlation coefficient -0.57, P less than 0.001). Following BDL for 21 days, groups of animals had internal biliary drainage for 7, 14 and 28 days, and external drainage for 14 days. Compared with obstructed animals, 14 days internal drainage was required to improve lymphocyte function (P less than 0.05). Animals which had 14 days of external drainage had significantly lower lymphocyte stimulation than internal drainage animals (P less than 0.05). The results demonstrate that obstructive jaundice produces a progressive reduction of T lymphocyte function. This can be reversed by biliary drainage, internal drainage being more effective than external drainage. ",22 1297,"The viscous fluid pump. We describe a device useful for injection of viscoelastic material into the vitreous cavity for internal tamponade. The instrument has proven to be reliable and ""user friendly"" in a clinical setting. ",10 1880,"Pharmacological reversibility of experimental cerebral vasospasm. Using a morphometric technique, the pharmacological reversibility of luminal narrowing after experimental subarachnoid hemorrhage (SAH) was investigated. For vasodilation, a ""cocktail"" consisting of 10(-4) M papaverine, 2 x 10(-4) M sodium nitroprusside, and 10(-5) M adenosine was administered intra-arterially. Forty-two rabbits were divided into six groups: control (normal animals); control plus cocktail (normal animals perfused with the cocktail before fixation); SAH (animals sacrificed 48 hours subsequent to intracisternal injection of 1.5 ml/kg of arterial blood); SAH plus cocktail (SAH plus perfusion with the cocktail); BaCl2 (animals sacrificed 10 minutes after intracisternal injection of 2 ml of 3 x 10(-3) M BaCl2); and BaCl2 plus cocktail (BaCl2 animals perfused with the cocktail). The diameter of the basilar arteries in the control and the control plus cocktail groups was not significantly different. BaCl2 reduced the diameter 44% and SAH reduced the diameter 27%. There were no significant differences between the diameter of the BaCl2 plus cocktail group and SAH plus cocktail group when compared with the control or the control plus cocktail group. Morphological examination by light and transmission electron microscopy showed luminal narrowing and corrugation of the elastic lamina with few degenerative or proliferative changes of the vessel wall in animals with SAH. These results suggest that cerebral vasospasm is caused initially by smooth muscle contraction rather than by proliferative vasculopathy and that it is not an irreversible process. ",13 2974,"Systemic amiloride inhibits experimentally induced neovascularization. Amiloride is an inhibitor of urokinase-type plasminogen activator, and might therefore have an inhibitory effect on neovascularization. Neovascularization was induced in rabbit corneas via local implantation of prostaglandin E1 pellets prepared in a slow-release polymer. Animals received daily intraperitoneal injections of 30 mg of amiloride, or an equivalent volume of saline solution for 5 days; both were well tolerated without severe untoward effect. Neovascular response, as documented by corneal photographs, was evaluated after 5 days of injections. The area of induced corneal neovascularization was decreased by 55% in animals receiving amiloride when compared with controls. Thus, amiloride and similar compounds may prove useful in the study and management of neovascularization. ",21 1406,"A glance at the urodynamic database. Three hundred sixty-four patients with urinary incontinence as their presenting complaint were evaluated in the urogynecology laboratory, Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York. Of them, 226 (62%) were found to have genuine stress urinary incontinence (GSI). This subset of demonstrably incontinent patients was characterized as to symptoms of stress and urge incontinence, incidence of nulliparity, occurrence of incontinence during intercourse and influence of weight on bladder pressure. Using clusters of symptoms did not accurately distinguish GSI from the other types of urinary incontinence. Four percent of the GSI patients were nulliparous. All had a reasonable explanation for incontinence other than anatomic relaxation. Twenty-three percent of the 154 sexually active GSI patients acknowledged having incontinence with intercourse. None of the anatomic and urodynamic parameters evaluated distinguished that group from their GSI counterparts who did not lose urine with intercourse. Increasing weight, expressed as the body mass index, correlated with an increase in the vesical pressure in the supine and standing positions. ",11 2339,"Clinical, laboratory and radiographic features in early rheumatoid arthritis. We evaluated disease status in relation to age, sex and disease duration using some short term indices of disease activity, laboratory tests, and radiological features in 315 patients with rheumatoid arthritis of duration varying from 3 to 36 months (mean 12 months). No differences were observed among various age groups in disease duration, female/male ratio, incidence of radiologic lesions and other indices of disease process. Some clinical markers of the disease process such as involvement of the flexor tendons of the hands and Ritchie's index (score greater than 9) were significantly more frequent in the women (p less than 0.0013 and p less than 0.04, respectively). In the patients with disease of recent onset women were slightly more numerous (56%) than men; however, in those with disease duration of 36 months there were significantly more women (72%) (p less than 0.039), suggesting a greater tendency to chronic disease in this sex. Radiological lesions of the small joints of the hands, feet, and/or wrists were found in 37% of the cases with disease duration of up to 4 months and in 91% at 36 months (p less than 0.0001). The lesions were associated significantly more frequently with Ritchie index (p less than 0.02) and with laboratory indices of inflammatory activity (erythrocyte sedimentation rate greater than or equal to 25 mm/h) (p less than 0.001) and immune response (latex test greater than or equal to 80) (p less than 0.0001). Logistic regression analysis showed that the duration of illness is the most important factor correlating with radiologic lesions. ",16 1817,"Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine-induced relaxation was markedly enhanced by cilazapril treatment. The tension achieved at maximal relaxation was 8 +/- 4% of norepinephrine contraction in the cilazapril-treated SHR versus 55 +/- 5% in the untreated SHR (p less than 0.001). Hydralazine had no significant effect. The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapril-treated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect. ",13 302,"Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. The infiltration of dendritic cells determined in 210 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. Dendritic cell infiltration was graded as ""slight"" and ""marked."" The 39% frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. The 5-year survival rate was 60.4% in patients with marked infiltration and 38.8% in those with slight infiltration, which was statistically different (P less than 0.01). The difference in survival rates was only statistically significant in those with cancer emerging from the serosa (P less than 0.001). There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced carcinoma (P less than 0.05). These findings indicate that infiltrating dendritic cells do not prevent the spread of tumor invasion but do prevent nodal involvement; therefore, for patients with a gastric cancer emerging from the serosa, the prognosis will be good. ",3 793,"Prevention of pancreatic fistula by modified pancreaticojejunal anastomosis. A major cause of morbidity after pancreatoduodenectomy is leakage from the pancreaticojejunal anastomosis. To prevent this complication, we have employed mucosal stripping from the proximal jejunum prior to end-to-end anastomosis in 19 patients with good results. ",5 321,"Cutaneous manifestations of postthymic T cell malignancies: description of five clinicopathologic subtypes. This study was undertaken to identify the cutaneous manifestations among different prognostic subgroups of postthymic T cell malignancies. Cutaneous involvement was demonstrated in 43 of 88 cases. We recognized five clinicopathologic subtypes: type I, classical cutaneous T cell lymphoma (CTCL) or mycosis fungoides, six cases; type II, primary large cell type CTCL, Ki-1 antigen (Ki-1+ or Ki-1-), seven cases; type III, primary angioinvasive T cell lymphoma, three cases; type IV, human T-lymphotropic virus type I (HTLV-I+) adult T cell leukemia/lymphoma (ATL), eight cases; type V, secondary cutaneous involvement by peripheral T cell lymphoma (PTL), 19 cases. Primary CTCL and ATL tend to involve papillary dermis with or without epidermotropism, whereas PTL and angioinvasive T cell lymphoma predominantly affect skin adnexae, vessels, and subcutis. Cutaneous lesions in type V PTL are heterogeneous and may be confused with panniculitis, vasculitis, or an eczematous eruption. Classic CTCL, Ki-1+ lymphoma, and angioinvasive T cell lymphoma have a chronic course, whereas ATL, Ki-1- large cell lymphoma, and PTL are clinically aggressive. ",3 388,"Treatment of fallopian tube carcinoma with cisplatin, doxorubicin, and cyclophosphamide. Primary carcinoma of the fallopian tube is uncommon and is often treated using regimens active in ovarian carcinoma. Evidence is scant that such therapies benefit patients with fallopian tube carcinoma. Between December 1979 and July 1988, we treated 18 patients who had adenocarcinoma of the fallopian tube with the combination of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) administered intravenously on 1 day every 28 days. Histologic confirmation of fallopian tube carcinoma was obtained before entry in the study. Three patients had stage I disease, five had stage II, nine had stage III, and one had stage IV. Sixteen patients received the combination therapy as first-line treatment after cytoreductive surgery, and two patients received it for recurrent carcinoma. Seven patients had clinically measurable disease at the start of therapy. Two of these patients had a complete clinical response, two had stable disease, and three had progressive disease. Eight of the 15 patients with stages II-IV disease underwent second-look laparotomy; four had a complete response to therapy and four had a partial response, making the overall response rate 53%. The toxicity of the regimen was moderate. The median survival was 81 months. Patients with stages II-IV disease had a median survival of 43.9 months and a progression-free survival of 22.5 months. This regimen appears to be active in fallopian tube carcinoma and can result in response rates comparable to those reported for epithelial ovarian cancer. ",3 3087,"A protocol for the investigation of pregnancy loss. A protocol for the evaluation of pregnancy loss should include a maternal history, dysmorphic examination of the fetus or abortus, photographs, autopsy, chromosome studies (in most cases), and radiographic or xeroradiographic studies. Selected cases with suspected ascending or transplacental infection may require microbiologic investigation. Increasing specialized laboratory techniques may help in the diagnosis of inborn errors of metabolism or storage disorders. Coordination of studies requires the interaction of OB/GYN, pathology, genetics, cytogenetics, and nursing in order to assure delivery of this clinical service. Knowledge of the causes of pregnancy loss and their typical time and mode of presentation can facilitate a focused evaluation, with a high chance of achieving an accurate diagnosis. The goal of all investigations is to provide families with recurrence risk data on which to base future childbearing decisions, as well as information on potential prenatal monitoring. ",22 117,"Chronic encephalitis caused by leukoencephalopathy. As mentioned previously, both MS and PML are demyelinating conditions of the CNS and pose diagnostic difficulties in their differentiation because of similarities in their clinical findings. However, certain features unique to each of these diseases are helpful in clinical diagnosis. MS, unlike PML, is a disease of unknown cause. Polygenetic influences in combination with exposure to an environmental agent and immune-mediated factors may be operative in the pathogenesis of MS. Age of onset peaks in the third to fourth decades with a predominance in women, as contrasted with PML, which peaks in the fifth to sixth decades in most non-AIDS-associated cases with a slight predominance in men. MS is more prevalent in areas farther from the equator: North America, Europe, Australia, and New Zealand. Common initial symptoms seen in MS include bilateral limb weakness (with the legs being affected twice as often as the arms), hyperreflexia, spasticity, optic neuritis, diplopia, incoordination, and paresthesias. (Paresthesias are typically found in the lower limbs in a symmetric pattern, but may follow no obvious anatomic distribution and often do not correspond to the distribution of sensory symptoms. Vibration and position sense are more frequently disturbed than pain and temperature.) Intellectual impairment and mental deterioration are uncommon early in MS, whereas they are a more frequent initial presentation in PML. In addition, the presence of speech impairment and monoparesis or hemiparesis with homonymous hemianopsia is more suggestive of PML. Brain stem involvement is infrequent. ",1 1147,"Putative neuroexcitation in cerebral ischemia and brain injury. Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults. ",9 2884,"Injury and disability in matched men's and women's intercollegiate sports. Eight matched men's and women's intercollegiate varsity teams were studied prospectively for one academic year to determine the incidence of athletic injury and resulting disability. Sports in which both men and women participated in a comparable manner were chosen: basketball, fencing, gymnastics, swimming, tennis, indoor track, outdoor track, and volleyball. Men (232) and women (150) were injured at comparable rates, 42 percent versus 39 percent. When adjusted for exposure time, seven of the eight sports continued to show similar injury rates. Women gymnasts, however, experienced .82 injuries per 100 person-hours of exposure as compared to .21 injuries for the men (p = .0001). Disability was greater in women gymnasts, 7.44 days per 100 person-hours versus 1.15 days for men (p = .0004). Percent of season lost to injury was also greater for women gymnasts. Types and sites of injury were similar for men and women, with sprains and strains accounting for over half of all injuries. We found no evidence for gender differences in matched sports except for gymnastics, in which technically diverse events may have accounted for the differences observed. ",20 77,"Seroprevalence of Helicobacter pylori in Seventh-Day Adventists and other groups in Maryland. Lack of association with diet. To evaluate the possible role of diet in the transmission of Helicobacter pylori, we compared H pylori seroprevalence among Seventh-Day Adventists (who are vegetarian and abstain from alcohol, caffeine, and meat; n = 94) and two non-Seventh-Day Adventist control groups (n = 168). With the use of an enzyme-linked immunosorbent assay H pylori antigen prepared in a French pressure cell, we found no difference in seroprevalence among these groups; however, seropositivity strongly correlated with age and black race. ",0 1416,"The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. A prospective study of four cycles of etoposide with ifosfamide and cisplatin (VIP) chemotherapy was conducted in 42 germ cell tumor (GCT) patients who were refractory to cisplatin with etoposide/vinblastine-based therapy. Forty patients were evaluable for response. Ten patients (25%) had a complete response: seven to chemotherapy alone and an additional three patients after surgical resection of viable GCT. With a median follow-up of 15 months, four complete responders relapsed, and six patients (15%) remain in remission. Hematologic and nephrotoxicity were moderately severe. Durable complete responses with VIP as second salvage were achieved and suggests that ifosfamide adds efficacy to standard first-salvage therapy. The observed nephrotoxicity and myelotoxicity are considerations in the design of ifosfamide-cisplatin-based regimens. Hematopoietic growth factors may be useful in ameliorating myelotoxicity. The early use of ifosfamide-based chemotherapy may reduce the nephrotoxicity exacerbated by prior cisplatin. A trial of VIP as first salvage after a relapse from a complete response to platinum-based induction therapy is warranted. The modest proportion of patients who achieve a durable remission to VIP as second salvage emphasizes the need for more efficacious salvage therapy for patients who do not achieve a durable complete response. ",11 8,"Itraconazole in tinea versicolor: a review. Itraconazole, a new orally active triazole antifungal, has been tested in patients with pityriasis versicolor. A number of studies have shown that itraconazole is effective for this mild fungal skin disease. The total dose required for effective treatment is 1000 mg, and it has been given as 200 mg for 5 days or 7 days. The organisms disappear slowly from the skin, even when dead, and the results should be assessed clinically and mycologically at around 3 to 4 weeks after treatment. Numerous studies have shown that itraconazole is superior to placebo and as effective as selenium sulfide, clotrimazole, and ciclopirox olamine. It is also better tolerated by patients than selenium sulfide. ",0 644,"Estrogen prophylaxis. The U.S. Preventive Services Task Force. Recommendation: Although routine postmenopausal estrogen replacement is not recommended, estrogen therapy should be considered for asymptomatic women who are at increased risk for osteoporosis, who lack known contraindications and who have received adequate counseling about potential benefits and risks. ",4 511,"Laser therapy for vaginal intraepithelial neoplasia after hysterectomy. In recent years there has been a marked increase in the number of reported cases of vaginal intraepithelial neoplasia (VAIN) after hysterectomy. Until about 10 years ago radiation or surgery had been the therapeutic modality mostly used for this disease. More recently, topical drugs, such as bleomycin and 5-fluorouracil cream, have been used, but they are often ineffective and poorly tolerated. For the last 14 years we have used the CO2 laser for the treatment of VAIN and have treated a total of 143 patients. Our use of a combination of wire sutures through the vaginal mucosa and the introduction of fluids into the underlying submucosal areas allows retraction and ballooning of the recesses and scars and permits us to place the vaginal mucosa at right angles to the laser beam to allow complete treatment. ",3 1940,"Thoracic epidural anesthesia improves global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. The aim of the present investigation was to study the effects of high thoracic epidural anesthesia (TEA), including the cardiac sympathetic segments, on ischemic ST-segment changes and left ventricular global and regional wall motion abnormalities. Ten patients with a two- or three-vessel coronary artery disease, all treated with the beta-adrenergic blocker metoprolol because of severe stable angina pectoris, performed two identical exercise stress tests, the first without TEA (control exercise) and the second with TEA (TEA exercise). Before each stress test, intravenous metoprolol was given to achieve maximal or near maximal beta-adrenoceptor blockade. Systolic and diastolic arterial pressures (radial artery cannula), heart rate, and rate-pressure product, as well as global and regional ejection fractions, using equilibrium radionuclide angiography in the left anterior oblique projection, were measured at rest and during maximal exercise. ST-segment analysis (V3 or V5) was performed, and the regional wall motion score was calculated at control exercise and TEA exercise. Intravenous metoprolol or intravenous metoprolol plus TEA at rest did not cause any significant changes of any of the variables. During TEA exercise, systolic arterial pressure, diastolic arterial pressure, and rate-pressure product, but not heart rate, were significantly lower compared to control exercise. The global and anterolateral ejection fractions were significantly higher (52.8% versus 46.5% and 53.2% versus 46.0%, respectively, P less than 0.05), and the regional wall motion score was significantly lower (8.8 versus 11.8, P less than 0.01) during TEA exercise than during control exercise. ST-segment depression was significantly lower during TEA exercise (-1.03 versus -1.84 mV, P less than 0.01). ",13 1699,"Endogenous vasopressin supports blood pressure and prevents severe hypotension during epidural anesthesia in conscious dogs. To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8-13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effects were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (beta-mercapto-beta, beta-cyclopenta-methylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg +/- 5 SE to 60 mmHg +/- 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg +/- 5 to 79 mm Hg +/- 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1-receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 +/- 0.3 pg.ml-1 to 16.2 +/- 3.2 pg.ml-1 after epidural anesthesia but did not change after epidural saline. ",13 1766,"Nonuniform regional deformation of the pericardium during the cardiac cycle in dogs. We hypothesized that local contact forces between the pericardium and the heart cause regional variation in pericardial deformation during the cardiac cycle, reflecting volume changes of the underlying cardiac chambers. To test this, we measured regional pericardial area over the right atrium (RA) and right ventricle (RV) with orthogonal pairs of sonomicrometers in six open-chest dogs. At a left ventricular end-diastolic pressure of 5 mm Hg, RV pericardial area paralleled RV volume, that is, shrinkage during ejection by 10 +/- 8% and expansion during filling. RA pericardial area was reciprocally related to RV pericardial area, with average expansion during ventricular ejection of 2 +/- 2%, thus paralleling RA volume during RV ejection. With volume loading, RV pericardial shrinkage during ejection increased to 14 +/- 6%, but the RA pericardial area change was no longer reciprocal (0 +/- 3% change during RV ejection). Elimination of contact forces by cardiac tamponade resulted in both marked attenuation of RV pericardial area changes and synchronization of the RV and RA pericardial area pattern; that is, both shrank during RV ejection. In two additional dogs, measurement of pericardial area over left ventricle and atrium showed similar results. We conclude that dynamic pericardial contact forces cause regional variation in pericardial deformation, which reflects volume changes of the underlying chambers. These findings imply that the influence of the pericardium on filling and ejection may be more complex than previously recognized, varying both by chamber and dynamically over the course of the cardiac cycle. ",13 1985,"The value of pulmonary artery and central venous monitoring in patients undergoing abdominal aortic reconstructive surgery: a comparative study of two selected, randomized groups. One hundred two patients undergoing abdominal aortic reconstructive surgery were prospectively, randomly allocated to two groups, one of which was monitored with a central venous catheter and the other with a pulmonary artery catheter. Patients with uncompensated cardiopulmonary or renal disease were excluded from the study. General anesthesia was administered for the surgical procedure, and the patients were followed through hospital discharge. No statistically significant differences occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequelae), mortality rate, duration of intensive care, postoperative hospital stay, or cost of hospitalization. The one statistically significant difference between groups was the professional fee charged for anesthetic care, which was higher for patients with pulmonary artery catheters than for those with central venous catheters. In conclusion, we prospectively gathered data from most patients presented for abdominal aortic reconstructive surgery. Our data seem to indicate that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic reconstructive surgery, and that for many patients pulmonary artery catheters are not necessary to give appropriate, adequate care. Because of the size of the sample, however, declarations of epidemiologic significance would be unfounded. Therefore large-scale, multicenter studies addressing such outcomes remain necessary. ",13 1480,"Peritoneal fluid fractions from patients with endometriosis do not promote two-cell mouse embryo growth. Peritoneal fluid (PF) from 10 infertile patients with endometriosis, obtained during the follicular phase of the cycle during laparoscopy, did not promote two-cell mouse embryo growth to the extent observed by fluid obtained from seven normal controls. Five molecular weight (MW) fractions were obtained by ultrafiltration, and each was used as media supplement in the assay and compared with PF fractions from normal controls. All fractions of PF from patients with endometriosis inhibited mouse embryo growth to a greater extent than did normal controls. However, the MW fractions greater than 100,000 daltons showed greater inhibition of embryo development than did fractions less than 100,000 daltons. This study of cell-free PF suggests the presence of a humoral factor greater than 100,000 daltons that is inhibitory on mouse embryo growth. ",12 1424,"Ionic strength affects diffusive permeability to an inorganic phosphate ion of negatively charged dialysis membranes. Electrolytes undergo electrostatic resistances in reaching membrane surfaces and passing through membrane pores when weakly charged dialysis membranes are used in hemodialysis treatments. Diffusive permeability to an electrolyte of weakly charged dialysis membranes depends upon the effective charge density of the membranes, which varies with ionic strength. The authors carried out dialysis experiments at a temperature of 310 K, with 32P-Na2HPO4 in aqueous NaCl and bovine serum, to obtain diffusive permeability to an inorganic phosphate ion of regenerated cellulose, and polymethylmethacrylate membranes of various fixed charge densities at varying ionic strengths ranging from 1.66 to 100 mol/m3. Diffusive permeability to an inorganic phosphate ion increased with ionic strength. Bovine serum, having an ionic strength of approximately 150 mol/m3, gave higher diffusive permeability to an inorganic phosphate ion. The internal structure of dialysis membranes, such as pore size, surface porosity, and tortuosity, also affects diffusive permeability. The electrolyte diffusion theory gives an effective charge density of -5.3 mol/m3 for the cellulosic membrane. In conclusion, ionic strength enhances diffusive permeability to an inorganic phosphate ion in both aqueous NaCl and bovine serum. Inorganic phosphate ion transport through negatively charged dialysis membranes depends upon the degree of dissociation of inorganic phosphate, the molecular size and valence of hydrated inorganic phosphate ion, the effective charge density and internal structure of the membrane, and ionic strength. ",11 1367,"Time-course of alterations of bladder function following acetone-induced cystitis. Although chemical cystitis is known clinically to cause decreased bladder function, there are few experimental studies on the progression of, and recovery from chemical cystitis. Mature male rabbits underwent intravesical instillation of 50% acetone solution through a urethral catheter. Micturition profiles showed a marked decrease of the mean and maximal micturition volume and an increase in number of micturitions as early as one day after treatment. The micturition profile gradually normalized between four and eight weeks after instillation. In vivo cystometry showed a very small bladder capacity and low compliance during the first week following instillation, and gradually recovered to control levels by four weeks. Functional studies using the in vitro whole bladder model showed a significant decrease in the ability of the bladder to generate pressure and to empty at three days after instillation. These parameters recovered partially by two weeks, and completely by four weeks. Chemical cystitis induced by intravesical acetone instillation resulted in a severe decrease in the bladder function, i.e. contracted bladder with low compliance and poor ability to generate pressure and empty. However, these changes were reversible within the two month period of study. ",11 481,"Generation of human monoclonal antibodies against colon cancer. Lymphocytes from regional lymph nodes of patients with colon cancer were fused with a human lymphoblastoid cell line with or without in vitro immunization. The efficacy of these two protocols for the generation of human monoclonal antibodies against colon cancer was investigated. The hyperplastic lymph nodes adjacent to the tumor were the best source of B lymphocytes. Fusion frequency and the number of tumor-reactive clones were markedly increased when the in vitro immunization protocol was applied prior to fusion. As a stimulant in in vitro immunization, the supernatant of pokeweed mitogen-stimulated T lymphocytes was superior to the supernatant of mixed lymphocytes culture. Carcinoembryonic antigen at 20 micrograms/L seemed to be the optimal dose for in vitro immunization. The reactivities of human monoclonal antibodies thus generated were measured by enzyme-linked immunosorbent assay and confirmed by immunoperoxidase staining. Combining in vitro immunization with lymphocytes of cancer patients may lead to the successful production of clinically useful human monoclonal antibodies. ",3 2104,"Left ventricular versus left atrial cannulation for the Thoratec ventricular assist device. In a retrospective study of 28 patients (23 men, 5 women) supported with ventricular assist devices greater than 3 days, the effect of LV cannulation versus LA cannulation on device performance was compared. Patients ranged in age from 12 to 67 years (mean 46 years) and were supported for 3-81 days (mean 15 years). Fifteen patients were supported with left VADs (6 LV and 9 LA), and 13 patients were supported with BVADs (5 LV and 8 LA). The mode of operation 91% of the time was the fill-to-empty mode. Ten data points were taken for each patient. LV cannulation results in higher VAD flow index at decreased preload, lower VAD systolic and vacuum pressures, and shorter diastolic durations. Eleven of the 28 patients survived. Although survival was greater in patients with LV cannulation, survival was more dependent upon reversibility of myocardial damage, eligibility for transplantation, or the development of complications. These data indicate that LV cannulation provides better VAD performance than LA cannulation in the fill-to-empty mode. ",13 2588,"Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry We have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against mast cell tryptase (AA1) and the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with beta 2-agonists alone and six normal subjects were studied. Over a period of 2 wk prior to bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, and twice-daily peak expiratory flow. Five days before bronchoscopy, methacholine responsiveness was assessed. Two biopsies were taken from the subcarinae, one of which was processed into araldite for immunostaining by the streptavidin biotin immunoperoxidase method and the other into Spurr resin for electron microscopy. The number of AA1 staining mast cells present in the bronchial mucosa was not significantly different in the epithelium or submucosa between the asthmatic and the normal subjects. However, in the biopsies from asthmatics, there were significantly greater numbers of EG2-staining eosinophils in the epithelium (median, 1.2/mm versus zero; p less than 0.005) and in the submucosa (median, 50/mm2 versus 1/mm2; p less than 0.001). Electron microscopy showed morphologic features of mast cell and eosinophil degranulation in the asthmatics. No correlation could be established between mast cell or eosinophil numbers and indices of disease activity of PC20 methacholine, which points to the complexity of mechanisms responsible for the symptoms and the airway hyperresponsiveness of asthma. ",19 3186,"Electrophysiologic effects of exogenous phosphocreatine in cardiac tissue: potential antiarrhythmic actions. The cellular electrophysiologic effects of exogenous phosphocreatine (PCr) were analyzed to ascertain its purported antiarrhythmic properties during myocardial ischemia and reperfusion. Transmembrane potentials were recorded from isolated guinea pig papillary muscles and Purkinje fibers studied in vitro. Under control, normoxic conditions, 10 mmol/L PCr significantly increased the action potential duration (measured at 90% of repolarization) in ventricular muscle by 14.6 +/- 3.3 msec and the effective refractory period by 11.5 +/- 3.8 msec (both p less than 0.01). Under ischemic-like conditions (hypoxia, lactic acidosis, elevated [K+]o, zero substrate) PCr had no effect. Phosphocreatinine, a related compound that is not a direct substrate in the creatine kinase reaction, acted similarly to PCr suggesting that alterations induced by PCr did not involve a change in the energy state of cells. However, PCr reduced free [Ca2+]o by nearly 20%, and its electrical effects under normoxic conditions could be largely reversed by a concomitant 20% increase in [Ca2+]o. In Purkinje fibers superfused with low [K+]o-Tyrode's solution to elicit conditions of Ca2+ overload, delayed afterdepolarizations and triggered responses were reversibly inhibited by PCr. These data suggest that the antiarrhythmic effects of PCr in situ may involve prolongation of the effective refractory period in nonischemic tissue or attenuation of membrane changes elicited by Ca2+ overload in ischemic cells. The mechanism by which PCr produces these effects may be related in part to changes in extracellular Ca2+ composition. ",22 2607,"Monitoring glucocorticoid therapy: a pharmacokinetic approach. Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6-hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens. ",19 1696,"Hemodynamic effects of diltiazem during vasoconstrictor pulmonary hypertension in sheep. Calcium channel blockers have been effective as pulmonary vasodilators in patients with pulmonary hypertension. The current study therefore compared the effects of prostaglandin E1, an effective pulmonary vasodilator, with the effects of the water-soluble calcium channel blocker diltiazem during pulmonary hypertension in sheep. Pulmonary hypertension was produced by continuous intravenous administration of U46619 to halothane-anesthetized sheep. Prostaglandin E1 decreased pulmonary artery pressure 29%, decreased pulmonary vascular resistance (Rp) 57%, and did not affect the ratio of pulmonary to systemic vascular resistance (Rp/Rs). Diltiazem decreased pulmonary artery pressure 15%, decreased Rp 50%, and did not affect Rp/Rs. When 0.33 mL/kg polyethylene glycol-ethanol vehicle (the vehicle used for nifedipine administration in a prior study) was administered during diltiazem infusion, pulmonary artery pressure increased 19%, Rp increased 72%, and Rp/Rs increased 29%. These results indicate that diltiazem is an effective pulmonary vasodilator and suggest that the previously reported unfavorable results of nifedipine may have been due to the vehicle used for nifedipine administration. ",13 1531,"Initiating a chorionic villus sampling program. Relying on placental location as the primary determinant of the sampling route. In initiating a chorionic villus sampling (CVS) protocol, we relied upon placental locations as the determinant in the choice of technique. An anterior or fundal location prompted a transabdominal (TA) CVS, while the transcervical (TC) approach was reserved for posterior placentas. A coaxial needle system was used for TA CVS (18-gauge, 15-cm guide needle and 20-gauge, 20-cm sampling needle), while TC CVS was accomplished with a 5.8-French, 27-cm polyethylene catheter. Between July 1988 and February 1989 our initial 118 procedures were performed for 115 consecutive pregnancies using this protocol. Testing indications and antenatal characteristics of the TA (n = 56) and TC (n = 63) groups were similar. One procedure failure occurred in the TC group, and a single aspiration was sufficient in 59% of the cases (TA, 30/55; TC, 39/63). In TC procedures an increased aggregate sample weight was observed as compared to TA cases (25.8 g vs. 16.9 g, respectively; P less than .001). This difference was not attributable to an increased number of placental aspirations in TC cases. One abnormal karyotype was observed (45X), and four pregnancy losses occurred (TC, 3; TA, 1). Using placental location to determine the choice of CVS technique appears to be feasible and may be associated with a lower failure rate during a facility's initial experience (when compared to reliance upon one technique alone). Trials comparing the safety of these two methods should consider placental location an independent variable before randomization. ",12 1366,"Determination of norepinephrine levels in the adult human prostate. Tissue levels of norepinephrine were measured in prostate tissue from 24 men ranging in age between 41 and 83 years. Prostatic tissue was obtained from men with subtle palpable prostate nodules undergoing transperineal needle biopsy. None of the patients were shown to have histologic evidence of adenocarcinoma. The severity of the symptoms of prostatism was evaluated prospectively using a standardized micturition symptom score questionnaire. Norepinephrine levels were quantified using a sensitive radioenzymatic assay (REA). Overall, the prostates contained relatively high levels of norepinephrine (1666 +/- 124 ng./gm.). Inverse correlations were observed between tissue norepinephrine levels and severity of symptoms of prostatism (r = -0.58; p = 0.003); age (r = -0.53; p = .008); and prostate size (r = -0.48; p = .02). Norepinephrine levels were also measured in tissue specimens obtained from men undergoing enucleation prostatectomy and transurethral resection of the prostate (TURP). The level of norepinephrine in these prostatectomy specimens (115 ng./gm.) was only 14% the level of the prostate biopsy specimens. The relatively low level of norepinephrine in the specimens obtained from patients with symptoms necessitating prostatectomy provides further evidence that norepinephrine levels are inversely related to the degree of symptomatic bladder outlet obstruction. ",11 248,"Oral contraceptives and breast cancer. Among women in general the risk of breast cancer through 59 years of age does not appear to be affected appreciably by the use of oral contraceptives. Nonetheless, concern continues to be expressed about the effects of early age at first use, long-term duration of use, formulation, and a variety of other factors thought to influence breast cancer risk in the presence of oral contraception. A number of recent studies restricted to young women suggest that long-term use may increase the risk of disease occurring very early, but the present lack of consistent findings in well-conducted epidemiologic studies prevents any certain conclusion with regard to cause-and-effect. However, if an increased risk were indeed present, the most plausible interpretation is that long-term oral contraception promotes earlier clinical manifestation of breast cancer in some women while having no net impact on their lifetime risk of the disease. ",3 2641,"Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. A panel of 20 human myelin basic protein (hMBP)-specific T-lymphocyte lines was generated from the peripheral blood of eight multiple sclerosis (MS) patients and two healthy donors, most of them expressing the HLA-DR2 haplotype, which is associated with an increased susceptibility to MS. Using HLA-DR gene-transfected mouse L-cell lines as antigen-presenting cells, we established that of the 20 hMBP-specific T-lymphocyte lines, 7 were restricted by the DR2a gene products of the DR2Dw2 haplotype. Four T-cell lines recognized hMBP in the context of the DR2b products of the DR2Dw2 haplotype. DR2b-restricted T-cell responses were demonstrable only in T-cell lines derived from MS patients. The hMBP epitopes presented by the DR2a heterodimer were mapped to peptides covering amino acid residues 1-44, 76-91, 131-145, or 139-153 and to a region spanning the thrombin-cleaved bond at Arg130-Ala131. DR2b-restricted T-cell lines recognized epitopes within amino acids 80-99 and 148-162. Peptide 139-153 was also presented in the context of HLA-DR1 molecules. Our data show that (i) in MS patients both the DR2a and DR2b products of the DR2Dw2 haplotype function as restriction elements for the myelin autoantigen hMBP, (ii) the DR2a molecule presents at least five different epitopes to hMBP-specific T lymphocytes, and (iii) anti-hMBP T-cell lines derived from individual donors can differ in their antigen fine specificity as well as in their HLA restriction. ",19 192,"Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases. Before surgery, 12 patients with suspected leiomyoma and 12 patients with suspected leiomyosarcoma were studied by endoscopic ultrasonography (EUS), computed tomography (CT), endoscopy, and barium swallow. The results were correlated with surgery and histology. Ten leiomyomas, one benign gastric ulcer, one carcinoid metastasis, eight leiomyosarcomas, two leiomyoblastomas, one mucus secreting adenocarcinoma, and one bronchial carcinoma were diagnosed. Eighteen additional patients suspected to have benign submucosal lesions by endoscopy and barium meal were treated non-surgically, and studied by EUS and CT. EUS was superior to other imaging techniques in the detection, staging, and follow-up of submucosal smooth muscle tumors because of clear imaging of the intramural abnormality and adjacent lymph nodes. ",3 2618,"Allergens as proteases: an Aspergillus fumigatus proteinase directly induces human epithelial cell detachment. Allergic bronchopulmonary aspergillosis (ABPA) is characterized by pulmonary and systemic allergic and inflammatory processes triggered by fungal antigens. Airway damage is a feature of this disorder, and although Aspergillus-derived proteinases have been described, the capacity of Aspergillus, however, to directly induce damage to human epithelium has not previously been studied. We therefore cultured Aspergillus fumigatus from two patients with ABPA, extracted mycelial products by sonication and filtration, and then evaluated their capacity to induce epithelial cell (EC) desquamation from basement membrane using an in vitro model that uses intact human amniotic EC and native basement membrane. A. fumigatus extracts induced detachment of EC in a dose-dependent fashion, producing up to 34% +/- 6% detachment (p less than 0.05 compared to medium alone). Enzyme analysis of A. Fumigatus extract using synthetic substrates revealed the presence of a number of different enzymes; therefore, studies with specific proteinase inhibitors were undertaken to identify the proteinase(s) responsible for detachment. A. Fumigatus-induced desquamation was partially inhibited by phenylmethylsulfonylfluoride and substantially inhibited by glutathione and N-acetylcysteine, but not by alpha 1-antitrypsin, 1,10 phenanthroline, ethylenediaminetetraacetic acid, aprotinin, or soybean trypsin inhibitor at concentrations that inhibit other serine- or metalloproteinases. Gel filtration of the extract with a Sepharose 6B column revealed that the major epithelium-detaching activity appeared in the 20 to 35 kd fraction. Comparison with proteinase standards suggested a role for a chymotrypsin-like proteinase. Thus, A. fumigatus releases a proteinase that is directly able to induce EC detachment. ",19 2826,"Replantation of the distal part of the leg. We successfully replanted five amputated legs in five patients and followed the patients for two years or more (average, six years and three months). Although some patients found it impossible to squat and to run because of joint contractures, muscle weakness, or deformities of the foot, all patients could perform other activities without difficulty. None had important pain or any intolerance to cold, and all were satisfied with the results of the replantation. ",20 2483,"Coupling of beta-cell desensitization by hyperglycemia to excessive stimulation and circulating insulin in glucose-infused rats. Nondiabetic rats were infused with glucose for 48 h to maintain moderate or marked hyperglycemia (mean blood glucose 13.2 +/- 0.7 or 22.8 +/- 0.3 mM, respectively). The two levels of hyperglycemia increased plasma insulin levels severalfold but decreased the insulin response to 27 mM glucose by 19 and 95%, respectively, versus saline infusion. Diazoxide (5 mg.kg-1.h-1), when continuously infused during the hyperglycemia protocols, completely inhibited the glucose-induced rise in plasma insulin levels. Diazoxide transformed beta-cell insensitivity to stimulation: glucose-induced insulin release was thus increased 318% after moderate hyperglycemia and 707% after marked hyperglycemia. These stimulatory effects of diazoxide were reversed by exogenous insulin infusion (8 or 2 U/24 h) in a dose-dependent manner. It is concluded that excessive beta-cell stimulation rather than glucotoxicity underlies hyperglycemia-induced beta-cell insensitivity. Effects of hyperinsulinemia can form part of the mechanisms whereby excessive stimulation affects beta-cell secretion. ",17 401,"Dioxin-inducible, Ah receptor-dependent transcription in vitro. We have developed a homologous in vitro transcription system that requires (i) 2,3,7,8-tetrachlorodibenzo-p-dioxin (called TCDD or dioxin), (ii) the Ah receptor, and (iii) a dioxin-responsive enhancer for activity. Unfractionated nuclear extracts from mouse hepatoma cells contain an inhibitor and fail to direct transcription in vitro. However, following phosphocellulose chromatography and reconstitution, the fractionated nuclear extract directs accurate transcription in vitro, using as a template the promoter/enhancer region from the mouse cytochrome P1-450 gene (Cyp1a1) linked to a ""G-free cassette"" (which generates a transcript with no guanosine residues). Extracts from TCDD-treated cells exhibit higher activity than extracts from untreated cells when transcribing a template containing both the promoter and enhancer but not when transcribing a template containing the promoter alone. Extracts from Ah receptor-defective cells fail to direct in vitro transcription in a TCDD-inducible fashion. A regulatory element that contains two binding sites for the liganded Ah receptor plus a truncated Cyp1a1 promoter suffices to direct TCDD-inducible, Ah receptor-dependent transcription in vitro. The inducible, receptor-dependent, enhancer-dependent properties of this system make it appropriate for analyzing in vitro the mechanism of dioxin action and the function of the Ah receptor. ",3 1425,"Rapid methods of estimating Kt/V: three formulas compared. Three rapid formulas for Kt/V were compared: 1) Kt/V-PRU = 0.04*PRU-1.2; 2) Kt/V-PRUopt = 0.026*PRU-0.46; and 3) KTV-LN = -In(R-0.03-UF/W). Accuracy was compared in a database of 339 3/week modeling sessions in 256 patients. The standard of comparison was Kt/V obtained by 3 point variable volume single pool modeling, using K values estimated from KoA, Qb, Qd, and UF rate. The most accurate formula was Kt/V-LN, which correlated with Kt/V to a high degree (0.994), and with a [%ERROR] of only 2.2 +/- 1.7 (SD). There was no correlation of %ERROR with the modeled Kt/V. The least accurate formula was Kt/V-PRU. Although the correlation of Kt/V-PRU with modeled Kt/V was high (0.962), the [%ERROR] was 12.0 +/- 11, and %ERROR correlated significantly with modeled Kt/V (0.68). The Kt/V-PRUopt showed a high correlation with modeled Kt/V (0.962), and a [%ERROR] of 5.0 +/- 3.8; the latter had a minimal correlation with modeled Kt/V (-0.168). The relative accuracies of the three formulae were: Kt/V-LN vs. Kt/V-PRU = 5.98, Kt/V-LN vs. Kt/V-PRUopt = 2.45. The results suggest that Kt/V-LN is a more accurate estimate of Kt/V than any formula based on PRU alone. ",11 2012,"Coarctation of the aorta and post-stenotic aneurysm formation. Despite earlier angiography, post-stenotic aneurysm of the aorta was an unexpected finding at operation in two patients with coarctation. One aneurysm was found in an intercostal artery in a 19 year old man and the other was a false aneurysm just distal to the coarctation site in a 7 year old boy. These aneurysms are fragile, apt to rupture, and difficult to diagnose preoperatively. Though local factors such as jet streams and bacterial endocarditis may influence their formation there must be an underlying generalised weakness in the arterial wall. A coarctation should not be regarded as an isolated arterial abnormality because it may be a feature of a more generalised disease. Because of the risk of rupture, which may not be prevented by antihypertensive treatment, operation should not be delayed in any age group. ",13 276,"Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients. Three radiation protocols currently used in treatment of leukemia patients before bone marrow transplantation (BMT) were investigated in a murine model (C57BL/6----C3H/HeJ) for BM allograft rejection. These include (a) a single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate of 0.2 Gy/min), (b) fractionated TBI (12 Gy administered in six fractions, 2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c) hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12 after BMT found in these groups were compared with results obtained in mice conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min, routinely used in this murine model. The results in both parameters showed a marked advantage for the single dose 8.5 Gy TBI over all the other treatments. This advantage was found to be equivalent to three- to fourfold increment in the BM inoculum when compared with hyperfractionated radiation, which afforded the least favorable conditions for development of donor-type chimerism. The fractionated radiation protocol was equivalent in its efficacy to results obtained in mice irradiated by single-dose 8 Gy TBI, both of which afforded a smaller but not significant advantage over the hyperfractionated protocol. This model was also used to test the effect of radiation dose rate on the development of donor-type chimerism. A significant enhancement was found after an increase in dose rate from 0.1 to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was increased to 1.3 Gy/min, but survival at this high dose rate was reduced. These results demonstrated indirectly that dose rate affects the expression of host-type pluripotent stem cells, the progeny of which appear 3 to 6 weeks after treatment with 8 Gy TBI delivered at a dose rate of 0.1 Gy/min, but which are eradicated if radiation is delivered at a dose rate of 1.3 Gy/min. ",3 725,"Circadian esophageal motor function in patients with gastroesophageal reflux disease. Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated. ",5 539,"Endoscopic and radiographic evaluation of the murine colon. Endoscopic and radiographic techniques have not been widely applicable in the evaluation of chemically induced murine colon cancer. The authors investigated methods of cleansing the rat colon and refined endoscopic and radiographic techniques. They compared total colonoscopy (TC) and air-contrast (ACBE) and single-contrast barium enema (SCBE) findings with those obtained at necropsy in rats with 1,2-dimethylhydrazine (DMH)-induced colon cancer. Gastrograffin enemas with bisacodyl suppositiories showed complete evacuation of solid feces. Sprague-Dawley rats treated with DMH had their colons cleansed and then underwent TC (5.0-mm Olympus bronchoscope) and either SCBE or ACBE. Colonoscopy and ACBE were equally sensitive (81.5% and 76.3%, respectively), although SCBE was significantly insensitive in identifying lesions (P less than 0.001). This study demonstrates that: (1) mechanical cleansing of the rat colon is feasible, (2) TC and barium radiology can be done routinely after mechanical cleansing, and (3) TC and double-contrast BE are sensitive in identifying colon lesions. These techniques will provide a means for manipulation of murine tumors and in vivo surveillance. ",3 80,"The national immunization program of The Netherlands. After a brief explanation of the immunization policy in the Netherlands, the national immunization program is described, with special attention given to coupling of the municipal population records with a computerized database of individual immunization records at the provincial level. The Dutch program achieves coverage rates greater than 90% for all routine immunizations. Participation in the program is free of charge to every child living in the country up to the age of 13 years, but there is no obligation or requirement to be immunized. Financing of the program is also discussed. ",0 1092,"A protocol for butalbital, aspirin and caffeine (BAC) detoxification in headache patients. The abuse of the combination drug containing butalbital 50 mg, aspirin 325 mg and caffeine 40 mg (or BAC), is commonly recognized by headache specialists as causing headaches. Despite this widespread problem, there is not a published treatment regimen for the BAC detoxification of patients. I describe such a protocol which was used four times in three patients. These patients fulfilled the diagnostic criteria of the IHS Headache Classification for headaches induced by chronic substance abuse (8.2) and analgesics abuse headache (8.2.2). These patients took between 150 and 420 BAC/month for 2-15 years. Two patients had previously undergone inpatient detoxification. One patient unsuccessfully tried detoxification twice as an outpatient. All patients were required to have psychological support prior to hospitalization for this protocol. BAC was discontinued. A pentobarbital challenge test corroborated butalbital dosage. The patients were given phenobarbital and caffeine which were tapered over several days. Dihydroergotamine (DHE) with metoclopramide was used (Raskin). Propranolol 60 mg bid was started. No narcotics were permitted. After hospital discharge, patients were allowed to continue subcutaneous DHE, as needed. One patient restarted BAC use after 8 months without it. The other two patients were still BAC free 18 and 14 months after detoxification. ",9 2342,"The temporomandibular joint in rheumatoid arthritis. Correlations between clinical and computed tomography features. Clinical and computed tomography (CT) examination of the temporomandibular joint (TMJ) was performed in 26 patients with rheumatoid arthritis (RA) and 26 control subjects. Each examination was scored. In the group with RA 61.2% had physical signs in the stomatognathic system compared to 42.3% in a control group (NS); 88.4% of the group with RA had erosive or cystic lesions of the TMJ compared to 57.6% of control subjects (p less than 0.05). The clinical dysfunction score did not correlate with the CT TMJ score in RA. It correlated with the number of slow acting antirheumatic drugs used, the rheumatoid factor titer and radiographic scores of the hands and cervical spine. In agreement with others, we believe that the only specific CT lesions of RA are erosions and cysts of the mandibular condyle, that there is no correlation between clinical and CT findings of TMJ in RA, and that the intensity of destructive lesions of TMJ on CT in RA is well correlated with the severity of the disease. ",16 1031,"The efficacy of oral steroids in the treatment of persistent otitis media with effusion. One hundred thirty-six children with otitis media with effusion of at least 2 months' duration were investigated in a strict, double-blind, randomized prospective study to evaluate the efficacy of oral steroids in the treatment of this disease. The results of our study showed a significant complete and partial recovery from otitis media with effusion in the group treated by a combination of antibiotics (amoxicillin) and oral steroids (prednisone), compared with an amoxicillin-treated group and a placebo-treated group. We believe that this treatment mostly benefits children aged 4 to 10 years without oversized adenoids. The findings of our study imply that a combined course of antibiotics and oral steroids deserves its place as a routine conservative trial before surgery. ",8 1533,"Intrapartum cocaine use. A case report. The use of cocaine during pregnancy appears to be reaching epidemic proportions. In the first reported case of intrapartum cocaine use, fetal heart rate abnormalities were detected. ",12 2101,"Light scattering detection of microemboli in an extracorporeal LVAD bovine model. Thromboembolization studies were performed on two calves supported by extracorporeal left ventricular assist devices (LVAD) using a light scattering (He Ne Laser) microemboli detector (LSMD). The LSMD system was placed on the outflow cannula of the LVAD in the extracorporeal loop of each animal. The measurements included the size, number, and rate of production of circulating microemboli in the range 20 microns less than microemboli diameter less than 1,000 microns. These data were compared to independently and concurrently obtained measurements of emboli shear rate (CPF), platelet count, red blood count (RBC), leukocyte count (WBC), plasma free hemoglobin, factors XIII, X, and V, and sorbitol dehydrogenase. Embolic number and volume were seen to be most dynamic in the very early phases of acute thromboembolization (0-40 minutes) with a peak embolic response within the first 30 minutes. The dynamics of reduced emboli volume, rather than number, may be implicated in the later stages of the thromboembolic passivation of these ventricles. The LSMD results generally showed an inverse correlation of microemboli volume rate with CPF measurements for each ventricle. LSMD, CPF, and leukocyte and platelet counts, showed a direct correlation with reduced counts for each additional ventricle for both calves. Factor XII was seen to have a more direct correlation in time with LSMD measurements for each ventricle than other parameters under investigation. This study represents the first time laser scattering and filtration methods have been applied simultaneously with hematologic assays in order to study the dynamics of device associated thrombogenesis. ",13 1483,"Serum HCG beta-core fragment is masked by associated macromolecules. To determine if beta-core fragment is present in serum from individuals with pregnancy and choriocarcinoma, samples were analyzed by gel filtration and fractions assessed by immunoassays (Mr = 15,000). In agreement with published reports, only minute amounts of beta-core fragment were detected (less than 0.1% of hCG level). A small amount of beta-core fragment activity was identified near the void volume of the column (Mr greater than 60,000). This high molecular weight material was pooled and dissociated with 3M ammonium thiocyanate, and gel filtration repeated. A much more significant beta-core fragment peak was then detected (Mr = 15,000). After dissociation, beta-core fragment was 18% (mol/mol) of the hCG level in early pregnancy serum, 91% in mid-pregnancy serum, 50% in term pregnancy serum, but only 1.3% in choriocarcinoma serum, pre-therapy. We conclude that the major form of beta-core fragment found in serum is associated with other macromolecules, which mask the beta-core fragment epitope to existing hCG beta antibodies. Measurements made on the dissociated beta-core fragment complex are much more in keeping with pregnancy levels found in urine. ",12 2326,"[125I]fibrin deposition occurs at both early and late intervals of IgE-dependent or contact sensitivity reactions elicited in mouse skin. Mast cell-dependent augmentation of fibrin deposition at early intervals in combined IgE-dependent and contact sensitivity reactions. When elicited in the skin of mice, either IgE-dependent immediate hypersensitivity reactions or T cell-dependent contact sensitivity (CS) reactions result in local extravasation of [125I]fibrinogen and deposition of [125I]fibrin. However, these two types of reaction differ in kinetics and in requirement for IgE, mast cells, or T cells. In the present study, we investigated the kinetics and magnitude of [125I]fibrin deposition in combined IgE-dependent and CS reactions elicited simultaneously at the same site and compared the results with those obtained when the two reactions were elicited at separate sites. We found that [125I]fibrin deposition in pure IgE-dependent reactions was greater at 2 or 6 h after challenge than at 24 h, but that significant fibrin deposition persisted at those sites 24 h after challenge. In CS reactions, [125I]fibrin deposition was detected as early as 2 h after challenge, indicating that fibrin deposition accompanies the ""early component"" of CS detected by Van Loveren et al. with the use of measurements of tissue swelling. But much more [125I]fibrin deposition was present in CS reactions at 24 h than at 2 or 6 h after Ag challenge. When IgE-dependent and CS reactions were elicited at the same site, [125I]fibrin deposition at early intervals (2 to 6 h) after challenge was increased three- to 25-fold compared with that seen in isolated CS reactions, but at 24 h the results in the combined reactions were virtually identical to those in CS responses. Studies in genetically mast cell-deficient and congenic normal mice indicated that mast cells were required for expression of the IgE-dependent augmentation of [125I]fibrin deposition observed at early intervals in combined IgE-dependent and CS reactions, but not for the [125I]fibrin deposition associated with ""pure"" CS reactions. These findings indicate that the net effect of IgE-dependent mast cell activation on CS responses is to increase the fibrin deposition associated with these responses, but this effect is appreciated only at early intervals after elicitation of the reaction. ",16 571,"Multimodal therapy in locally advanced breast carcinoma. Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease. ",3 3104,"Hemodialysis-associated febrile episodes: surveillance before and after major alteration in the water treatment system. Surveillance for bacteremic or pyrogenic episodes associated with hemodialysis was undertaken before and after the reconstruction of the water treatment system at our University medical center. The new water system included a holding tank with iodination treatment. The water delivered to individual dialysis stations had only occasional positive bacterial cultures (3 of 21 samples before completion of construction, 2 of 16 samples afterwards) and intermittent detection of endotoxin (6 of 21 samples before completion of construction, 9 of 16 samples afterwards) at monthly sampling. Among 51 individual dialysis treatments (25 patients) before reconstruction and 56 treatments (29 patients), after, only 2 and 3 febrile events were identified, respectively. All of these were associated with underlying infectious illness and not with the hemodialysis procedure itself. Overall, we conclude that pyrogenic episodes associated directly with hemodialysis treatment are infrequent, and that the addition of a water storage tank with iodination treatment does not appear to increase the risk of bacteremia or pyrogenic episodes. ",22 2533,"Effects of repetitive administration of corticotropin-releasing hormone combined with lysine vasopressin on plasma adrenocorticotropin and cortisol levels in secondary adrenocortical insufficiency. To examine the functioning of the hypothalamo-pituitary-adrenocortical axis in secondary adrenocortical insufficiency, we administered 100 micrograms synthetic human CRH, iv, plus 10 U lysine-8-vasopressin (LVP), im, three times daily for 3 consecutive days. The changes in plasma ACTH and cortisol levels during the administration and the response to an insulin tolerance test (ITT) conducted before and after the administration were determined. In three patients with isolated ACTH deficiency, basal plasma ACTH and cortisol levels were undetectablly low, and there was no response noted in the ITT or during CRH-LVP administration throughout the observation period. In four patients with adrenocortical insufficiency who had undergone successful transsphenoidal microadenomectomy for Cushing's disease and in six patients who had undergone curative unilateral adrenalectomy for Cushing's syndrome, basal plasma ACTH levels were low, but responded considerably to both stimulation tests. Along with the 3 days of CRH-LVP stimulation, however, neither the peak nor the time-integrated ACTH response was significantly enhanced, because of the variability of the responses among the patients. Compared with the ACTH response on the last day of CRH-LVP stimulation, the subsequent ITT tended to induce a lower ACTH response in the post-Cushing's disease patients and a higher response in the post-Cushing's syndrome patients. Regarding the plasma cortisol levels, the basal, peak, and integrated responses tended to increase daily during CRH-LVP administration. Conversely, the ITT after repetitive CRH-LVP administration induced a higher cortisol response than the test before CRH-LVP administration in the post-Cushing's disease patients. No serious complications were noted in any of the patients during or after the treatment. The present findings indicate that 1) repetitive administration of CRH in combination with LVP is a safe and valuable provocation test to examine the pituitary ACTH reserve and the integrity of the pituitary-adrenocortical axis; 2) isolated ACTH deficiency is usually due to a defect at the pituitary level; 3) with respect to adrenocortical responsiveness, post-Cushing's disease patients show a better accumulation of the provocative effect than do post-Cushing's syndrome patients; and 4) both hypothalamic and pituitary dysfunction are responsible for adrenal hypofunction in patients after hypercortisolemia, but post-Cushing's syndrome patients (especially those with a short period of hypercortisolemia) appeared to have less impairment of hypothalamic ACTH-releasing activity than post-Cushing's disease patients. ",18 2331,"Cyclosporin A in combination with photochemotherapy (PUVA) in the treatment of psoriasis. Forty patients with relapsing plaque psoriasis involving more than 20% body surface were treated either with cyclosporin A (CyA) plus PUVA or the retinoid etretinate plus PUVA (RePUVA). They initially received either CyA (2 weeks) or etretinate (1 week) alone and then PUVA was given concomitantly until complete remission. The patients were monitored over a period of 6 months and any relapse recorded. With each combined treatment regimen, CyA plus PUVA and RePUVA, the patients cleared within comparable periods of time (mean treatment period of 5.3 vs. 4.7 weeks after initiation of therapy and 3.3 vs. 3.7 weeks after initiation of PUVA). However, the cumulative UVA dose required for clearance (110.9 J/cm2 vs. 62.1 J/cm2 (P less than 0.05)) and the incidence of severe and early relapses were significantly higher in the CyA cohort. Within 6 months severe relapses had occurred in 58% of CyA plus PUVA but only in 15% of RePUVA-treated patients (P less than 0.001). This suggests that the CyA plus PUVA regimen as performed in this study is less effective than RePUVA. ",16 2517,"Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. Differential solute clearances were used to examine the effects of a 90-day course of enalapril on glomerular barrier function in 16 proteinuric patients with diabetic glomerulopathy. By day 90, plasma renin and prorenin became elevated, and arterial pressure declined. Transglomerular passage of dextrans of broad size distribution (radii 28-60 A) was lowered significantly. In a subset of 8 patients, withdrawal of enalapril was followed after an additional 30 days by a return of renin levels and arterial pressure to pretreatment levels. The dextran-sieving profile also returned to baseline, becoming uniformly elevated above treated day-90 levels. A theoretical analysis of the serial dextran-sieving profiles indicated that enalapril shifted glomerular pore size distribution to smaller size. These changes in barrier size selectivity were associated with a reduction in fractional albumin and IgG clearances during enalapril therapy and a subsequent rise in these quantities after its withdrawal; urinary protein excretion rate tended to vary in parallel. We conclude that inhibition of converting enzyme in humans with established diabetic glomerulopathy diminishes glomerular permeability to proteins by enhancing barrier size selectivity. Because neither enalapril therapy nor its withdrawal influenced the glomerular filtration or renal plasma flow rates significantly, we propose that the primary action of enalapril may be to modulate the intrinsic membrane properties of the glomerular barrier. ",18 534,"Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity. Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs. ",3 958,"Six-month isoniazid-rifampin treatment for pulmonary tuberculosis in children. One hundred and seventeen children with pulmonary tuberculosis underwent treatment with a 6-month daily regimen of rifampin (15 mg/kg/day) and isoniazid (10 mg/kg/day). The criteria for the diagnosis of pulmonary tuberculosis were (1) clinical symptoms and signs in 93 children (79%), (2) history of direct contact with an adult with tuberculosis in 106 children (91%), (3) tuberculin reaction of 5 mm or more, without previous bacillus Calmette-Guerin (BCG), in 45 children (38%), (4) suggestive radiologic alterations in all patients, and (5) positive bacteriology or histology in four patients (3%). The treatment was completed by 97 children (83%). The mean weight gain during therapy was 2,145 g. There was an excellent clinicoradiologic response to the treatment, and improvement in chest roentgenograms was observed in all patients at the end of therapy. No relapses occurred among the patients followed for an average of 21.4 months. This study indicates that the treatment of primary pulmonary tuberculosis in children with a combination of rifampin and isoniazid daily for 6 months is efficacious and does not result in any relapse. ",7 467,"Receptor imaging: application to MR imaging of liver cancer. A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors. ",3 100,"Calcitonin gene-related peptide levels are elevated in patients with sepsis. Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state. ",0 1445,"Screening for prostatic carcinoma. Routine testing for prostatic carcinoma by digital rectal examination, transrectal ultrasonography and prostate specific antigen determination has been proposed to reduce deaths by earlier diagnosis. The questionable reliability of results, cost of screening, and inability to establish a balance between the benefits of treatment and the adverse effects on the quality of life of the men screened make screening experimental until controlled studies prove its value. ",11 1271,"Epiphora: treatment by means of dacryocystoplasty with balloon dilation of the nasolacrimal drainage apparatus A new interventional radiologic procedure was developed for treatment of epiphora. A small-bore, soft-tipped guide wire was introduced through the superior canaliculus and guided under fluoroscopic control through the nasolacrimal drainage system for retrieval through the nasal aperture. A small-bore angioplasty catheter was then introduced in a retrograde direction into the nasolacrimal drainage apparatus and dilated under fluoroscopic control. The procedure was attempted in 18 eyes of 17 patients with moderate to severe epiphora and was technically completed in 16; 13 of these cases demonstrated improvement, with 11 patients showing complete resolution of symptoms. In the three patients whose epiphora did not improve, no worsening of symptoms occurred. These results are preliminary; follow-up ranged from 7 weeks to 6 months. The authors believe that this technique may hold promise in the treatment of epiphora and may obviate the use of more invasive procedures. ",10 1869,"Repair of transposition of the great arteries with intact ventricular septum and left ventricular outflow tract obstruction. Repair of transposition of the great arteries in patients with intact ventricular septum and fixed left ventricular outflow tract obstruction has been restricted to atrial baffle procedures, with or without attempts to relieve or bypass the left ventricular outflow obstruction. However, the suboptimal results of these procedures, coupled with excellent functional results with the arterial switch operation in patients without obstruction, has made anatomic correction the goal in repairing these anomalies. We report a technique for the anatomic correction of transposition of the great arteries, intact ventricular septum, and fixed left ventricular outflow tract obstruction. Its consideration in these difficult cases is advocated. ",13 1413,"Serum levels of sex hormone binding globulin and oestradiol in patients with testicular cancer. Serum testosterone (T), oestradiol (E-2) and sex hormone binding globulin (SHBG) were measured in 84 orchiectomised testicular cancer patients before further treatment and 4 to 6 and 12 to 15 months after therapy. Patients were divided into 3 groups according to treatment: Group 1: cisplatin-based chemotherapy (27 patients); Group 2: abdominal radiotherapy (32 patients); Group 3: no antiproliferative treatment (chemotherapy/radiotherapy) (25 patients). Between 4 and 6 months after antiproliferative treatment, particularly after chemotherapy, a reversible significant increase in E-2 and SHBG was observed. Patients without antiproliferative treatment showed no significant changes in their comparable hormone levels; 15% of all normal T values were associated with elevated levels of SHBG and E-2. Although the aetiology of these hormonal changes remains unknown, they may be related to the clinical symptoms of hypogonadism displayed by 10 to 30% of patients undergoing treatment for testicular cancer. ",11 315,"Performing screening flexible sigmoidoscopy using colonoscopes: experience in 500 subjects. There is still controversy regarding the optimal length of flexible sigmoidoscopes. We performed screening distal colon examinations using 168-cm colonoscopes in 500 asymptomatic subjects who were unsedated and had sigmoidoscopy cleansing preparation. The mean depth of penetration was 66 cm and was similar in persons in whom the examination was discontinued because of poor preparation versus those with discomfort. Polyps were detected in 87 patients, but only 5 subjects had polyps detected above 60 cm. We conclude that in a group of unsedated subjects scheduled for flexible sigmoidoscopy after a sigmoidoscopy prep, the use of instruments longer than 60 cm gives very little additional yield. ",3 852,"Surgical pocket reduction. It is not possible within the scope of this paper to describe in any detail each of the aforementioned procedures. These can be found in the various textbooks and journals on clinical periodontology. Instead, the objectives of treatment, the spectrum of techniques available, and the rationale for their use have been described. Periodontal surgery should be performed only under certain conditions: the patient must be physically and mentally competent to undergo any type of surgery, and should understand and agree to the procedure and to postoperative management. Finally, periodontal surgery should only be considered when nonsurgical therapy will not accomplish the desired result. When periodontal surgery for pocket elimination is performed for selected defects that have been properly evaluated after a debridement and healing period, and is executed with technical competence and proper postoperative care, it can preserve the dentition affected by periodontal disease. ",6 3213,"Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study. Opioid analgesia requirements, distribution into breast milk, and influence on neonatal neurobehavior were evaluated in ten parturient-neonate pairs nursing after elective cesarean section during epidural anesthesia. Five patients received first a loading dose of intravenous meperidine after umbilical cord clamping, then patient-controlled analgesia (PCA) with intravenous meperidine, and finally meperidine tablets as needed. Five patients received morphine in the same manner. Treatment groups showed no differences with respect to neonatal Apgar scores or visual analog scale (VAS) pain or satisfaction scores at 24 and 48 h postpartum. Breast milk specimens, obtained at 12, 24, 36, 48, 72, and 96 h postpartum and analyzed for opioids and metabolites, showed persistently elevated normeperidine concentrations in the meperidine group. A blinded psychologist evaluated each infant once on the 3rd day of life with the Brazelton Neonatal Behavioral Assessment Scale (NBAS). A priori, the ""alertness"" and three ""human orientation"" outcomes of the NBAS were chosen for analysis as best measures of opioid-induced effects. On all four outcomes, neonates in the morphine group scored significantly higher (P less than 0.05) than neonates in the meperidine group. We conclude that post-cesarean delivery PCA with morphine provides equivalent maternal analgesia and overall satisfaction as that provided by PCA with meperidine, but with significantly less neurobehavioral depression among breast-fed neonates on the 3rd day of life. ",22 1455,"Serum levels of anticardiolipin antibodies are pathologically increased after active immunization of patients with recurrent spontaneous abortion. Although the pathophysiological mechanisms leading to recurrent spontaneous abortion are still not fully understood, treatment schemes based on immunological principles have been advocated in recent years claiming that the production of the so-called blocking factor is being specifically stimulated. We investigated, retrospectively, whether active immunization can affect the production of immunoglobulin (Ig)G and IgM anticardiolipin antibodies. In a group of untreated recurrent spontaneous abortion patients (n = 9), the range of variation of cardiolipin antibodies, during consecutive controls taken at the same time interval as after immunization, was not statistically significant. In contrast to this, significant increases of both IgG and IgM antibodies occurred after active immunization with paternal leucocytes in 10 of 15, and in 6 of 15 cases, respectively. The mean basal and posttransfusion levels were: 7.26 +/- 2.53 and 30.15 +/- 23 U/mL for IgG and 2.26 +/- 1.2 and 6.82 +/- 5.6 U/mL for IgM, respectively. We conclude that active immunization with human lymphocytes leads to the production of antibodies against cardiolipin. This effect is exerted on both IgM and IgG antibodies. ",12 2942,"Living with artificial grass: a knowledge update. Part 2: Epidemiology. Part 2 of our study evaluated the effect of artificial grass on the athletes that play on it. In this section we have reviewed the epidemiological studies that have evaluated the influence that artificial grass has on the frequency and site of injury to American football players. From this review we have concluded that play and practice on an artificial surface is probably responsible for an increase in the relative risk of injury to the lower extremity of the participants. However, it is evident that more well controlled studies are necessary to completely clarify this issue. ",20 811,"Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome. We examined whether patients with irritable bowel syndrome have increased airway responsiveness by measuring forced expiratory volumes in 1 second (FEV1) after inhalation of increasing concentrations of methacholine. Responses obtained in 11 IBS patients were compared with those obtained in 11 normal subjects and in 11 subjects with organic disease of the gut or its related organs. All subjects were selected so that other factors that might contribute to increased airway responsiveness were excluded. The methacholine concentration that caused a 20% fall in the FEV1 (PC20), as well as the reduction in FEV1 induced by each methacholine concentration, were used to assess airway responsiveness. The geometric mean PC20 was 197.6 mg/mL (%SEM, 1.15) for normal subjects, 83.9 mg/mL (%SEM, 1.51) for subjects with organic bowel disease (P = 0.012), and only 12.8 mg/mL (%SEM, 1.74) for IBS patients (P less than 0.0001). The 22.5% +/- 2.5% decrease in FEV1 induced by 64 mg/mL of methacholine in IBS patients was significantly greater than that of 12.3% +/- 1.5% observed in healthy subjects (P = 0.003). In contrast, the 15.7% +/- 2.0% decrease in FEV1 observed in patients with organic disease was not different from that seen in normal subjects (P = 0.189). We conclude that IBS is associated with increased airway responsiveness following challenge with methacholine. ",5 563,"Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Endothelial leukocyte adhesion molecule-1 (ELAM-1) is an endothelial cell adhesion molecule that allows myeloid cells to attach to the walls of blood vessels adjacent to sites of inflammation. ELAM-1 recognizes the sialyl-Lewis X (sialyl-Lex) determinant, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, a granulocyte carbohydrate also found on the surface of some tumor cell lines. Binding of myeloid cells to soluble ELAM-1 is inhibited by a monoclonal antibody recognizing sialyl-Lex or by proteins bearing sialyl-Lex, some of which may participate in humoral regulation of myeloid cell adhesion. Stimulated granulocytes also release an inhibitor of ELAM-1 binding that can be selectively adsorbed by monoclonal antibody to sialyl-Lex. ",3 2957,"Tardive dyskinesia: managing a common neuroleptic side effect. Neuroleptics are useful medications for the treatment of psychosis and severe behavioral disturbances in the elderly. Unfortunately, older patients are at a high risk of developing deleterious side effects from these medications, especially persistent tardive dyskinesia (TD). Diagnosis, risk factors, and cause and treatment of TD are discussed. It is important to do a careful assessment as to the indications for neuroleptic use, monitor closely for the development of TD and other side effects, and work closely with the patient and family in making decisions about neuroleptic use. ",20 2390,"Overview of hemochromatosis. Hemochromatosis is an autosomal recessive genetic disorder that occurs with high prevalence in populations of European origin. The gene that is abnormal in hemochromatosis is found on the short arm of chromosome 6 in close proximity (approximately 1 centimorgan) to HLA-A, but the product coded for by that gene is unknown. The pathogenetic mechanism in hemochromatosis is that of continued, excessive absorption of dietary iron with loss of normal control mechanisms, leading to a gradual but vast expansion of storage iron as ferritin and especially as hemosiderin. Through mechanisms that probably include peroxidation of lipid membranes, the excess iron injures hepatocytes, islet B cells, gonadotropes in the anterior pituitary, myocardium, synovial cells, and chondrocytes, and probably other cells and tissues as well. Most patients with hemochromatosis remain undiagnosed throughout life. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis when begun early and will significantly improve survival in virtually all patients. It is important, therefore, that the diagnosis of hemochromatosis be considered much more frequently in clinical medicine in order that this effective therapy be utilized. ",17 45,"Restriction endonuclease analysis of total cellular DNA of Aspergillus fumigatus isolates of geographically and epidemiologically diverse origin. No typing system exists for Aspergillus fumigatus, though isolates are distinguishable by phenotypic characteristics. DNA was prepared by lysis of protoplasts, followed by deproteination, phenolchloroform extraction, and dialysis. DNA prepared was of uniform size and exceeded 60 kb. After digestion with SalI and XhoI endonucleases, DNA was electrophoresed, stained, and photographed. Differences in the mobilities of 10- to 50-kb bands distinguished isolates. Reproducibility was shown by repeated preparations and animal passage. By use of a proposed notation system for describing restriction fragment length polymorphism patterns, 31 epidemiologically characterized isolates from three continents revealed 24 patterns (DNA types). Three DNA types were represented by 3 isolates each and 1 DNA type by 2 isolates; 20 types were unique. Two groups of 3 isolates of the same DNA type were from Stanford University Hospital. One patient isolate from Stanford was the same DNA type as a sewage isolate from New Jersey. Another Stanford isolate was the same as a German isolate. These observations indicate widespread dispersal of some clones and restricted locales for others. Paired isolates from airway fluids of three patients had two DNA types in each. Restriction endonuclease typing shows promise for investigating the epidemiology and ecology of A. fumigatus. ",0 1288,"Recession of the superior oblique tendon in A-pattern strabismus. We performed 9 to 12 mm of recession of the superior oblique tendon for A-pattern strabismus in 10 patients. The average preoperative A-pattern measured 29.4 prism dioptres (PD), and the average pattern correction was 29.3 PD. All patients had a residual pattern of 6 PD or less (average 2.3 PD). No patient experienced significant underaction of the superior oblique, and other surgical complications, such as ptosis, Brown's syndrome, and laceration of the vortex vein or superior rectus, did not occur. The procedure corrected 14 to 40 PD of A-pattern. The amount of pattern corrected was correlated with the size of the preoperative A-pattern but not with the total amount of recession done. No significant shift in esodeviation in primary position was noted in the patients who underwent only superior oblique recession. The procedure appears to be of particular value in patients with moderate superior oblique overaction. The advantages of recession of the superior oblique tendon include the potential for reversibility and reoperation, low risk of induced superior oblique palsy, allowance for asymmetric surgery and potential for adjustable suture technique. ",10 501,"Parosteal osteosarcoma. Treatment by wide resection and prosthetic replacement. We have reviewed 20 cases of parosteal osteosarcoma treated by wide local resection and prosthetic replacement and followed up for six to 17 years. Limb function was excellent in 85%. One patient with grade III histological disease developed pulmonary metastases. Four patients had local recurrences, which were related to repeated preliminary biopsies, inappropriate siting of biopsy and vascular encroachment by the tumour. After this mode of treatment, the outcome was not related to medullary invasion by the tumour. ",3 138,"CD4+ monocyte counts in persons with HIV-1 infection: an early increase is followed by a progressive decline. In this study, we asked whether there is a difference in the number of CD4+ and CD4- peripheral blood monocytes as CD4+ T cells decrease during HIV-mediated immunodeficiency. Monocytes and T cells from 90 HIV-positive and 43 HIV-negative persons were analyzed by flow cytometry. The 90 HIV-positive patients represented the entire spectrum of CD4+ T-cell counts. We report that as CD4+ T cells decrease, the number of CD4+ monocytes decrease in parallel. Moreover, significantly higher CD4+ monocyte counts were observed in persons with early stage HIV disease, i.e., greater than 800 CD4+ T cells/mm3, than in HIV-negative persons with greater than 800 CD4+ T cells/mm3. Potential implications of these findings are discussed. ",1 1883,"Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial. The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers. ",13 2685,"Predicting the need for hospitalization in children with acute asthma. In an attempt to identify factors which influence the decision of physicians to admit patients with acute asthma to the hospital, we studied prospectively 200 children (age 5.6 +/- 3.1 years, mean +/- SD) presenting to our emergency room with acute asthma. The children were assessed on arrival, and on disposition from the Emergency Room by one of the investigators. After obtaining historic data, a clinical score was assigned, and oxygen saturation and pulmonary function were measured. Of the 134 (67 percent) children who were discharged home from the Emergency Room, five returned within seven days and one was subsequently admitted. The clinical score on disposition was the sole variable found to best predict the decision for hospitalization (sensitivity 73 percent, specificity 95 percent). Of the variables obtained at presentation, the resulting decision tree found the clinical score to predict the decision for hospitalization (sensitivity 79 percent, specificity 75 percent). When the individual components of the clinical score were analyzed, the degree of dyspnea, as assessed by the investigator, was chosen as the rule to predict the hospitalization decision (sensitivity 88 percent, specificity 71 percent). We conclude that the decision with respect to the need for hospitalization in acute childhood asthma, is in practice based mainly on careful clinical evaluation. Pulmonary function and SaO2 measurements, although helpful adjuncts in the assessment of acute asthma, do not appear to contribute to the identification of patients who need hospital admission. ",19 2583,"Effect of exercise on complement activity. Complement measurements of C1, C1q, C2, C3, C4, C5; the anaphylatoxins, C3a, C4a, and C5a; and total hemolytic activity of the classical and alternative pathways were made in 26 experienced adult runners before and after shortterm aerobic exercise. The baseline results were compared with those of nonexercising age-matched controls. In most subjects tested, running resulted in nanogram increases in C3a and C4a with corresponding decreases in the hemolytic activity of C4 (C4H). Baseline values of C3 and C4H were decreased significantly in runners when compared with nonexercising controls. Preliminary studies measuring the effect of exercise on C3a levels were also done in three asthmatic runners. Mean resting and postexercise levels, and exercise-induced increases in C3a anaphylatoxin in the asthmatic subjects were significantly higher than in the nonasthmatic subjects. The findings indicate that short-term exercise results in the activation of C3 and C4 and subsequent generation of C3a and C4a anaphylatoxins, and suggest that both activation of the classical pathway of complement and a selective downregulation of C3 production may occur in persons regularly engaged in aerobic exercise. The exaggerated generation of C3a by asthmatic subjects during exercise raises the possibility that anaphylatoxins play an etiologic role in exercise-induced asthma. ",19 2332,"Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil. Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth. ",16 2185,"Intrauterine growth retardation: diagnosis based on multiple parameters--a prospective study. A scoring system has previously been developed to diagnose intrauterine growth retardation (IUGR) based on three parameters: estimated fetal weight, amniotic fluid volume, and maternal blood pressure status. To test the IUGR score prospectively, the authors computed the score in 356 third-trimester fetuses, 39 growth retarded and 317 normal, scanned within 2 weeks prior to delivery. The IUGR score identified three groups, each with a distinct probability of IUGR: A score below 50 virtually excludes IUGR (3% probability), a score above 60 allows confident diagnosis (74% probability), and score of 50-60 is indeterminate (13% probability). The IUGR score performed best in patients with accurate dating by early ultrasound (US), but even among patients lacking accurate dating, the performance of the IUGR score was superior to that previously reported for any single sonographic parameter. The IUGR score can be used in any US facility to diagnose or exclude third-trimester IUGR. ",15 1868,"Glomerular hyperfiltration indicates early target organ damage in essential hypertension In 111 patients with essential hypertension (World Health Organization stage I or II), we examined the relationship between renal hemodynamics and left ventricular hypertrophy. Left ventricular structure was determined by two-dimensional guided M-mode echocardiography, renal blood flow by iodine I 131 aminohippuric acid clearance, and glomerular filtration rate by creatinine clearance. The glomerular filtration rate correlated with left ventricular mass (r = .52) and left ventricular cross-sectional area (r = .21). Conversely, at a similar age, body mass index, body surface area, and arterial pressure, hypertensive patients with left ventricular hypertrophy disclosed a higher glomerular filtration rate and filtration fraction than those without left ventricular hypertrophy, whereas renal blood flow and renal vascular resistance measurements were not significantly different. Thus, at similar levels of arterial pressure and renal blood flow, glomerular hyperfiltration was linked to early cardiac structural changes in essential hypertension. We conclude that, in a hypertensive patient with normal renal function, a high glomerular filtration rate may be an indicator for early target organ damage in essential hypertension. ",13 3294,"Recognising failure to thrive in early childhood. The maximum weight centile achieved by a child between 4 and 8 weeks of age was found to be a better predictor of the centile at 12 months than the birth weight centile. Children whose weight deviated two or more major centiles below this maximum weight centile for a month or more showed significant anthropometric differences during the second year of life from those who showed no such deviation. It is suggested that this leads to a logical and practical definition of failure to thrive. ",22 2183,"Colony-stimulating factors. Recombinant hematopoietic colony-stimulating factors have profound effects on developing and mature granulocytes, macrophages, and lymphocytes. Use of these agents for treatment of disease may result in a variety of adverse cutaneous reactions. The recent discovery of colony-stimulating factor production by keratinocytes and dermal cells suggests that these agents may also be significant in cutaneous homeostasis and in the pathogenesis of cutaneous diseases. ",14 1525,"Twin pregnancy after diagnosis and treatment of ectopic implantation by retrograde selective salpingography and intraluminal methotrexate injection. In this case report, a patient with a right tubal pregnancy was managed by a new procedure combining retrograde salpingography and local MTX injection. A twin pregnancy occurred shortly after treatment. We conclude that retrograde tubal cannulation may provide an alternative method for the diagnosis and treatment of selected EPs. ",12 2207,"The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). BACKGROUND AND METHODS. Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (delta F508) on chromosome 7 and compared the results with the clinical manifestations of the disease. RESULTS. The prevalence of the delta F508 allele in the cohort was 71 percent; 52 percent of the patients were homozygous for the mutation, 40 percent were heterozygous, and 8 percent had other, undefined mutations. The patients who were homozygous for the mutation had received a diagnosis of cystic fibrosis at an earlier age and had a greater frequency of pancreatic insufficiency; pancreatic insufficiency was present in 99 percent of the homozygous patients, but in 72 percent of the heterozygous patients and only 36 percent of the patients with other genotypes. The patients with pancreatic insufficiency in all three genotype groups had similar clinical characteristics, reflected by an early age at diagnosis, similar sweat chloride values at diagnosis, similar severity of pulmonary disease, and similar percentiles for weight. In contrast, the patients in the heterozygous-genotype and other-genotype groups who did not have pancreatic insufficiency were older and had milder disease. They had lower sweat chloride values at diagnosis, normal nutritional status, and better pulmonary function after adjustment for age. CONCLUSIONS. The variable clinical course in patients with cystic fibrosis can be attributed at least in part to specific genotypes at the locus of the cystic fibrosis gene. ",15 1207,"Infarction in the territory of the medial branch of the posterior inferior cerebellar artery. We report 10 cases of cerebellar infarction in the territory of the medial branch of the posterior inferior cerebellar artery (mPICA). Axial sections on MRI through the middle of the medulla and the cerebellum showed the infarction as a triangular area with a dorsal base and a ventral apex directed towards the fourth ventricle. The infarct also involved the lateral and dorsal medulla when the mPICA supplied all or part of these regions. Three clinical patterns were observed: 1) pseudolabyrinthine signs with or without dysmetria and ataxia when the medulla was spared; marked axial lateropulsion was present in most cases; 2) complete or incomplete Wallenberg's syndrome, when the medulla was involved; 3) silent infarction. These syndromes are precisely those previously attributed to PICA occlusion without distinction of the branch involved. No alteration of consciousness was recorded and spontaneous recovery was the rule. Cerebellar infarction in the distribution of the mPICA can be regarded as a benign condition with a good prognosis. ",9 1735,"Putative mechanism of blood pressure reduction induced by increases in dietary calcium intake. An increase in dietary calcium intake lowers blood pressure in spontaneously hypertensive rats and in some patients with arterial hypertension. The mechanisms by which this decrease come about are not clear. A membrane-stabilizing effect wrought by an increase in extracellular calcium would appear unlikely, since the increases in extracellular calcium concentration with increased dietary intake are minimal. Calcium regulatory hormones may be the mediators, and a cybernetic framework has been suggested. Striking defects have been reported in the calcium handling and hormonal household of the spontaneously hypertensive rat. However, a clear cut relationship in terms of a hormonal ""template"" has not yet been identified in prospective experiments. Data have been presented to show that increased calcium intake has a direct effect on regulatory areas in the brain. However, the mechanisms by which such a response would be mediated are entirely unknown. Increased calcium intake may induce natriuresis. It has been suggested that increased calcium intake helps the ""salt sensitive""; however, prospective studies to this effect have not been presented. Increased calcium intake may induce phosphaturia. However, the evidence that blood pressure lowering effects are mediated by phosphate depletion are unconvincing. Some evidence suggests that increased calcium intake may influence local regulatory processes which in turn influences cell integrity and growth. At this point, a unifying hypothesis is not available. However, the clues to various possibilities are intriguing. ",13 569,"Characteristics of duodenal wall gastrinomas. Fifteen patients with duodenal wall gastrinomas (DWGs) and the Zollinger-Ellison syndrome have been treated since 1960. In 6 of 11 patients, DWGs were recognized at operation and totally excised. In four patients, the tumor was subsequently found in the proximal duodenum of the surgical specimens. In 12 patients, DWGs were single and lymph node metastases were present in 8. In three patients, DWGs were multiple and lymph node metastases were present in two. All DWGs were submucosal and all were located in the first or second portions of the duodenum except one found in the fourth portion. Tumor size ranged from 1 to 15 mm, and nine were less than 5 mm. Of 12 patients with single DWGs, 9 have remained eugastrinemic after resection (mean follow-up: 5.5 years). None of the patients with multiple DWGs became eugastrinemic after surgery. DWGs are characteristically single, small or microscopic, submucosal, located in the proximal duodenum, rarely metastasize to the liver, and are usually curable by surgical resection. ",3 825,"Normal small bowel biopsy followed by coeliac disease. We report four patients (two children, one adolescent, and one adult) having normal small bowel mucosa shown on a biopsy specimen taken before the initial diagnosis of coeliac disease was made. The first biopsy was undertaken in two cases because of suspected malabsorption, in the third because of suspected dermatitis herpetiformis, and in the fourth as part of a coeliac disease family study. After a further 2.6 to 9 years on a diet containing gluten, small bowel villous atrophy with crypt hyperplasia compatible with coeliac disease was found on a second biopsy specimen. The HLA type of the patients was that typical for coeliac disease; all were DR3 positive. Within the families three other patients with coeliac disease have been diagnosed, two earlier and one at the time the first biopsy was undertaken. Four other HLA-DR3 positive haploidentical first degree relatives were found and had biopsies. All four had normal small bowel villous architecture, one had an increased intraepithelial cell count, and another was positive for reticulin and endomysium antibodies. Coeliac disease may exist latent in patients having normal mucosa when eating a normal diet containing gluten. ",5 2817,"The latissimus dorsi musculocutaneous flap for extremity reconstruction in orthopedic surgery. The latissimus dorsi was transferred as a pedicle flap in ten patients and as a free vascular flap in ten others for extremity reconstruction. Group I comprised ten patients in whom the transfer was used solely to cover a skin or soft-tissue defect. Although there was partial necrosis of the transferred skin in one patient, the remaining nine patients obtained complete coverage without further reconstructive surgery. Group II comprised five patients in whom transfer of the latissimus dorsi was performed for active flexion or extension of the elbow or for abduction of the shoulder. Postoperatively, muscle strength obtained was classified from Grades 0 to 5 according to the muscle testing method. Three patients obtained muscle strength of Grade 3, while two obtained Grade 2. Group III comprised five patients who had brachial plexus palsy after high-dose irradiation. Coverage of the skin and soft tissue was performed after neurolysis of the brachial plexus palsy to free the tissue bed of scarred tissue. Postoperatively, sensory and motor disturbances were alleviated in four of five patients. ",20 3147,"Effects of menstrual phase and amenorrhea on exercise performance in runners. There are few well controlled studies in terms of subject selection, menstrual classification, and exercise protocol that have examined both maximal and submaximal exercise responses during different phases of the menstrual cycle in eumenorrheic runners and compared these runners to amenorrheic runners. Thus, the purpose of this study was to measure selected physiological and metabolic responses to maximal and submaximal exercise during two phases of the menstrual cycle in eumenorrheic runners and amenorrheic runners. Eight eumenorrheic runners (29.0 +/- 4.2 yr) and eight amenorrheic runners (24.5 +/- 5.7 yr) matched for physical, gynecological, and training characteristics were studied. The eumenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run during both the early follicular (days 2-4) and midluteal (6-8 d from LH surge) phases. The amenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run. Cycle phases were documented by urinary luteinizing hormone and progesterone assays and by plasma estradiol and progesterone assays. No differences were observed in oxygen uptake, minute ventilation, heart rate, respiratory exchange ratio, rating of perceived exertion, time to fatigue (maximal), and plasma lactate (following the maximal and submaximal exercise tests) between the follicular and luteal phases in the eumenorrheic runners and the amenorrheic runners. We conclude that neither menstrual phase (follicular vs luteal) nor menstrual status (eumenorrheic vs amenorrheic) alters or limits exercise performance in female athletes. ",22 650,"Type XI collagen-degrading activity in human osteoarthritic cartilage. Homogenates of 6 samples of human osteoarthritic cartilage were shown to degrade exogenous type XI collagen. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the cleavage products generated by each homogenate were similar, and they were identical to those obtained by cleavage of the substrate with purified gelatinase. Enzyme activity, which was inhibited by EDTA, was greater in extracts of fibrillated osteoarthritic cartilage than in extracts of grossly normal cartilage from the same joint or in extracts of cartilage from joints with osteonecrosis. Activation with APMA enhanced digestion, but breakdown was apparent in extracts of fibrillated osteoarthritic cartilage even without APMA. Enzymatic degradation of type XI collagen could play a significant role in the turnover of articular cartilage in health and disease states. ",4 2375,"Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients. Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01). ",17 2537,"Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity. Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G----T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46,XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein approximately 5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo. ",18 971,"Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia. The effects of iv salbutamol on respiratory mechanics were studied in six infants with bronchopulmonary dysplasia. Salbutamol was infused at a dose of 30 micrograms/kg over 30 min in five infants; a sixth infant received 66.7 micrograms/kg over 4 min. Salbutamol caused improvement in total respiratory system compliance and in airflow resistance. There was no correlation between salbutamol serum concentration and pulmonary function. Elimination half-time appears to be dictated in these infants more by the distribution volume (Vd) than by clearance (Cl). The area under concentration-time curve of salbutamol correlated inversely to the change in heart rate (HR). There was a significant positive correlation between Vd and percent HR change. These data provide evidence that preterm infants have measurable activity of bronchiolar beta 2 receptor responsive to salbutamol. ",7 227,"Neonatal intracranial teratomas. Two neonates with intracranial teratomas presented with cranial enlargements a few weeks after birth. Both cases underwent surgery: one died intraoperatively; the other is the longest known survivor, alive 7 years and 9 months after subtotal excision of a mature teratoma of the left sylvian fissure. Previous operations have been relatively few and nearly all have been unsuccessful. Size and favorable location may be the most important prognostic features regardless of the histologic classification as mature or immature. One of our cases demonstrates that even subtotal excision of a mature teratoma can result in long-term survival. ",3 2028,"Insulin resistance and blood pressure in young black men. Insulin resistance, independent of obesity or non-insulin-dependent diabetes mellitus, has been demonstrated to be associated with high blood pressure. To determine if insulin resistance could be an antecedent to hypertension in a high-risk population, we studied normotensive (112 +/- 12/70 +/- 10 mm Hg) and borderline hypertensive (135 +/- 8/85 +/- 5 mm Hg) lean young black men (22-26 years old) with the euglycemic hyperinsulinemic clamp technique. All subjects had clinically normal oral glucose tolerance. Body mass index and percent adipose mass were the same in both groups. Fasting plasma insulin concentration was significantly higher in the borderline hypertensive group (p less than 0.01). Insulin-directed exogenous glucose metabolism at the same degree of steady-state hyperinsulinemia was significantly lower in the borderline hypertensive group (5.98 +/- 2.22 versus 8.22 +/- 1.96 mg/kg/min; p less than 0.01). For the total population, a significant inverse correlation existed between the glucose infusion rate and systolic blood pressure (p less than 0.01). These data indicate that there is a relation between insulin-mediated glucose uptake and blood pressure. Furthermore, in this high-risk population insulin resistance may precede the onset of established essential hypertension. ",13 2577,"Isolation of human immunodeficiency virus (HIV) at autopsy one to six days postmortem. Blood and tissue were studied for potential infectivity at autopsy of ten patients with human immunodeficiency virus (HIV) infection. Special attention was paid to the possibility of detecting HIV in bone at craniotomy. Postmortem intervals were one to six days. Specimens for HIV isolation included skull bone, brain, blood, bone marrow, spleen, and lymph node, and cerebrospinal fluid in one case. HIV grew in culture from at least one specimen from eight autopsies, one of which was performed six days postmortem. HIV was recovered from the blood of five patients and the tissue of five patients, including three with negative blood cultures. Skull bone contained HIV in two cases. HIV also grew from native spleen specimens stored for up to 14 days postmortem at 20 degrees C. Recommended precautions, including those for bone, are indicated at autopsy of HIV-infected patients even after long postmortem intervals. ",19 2714,"Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. We have used immunohistochemistry and monoclonal antibodies to analyze the phenotypic composition and activation status of the cellular infiltrate of bronchial biopsies obtained by fiber optic bronchoscopy of 11 atopic asthmatic subjects (FEV1% predicted range 78 to 114), 9 atopic nonasthmatic control subjects, and 10 normal healthy subjects. Examination of mucosal biopsies obtained from both central (level I) and subsegmental (level II) bronchi showed that the highest number of CD45-, DC3-, DC4-, and CD8-positive cells were found in the group with asthma. There was a significant increase in the number of interleukin-2 receptor (CD25)-positive cells (a marker of lymphocyte activation) at airway level I in the asthmatic group compared with both nonasthmatic atopic (p less than 0.05) and normal control subjects (p less than 0.01). Eosinophil numbers were significantly increased in asthma at both airway levels and at airway level II in the nonasthmatic atopic group when compared with normal healthy control subjects (p less than 0.05). EG2-positive cells (an index of secretion of eosinophil cationic protein following activation) were found at both airway levels in the asthmatic group and at level I in the nonasthmatic atopic control group (p less than 0.05). When asthmatic subjects were compared with normal healthy subjects, there was a reduction in the number of neutrophil elastase-positive cells in the asthmatic subjects which, as a percentage of leukocytes, was significant (p = 0.05). ",19 1405,"The prevalence of subfertility: a review of the current confusion and a report of two new studies. The difficulties inherent in measuring the prevalence of subfertility are discussed. Four subtypes of subfertility are defined, enabling comparisons to be made between the widely different approaches previously reported. A detailed assessment was made of the prevalence of subfertility in two different samples of British women aged 25 to 44 years, using interviews, postal questionnaires, and medical record searches. Data were collected on 872 women from a general practice and 702 hospital patients. The combined data showed that 24% of all women attempting to conceive experience an episode of subfertility at some stage in their reproductive life. Thirteen percent experience this in attempting to conceive their first child, and 17% when attempting to conceive a subsequent child. Three percent of women are involuntarily childless and 6% of parous women are not able to have as many children as they would wish. ",11 2557,"Soluble mediators of articular cartilage degradation in juvenile rheumatoid arthritis. Juvenile rheumatoid arthritis (JRA) involves a wide range of joint tissues. Tissue changes include proliferation of synovial cells, alterations in synovial fluid, and degradation of articular cartilage. Synovial cell proliferation results in increased numbers of fibroblasts and lymphocytes. Changes in the synovial fluid include increased content of antibodies, altered complement ratios, increased levels of factors stimulating cartilage-mediated proteoglycan degradation, and decreased levels of insulinlike growth factor I. Levels of cytokine such as interleukin-1 and interleukin-2 vary with cell culture and assay technique. Cartilage degradation is apparent from increased quantities of proteoglycan and glycosaminoglycan in serum and synovial fluid. Type II collagen peptide antibodies are also prevalent in JRA patients. Cartilage degradation appears linked to factors in JRA synovial fluid. Conditioned medium of peripheral blood mononuclear cells from patients with JRA also stimulates increased release of cartilage proteoglycan. Thus, the outcome in JRA likely reflects activities of interacting soluble factors that directly influence cartilage homeostasis. ",19 1594,"Changes in left ventricular diastolic performance after aortic balloon valvuloplasty: acute and late effects To evaluate acute and follow-up changes in left ventricular diastolic performance, simultaneous digital left ventriculography and micromanometry were performed in 49 patients undergoing aortic balloon valvuloplasty. All patients improved symptomatically after valvuloplasty, and 26 returned 6.3 +/- 1.5 months later for follow-up catheterization. Immediately after valvuloplasty, aortic valve area increased (before 0.5 +/- 0.2 versus after 0.8 +/- 0.2 cm2, p less than 0.01), cardiac output (before 4.3 +/- 1.2 versus after 4.4 +/- 1.3 liters/min) and ejection fraction (before 51 +/- 18% versus after 52 +/- 17%) did not change and diastolic indexes worsened, signified by a decrease in peak filling rate (before 247 +/- 80 versus after 226 +/- 78 ml/s, p less than 0.01) and increase in the time constant of isovolumetric relaxation (tau) (before 78 +/- 29 versus after 96 +/- 40 ms, p less than 0.01) and the modulus of chamber stiffness (before 0.107 +/- 0.071 versus after 0.141 +/- 0.083, p less than 0.01). At follow-up catheterization, 16 patients continued to have symptomatic improvement (group 1) and 10 had recurrence of symptoms (group 2). Aortic valve area, cardiac output and ejection fraction at follow-up catheterization in both groups were similar and unchanged from values before valvuloplasty. ",13 1974,"Left ventricular regional wall stress in dilated cardiomyopathy. Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM. ",13 686,"The effects of synthetic human secretin on calcium carbonate solubility in human bile This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for calcium carbonate precipitation. ",5 1022,"The nasolabial flap as a single-stage procedure. The nasolabial flap is a useful reconstructive technique for the repair of defects on the nose. An improved technique used in 32 patients is presented, which allows use of this procedure as a single-stage rather than the more commonly seen two-stage procedure. The alterations include the following: (1) the excision of a Burow's triangle superior edge of the defect toward the inner canthus; (2) the use of a periosteal or suspension suture to minimize tenting across the concave junction of the nose and cheek; (3) wide undermining of the skin surrounding the defect to create a stabilizing platelike scar; (4) significant thinning of the donor flap; and (5) adjust the size of the flap to recreate the original preincisional skin tension on the flap after suturing. None of the 32 patients presented required a second-stage procedure to correct trapdoor defects or to recreate natural folds or creases. ",8 719,"Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats. The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a ""chronic"" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis. ",5 2187,"The association of intrapartum asphyxia in the mature fetus with newborn behavior. A matched cohort study of mature newborns with biochemically determined intrapartum fetal asphyxia and mature newborns with normal blood gas and acid-base assessments at delivery were studied to demonstrate the effect of fetal asphyxia on newborn behavior as expressed by the Brazelton newborn behavioral assessment scale. The newborn behavioral assessment scale was administered 3 days after delivery and again 2 weeks after delivery. The Lester newborn behavioral assessment scale summary scores for the group with asphyxia were of the same order as those in the control group. This was also true of the group of newborns with asphyxia with the more severe metabolic acidosis and those with low Apgar scores. These findings support the contention that many newborns who have undergone an intrapartum asphyxial insult will not have evidence of central nervous system injury and that the threshold of central nervous system injury is at the severe end of the spectrum of asphyxia as expressed by a metabolic acidosis. ",15 600,"Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment. ",4 2011,"Diagnostic echocardiographic features of the sinus venosus defect. To establish the diagnostic criteria for a sinus venosus atrial septal defect cross sectional echocardiograms, cineangiograms, and surgical notes of all patients with this diagnosis seen at the Children's Hospital of Pittsburgh between 1986 and 1988 were reviewed. Seven patients were identified. In each the extent of the atrial septum and the nature of the junction of the superior vena cava with the atria were evaluated echocardiographically from the subcostal position. All had overriding of the superior vena cava and abnormally connected right pulmonary veins. Six patients had undergone cardiac catheterisation and cineangiography. Five patients underwent surgical repair. The operative findings were consistent with the expected morphology in all five, and these features were additionally confirmed in a specimen from the cardiopathological museum. Therefore, the basic anatomical feature of a superior sinus venosus interatrial communication is a biatrial connection of the superior vena cava. This, together with anomalous drainage of the right sided pulmonary veins, results in an interatrial communication outside the confines of the true atrial septum. Overriding of the superior vena cava across the upper rim of the oval fossa is suggested as the pathognomonic diagnostic feature that can clearly be demonstrated echocardiographically from the subcostal position. In essence the lesion is an interatrial communication rather than an atrial septal defect. ",13 3080,"Radionuclide imaging of asymptomatic versus symptomatic total knee arthroplasties. Ninety-eight total knee prostheses were evaluated by roentgenograms and bone scans. Fifty-three were asymptomatic, and 45 were symptomatic. Thirteen prostheses required revision surgery. At a mean of 54 months, asymptomatic knee replacements generally showed only mild uptake in one or more zones. Only one knee had uptake equal to surrounding bone. However, symptomatic knee replacements showed significantly greater uptake in the patella, femur, and medial and lateral tibial plateau regions (Mann-Whitney two-sample rank test). Bone scans in the symptomatic group were obtained at a mean of 44 months. Excluding those patients who had revision surgery, the differences remained significant. Furthermore, symptomatic knee replacements with normal roentgenograms also had significantly greater uptake. Radiolucent lines were noted in 30% of asymptomatic patients, whereas 29% of symptomatic knees had radiolucencies. Radiolucencies were not generally associated with significantly greater uptake. Lateral release had no effect on the patellar score. ",22 591,"The influence of joint line position on knee stability after condylar knee arthroplasty. Using a special knee-testing device, ten knees obtained at autopsy were subjected to varus-valgus, anterior-posterior, and flexion-rotation analysis in the intact state and after total knee arthroplasty. The ten knees showed no significant change in stability after knee replacement when the joint line was maintained in its natural position. When the femoral component was repositioned 5 mm proximally and 5 mm anteriorly, a significant increase in laxity occurred during midflexion. When the joint line was shifted 5 mm distal and 5 mm posterior to its anatomic location, significant tightening occurred in midrange of motion. Coupled rotation of the tibia with knee flexion was decreased after surgery in all knees with no specific relationship to joint line position. Coupled rotation with varus-valgus testing, however, remained within the normal range through the first 30 degrees of flexion only when the joint line was restored to its normal anatomic position. Stability in condylar knee arthroplasty is in part dependent on position of the joint line. Surgical techniques that rely on restoring the flexion and extension gap without regard to joint line position may result in alteration of varus-valgus or anterior-posterior displacement in midrange flexion. ",4 2908,"The lateral arm fascial free flap: its anatomy and use in reconstruction. Free fascial transfer has been used for reconstruction of gliding surfaces of the upper and lower extremities or when thin, pliable coverage is required (hand, heel, nose, and ear). In our experience with the lateral arm fasciocutaneous flap, we have found that the fascia alone is an excellent source of tissue for free flap transfer. A thorough investigation of the microscopic, gross, and radiographic anatomy of the lateral arm fascia was undertaken by the study of 25 fresh cadavers. Vascular pathways were mapped, their locations were analyzed, and then they were correlated with the elevation, design, and transfer of the flap. The lateral arm has a large fascial component located anterior and posterior to the lateral intermuscular septum, which itself lies between the triceps and the brachialis and brachioradialis muscles. It is perfused by the posterior radial collateral artery (PRCA), one of the terminal branches of the profunda brachii. This vessel (PRCA) provides at least four fascial branches from 1 to 15 cm proximal to the lateral epicondyle, the largest of which is located an average of 9.7 cm superior to the lateral epicondyle. Fascia up to 12 x 9 cm may be used with good axial perfusion. The histologic cross sections demonstrate the complex anatomy of the fascia itself, as well as its relation to the nutrient vessels. We have applied the lateral arm fascial flap in five cases of upper extremity reconstruction. We have also found this flap valuable in preservation of underlying anatomic detail for total reconstruction of the ear and nose when local tissue and more conventional flaps were not available. ",20 292,"Cholecystectomy and right colon cancer in Puerto Rico. A case-control study was undertaken to evaluate the possible relationship between cholecystectomy and right colon cancer. Two hundred patients with adenocarcinoma of the cecum or ascending colon (diagnosed between 1984 and 1989) were compared with 200 matched neighborhood controls. Cholecystectomy history was obtained through interviews using structured questionnaires and subsequently validated from hospital records. A statistically significant association (odds ratio = 2.14) was found between right colon cancer and a history of prior cholecystectomy. The altered bile metabolism which occurs after removal of the gallbladder may have a carcinogenic effect on the right colon. Dietary habits of the colon cancer patients in our study were consistent with prior reports in the literature, showing that this group has a lower intake of vegetables and cereal fiber than the control population. ",3 2068,"Central retinal vein obstruction and axial length. The axial lengths of 24 consecutive adult eyes with unilateral central retinal vein obstruction (CRVO) were compared with those of contralateral unaffected eyes and those of a control population. The lengths of the two eyes of persons with a unilateral CRVO were not significantly different. By contrast, eyes of persons with CRVO averaged 0.67 mm (approximately 2 diopters) shorter than their control counterparts (P = .03). This anatomic difference may be a factor in the development of CRVO. ",13 760,"Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches. To investigate the nature of the morphological changes that occur in ileal pouches, 26 biopsy specimens from patients with functioning ileo-anal pouches (eight with pouchitis) were studied. Normal ileum (n = 10) was used as a control. Mucosal morphometry (using linear measurements), crypt cell proliferation (CCP) (using the monoclonal antibody Ki67), and epithelial HLA-DR expression (monoclonal antibody CR3/43) were assessed. CCP (expressed as the percentage of Ki67 positive nuclei for each crypt) was significantly higher in pouches with pouchitis, compared with those without, and in pouches without pouchitis compared with normal ileum. CCP values in some pouches without pouchitis approached values found in those with pouchitis. CCP was related inversely to villous height and an index of villous atrophy (VH/TMT), and directly to crypt depth. In the presence of pouchitis there was intense epithelial HLA-DR expression that extended into the crypts. In some pouches with high CCP values, but without clinically important inflammation, surface epithelial HLA-DR expression was weak and patchy. It is concluded that villous atrophy and crypt hyperplasia in ileal pouches are associated with high CCP values. These may be increased even in the absence of active inflammation, and this increase may occur as a response to the new luminal environment. ",5 1843,"Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation. To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations. ",13 1204,"What practicing physicians in North Carolina rate as their most challenging geriatric medicine concerns. We recently surveyed a random sample of 500 physicians in family practice, general practice, and internal medicine in North Carolina, to discover their most challenging geriatric concerns. Using a three-stage survey technique, respondents were asked to answer two open-ended questions about the most challenging geriatric problems they face and what specific geriatric content areas would attract their participation in an educational program. They were then asked to rank 34 topics on which they would like more information. A total of 242 responses were received for a 55% response rate (63 of the 500 were undeliverable). Responses indicated that physicians are more concerned with management than diagnosis and revealed considerable evidence of empathy and concern. The top three topics had to do with the management of dementia, multiple problems, and depression. Approximately 25% of physicians consider problems of financing health care as among the most challenging problems. ",9 1808,"Single lung transplantation for primary pulmonary hypertension. Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension. ",13 2601,"HIV infection among Quebec women giving birth to live infants This is the first anonymous unlinked seroprevalence study in Canada to use serum samples from newborns to determine the seroprevalence rate of human immunodeficiency virus (HIV) infection among childbearing women. Of the 68,808 samples tested 42 were confirmed as positive, for an overall crude seroprevalence rate of 6.1 per 10,000 live births (95% confidence interval [CI] 4.4 to 8.3), or 1 woman in 1638. Women who lived on Montreal island had an overall rate of 17.9 per 10,000 live births (95% CI 12.2 to 25.4), or 1 woman in 559. We observed a significant association between revenue index and seroprevalence; the rates were as high as 46.4 per 10,000 live births (95% CI 18.7 to 95.3), or 1 woman in 216, for Montreal island postal code areas with revenue indexes 20% or more below the provincial median. Extrapolation of the data suggested that 56 women with HIV infection gave birth to a live infant during 1989 in Quebec. Even though attempts to generalize the data from childbearing women to women of childbearing age have an inherent conservative bias, the results of our study suggest that 988 women (95% CI 713 to 1336) aged 15 to 44 years in Quebec had HIV infection in 1989. The actual number is likely substantially higher. The need for well-designed, creative interventions to prevent further HIV transmission to women is evident. Planning for the provision of medical and psychosocial services sensitive to specific needs of women who are already infected should start immediately. ",19 1357,"Stress incontinence and low urethral closure pressure. Correlation of preoperative urethral hypermobility with successful suburethral sling procedures. Forty-eight women with genuine stress incontinence and low urethral closure pressure were treated with a suburethral sling procedure using polytetrafluoroethylene. All patients underwent a preoperative clinical evaluation and multichannel urodynamic testing. The clinical examination included a ""Q-tip"" test to determine the presence or absence of urethral hypermobility. Urethral hypermobility was defined as a maximal angle change of greater than or equal to 30 degrees from the horizontal, measured during straining or coughing in the lithotomy position. Thirty-four patients underwent repeat multichannel urodynamic testing three months postoperatively to determine the objective surgical success. Ninety-three percent of patients (27/29) with a positive preoperative Q-tip test were cured. Of patients with a negative preoperative Q-tip test, only 20% (1/5) were cured. Preoperative urethral hypermobility was a good prognostic indicator of operative success when a suburethral sling procedure was used to treat genuine stress incontinence and low urethral closure pressure. ",11 2971,"Synergism between hepatic injuries and a nonhepatotropic reovirus in mice. Enhanced hepatic infection and death. Reovirus type 1, after intravenous inoculation in the adult mouse, is secreted via bile into the intestine in an infectious form. Although reovirus type 1 is rapidly removed from systemic circulation by the liver and the lung, very few hepatocytes express reovirus antigen during infection. In intestinal cells, reovirus replicates selectively in the crypts. This site preference may be due to active cell proliferation in the crypts. We hypothesized that the state of the cell may affect virus replication and tested this hypothesis by using chemical and surgical means to increase hepatic mitotic activity. Adult mice were treated with carbon tetrachloride or surgical trauma, inoculated with reovirus type 1 intravenously, and subsequently killed. Virus antigen was identified using a highly specific immunohistochemical technique. Liver sections were stained using immunoperoxidase with specific rabbit antireovirus antibody. Hepatotoxin and surgical trauma increase reovirus antigen detection in both Kupffer cells and hepatocytes. Only the sequential administration of CCl4 and virus caused mortality at doses sublethal for each alone. These data demonstrate a synergism between hepatic injury and reovirus which results in a significant increase in the magnitude of viral infection and contributes to mortality. Such synergism may be important in idiopathic liver disease. ",21 1741,"Possible mechanisms of abnormal norepinephrine sensitivity and reactivity of resistance vessels and the development of hypertension in spontaneously hypertensive rats. A hypothesis. This study examined structural and functional changes of mesenteric resistance vessels in early, developing, and established stages of hypertension development in spontaneously hypertensive rats in an attempt to identify possible mechanisms of the development and maintenance of hypertension. Our results suggest that the development of hypertension in spontaneously hypertensive rats may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by hyperreactivity to norepinephrine through an altered signal transduction process, including the regulation of protein kinase C in smooth muscle cells of resistance vessels in spontaneously hypertensive rats. ",13 1104,"Unusual blink reflex with four components in a patient with periodic ataxia. Characteristic findings in blink reflex are reported in a 55-year-old female with periodic ataxia. The blink reflexes on the side ipsilateral to the stimulation consisted of four components with latencies of 11, 21, 35 and 47 ms, instead of the usual two components seen in normal subjects. On the contralateral side, the last three components were also present. The second component was different from the normal R2 response in that its latency was shorter than normal and it did not habituate by stimulation at a rate of 10 Hz. In addition, it was more affected by diazepam than the third or fourth components. It is considered that R2 may have consisted of three components and that a shorter latency of the second component could be explained by facilitation. ",9 204,"Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis. ",3 2195,"Fontan operation in 176 patients with tricuspid atresia. Results and a proposed new index for patient selection. Between 1973 and March 1989, 176 patients with tricuspid atresia had the Fontan procedure performed at the Mayo Clinic. Age range at the time of surgery was 7 months to 42 years, with 43 patients (24%) 16 years old or older. Hospital mortality rates were 17% (nine of 54) from 1973 through 1980 and 8% (10 of 122) from 1981 through 1989. There have been 10 late cardiovascular deaths. Postoperative follow-up of 139 survivors (range, 6 months to 14 years; mean, 5.5 years) revealed 91% to be in excellent or good condition and 9% to be in fair or poor condition. Patients in fair or poor condition had poor stamina and/or fluid retention with intermittent pleural effusion, ascites, and so on. Two factors that clearly influence operative and late results are preoperative pulmonary arteriolar resistance (Rpa) and left ventricular diastolic function. A preoperative catheterization index devised by adding Rpa to left ventricular end-diastolic pressure divided by QpI plus QsI may be helpful in selecting candidates most likely to survive and benefit from the Fontan operation. In our experience, if this index is less than 4.0, then the postoperative right atrial mean pressure will be 20 mm Hg or less, a circumstance associated with 95% early and 89% overall survival rates. ",15 2944,"Injury patterns in Scottish heavy athletics. As interest and participation in the athletics of Scottish-American Highland games has increased throughout the United States, the aim of this study was to define injury patterns and risk factors. Field events of modern track and field evolved in part from the seven events of the ""heavy athletics."" A retrospective and prospective study of 170 athletes with at least 3 years of experience was carried out over 10 years. There were 729 injuries, 60% of which involved the upper extremities and back. The incidence of injury was 42.9%; there was an injury exposure rate of 0.3 per 40 hours of competition or training. With appropriate instruction, a consistent weight program, and exercise, few injuries were serious. ",20 2645,"New antiretroviral agents in the clinic. Since the first controlled clinical trial of zidovudine (ACT) was terminated in the fall of 1986, much has been learned concerning the use of this agent in the treatment of human immunodeficiency virus (HIV) infection. The recent report of HIV resistance associated with long-term AZT therapy has accelerated the sense of urgency about the development of additional agents for use--either alone or in combination with AZT--against this infection. Several new agents are in various stages of preclinical or clinical evaluation. Some, such as dideoxycytidine, dideoxyinosine, dideoxydidehydrothymidine, azidouridine, and foscarnet, inhibit viral DNA synthesis through inhibition of reverse transcriptase. Other potentially useful agents presumably act at different stages of infection. Soluble CD4, for example, is a soluble form of the receptor to which HIV must bind to infect cells, and castanospermine represents a new class of compounds that block the maturation process of the viral glycoprotein. An apparently more potent and less toxic analogue of the latter agent, N-butyl-deoxynojirimycin, is currently in phase I testing. ",19 1168,"Cerebrospinal fluid as a reflector of central cholinergic and amino acid neurotransmitter activity in cerebellar ataxia. Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients. ",9 60,"Early postoperative care of the cardiac transplantation patient: routine considerations and immunosuppressive therapy. The authors have attempted to outline the current state of the art with respect to the early postoperative management of the cardiac transplant recipient with special attention to immunosuppressive therapies. The commonly used agents, as well as the most successful combination regimens, have been described along with the current levels of expectation regarding rates of rejection and infection. Much has been learned regarding the management of these problems. Much remains to be learned to further decrease the incidence of postoperative infection and rejection and, equally if not more importantly, studies to investigate the etiology of transplant coronary artery disease need to be undertaken such that measures to delay or prevent its occurrence and/or arrest its progression can be instituted. ",0 1348,"A reverse (antibody capture) enzyme-linked immunosorbent assay for detection of antisperm antibodies in sera and genital tract secretions. A reverse (antibody capture) enzyme-linked immunosorbent assay (ELISA) for detection of antisperm antibodies has been developed. The assay enables detection of immunoglobulin (Ig) M, IgG, IgA, or IgM, IgG, and IgA--antisperm antibodies in serum, cervical mucus, and seminal plasma samples. The reverse ELISA is more specific and sensitive than conventional ELISA in detecting human antisperm antibodies of different isotypes. Using this assay, statistically significant differences in levels of antibodies between infertile and fertile individuals were demonstrated in sera and in genital tract secretions. Studies with 143 infertile couples revealed that the presence of antibodies in sera was not necessarily reflected in individual's genital tract secretion and vice versa. These data emphasize the importance of detecting antisperm antibodies in sera as well as in genital tract secretions for correct evaluation of sperm immunity. ",11 2349,"Impact of glucose self-monitoring on non-insulin-treated patients with type II diabetes mellitus. Randomized controlled trial comparing blood and urine testing. The goal of this study was to compare the relative efficacy and cost of self-monitoring of blood glucose (SMBG) with routine urine testing in the management of patients with type II (non-insulin-dependent) diabetes mellitus not treated with insulin. Fifty-four patients with type II diabetes mellitus, not treated with insulin, who had inadequate glucose control on diet alone or diet and oral hypoglycemic agents were studied. Patients performed SMBG or urine glucose testing as part of a standardized treatment program that also included diet and exercise counseling. During the 6-mo study, both the urine-testing and SMBG groups showed similar improvement in glycemic control; within each group, there were significant improvements in fasting plasma glucose (reduction of 1.4 +/- 3.2 mM, P less than 0.03) and glycosylated hemoglobin (reduction of 2.0 +/- 3.4%, P less than 0.01) levels. Seventeen (31%) of 54 patients actually normalized their glycosylated hemoglobin values, 9 in the urine-testing group and 8 in the SMBG group. Comparisons between the urine-testing and SMBG groups showed no significant differences in mean fasting plasma glucose (P greater than 0.86), glycosylated hemoglobin (P greater than 0.95), or weight (P greater than 0.19). In patients with type II diabetes mellitus not treated with insulin, SMBG is no more effective, but is 8-12 times more expensive, than urine testing in facilitating improved glycemic control. Our results do not support widespread use of SMBG in diabetic patients not treated with insulin. ",17 688,"Pemoline-associated hepatic injury. Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic. ",5 2992,"The effect of prolonged hypothermia on cardiac function in a young patient with accidental hypothermia. A 20-year-old man had accidental, prolonged, and severe hypothermia. Serial radionuclide ventriculography disclosed reduced myocardial contractility during hypothermia that resolved after warming. The effects of hypothermia on cardiac function are discussed. ",22 1278,"Hydrogen peroxide localization in experimental optic neuritis. The association of reactive oxygen species to altered permeability of the blood-brain barrier in acute experimental encephalomyelitis was investigated by ultrastructural cytochemical localization of hydrogen peroxide (H2O2) to sites in the optic nerve previously identified by extravasation of intravascular horseradish peroxidase. Using a modified cerium method, we found electron-dense cerium-derived H2O2 reaction product was localized to the perivascular space at the lamina retinalis, lamina choroidalis, and lamina scleralis. In the optic nerve head, electron-dense reaction product was observed in the presence of intravascular leukocytes, although adjacent perivascular and interstitial inflammatory cells at this site were scant. In the myelinated retrobulbar optic nerve, cerium-derived H2O2 reaction product was seen in the intravascular space of blood vessels and surrounding perivascular and interstitial foci of inflammatory cells. Reaction product was also observed in the extracellular space adjacent to the plasmalemma of axons and glial cells in the optic nerve head and retrobulbar nerve. The perivascular and intravascular distribution of cerium-derived reaction product suggests that H2O2 may play a role in the pathogenesis of altered vascular permeability in experimental optic neuritis and supports our previous observations of suppression of blood-brain barrier permeability by detoxification of H2O2 with the exogenous administration of antioxidant enzymes. ",10 1282,"Topical use of cyclosporine in the treatment of vernal keratoconjunctivitis. We treated 11 patients with vernal keratoconjunctivitis for four to nine months with topical cyclosporine as a 2% dilution in castor oil. No significant side effects occurred, except for mild and transient burning upon administration. Within the first 15 days, both symptoms and signs of the condition improved significantly, and these results were maintained throughout the entire treatment. Relapses of the disease occurred two to four months after the end of the therapy. A double-masked clinical trial of nine patients (2% cyclosporine in castor oil vs castor oil alone) confirmed the results. Treated eyes improved significantly for both signs and symptoms as compared to control eyes. Topical cyclosporine may, therefore, be considered an effective substitute for corticosteroids, with an excellent anti-inflammatory activity in patients with both corticosteroid-dependent and corticosteroid-resistant vernal keratoconjunctivitis. ",10 1871,"Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion. This study tests the hypothesis that total vented bypass can attenuate the regional ischemic effect during a defined time interval before controlled blood cardioplegic reperfusion. Thirty-three dogs underwent 2 or 4 hours of occlusion of the left anterior descending coronary artery and then received a regional blood cardioplegic reperfusate on total vented bypass. Cardiopulmonary bypass and reperfusion were started after 2 hours of ischemia in eight dogs, and after 4 hours of ischemia in 25 others. Among the 25 dogs, seven had total vented bypass started after the first 2 hours of the 4 hours of regional ischemia. Segmental shortening (ultrasonic crystals), tissue water content (wet/dry weight), and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours after reperfusion. Dogs reperfused after 2 hours of ischemia recovered 73% +/- 8% of control systolic shortening and sustained only 11% triphenyltetrazolium chloride nonstaining. Dogs undergoing 4 hours of regional ischemia, but with total vented bypass 2 hours before reperfusion had improved recovery of systolic shortening (49% versus 31%, p less than 0.05), limited epicardial edema (79.6% versus 81.1% water content, p less than 0.05), and reduced histochemical damage (24% versus 39% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings imply that institution of total vented bypass during ischemia attenuates the infarct process, increases regional recovery of contractility, limits edema and restricts histochemical damage, and may be a useful adjunct to myocardial salvage when controlled reperfusion can be provided. ",13 3136,"Disability from bicycle-related injuries in children. Bicycle crashes are a major cause of injuries in childhood. The goal of this study was to determine the long-term disabilities caused by bicycle-related injuries, and to clarify the long-term treatment priorities of injured children. Hospital records of 372 children (ages 2-15 yr, median 9 yr; 232 boys and 140 girls) admitted with bicycle-related injuries from 1979 through 1986 provided clinical information, social service visits, in-hospital and outpatient rehabilitative interventions, and physical status at discharge. More complete evaluations were made by contacting parents by telephone (82 children), and by personal interview and physical examinations (27). Head injuries predominated (69.1%). Twelve (3.2%) died, all from major head injuries. Four suffered permanent severe impairment from cervical spinal injuries and head injuries and remain institutionalized (1.4%). One third had a persistent disability noted at the time of discharge in the medical record (33.6%), reported by telephone interview (31.7%), or confirmed by physical examination (37.0%). Still, only 11.0% received physical therapy consultations during hospitalization, and 22.8% received social service assistance. Only 39.0% were seen by a surgeon or pediatrician after discharge, and few (7.3%) received outpatient physical therapy. Cognitive or behavior changes were noted in 31.7%, many noting changes in school performance (worse in 20.7%), behavior (13.4%), and sleep, particularly nightmares (34.1%). Recurrent injuries occurred in 52 children (14.4%), of whom ten (2.8%) required further hospital admission. Bicycle-related injuries cause significant short- and long-term disabilities among children. ",22 1818,"Pressor systems in hypertension and congestive heart failure. Role of vasopressin [clinical conference] Elevated peripheral vascular resistance, which characterizes hypertension and congestive heart failure (the latter regardless of absolute blood pressure level) is maintained to a large extent by the combined effects of three major neurohormonal pressor mechanisms: the renin-angiotensin system, the sympathoadrenal system, and arginine vasopressin. Blockade of one of these mechanisms may lead to compensatory stimulation of the others, thus offsetting in part the hemodynamic benefits of a specific intervention. Combination therapy, designed to attack all three systems (with use of an angiotensin converting enzyme inhibitor, a sympathetic blocker such as clonidine, and an antagonist of the vasopressor action of vasopressin), may help in the treatment of such cases. To illustrate this strategy, two experimental studies, one case of malignant hypertension, and one case of congestive heart failure are presented. ",13 468,"Invasive papillary carcinoma of the breast: mammographic appearance. The mammographic findings in 18 patients with invasive papillary carcinoma were studied retrospectively. The mammograms of 10 patients showed a multinodular pattern, and seven patients had solitary nodules. One patient had an irregular, ill-defined mass in the retroareolar region. Two patients were found to have carcinoma in the contralateral breast, and two patients had intraductal carcinoma adjacent to the invasive papillary carcinoma. The varied mammographic features that may occur with this rare breast malignancy are discussed. ",3 1143,"Effects of MK-801 on recovery from sensorimotor cortex lesions. Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage. ",9 1446,"Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis. The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats by examining the histological findings and cell proliferative activity. The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in-vitro labeling technique. After eight weeks of treatment with drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed at the end of week 16, and the resected bladder was sutured with dexon or silk. There was no difference in the incidence of papillary or nodular (PN) hyperplasia between the control and partial cystectomy groups. However, the incidence of cancer in the group given partial cystectomy was much higher than that in the control. All the cancers in the control group were grade-1 superficial tumors, whereas grade-2 or invasive tumor was observed in six of 40 animals in the partial cystectomy group. The 31.0% labeling index of cancer in the partial cystectomy group was greater than the 24.1% in the control group. There was also a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia between the control and partial cystectomy groups. These findings indicate that partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase in DNA synthesis found in PN hyperplasia and cancer may be associated with the induction of bladder tumors. ",11 1122,"Limited selective posterior rhizotomy for the treatment of spasticity secondary to infantile cerebral palsy: a preliminary report. A limited selective posterior rhizotomy was performed on 30 children suffering from spasticity secondary to infantile cerebral palsy. As opposed to standard techniques that stimulate and divide the dorsal rootlets from L2 to S1, we dissected L4, L5, and S1 dorsal roots through an L5 to S1 laminectomy. Eight to 12 rootlets from each root were electrically stimulated with two unipolar electrodes (pulse width, 50 microseconds; 10-50 V). The muscle responses were observed visually and registered by electromyography. Those rootlets associated with an abnormal motor response as evidenced by sustained muscular contraction or by prolonged electromyographic response were divided. Spasticity was scored from 0 to +. The muscular groups assessed were those involved in the flexion of the shoulder, elbow and wrist in the upper limbs, and those involved in flexion and adduction of the hip, flexion of the leg, and plantar flexion in the lower limbs. The patients were assessed 1 week before and 6 months after the operation. Reduction of spasticity was observed in all the muscular groups, and all the patients presented functional improvement of motor abilities. These preliminary results indicate that a limited procedure that reduces the extension of the laminectomy and the length of the operation could be effective for treating spasticity secondary to infantile cerebral palsy. ",9 1794,"Deferoxamine fails to improve postischemic cardiac function in hypertrophied hearts. Myocardial hypertrophy is a well-recognized risk factor in congenital cardiac surgery. Hypertrophied hearts have been demonstrated to have an increased vulnerability to ischemia/reperfusion injury. We studied the effects of the iron chelator and hydroxyl radical scavenger deferoxamine given during early reperfusion in a model of isolated retroperfused rabbit hearts made hypertrophic by aortic banding early in life (1 week of age). The rabbits were studied at 6-8 weeks of age, and the hearts were subjected to 30 minutes of 37 degrees C ischemia followed by 30 minutes of reperfusion. Postischemic recovery of isovolumic developed pressure was measured by using an intracavitary balloon in both the untreated (n = 6) and the deferoxamine-treated (n = 6) groups and compared with normal age-matched controls. Deferoxamine (50 mumol/kg) was given to one group with the hypertrophied hearts during the first 10 minutes of reperfusion. The left ventricular weight/body weight ratio in the hypertrophied hearts was 2.9 +/- 0.4 x 10(-3) (n = 14) versus 2.0 +/- 0.1 x 10(-3) in the age-matched controls (p less than 0.05). Postischemic peak developed pressure recovered to 102 +/- 6% of the preischemic value in the normal hearts after 30 minutes of reperfusion compared with 75 +/- 5% for the untreated and 71 +/- 4% for the deferoxamine-treated hearts (p less than 0.05 vs. control). We conclude that chronic hypertrophy from early in life leads to increased susceptibility to ischemia and that the iron chelator deferoxamine is not effective in preventing the injury of reperfusion in hypertrophied hearts. ",13 2646,"Cytomegalovirus: where have we been and where are we going? Nearly 30 years have elapsed since Rowe and Weller and their colleagues discovered human cytomegalovirus (CMV). Because of its complex structure, long replicative cycle, low yield in vitro, and highly species-specific cell-substrate requirement, the cellular and molecular biologic analyses of human CMV have been slow, but recombinant DNA and monoclonal antibody technologies are bringing about rapid changes. Because of the long period of latency and wide range of disease presentations, epidemiologic and medical insights have also come slowly. However, the clinical events that occur during iatrogenic immunosuppression (transplantation and cancer therapy) and as a result of immunocompromise due to human immunodeficiency virus infection are currently promoting our understanding of the epidemiology of CMV disease and the definition of its clinical spectrum. Rapid diagnostic methods, antiviral drugs, and vaccines for CMV are becoming available. We may not yet understand completely the impact of this agent on the nonimmunosuppressed or aspects of its pathogenesis: e.g., the immune functions controlling recrudescence and the possibility of increased disease severity in those with no detectable immune defect. With the availability of new approaches, other issues should be clarified, such as the functions of host and virus involved in the mechanism of persistence. ",19 2090,"Differential light scattering cuvettes for the measurement of thromboemboli in high shear blood flow systems. Newly developed optical scattering cuvettes were constructed as a modification of our existing 1.0 mm and 3.0 mm internal diameter (ID) cuvettes to facilitate the measurement of platelet microemboli ranging from 20 microns to 1,000 microns diameter in whole blood in 0.9 mm ID flows ranging from 250 to 4,000 ml/min. A perturbation solution to the one-speed radiative transport equation was used in the design and calibration of these cuvettes. A series of tests were performed with these cuvettes in an extracorporeal left ventricular assist device bovine model, and in a recirculating closed-loop flow system containing anticoagulated whole baboon blood, to determine to what extent they affect platelet and erythrocyte function ex vivo and in vitro. Serial hemolysis tests, thromboxane radioimmunoassay measurements, platelet counts, and activated partial thromboplastin times were measured. All of these tests with cuvettes in the extracorporeal and in vitro circuits were statistically indistinguishable from baseline measurements, suggesting the usefulness of this system for the measurement of microemboli in blood-contacting materials of extracorporeal circuits and cardiac assist devices. ",13 1217,"Study of verbal description in neuropathic pain. The aim of this paper is to study the quality of verbal description and its diagnostic value in neuropathic pain. The verbal description of pain as assessed by a French adjective list questionnaire (QDSA) is compared between a group of 100 patients with neuropathic pain and a mixed group of 97 chronic benign and cancer non-neuropathic pain patients. Seventeen descriptors of the 61 QDSA descriptors have a significant intergroup frequency difference. By principal component analysis and Varimax rotation of the intercorrelation matrix of descriptors in the neuropathic group. 7 factors accounting for 66.0% of the total variance are derived. Six factors reflect purely sensory or affective aspects of the pain experience. Seven descriptors from the discriminant analysis function correctly assign 77% of neuropathic pain patients and 81% of the non-neuropathic pain patients. In a second neuropathic pain group of 32 patients, the discriminant function coefficient permits correct diagnostic categorization in 66% of the cases. Implications for clinical practice and trials are discussed. ",9 279,"Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers. The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. Of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. The epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P less than 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes. ",3 1749,"Prospective evaluation of a protocol for induction of sustained ventricular tachycardia in patients referred to a tertiary centre. All eight stages of a stimulation protocol that used one then two extrastimuli from the right ventricular apex in sinus rhythm and three ventricular drive rates (100, 120, and 140 beats/min) were performed in 24 patients with recurrent spontaneous sustained ventricular tachycardia despite drug treatment. Twenty two of the patients had sustained a previous myocardial infarct and 18 were on long term treatment with amiodarone. Sustained (greater than 30 s) ventricular tachycardia was induced in all patients. Two extrastimuli were significantly more likely to induce sustained ventricular tachycardia than one extrastimulus, both overall and individually for the three ventricular drive rates. A ventricular drive rate of 140 beats/min was significantly more likely to induce ventricular tachycardia than ventricular drive rates of 100 and 120 beats/min which were significantly more effective than sinus rhythm. A ventricular drive rate of 140 beats/min with one or two extrastimuli induced ventricular tachycardia in 23/24 (95%) of the patients in this study. The full eight stage protocol was progressive separately for both extrastimuli and ventricular drive rate but the last two stages (ventricular drive rate of 140 beats/min with one or two extrastimuli) were as effective as the entire protocol in inducing ventricular tachycardia. ",13 3012,"Pancreatogastrostomy: a safe drainage procedure after pancreatoduodenectomy. The purpose of this study was to evaluate the role of pancreaticogastrostomy as an alternative method of restoring pancreaticointestinal continuity after pancreaticoduodenectomy. Since 1975, 45 patients have undergone pancreaticogastrostomy after pancreaticoduodenectomy at our institution. Pancreaticoduodenectomy was performed for pancreatic carcinoma (24 patients), ampullary carcinoma (8 patients), duodenal carcinoma (4 patients), common bile duct carcinoma (4 patients), pancreatic islet cell carcinoma (1 patient), trauma (1 patient), extensive colon carcinoma (1 patient), chronic pancreatitis (1 patient), and gastroduodenal artery aneurysm (1 patient). There was one operative death, for an overall operative mortality rate of 2%, and seven patients had major postoperative complications, for an overall morbidity rate of 15%. No pancreatic anastomotic leaks or other complications related to the pancreaticogastrostomy occurred. Twenty-four patients have died of recurrent carcinoma, with a mean survival of 25 months (range, 5 to 66 months), and 20 patients are alive and well, with a mean follow-up of 27 months (range, 2 to 106 months). Eight of these patients are alive 2 or more years after operation and four do not have exocrine pancreatic insufficiency. This experience confirms that pancreaticogastrostomy is a safe method of pancreatic drainage after pancreaticoduodenectomy and suggests that it may have technical advantages and therefore merits more widespread application. ",22 2135,"Increased serum IgE and increased prevalence of eosinophilia in 9-year-old children of smoking parents. We studied the relationship of serum IgE levels and eosinophil counts with passive smoking in 9-year-old, nonselected children from three Italian towns near Rome. Male children of smoking parents had a significantly higher total count and percentage of eosinophils (p = 0.008) and higher IgE levels (p = 0.01) than male children of nonsmoking parents. Prevalence of eosinophilia (defined as greater than or equal to 4% of total white blood cell count) was significantly correlated with the number of cigarettes smoked by parents among boys (p = 0.003) but not among girls (p = 0.20). There was a significant trend (p = 0.008) for prevalence of eosinophilia to increase with increasing levels of serum IgE. For any given level of serum IgE, the frequency of eosinophilia was higher among children of smoking parents than among children of nonsmoking parents. When parental smoking was studied in a multivariable analysis and after controlling for the other variable, it was still significantly associated with eosinophilia in the children of these smoking parents but not with serum IgE levels. We conclude that parental smoking is associated with a significant enhancement of the expression of the most important markers of allergic sensitization in the children of smoking parents. This is particularly evident for boys and may explain, at least in part, the increased frequency of respiratory symptoms in children of smoking parents. ",14 659,"Making core decompression work. Meaningful assessment of a treatment modality for osteonecrosis (ON) must take into account a number of factors: (1) an accurate diagnosis, (2) consistent staging of the disease process, (3) understanding of the variability of the disease, (4) consistent application of the treatment modality (or the surgical technique), and (5) a clear understanding of the goal of the treatment used. This article reviews the important steps of a diagnostic algorithm that has been used to accurately diagnose and stage the disease process of ON. A consistent surgical technique with clearly defined goals is also outlined. The results of two clinical studies that were based on these diagnostic and therapeutic philosophies and that assess the role of core decompression in the treatment of ON are reviewed. The first study compared core decompression to conservative management in a prospective randomized study of 55 hips. Decompression provided more predictable pain relief and changed the indications for further surgical intervention more consistently than did conservative management. The second study represents a preliminary review of a ten-year study of the decompression procedure; it showed that core decompression was particularly useful in Stage I and Stage II ON. Roentgenographic stabilization was most predictable for Stage I hips. Core decompression can be a safe, effective, and predictable procedure in the treatment of Stage I and Stage II ON. ",4 1518,"Serum concentrations of CA 125 and aminoterminal propeptide of type III procollagen (PIIINP) in patients with endometrial carcinoma. Serum CA 125 (a marker of coelomic epithelial cells) and aminoterminal propeptide of type III procollagen (PIIINP; an indicator of collagen metabolism) concentrations were measured in 148 patients with endometrial carcinoma. An initial serum concentration of CA 125 was pathologic in 17% of the patients, the frequency of abnormal values being higher (P = 0.0001) in advanced (63%) than in early disease (10%). The serum PIIINP concentration was increased in 35% of the patients and more often (P less than 0.05) so in advanced (63%) than in early disease (31%). Among all the patients, at least one of the tumor markers was increased in 43% of the cases. In early disease 12 of 108 patients contracted recurrent cancer. The accuracy of the pathologic CA 125 (9%) and PIIINP (18%) concentrations in their prediction was poor. In the total material, pathologic CA 125 and PIIINP concentrations appeared simultaneously in 11 patients, of whom eight had poor prognoses. In monitoring of treatment response of 24 patients, regression was accompanied by normal or decreasing CA 125 and PIIINP values. The persistence of pathologic CA 125 and/or PIIINP concentration predicted relapse of the malignancy. In progressive disease, CA 125 and PIIINP concentrations together or separately remained at a pathologic level or increased continuously. In clinically stable endometrial carcinoma, CA 125 gave false-negative results in 71% of the determinations and PIIINP only in 12%. The current results suggest the use of CA 125 and PIIINP, simultaneously, in monitoring the clinical course of advanced endometrial carcinoma. ",12 417,"Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer. ",3 684,"Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. Fecal clearance of plasma alpha 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the alpha 1-antitrypsin concentration in stool and the plasma clearance of alpha 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in alpha 1-antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation (P less than 0.001) between alpha 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the alpha 1-antitrypsin clearance exceeds 180 mL/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of alpha 1-antitrypsin; by contrast, abnormal alpha 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal alpha 1-antitrypsin concentration is not a reliable index of abnormal alpha 1-antitrypsin clearance. ",5 658,"Capacitive coupling as an adjunctive treatment for avascular necrosis. The purpose of this study was to determine the effectiveness of capacitive coupling, a noninvasive method for applying electrical stimulation to biologic tissues, when used as an adjunct to decompression and grafting in the treatment of avascular necrosis (AVN) of the femoral head. It also compared the results of core decompression and grafting with nonoperative management. Forty patients with Stages I-III AVN of the femoral head were treated with core decompression and grafting. All wore capacitive coupling units with electrodes placed over the femoral head continuously for six months. One-half of these units were active and one-half were inactive. Patients were followed for two to four years. Results were determined by preoperative and postoperative Harris ratings, quantitative roentgenographic measurements, and the number of hips that required total hip arthroplasty (THA). After all evaluations were completed, patients were divided into stimulated and nonstimulated groups. Patients in both groups were similar regarding gender, etiology, and roentgenographic stage of involvement. Results were also compared to 55 hips previously treated symptomatically, without surgery or electrical stimulation. There were no fractures, infections, or other significant complications in any of the hips operated on. Hips treated with decompression and grafting, both with and without electrical stimulation, were more satisfactory than hips treated symptomatically in regard to roentgenographic progression and the need for THA. There was, however, no indication that the addition of capacitive coupling gave better results than decompression and grafting alone. ",4 1139,"Growth factor expression after stroke. Fibroblast growth factors are polypeptides with potent trophic effects on central nervous system cells. Both acidic and basic forms of fibroblast growth factor are found in the mammalian brain. We have examined the expression of these factors after focal brain injury or stroke. After infarction of the lateral cerebral cortex in the mature rat brain, we found a twofold to threefold increase during the first 3 weeks after stroke in levels of fibroblast growth factors in tissue surrounding infarcts. This increase persisted for at least 2 months and appeared mainly to be due to increased levels of basic, but not acidic, fibroblast growth factor. Because of its gliotrophic, angiogenic, and neuronotrophic properties, basic fibroblast growth factor may play an important role in the cascade of cellular reactions that contributes to wound healing and functional recovery after stroke. ",9 3243,"Peripheral opioid receptors mediating antinociception in inflammation. Evidence for activation by enkephalin-like opioid peptides after cold water swim stress. This study utilized inhibitors of the enzymatic degradation of enkephalins to investigate the possibility that this class of opioid peptides contributes to the stress-induced antinociception seen in inflamed peripheral tissues of rats with Freund's complete adjuvant-initiated unilateral hind paw inflammation. Following a 1-min cold water swim stress, rats previously injected in both hind paws with vehicle showed a transient elevation of paw pressure threshold, which was much greater in inflamed than in noninflamed paws and returned to control levels within 15 min. This preferential antinociception was significantly pronounced and prolonged in rats previously injected bilaterally with a cocktail of the enkephalinase inhibitors thiorphan (0.2 mg intraplantar) and bestatin (0.2 mg intraplantar). The enhancement of stress-induced antinociception by thiorphan/bestatin was dose-dependently antagonized by tertiary naloxone (0.125-2 mg kg-1 s.c.). Evidence for a peripheral site of action of enkephalin-like peptides in this model was provided by the antagonism of the actions of thiorphan/bestatin by quaternary naltrexone (10-20 mg kg-1 s.c.). Systemic administration of the orally active enkephalinase inhibitor SCH 34826 (5-40 mg kg-1 i.p.) was also able to dose-dependently potentiate the preferential stress-induced antinociception in a naloxone (1 mg kg-1 s.c.) reversible manner. ",22 2552,"Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells. The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis. ",19 1595,"Coronary angioplasty in patients with severe left ventricular dysfunction. The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event-free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function. ",13 1527,"Neosalpingostomy for distal tubal obstruction: prognostic factors and impact of surgical technique. We reviewed the clinical records of all women who underwent microsurgical terminal neosalpingostomy for distal tubal obstruction between January 1983 and June 1988. We identified 95 women whose preoperative evaluation revealed no other contributory factors for infertility and analyzed their pregnancy outcome after this procedure. Pregnancy success was inversely related to the extent of tubal distortion (dilation, rugal integrity, and status of the fimbria) and degree of adnexal adhesions. Using our classification system for distal tubal obstruction, patients with mild disease had an 80% pregnancy rate, whereas patients with moderate and severe disease had a 31% and 16% success rate, respectively. We found no statistically significant difference in pregnancy outcome when we compared this series with our previous group, reported in 1978, where contemporary microsurgical technique was not used. Although we feel that optimal surgical technique is important to maximize success, we conclude that the most important prognostic factor in pregnancy outcome after neosalpingostomy for distal tubal disease is the anatomical and functional integrity of the tube. ",12 2208,"Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif. ",15 1803,"Increased erythrocyte sodium-lithium countertransport activity in essential hypertension is due to an increased affinity for extracellular sodium. 1. Sodium-lithium countertransport activity in a standard assay, its sodium affinity constant and maximum velocity were measured in erythrocytes from normal subjects and from essential hypertensive patients with and without a family history of hypertension. 2. In normal subjects the sodium concentration used in the standard assay was similar to the sodium affinity constant so that the activity measured in this assay was less than the maximum velocity. 3. In patients with essential hypertension and a positive family history, 33% had a sodium-lithium countertransport activity greater than the upper limit of the normal control range (0.4 mmol of Li+ h-1 l-1 of cells). 4. The reason for the raised sodium-lithium countertransport activity was an increased sodium affinity (lower sodium affinity constant) at the outside ion-binding site. 5. Of the patients with essential hypertension and a positive family history but sodium-lithium countertransport activity within the normal range in the standard assay, 30% also had a low sodium affinity constant. 6. A low sodium affinity constant at the outside site of the sodium-lithium countertransporter may be a more specific indicator for a group of patients with inherited hypertension than the standard sodium-lithium countertransport activity assay. ",13 2062,"Patient profiling: individualization of hypertension therapy. Although the stepped-care approach remains the cornerstone of antihypertensive therapy, the patient's profile must also be considered. Important issues include the patient's age, race and activity level, potential for hypertensive complications, presence of other diseases, cost of medications and probability of adherence to the recommended drug regimen. Nonpharmacologic treatment based on lifestyle changes is a useful adjunct to drug therapy, but it is not sufficient to control hypertension in most patients. Selection of pharmacologic therapy must be based on a knowledge of each drug's mode of action and side effects, as well as the characteristics of special patient populations. ",13 1627,"Prolongation of ventricular refractoriness by class Ia antiarrhythmic drugs in the prevention of ventricular tachycardia induction. The effects of class la antiarrhythmic drugs (procainamide, quinidine) on the right ventricular effective refractory period (VERP) and intraventricular conduction time were assessed during serial invasive electrophysiologic studies for sustained monomorphic ventricular tachycardia (VT). In 47 patients with remote myocardial infarction, sustained VT was inducible by up to two extrastimuli after the basic drive at one of two basic cycle lengths at the right ventricular apex. With oral drug administration, sustained VT was no longer inducible (group I) in 27 patients but remained inducible (group II) in 20 with the same protocol. Class la drugs prolonged the VERP in both groups, but there was greater lengthening when drugs were effective (e.g., +32 +/- 14 msec in group I vs +12 +/- 19 msec in group II; p less than 0.005, basic cycle length 600 to 700 msec). Prolongation of the VERP by greater than 30 msec had an 88% positive predictive value for prevention of sustained VT induction. In all except one patient in group I, drugs prolonged the VERP such that the coupling intervals that had resulted in sustained VT induction under control conditions were no longer attainable. In contrast, conduction time through the ventricle (surface QRS duration) in sinus rhythm and during right ventricular pacing was prolonged similarly regardless of efficacy (e.g., +33 +/- 21 msec vs +27 +/- 27 msec at a cycle length of 400 msec). The presence of similar plasma levels of drug did not imply equivalent prolongation of the VERP in the two groups. These results suggest that greater prolongation of the VERP by oral procainamide or quinidine correlates with drug efficacy against VT induction and is a better predictor of drug effect than achievement of a ""therapeutic plasma level."". ",13 3036,"A comparison of parallel versus perpendicular placement of retention sutures in abdominal wound closure. A new technique for placement of retention sutures is described. Twenty-five rats underwent midline laparotomy incision. The control group was closed with traditional placement of through-and-through retention sutures placed in a perpendicular direction to the wound. The experimental group was closed with retention sutures placed in a parallel direction to the wound as described below. Wound bursting strength was significantly (P less than 0.001) greater at one to five days in the experimental group compared with the control animals. In addition, inflammatory reaction and pressure necrosis were greater in the control group. It appears that parallel placement of sutures has less of a tendency to cut through tissue when subjected to the distracting forces on a midline wound. ",22 3217,"Effects of inflammatory mediators on the responsiveness of isolated human airways to methacholine. Several studies have suggested that in asthmatics the quantities of inflammatory mediators such as histamine, thromboxane A2 (TxA2), prostaglandin D2 (PGD2), prostaglandin F2 alpha (PGF2 alpha), and leukotriene C4 (LTC4) that are present in the airway lumen are related to the degree of bronchial responsiveness to inhaled methacholine (MCh). Therefore, we studied the effect of these mediators on the cholinergic responsiveness of isolated human airway segments. Lung tissue collected at thoracotomy from 30 patients was studied. Dose-response curves to MCh were obtained from bronchial segments before, during, and after incubation with either a subthreshold or a threshold concentration of histamine (10(-10) or 10(-8) M), the stable TxA2 analogue U46619 (10(-11) or 10(-9) M), PGD2 (5 x 10(-9) or 5 x 10(-7) M), PGF2 alpha (10(-9) or 10(-7) M), or LTC4 (10(-11) or 10(-9) M). With the exception of LTC4, the presence of any of these mediators at either concentration increased the sensitivity to MCh by a factor of 1.1 to 2 (p less than 0.05, ANOVA). This increase did not depend on the dose of the mediator (p greater than 0.05, ANOVA). These data indicate that mediator-induced muscle hypersensitivity can explain a small part of the leftward shift of the dose-response curve to inhaled MCh as observed in asthma. ",22 1137,"Progressing cerebral infarction in relation to plasma glucose in gerbils. We studied neurologic morbidity and its evolution during hyperglycemia induced immediately after permanent unilateral common carotid artery ligation in Mongolian gerbils. A total of 60 animals were divided into five groups: one experiencing severe hyperglycemia for 1 hour after the onset of ischemia (brief hyperglycemia group, n = 13), a normoglycemic control group for the brief hyperglycemia group (n = 12), a group with severe hyperglycemia for 4 hours after the onset of ischemia (prolonged hyperglycemia group, n = 11), a normoglycemic control group for the prolonged hyperglycemia group (n = 13), and a hyperosmolar normoglycemic control group for the prolonged hyperglycemia group (n = 11). Neurologic morbidity and mortality were higher in the two hyperglycemic groups than in the three normoglycemic control groups. The neurologic deficit progressed according to the duration of severe hyperglycemia. In the three normoglycemic control groups neurologic status stabilized 120 minutes after the onset of ischemia, in the brief hyperglycemia group stabilization occurred at 210 minutes, and in the prolonged hyperglycemia group neurologic deficit progressed for approximately 360 minutes, coinciding with the death of all but one gerbil, in which the neurologic deficit remained stable until death 23 hours after ischemia. We suggest that hyperglycemia is another cause of progressing cerebral infarction. ",9 2581,"Antidepressant pharmacotherapy of depression associated with multiple sclerosis. In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder, 14 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy. Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group. This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores. Side effects limited desipramine dosage in half of the treated patients. The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease. ",19 2742,"The AO dynamic hip screw and the Pugh sliding nail in femoral head fixation. We compared, under laboratory conditions, the resistance to cutting out of the AO dynamic hip screw and the Pugh sliding nail. The mean load at cut out, adjusted for bone strength, was 70% greater for the Pugh sliding nail. The reasons for this difference are discussed. ",20 923,"Permeability pulmonary edema following lung resection. The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane. ",7 1740,"Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat. A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension. ",13 2959,"Shielding of the patient's gonads during intramedullary interlocking femoral nailing. Levels of exposure to radiation were recorded at sixty sites in fifteen patients during intramedullary interlocking femoral nailing. Radiation film dosimeters were placed at four gonadal sites on each subject. A standard male-gonad cup or a pelvic drape of 0.5-millimeter-thick lead-equivalent was put in place to shield the gonads. A second set of four dosimeters was placed external to the shield to approximate unprotected exposure. The total duration of the fluoroscopy averaged five minutes (range, thirty seconds to fourteen minutes). The total exposure to radiation external to the shield was 35 +/- 34 millirems at the male gonadal sites and 17 +/- 11 millirems at the female gonadal sites. With use of the gonadal shield, exposure to radiation was not measurable in thirteen of the fifteen patients. The differences between the exposures of the shielded and unshielded sites to radiation were statistically significant (p less than 0.001). The highest level of gonadal exposure was found with the treatment of proximal femoral fractures and with the use of statically locked nails. Regardless of the conditions, and for all types of fractures and locations, our results demonstrated that gonadal shielding is justified. ",20 2864,"A comparison of familial and nonfamilial male alcoholic patients without a coexisting psychiatric disorder. Both family history of alcoholism and the presence of additional psychiatric disorder in male alcoholic patients are associated with an earlier onset of problem drinking, greater alcoholism severity and poorer clinical outcomes. To assess the relative contribution of family history alone, a sample of 212 male alcoholics not positive for any other psychiatric disorder was selected and divided into those with a family history of alcoholism (FH+) or no family history of alcoholism (FH-) among first degree relatives. Although FH+ alcoholics reported a younger age of onset of problem drinking and greater severity of some alcohol-related sequelae, the differences were not as extensive or pronounced as those found in a previous study of a sample of psychiatrically heterogeneous patients (Penick et al., 1987). A bi-dimensional typology of alcoholism incorporating both additional psychiatric diagnoses and a positive family history of alcoholism is suggested. ",20 518,"Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome. The recovery time of the hypothalamic-pituitary-adrenal (HPA) axis after curative resection of adrenal tumors in patients with Cushing's syndrome is poorly documented. Eight consecutive patients were treated with a standardized hydrocortisone replacement strategy after curative resection of a cortisol-secreting tumor and the time to recovery of the HPA axis was determined. Hypercortisolism was documented by elevated 24-hour urinary free cortisol levels. Cure was documented by undetectable postoperative morning serum cortisol levels. Each patient received replacement hydrocortisone after surgery and was reevaluated every 3 to 6 months with an adrenocorticotrophic hormone (ACTH) stimulation test. Each patient was also monitored carefully for symptoms and signs of adrenal insufficiency, which was defined as symptoms consistent with this diagnosis that responded to increases in hydrocortisone levels. After surgical resection, each patient was cured of hypercortisolism. Subsequently, despite replacement hydrocortisone, each patient had symptoms of hypocortisolism, and in four of eight patients the dose of hydrocortisone was increased to relieve the symptoms. Patients required a median time of 15 months (range, 9 to 22 months) to recover a normal ACTH stimulation test and 19 months (range, 12 to 24 months) to allow discontinuation of replacement doses of hydrocortisone. The results suggest that surgical resection of a cortisol-secreting adrenal tumor will result in rapid cure of hypercortisolism, but complete recovery of the HPA axis and discontinuation of replacement steroids will require between 1 and 2 years. Normal adrenal function, as assessed by the cortisol response to ACTH, returns despite replacement doses of hydrocortisone, and replacement doses of hydrocortisone can be tapered rapidly or discontinued after a normal ACTH stimulation test. ",3 849,"Salivary gland cancer. A case-control investigation of risk factors. Unlike most upper aerodigestive tract cancers, salivary gland cancers are relatively infrequent, are characterized by a diversity of histologic subtypes, and have never been etiologically associated with tobacco exposure. We present the results of a case-control study of risk factors for these cancers, with risk estimates derived from self-administered comprehensive risk-factor questionnaires distributed to patients at The University of Texas M. D. Anderson Cancer Center, Houston. Cases were 64 patients with histologically confirmed salivary gland cancer. Control subjects, randomly selected from the same patient population excluding patients with cancer of the head and neck or nonmelanoma skin cancer, were frequency-matched to the cases by age, sex, and ethnicity to achieve a 2:1 control subjects/cases ratio. On multivariate analysis, prior radiotherapy was a significant risk factor for both men (odds ratio [OR] = 2.1) and women (OR = 2.3). Among women, higher educational attainment (OR = 2.4), alcohol use (OR = 2.0), and hairdye use (OR = 2.5) were also significantly associated with risk. There were no significant differences between cases and control subjects with respect to tobacco exposure or specific occupational or leisure-time exposures. There is biological plausibility for associations with hairdye use and alcohol exposure. ",6 1224,"Changes in thermal and mechanical pain thresholds in hand amputees. A clinical and physiological long-term follow-up. In a previous study, allodynia to cold and vibratory stimuli was found in the finger stumps of 24 patients with amputations, control values being obtained from fingers of the intact contralateral hand. When treated with regional intravenous guanethidine block (RGB), some of the patients only had short-lasting relief of symptoms, whereas others experienced a more long-lasting beneficial effect. In the present long-term follow-up study the patients were re-examined 6 years after the RGB treatment. The aim was to investigate whether the earlier symptoms and signs persisted, and whether there were any differences in these respects, between patients with long-lasting (group 1) and short-lasting relief of symptoms after RGB (group 2). All 24 patients were asked to answer a questionnaire concerning their clinical symptoms. In addition, 14 of them visited the laboratory for determination of thermal and vibration-induced pain thresholds. Comparisons were made with values obtained at the first examination before RGB treatment and with values from 14 healthy subjects tested in a similar way on 2 occasions with an interval of 8 years. Twenty of 23 patients reported that cold exposure still evoked stump pain. However, the threshold measurements showed that with time the patients had become more tolerant to thermal stimuli not only in the injured but also in the uninjured hand. A rise in pain threshold was also observed when vibration-induced pain was tested in the injured hand. There was no significant difference between groups 1 and 2. Similar changes in pain thresholds with time were not observed in the group of healthy control subjects. ",9 1907,"Beta blockers and the primary prevention of nonfatal myocardial infarction in patients with high blood pressure. A population-based, case-control study was conducted to determine whether beta blockers, used for the treatment of high blood pressure, prevent first events of coronary heart disease. All study subjects were health-maintenance organization enrollees with pharmacologically treated hypertension. Patients presented in 1982 to 1984 with new coronary heart disease, and control subjects were a probability sample of eligible hypertensive enrollees free of coronary heart disease. With the investigators blind to case-control status, the subjects' medical records were reviewed for other coronary risk factors, and the health-maintenance organization's computerized pharmacy database was used to ascertain the use of beta blockers. A larger proportion of controls than cases were using beta blockers. This difference was confined to the subgroup with nonfatal myocardial infarctions. For current use, the estimated relative risk for nonfatal myocardial infarction was 0.62 (95% confidence interval, 0.39 to 0.99). Among current users of beta blockers, higher doses conferred greater protection. Past use and total lifetime intake of beta blockers were only weakly associated with case-control status. The current use of beta blockers may prevent first events of nonfatal myocardial infarction in patients with high blood pressure. ",13 2751,"An aid to the management of pediatric trauma in peripheral centers--a proposal for a pediatric trauma board. In 1986, 630,000 children under the age of 15 were living in Queensland. This accounted for 17% of Australia's pediatric population. That year there were 39 pediatric deaths in Queensland resulting from road traffic incidents. Another 408 injured children were admitted to hospital. Less than 20% of these children were treated in an accident and emergency (A&E) department staffed by a qualified pediatrician. Only 35% of the A&E departments were staffed by a qualified emergency physician. A Pediatric Trauma Board is proposed, which will lead to improvement in the care of injured or critically ill pediatric patients. This board is made of pre-marked whiteboard and includes normal pediatric values and replacement fluid flow charts; it is approximately three feet in height and six feet in width. The Board is aimed primarily at nonpediatric clinicians who may or may not be specifically trained or interested in emergency medicine. It provides quick, easy access to the normal values of vital signs for children of different ages and sizes. It enables accurate calculation of the fluid requirements for resuscitation and provides a means for following the response to this therapy. Drug doses per weight are provided. A copy of the board can be made on size A4 photostats for inclusion in the hospital chart as part of the admission notes. ",20 1664,"Use of technetium-99m sestamibi to determine the size of the myocardial area perfused by a coronary artery. The value of the new radionuclide tracer, technetium-99m (Tc-99m) sestamibi, to demonstrate myocardial perfusion in areas supplied by specific coronary arteries was evaluated in patients injected with the agent during cardiac catheterization. Tc-99m sestamibi differs from thallium-201 in its physical characteristics (photon energy 140 keV), half-life (6 hours) and lack of significant redistribution, allowing its administration during an episode of chest pain or ischemia occurring outside the nuclear medicine laboratory with later imaging to visualize the distribution. In 13 patients Tc-99m sestamibi was administered intravenously during balloon-occlusion angioplasty. In 11 of 13 patients, defects of the single photon emission computed tomography images corresponded to the area made ischemic during angioplasty. In the remaining 2 patients, abundant collateral flow was present and no defects were seen. In a second study, 15 patients had Tc-99m sestamibi selectively injected into a coronary artery during angiography. Later imaging identified the area supplied by the artery injected. Tc-99m sestamibi imaging can detect perfusion defects associated with short episodes of ischemia, and the area supplied by the different coronary arteries. ",13 3233,"The Marinesco-Sjogren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. The Marinesco-Sjogren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sjogren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord. The pattern of atrophy resembled that seen in diffuse leukoencephalopathies. Measurements of local cerebral glucose metabolic rates with positron emission tomography revealed no statistically significant differences from normal control subjects in most regions, but metabolic rate was decreased in the thalamus in one patient. The findings support a diffuse white matter disorder in Marinesco-Sjogren syndrome. ",22 2819,"Acute intoxication. Acute alcohol intoxication is a commonly encountered clinical presentation in Emergency Medicine. Its role should be considered in many Emergency Department presentations, specifically in major and minor trauma, and in gastrointestinal, metabolic, neurologic, and psychiatric disorders. The differential diagnosis of change in mental status must be considered in all intoxicated patients. Management of intoxicated patients is generally supportive although complications of chronic alcoholism should be considered. Management should consist of correction of complications resultant from intoxication, as well as observation and the provision of a safe environment for the patient during the recovery phase of acute intoxication. ",20 1121,"Structure, expression and function of a schwannoma-derived growth factor. During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts. ",9 956,"Respiratory health effects of the indoor environment in a population of Dutch children. The effect of indoor exposure to nitrogen dioxide on respiratory health was studied over a period of 2 yr in a population of nonsmoking Dutch children 6 to 12 yr of age. Lung function was measured at the schools, and information on respiratory symptoms was collected from a self-administered questionnaire completed by the parents of the children. Nitrogen dioxide was measured in the homes of all children with Palmes' diffusion tubes. In addition, information on smoking and dampness in the home was collected by questionnaire. There was no relationship between exposure to nitrogen dioxide in the home and respiratory symptoms. Respiratory symptoms were found to be associated with exposure to tobacco smoke and home dampness. There was a weak, negative association between maximal midexpiratory flow (MMEF) and exposure to nitrogen dioxide. FEV1, peak expiratory flow, and MMEF were all negatively associated with exposure to tobacco smoke. Home dampness was not associated with pulmonary function. Lung function growth, measured over a period of 2 yr, was not consistently associated with any of the indoor exposure variables. The development of respiratory symptoms over time was not associated with indoor exposure to nitrogen dioxide. There was a significant association between exposure to environmental tobacco smoke in the home and the development of wheeze. There was also a significant association between home dampness and the development of cough. ",7 1855,"Hypertension and acculturation in elderly Mexican Americans: results from 1982-84 Hispanic HANES. The purpose of our study was to describe the relationship between acculturation and hypertension in elderly Mexican Americans. Two age groups, 55-64 and 65-74, were examined from data provided in the Hispanic Health and Nutrition Examination Survey (HHANES). The prevalence of hypertension among subgroups of different acculturation was ascertained based on the modified Cuellar Acculturation Scale. Each age group was also stratified using the HHANES poverty index, with those above the index compared to those below. A stepwise logistic regression was performed among the variables of poverty, gender, age, and acculturation in relation to hypertension. The results indicate that acculturation and age are stronger predictors of hypertension than poverty in elderly Mexican Americans, with acculturation being a stronger predictor among those age 55-64. Factors related to acculturation may have a stronger influence on the prevalence of hypertension in older Mexican Americans than differences related to socioeconomic status. ",13 674,"Intermittent obstruction of an incarcerated hiatal hernia with a total thoracic stomach. A case of intermittent obstruction of a sliding hiatal hernia is presented. The obstruction occurred when the patient's stomach was totally above the diaphragm. The anatomy of sliding hiatal hernias is discussed, as well as the presenting signs and symptoms of obstruction in sliding hiatal hernias. ",5 58,"Immunogenicity of Haemophilus b conjugate vaccine (meningococcal protein conjugate) in children with prior invasive Haemophilus influenzae type b disease. Children younger than 2 years of age with previous invasive Haemophilus influenzae (Hib) type b disease may not develop protective antibodies to antigens of Hib and may be at risk of developing a second episode of Hib disease. Twenty-three children with prior Hib disease were immunized with Haemophilus b conjugate vaccine (meningococcal protein conjugate). Children 12 to 24 months of age were given one dose of vaccine and children younger than 12 months of age were given 2 doses 2 months apart. Antibody to the polysaccharide capsule of Hib (PRP) was measured by radioimmunoassay. Eighteen children had preimmunization serum antibody concentrations less than 0.150 micrograms/ml. All 18 children responded with greater than 0.150 micrograms/ml of antibody after a single dose of vaccine. Only 1 of the 23 children had a preimmunization serum antibody concentration greater than 1.000 micrograms/ml. Seventeen children ultimately responded with greater than 1.000 micrograms/ml of antibody (P less than 0.0001), concentrations of antibody thought to correlate with protection. Haemophilus b conjugate vaccine (meningococcal protein conjugate) is immunogenic in children with invasive Hib disease. Children younger than 2 years of age with invasive Hib disease should be subsequently immunized with a Hib conjugate vaccine. ",0 1765,"Usefulness of digital angiography in the assessment of left ventricular ejection fraction. With modern digital cardiac systems the image data are digitized on-line and in real-time, allowing the replay and subsequent interpretation and analysis during or directly after the cardiac catheterization procedure. In this study we have evaluated the advantages and limitations of a manual tracing technique for left ventricular digital angiograms on the Phillips DCI system. Thirty-three patients who were catheterized for suspected coronary artery disease were studied. The manual tracings were performed by a senior cardiologist and an experienced function-analyst. It was found that the short- and long-term intraobserver variabilities in the assessment of the global ejection fraction were very small; short-term mean difference +/- standard deviation (correlation coefficient): 0.5 +/- 2.7 (r = 0.97) global EF%-units; long term; 0.7 +/- 2.7 (r = 0.96) EF%-units. The interobserver variabilities (5.1 +/- 4.8 (r = 0.93) EF%-units) were slightly higher than the intraobserver variabilities. A decrease by 25% in the amount of contrast medium administered did not significantly influence the variabilities in the contour tracings, which would suggest the use of smaller doses. At the average, the cardiologist and the function-analyst required 6 and 11 min of analysis time for a left ventricular study, respectively, emphasizing the need for further developments towards automated contour detection. Finally, an excellent correlation was found with a standard off-line cinefilm analysis procedure. Thus, it may be concluded that quantitative digital left ventricular angiography based on manual tracing of the outlines performed immediately following the cardiac catheterization (post-processing) is feasible as a routine procedure for the assessment of left ventricular function. ",13 156,"Echinococcus infestation of the biceps brachii. A case report. Echinococcus is a genus of tapeworm endemic in certain parts of the world but found only rarely in the United States. An extremely unusual case of an intramuscular infestation involving an extremity occurred in a 41-year-old man. Since the infestation closely resembled a soft-tissue tumor on clinical and roentgenographic examination, the patient was treated with an incisional biopsy of the mass, which consisted of a cystic cavity filled with clear fluid. The diagnosis of an Echinococcus cyst was made only after permanent section analysis revealed numerous scoleces within the cyst lining. The patient was asymptomatic six months after cyst excision but still remains at risk for recurrence of the infestation. The present report serves to alert the reader to this rare but potentially fatal condition. Preoperative diagnosis is imperative to avoid inadvertant rupture of a hydatid cyst, which releases viable scoleces into the systemic circulation and may precipitate an anaphylactic reaction. ",2 2475,"Growth in obese children treated for obesity. This study assesses the growth patterns during a 5-year period in children aged 6 to 12 years treated for obesity using behavioral family-based treatment procedures. Previous studies have suggested a decrease in height velocity after weight reduction, but these results did not consider either the height of the parent or the greater height of obese than nonobese children. Results show that at entry, obese children are taller than their nonobese peers (74th percentile), and that even after 5 years, they remain taller than the norm (65th percentile). Child weight and level of physical maturity accounted for 54% of the variance in predicting baseline height percentile. Entrance height and parental height accounted for 9% of the variance in changes in height percentile, both adjusted for parental height. Weight change did not correlate with growth adjusted for parental height. These results do not suggest that negative effects on height are a long-term side effect of child weight control. ",17 2954,"Motor unit numbers and contractile properties after spinal cord injury. The number of motor units in the thenar muscle group was estimated in 11 patients with cervical spinal cord injuries. The surface electromyogram and twitch force, in response to maximal stimulation of the median nerve was divided by the average surface electromyogram and twitch of single units. The average single unit size was obtained by intramuscular microstimulation of motor nerve branches and by graded whole nerve stimulation, which provided three independent estimates, two based on the electromyogram and one based on force. The motor unit estimates from the patients covered a wide range. Some had essentially normal motor units both in numbers and contractile properties, while others had varying reductions in numbers of units. Those patients who showed a large reduction in motor unit numbers also had greatly enlarged units, which produced an average of up to sixfold the normal force. These enlarged units summed to produce maximal compound action potentials and twitches that were sometimes indistinguishable from normal. Magnetic resonance imaging scans of the cervical spine obtained from some patients provided independent evidence that patients with low motor unit counts had sustained direct injury to the anterior aspect of the spinal cord at the relevant segmental levels. Some patients showed a normal number of motor units long after the injury. No evidence of transneuronal degeneration could be demonstrated in the thenar group in these patients with the current techniques. ",20 1758,"Probe angioplasty of total coronary occlusion using the Probing Catheter technique. Coronary angioplasty (PTCA) of total coronary occlusion is limited by the inability of guidewires and conventional dilating catheters to cross all such lesions. A new technique was therefore prospectively evaluated for PTCA of these lesions using the ultra-low-profile Probe ""balloon on a wire"" device. An intracoronary Probing Catheter was used to facilitate crossing the stenosis with a guidewire and then to deliver a Probe into the obstruction for balloon dilatation. This technique was utilized in 64 consecutive patients with ""absolute"" coronary occlusions demonstrating no angiographically detectable antegrade coronary flow. Successful dilatation was achieved in 47 (73%). Among 33 occlusions of less than 3 mo duration 31 (94%) were successfully dilated whereas only 16 of 31 more chronic occlusions were dilated (P less than .01). Chronic occlusions with a tapered morphology and those located more than 1 cm from a branch point were more frequently dilatable. There were no serious complications including no vessel perforations with this technique. The Probing Catheter technique offers a safe and effective method for the dilatation of recent coronary occlusions by using balloon on a wire technology. ",13 3196,"Analysis of DNA polymorphisms suggests that most de novo dup(21q) chromosomes in patients with Down syndrome are isochromosomes and not translocations. Down syndrome is rarely due to a de novo duplication of chromosome 21 [dup(21q)]. To investigate the origin of the dup(21q) and the nature of this chromosome, we used DNA polymorphisms in 10 families with Down syndrome due to de novo dup(21q). The origin of the extra chromosome 21q was maternal in six cases and paternal in four cases. Furthermore, the majority (eight of 10) of dup(21q) chromosomes were isochromosomes i(21q) (four were paternal in origin, and four were maternal in origin); however, in two of 10 families the dup(21q) chromosome appeared to be the result of a Robertsonian translocation t(21q;21q) (maternal in origin in both cases). ",22 1879,"Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography. A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels. ",13 2086,"Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension. ",13 2871,"Neuroleptic malignant syndrome: a unique association with a tricyclic antidepressant. We report the lst case of neuroleptic malignant syndrome occurring in a patient receiving desipramine, a tricyclic antidepressant, with no exposure to neuroleptics. Our case suggests that this syndrome may be caused by a central imbalance between norepinephrine and dopamine, and not by dopamine depletion alone. ",20 1687,"Cardiac contractility and conduction: a comparison of antihypertensives. The four classes of first-line antihypertensive agents recommended in the 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure are reviewed here. Particular consideration is given to the effects of these agents on heart rate, atrioventricular nodal conduction, and myocardial contractility in patients with other cardiovascular diseases. Diuretics and angiotensin-converting enzyme inhibitors have no significant direct effects on cardiac function. beta-Blockers inhibit catecholamine stimulation of the heart and may be particularly beneficial in treating patients with a history of myocardial infarction. Calcium channel blockers reduce blood pressure by dilating arterial resistance vessels. They are structurally heterogeneous and highly selective in their sites of action. As a consequence, cardiac effects can be minimized by selecting a calcium channel blocker with more potent peripheral vasodilatory effects. A new calcium channel blocker, isradipine, currently undergoing clinical trials, is highly selective for arterial smooth muscle and appears to be a safe and effective antihypertensive agent. ",13 869,"Activation of T cell subsets in the peripheral blood of patients with Sjogren's syndrome. Multicolor flow cytometric analysis. Using 3-color flow cytometry, we determined the proportions of activated T cells (DR+), including CD4+ cells, CD8+ cells, and their subsets, in the peripheral blood of 17 patients with Sjogren's syndrome (SS). Activated T cells were significantly increased in CD4+ cells, CD8+ cells, and T suppressor inducer (CD4+, Leu-8+), T helper (CD4+, Leu-8-), and T cytotoxic (CD8+, CD11-) subsets, but not the T suppressor/natural killer subset (CD8+, CD11+), in patients with SS as compared with the controls. Furthermore, the proportions of activated T cells in the CD4+, Leu-8- subset, the CD8+ subset, or the CD8+, CD11- subset showed a positive correlation with serum gamma globulin levels in the SS patients. Our findings suggest that a certain immunoregulatory balance between T helper and T suppressor activities is maintained in SS patients, although this balance seems to occur at highly activated levels, and that quantitative changes of some lymphocyte subsets are important factors in maintaining this balance. We discuss the possibility that CD4+, Leu-8+ cells recirculate into peripheral lymph nodes, while CD4+, Leu-8- cells migrate into inflammatory tissues such as salivary glands, since the Leu-8 antigen is reported to be a homing receptor in peripheral lymph nodes. This process might be accelerated in SS, and each T cell subset may further participate in immunologic activation in the lymph nodes or target tissues. ",6 1558,"Retrograde recanalization of an occluded posterior tibial artery by using a posterior tibial cutdown: two case reports. Recanalization of two occluded posterior tibial arteries was successfully achieved by utilizing a retrograde approach via a posterior tibial artery cutdown at the level of the ankle. Both cases were previously unsuccessfully attempted by using an antegrade approach. Thus, the choice of access vessel (arterial entry site) becomes a crucial determinant of angioplasty success. ",13 1011,"Ligmaject system for local anaesthesia in otology. The Ligmaject syringe for local anaesthetic injection incorporates a pistol-grip handle and a ratchet system designed to inject a very tiny aliquot of anaesthetic per 'click'. This instrument was used to provide local anaesthesia for 22 otological procedures on consenting adults. The performance of the Ligmaject syringe compared favourably with that of the conventional dental syringe in terms of patient acceptability and user convenience. ",8 1219,"Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy. The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord. ",9 2634,"The HIV-testing policies of US hospitals To determine the human immunodeficiency virus-testing policies adopted by US hospitals, we surveyed a stratified random sample of all nonfederal general acute care hospitals, drawn from the American Hospital Association's 1987 database. Interviews were completed with the chief administrator in 561 hospitals (response rate, 78.4%). Two thirds of hospitals have admitted at least one patient with the acquired immunodeficiency syndrome, and over 83% have formal written policies about human immunodeficiency virus testing. Most contain provisions protecting patients' rights; eg, 78% require pretest informed consent, 66% require a special human immunodeficiency virus-testing consent form, and 75% require that patients who test seropositive be so informed. Many policies also contain provisions that protect providers; eg, 56% require that test results appear in patients' records, 38% require review of treatment plans when a patient tests seropositive, and 3% require transferring such patients. Hospital characteristics are not strongly associated with the adoption of testing policies. ",19 2547,"Hyperparathyroidism and cellular mechanisms of gastric acid secretion. Patients with hyperparathyroidism appear to be a particular risk for peptic ulcer disease. To test the hypothesis that hypercalcemia or parathyroid hormone plays a role in promoting ulcer disease, we studied the effect of varying concentrations of extracellular calcium on acid secretion using in vitro isolated rabbit gastric glands. Acid secretion was assessed by the accumulation of carbon 14-labeled aminopyrine (14C-AP). Glands were incubated with varying calcium concentrations in the unstimulated state and with histamine or carbachol (10(-7) to 10(-4) mol/L) in 1 or 2 mmol/L calcium medium. The effect of parathyroid hormone was also examined under identical conditions. Compared to 1 mmol/L standard calcium medium, unstimulated 14C-AP accumulation was significantly inhibited (p less than 0.05) at both lower (0.33 mmol/L) and higher (2 and 2.5 mmol/L) calcium concentrations. Accumulation of 14C-AP in response to histamine stimulation was unaffected by alteration of extracellular calcium (p greater than 0.2). Carbachol-stimulated 14C-AP accumulation was significantly augmented (p less than 0.01) by an increase in calcium concentration from 1 to 2 mmol/L. The addition of parathyroid hormone (10(-7) to 10(-4) mmol/L) alone or in combination with carbachol or histamine (10(-6) mmol/L) incubation did not alter 14C-AP accumulation. These data suggest that elevations in extracellular calcium play an active role in the potentiation of cholinergic-mediated gastric gland acid secretion and may thereby play a role in hyperparathyroid-related ulcer disease. ",18 2064,"Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients. The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group. ",13 2721,"Rapid and specific diagnosis of HIV-1 and HIV-2 infections: an evaluation of testing strategies. To identify cost-effective testing strategies for HIV-1 and HIV-2 infections, we evaluated different combinations of tests on serum specimens from 1134 consecutive patients attending tuberculosis treatment centers in Abidjan, Cote d'lvoire. Virus-specific whole-virus enzyme-linked immunosorbent assay (WVE), Western blot (WB) and synthetic peptide enzyme-linked immunosorbent assay (SPE) were used in sequential fashion to determine the true prevalence of infection; 27% were reactive to HIV-1, 5% to HIV-2, and 10% to both viruses. Of 239 specimens positive on WB for both HIV-1 and HIV-2, SPE diagnosed 38% as HIV-1-reactive and 16% as HIV-2-reactive, while 46% remained reactive to both viruses. Using WVE or one of two rapid (5-10 min) mixed (HIV-1 and HIV-2) antigen tests (RMATs) as a screening test, followed by SPE as a supplemental test, gave results with sensitivity of 97.3-99.2%, specificity of 99.5-99.7%, and positive predictive value for diagnosing HIV infection of 99.4-99.6%, with important savings in time and reagent costs. SPE allows more specific distinction between HIV-1 and HIV-2 infections than WB, and could replace it as a supplemental test in many settings. WB may be required for specimens reactive on screening tests but negative on SPE, until sensitivity of the SPE is further evaluated. A mixed antigen screening test followed by SPE seems to be an efficient testing strategy for diagnosing HIV-1 and HIV-2 infections. ",19 2665,"Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty-seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated. ",19 2671,"Tracking the spread of the HIV infection epidemic among young adults in the United States: results of the first four years of screening among civilian applicants for U.S. military service. Because the period from infection to clinically apparent disease is long, variable, and changing as new therapies are developed and applied, AIDS data are inadequate for tracking current values of critical parameters of HIV infection epidemics: prevalence of infection, rate of acquisition of new infections (incidence rate), and direction and rate of change of infection incidence over time (acceleration). These ""vital signs"" of infection epidemics can be tracked using serial cross-sectional seroprevalence data, however. From October 1985 through September 1989, more than 2.3 million applicants for U.S. military service were screened for antibody to HIV. The overall seroprevalence was 1.31 per 1,000 (3,014/2,300,675). Seroprevalences were highest near urban centers of the AIDS epidemic and were independently associated with age, race/ethnicity, and gender. Based on age seroprevalence trends, it was crudely estimated that at least one of 2,000 young men and one of 7,000 young women are infected with HIV annually in the U.S. Infection incidence rates, estimated from age and temporal trends, were estimated to be highest among black males (1.40/1,000/year) and lowest among white females (0.03/1,000/year). Poisson regression analysis of seroprevalence trends suggested that infection incidence rates accelerated among black females during the first 3 years of screening. Since selection factors undoubtedly changed over the period, estimates based on these data probably underestimate actual values in the general population, particularly near urban AIDS epicenters. Nonetheless, even crude estimates of these critical values, particularly among adolescents and young adults, are useful to guide policy development, to allocate resources, and to monitor program effects. ",19 969,"Amiodarone: a postmarketing evaluation of monitoring for drug-induced toxicity. Amiodarone, an antiarrhythmic drug with predominantly class III effects, has demonstrated serious adverse drug reactions and interactions. The Departments of Pharmacy and Cardiology retrospectively evaluated the monitoring parameters at this institution. Criteria based on current literature were developed. Twenty-six patients were administered amiodarone, qualifying for entry into the audit. Of these patients, seven were excluded because their medical records were unavailable or incomplete. The 19 eligible patients were hospitalized during initiation of therapy and followed in the Outpatient Cardiology Clinic. The collected data extracted from the medical charts were compared with the following elements of the criteria selected: baseline evaluation prior to the start of therapy; monitoring for signs of pulmonary, hepatic, thyroid, cardiac, ophthalmologic, neurologic, and dermatologic toxicity; and evaluation of potential drug interactions with digoxin and warfarin-type anticoagulants. The percentage of criteria elements appropriately monitored on each patient ranged from 82 to 100 percent, with an average of 91 percent. The most frequently overlooked parameters were warning the patient of a possible photosensitivity reaction, decreasing the digoxin dose if the patient was concurrently taking amiodarone, and performing a slit-lamp examination every six months. Frequent examination of the patient's total organ system and laboratory tests, in addition to patient education, are essential to safe monitoring of amiodarone therapy. ",7 1468,"Ectopic pregnancy: ten common pitfalls in diagnosis. Ectopic pregnancy (EP) is a common, life-threatening complication of pregnancy. Modern technology (ultrasonography and improved pregnancy tests) should facilitate the diagnosis of EP. However, in a retrospective review of 65 cases of confirmed EP managed over 18 months at an urban teaching hospital, only 37 of 65 patients (57%, Cl95 = 44%, 69%) received prompt diagnosis and treatment; delays occurred in 28 patients (43%). In 10 of the 27 delayed cases, the diagnosis of EP was not even considered at the time of the first visit. In patients with a delayed diagnosis, morbidity (transfusions, cardiovascular instability, progression of illness) did occur. Diagnostic pitfalls that resulted in delayed care were reviewed, delays most commonly occurred in patients with a benign examination or ""atypical"" pain. Risk factors for EP were missed (7 patients, 25%), subtle clues to blood loss were often ignored (10 patients, 36%), and passage of tissue was thought to exclude EP (2 patients). Ultrasound was only helpful for half of the diagnoses and was misinterpreted in 27%. A dry or serous culdocentesis occurred frequently. In five patients, a falling or low quantitative human chorionic gonadotropin level was believed to indicate a completed abortion. The authors conclude that almost half of EPs are still missed on the first physician visit; errors and pitfalls in diagnosis are still common in the 1980s. ",12 2281,"Treatment of chromoblastomycosis. Treatment of chromoblastomycosis is frequently difficult and unsatisfactory. A representative case is presented of this chronic subcutaneous fungal infection, characterized by warty, cauliflower-like lesions usually on the extremities. Chromoblastomycosis and its treatment are reviewed, with attention to itraconazole, a new triazole compound, as the possible drug of choice. ",16 1316,"Patient selection for, results of, and impact on tumor resection of potency-sparing radical prostatectomy. Our results show that by using the nerve-sparing radical retropubic prostatectomy, potency can be preserved in the majority of appropriately selected patients without compromising the adequacy of tumor excision. However, proper patient selection is important. Patients with focal, well-differentiated tumors, especially young patients with stage A or B1 tumors, are ideal candidates. In patients with more extensive and less well-differentiated tumors, there is a higher risk of incomplete tumor excision. Although we suspect that the adequacy of tumor excision is determined more by the extent of the tumor than by the technique of radical prostatectomy used, we believe that nerve-sparing surgery should be used with great caution, if at all, in patients with extensive or high-grade tumors. In these patients, microscopic extracapsular tumor extension is extremely common, can be impossible to detect at the time of operation, and is less likely to be adequately encompassed by nerve-sparing techniques. On the other hand, our current data provide little evidence that excision of the neurovascular bundles is beneficial. It is possible that more extensive resections will not materially alter the incidence of positive margins or cure rates. Finally, it might be argued that all forms of radical prostatectomy are inappropriate for patients with poorly differentiated clinical stage B2 prostate cancer for whom there are no really effective treatment options. We continue to recommend radical prostatectomy for these patients based on the finding that patients with clinical stage B2 disease who have organ-confined tumors can be expected to have excellent long-term disease-free survival rates similar to those of clinical stage B1 patients. In the remaining patients who are clinically understaged, the prospects for the minimal microscopic tumor remaining being controlled with adjunctive radiation therapy may be better than those of controlling the bulky primary tumor with radiation therapy alone. This hypothesis will need to be tested in a randomized clinical trial. ",11 1660,"Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half-life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5-minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression. ",13 2752,"Scroto-abdominal impalement injury in a skateboard rider. The injuries sustained by skateboard riders vary from minor cuts and abrasions to fractures. This report describes a unique injury sustained by a young skateboard rider who was impaled on a metal rod. Literature review of over 1,254 skateboard injuries did not reveal any other instances of penetrating abdominal trauma. ",20 949,"Local and global function of the right ventricle in a canine model of pulmonary microembolism and oleic acid edema: influence of ventilation with PEEP. Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P less than 0.01). Diastolic segment length increased in RVIT (P less than 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%; P less than 0.01) and CI (-11%; P less than 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%; P less than 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and -69%; P less than 0.05) and work (-26% and -59%; P less than 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP. ",7 594,"Biomechanical comparison of single- and double-pin fixation for acute slipped capital femoral epiphysis. Biomechanics of pin fixation for acute slipped capital femoral epiphysis (SCFE) was studied in an in vitro immature canine model. Acute SCFE were created in 24 paired femurs. The paired specimens were pinned with either one or two pins and loaded to failure. Strength and stiffness of the paired limbs were expressed as percentages of the loads necessary to create the initial SCFE in the intact specimen. Strength and stiffness were equivalent statistically for the intact physis and the fractured physis fixed with two pins. Single pinning was only 83% as strong and 78% as stiff as the intact physeal plate. Double-pin fixation is recommended over single-pin fixation for acute SCFE. These data, however, should not be extrapolated to the clinical situation of fixation for chronic SCFE. ",4 3340,"Proliferation and substrate effects on endothelial cell thrombogenicity. The effects of the cellular differentiation status and the adhesive-substrate on endothelial cell function in cell culture were measured with an enzyme based assay of surface thrombogenicity. A solid plastic, microporous polymeric, and fibronectin (FN) treated microporous polymeric were used as substrates for growth of endothelial cells. The microporous and FN treated synthetic substrates have been shown to aid in the induction of cellular differentiation mechanisms. Cells were studied under proliferative and nonproliferative growth conditions. The thrombogenicity of the surface created by the endothelial cell monolayers under various experimental conditions was determined using an enzyme based assay of fibrin deposition. Actively proliferating cells on the solid plastic substrate produced the most thrombogenic surface, while confluent endothelial cell monolayers grown on FN treated microporous substrate were the least thrombogenic surfaces. These data suggest that endothelial cell surface thrombogenicity is under substrate control, and also related to the cellular differentiation status. These findings are being used to design a novel approach to the small diameter synthetic vascular graft problem. ",22 1012,"Comparison of electro and chemical cautery in the treatment of anterior epistaxis. In the ENT Department of the Royal Victoria Hospital, Belfast, the impression (supported only by anecdotes) was that electro-cautery was superior to chemical cautery in the treatment of simple anterior epistaxis. Since no evaluation of the relative merits of electro and chemical cautery has been reported, a prospective randomized study was conducted to assess the effectiveness of electro-cautery and cautery with silver nitrate. The results of the study showed that there was no statistically significant difference between the two methods in either controlling the epistaxis or in the incidence of complications. It is concluded that since cautery with a silver nitrate tipped applicator is simpler, and of equal effectiveness, it would appear to be the treatment of choice for simple anterior epistaxis. ",8 1981,"A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. Experiments were carried out to test the hypothesis that familial aortic aneurysms, either thoracic or abdominal, are caused by mutations in the gene for type III procollagen (COL3A1) similar to mutations in the same gene that have been shown to cause rupture of aorta and other disastrous consequences in the rare genetic disorder known as Ehlers-Danlos syndrome type IV. A family was identified through a 37-yr-old female captain in the United States Air Force who was scrutinized only because many of her direct blood relatives had died of ruptured aortic aneurysms. The woman was heterozygous for a single-base mutation that converted the codon for glycine 619 of the alpha 1(III) chain of type III procollagen to a codon for arginine. Studies on cultured skin fibroblasts demonstrated the mutation caused synthesis of type III procollagen that had a decreased temperature for thermal unfolding of the protein. The same mutation was identified in DNA extracted from pathologic specimens from her mother who had died at the age of 34 and a maternal aunt who died at the age of 55 of aortic aneurysms. Examination of DNA from samples of saliva revealed that the woman's daughter, her son, a brother, and an aunt also had the mutation. The results demonstrated that mutations in the type III procollagen gene can cause familial aortic aneurysms and that DNA tests for such mutations can identify individuals at risk for aneurysms. ",13 862,"Balancing dental service requirements and supplies: epidemiologic and demographic evidence. As a counterpoint to negative interpretations of recent trends, this article presents a positive picture of dentistry in the 1990s and 21st century. Reported trends show large increases in older dentate adults who are retaining more of their natural dentition, new diagnosis and treatment technologies, increased incidence of dental caries in older adults, increased awareness of periodontal diseases, greater interest in esthetic dentistry, and generally higher expectations for health and fitness in our society. All of these factors point to a greater need for adult dental services. Therefore, in the next 30 years, the dental profession should be prepared to provide increased amounts of diagnostic, preventive, adult operative, fixed prosthodontic, and endodontic and orthodontic services. Declines in need should be expected in children's operative dentistry, extractions, and complete dentures. ",6 1129,"Signs distinguishing spasmus nutans (with and without central nervous system lesions) from infantile nystagmus. Clinical findings as well as eye and head movement recordings were analyzed from 23 patients with spasmus nutans without central nervous system (CNS) changes, 10 patients with spasmus nutans-like disease (head nodding, intermittent nystagmus associated with intracranial anomalies or visual pathway disorders), and 25 patients with infantile nystagmus. Ten diagnostic signs were established to differentiate between the patient groups. Although they were helpful in separating patients with infantile nystagmus from those with spasmus nutans, no difference was found between the patients with spasmus nutans with and without CNS lesions. This study indicates that eye and head movement recordings do not allow differentiation between benign spasmus nutans and spasmus nutans-like disease. The differentiation must be made on the basis of neuroimaging. ",9 33,"History of antifungals. Until two to three decades ago, only a few drugs were available for the treatment of fungal infections. The status of antifungal therapy changed dramatically in the late 1960s with the introduction of newer broader spectrum agents, such as the iodinated trichlorophenols and the imidazoles, that acted by disruption of the fungal cell membrane. Some of the more recently developed broad-spectrum antifungal drugs include the triazoles terconazole, itraconazole, and fluconazole and the dimethylmorpholine amorolfine. The allylamines represent one of the newest classes of compounds shown to be effective in the management of fungal disorders. The two members of this unique chemical class that have been studied clinically, naftifine and terbinafine, are effective against a wide spectrum of fungal organisms. Terbinafine has the added advantage of both topical and oral activity. ",0 304,"Complications associated with limb salvage for extremity sarcomas and their management. A retrospective clinical review of 100 consecutive patients with extremity sarcomas managed by limb salvage operations was performed to evaluate local tumor control and morbidity. The mean follow-up period was 45.1 months. Overall survival was 86%. There were local recurrences in 3% of patients, and 26 complications in 22 patients. Wound necrosis was the most frequent complication. Failure of allogeneic bone graft operations occurred in 25 patients. Most of the complications were salvageable without loss of limb. Limb salvage is an acceptable surgical treatment of extremity sarcomas based on adequate local control and minimal morbidity. ",3 2574,"The relationships among shrimp-specific IgG subclass antibodies and immediate adverse reactions to shrimp challenge. High levels of shrimp-specific IgE, in association with a positive prick test, are not always predictive of a positive, immediate response to double-blind, placebo-controlled, food challenge (DBPCFC) with shrimp. The observation that shrimp-sensitive individuals in general have increased levels of circulating shrimp-specific IgG is of interest because antigen/allergen-specific IgG subclasses have been associated with adverse reactions to foods. Therefore, this current study measured shrimp-specific IgG subclass and IgE antibodies in 31 individuals with histories of immediate, adverse reactions to shrimp immediately before DBPCFC and 20 shrimp-tolerant subjects. Individuals with a history of shrimp sensitivity had significantly raised shrimp-specific IgG2 and IgG4 compared to shrimp-tolerant individuals. Challenge-positive subjects were distinguished from subjects with negative or equivocal responses by an increased IgG2 (p less than or equal to 0.001). Specific IgG4 was not raised (p less than or equal to 0.065). These studies indicate that some shrimp-specific IgG subclass levels are increased in shrimp-sensitive subjects. However, none of the subclass responses were significantly predictive of a positive response to DBPCFC and therefore were not diagnostic of shrimp intolerance. ",19 1736,"Calcium regulating hormones in essential hypertension. Importance of gender. Alterations of calcium metabolism have been described in human essential hypertension and experimental hypertension. We investigated the interrelationship of parathyroid hormone (PTH) and 1,25(OH)2-vitamin D (1,25(OH)2D) in patients with untreated essential hypertension as compared to normotensive controls. The hypertensive subjects (n = 75; 43 men, 32 women) had a mean blood pressure of 138 +/- 8/95 +/- 5 mm Hg as compared with 120 +/- 11/80 +/- 8 in the normotensive group (n = 40; 22 men, 18 women). Serum PTH was measured with an intact molecule immunochemiluminometric assay and 1,25(OH)2D was measured with radioimmunoassay after HPLC separation. Hypertensive men had PTH levels that were 36% higher than normotensive men (5.3 +/- 2.9 v 3.9 +/- 0.8 pmol/L, P = .005). When blood pressure was analyzed as a continuous variable, there was a direct correlation between it and serum PTH in men (r = .31, P = .004). In women, by contrast, there was no difference in serum PTH between hypertensive and normotensive subjects and no relationship between blood pressure and the serum PTH concentration. Blood pressure was inversely correlated with serum phosphorus levels in both sexes (r = -0.20, P = .04). In men, the elevated serum PTH levels and depressed serum phosphorus levels would have predicted that serum 1,25(OH)2D would be higher in the hypertensive subjects. However, that was not observed, as serum 1,25(OH)2D was slightly lower in hypertensive (38.3 +/- 15.2 pg/mL) than normotensive men (42.7 +/- 11.3, P = .21). ",13 3112,"Traction injury in the internal mammary artery. Report of a case and review of the literature. The internal mammary artery (IMA) is now used routinely along with saphenous vein for myocardial revascularization procedures. We have documented a particular form of non-perforating injury which may reduce blood flow during operation or may lead to early closure of the IMA bypass graft. Traction injury to the intima is well documented in other vessles but has not been previously reported in the IMA. We present a potentially disastrous example of traction injury to the IMA. ",22 1057,"Auditory brain stem implant: effect of tumor size and preoperative hearing level on function. The auditory brain stem implant is an investigational device designed to provide hearing sensations to patients without functioning auditory nerves. We analyzed results from 17 implants in 15 patients to determine if tumor size or preoperative hearing level might be related to proper device function. We found no significant correlation between preoperative hearing level or tumor size and device function. We also found no significant correlation between preoperative hearing level and tumor size in these 15 patients. ",9 2794,"Laboratory tests in the follow-up of treated alcoholics: how often should testing be repeated? The study group consisted of 60 male and 13 female alcohol-dependent employed patients who participated in inpatient treatment for alcoholism. They were followed up bimonthly for eight months after the treatment period. The results with GGT, ASAT, ALAT, MCV and the combination of GGT and MCV were studied with respect to the effect of taking the tests once (at eight months), twice (once every four months) or four times (bimonthly). According to our definition, the treatment outcome was good when the laboratory test values were within the normal range during the whole follow-up period. The differences in observed outcome (at eight months after treatment) were small whether one took the tests once at the end of the follow-up period or up to four (i.e. bimonthly) times. Nevertheless, there were some differences between the laboratory markers. To get the most accurate picture of drinking during the follow-up period one should repeat the test bimonthly with ASAT or ALAT, once every four months with GGT (or combined GGT and MCV), and once after eight months with MCV. When the time course of relapses is important for the study the more frequent test taking is also indicated. ",20 1943,"Effects of ketamine on the cardiac papillary muscle of normal hamsters and those with cardiomyopathy. The effect of ketamine (10(-5) and 10(-4) M) on the intrinsic contractility of left ventricular papillary muscle from normal hamsters and those with cardiomyopathy (BIO 82.62, 6-month old) was investigated. At these concentrations, ketamine induced a positive inotropic effect on normal papillary muscle, as shown by an increase in maximum unloaded shortening velocity (+19 +/- 4 and +34 +/- 5%, P less than 0.05), active isometric force (+32 +/- 8 and +57 +/- 11%, P less than 0.05), and peak power output (+40 +/- 8 and +80 +/- 16%, P less than 0.05), and induced a slight decrease in sarcoplasmic reticulum function. Ketamine had no effect on the curvature of the total force-velocity curve, suggesting that it does not modify myothermal economy. Contractility of papillary muscle from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in isometric active force (-41%, P less than 0.02), peak power output (-33%, P less than 0.05), and sarcoplasmic reticulum function. The positive inotropic effect of ketamine on papillary muscle from hamsters with cardiomyopathy was less marked than in controls and almost suppressed in some cases: only the maximum unloaded shortening velocity was significantly increased with 10(-5) M ketamine (+7 +/- 6%, P less than 0.05), whereas no significant changes were observed in active isometric force (+14 +/- 8 and +13 +/- 11%; nonsignificant [NS]) and peak power output (+9 +/- 5 and +13 +/- 8%; NS) with ketamine (10(-5) and 10(-4) M, respectively). ",13 1641,"Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris. Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001). ",13 1213,"Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome. Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG. ",9 610,"Bone loss in the distal anterior femur after total knee arthroplasty. Bone loss in the distal anterior femur in asymptomatic total knee arthroplasty (TKA) patients has been noted roentgenographically and during revision surgery. A retrospective roentgenographic review of 147 TKA cases was carried out to document bone loss. The influence that the mode of fixation (porous coated and cemented) and the implant design have on bone loss was examined. The time of onset and the progression of bone loss were studied. Bone loss occurred in the distal anterior femur in the majority of cases reviewed (68%). The prevalence of bone loss was independent of the mode of fixation and the implant design. By qualitative observation, roentgenographically detectable bone loss occurred within the first postoperative year and did not progress further. Previously three-dimensional finite element analysis demonstrated that the replacement of the bearing surface of the femur with a stiff metallic implant reduces the stress in the distal anterior femur by at least one order of magnitude. It is therefore speculated that the observed bone loss results from stress shielding. The apparent lack of progression may reflect the development of a new remodeling equilibrium under the altered stress conditions. The bone loss in the distal anterior femur described has not been implicated as a source of failure. However, since the bone strength in the femoral region is compromised as it becomes osteopenic, bone failure may occur with longer periods of cyclic loading. Furthermore, as a result of bone loss, revision arthroplasty may be more difficult. ",4 519,"Posttranslational gastrin processing depends on tumor morphology. Extracellular matrices have recently been demonstrated to alter cell morphology in culture. Altered cell morphology has been associated with changes in gene transcription and translation, but it is not known whether it also affects posttranslational processing. Using tyrosine-O-sulfation as a marker of processing, we studied the effects of various substrates on biologically active gastrin (IRG) production and sulfation in gastrin-containing tumor cells (GT cells). Dispersed GT cells were plated onto different substrates and then incubated. Culture media from days 4, 7, and 28 were assayed with specific antibodies that recognize total IRG and nonsulfated IRG. Cells cultured on plastic and dried films of laminin, collagen, and Matrigel (Collaborative Research Inc., Lexington, Mass.) flattened and formed monolayers of GT cells. Cells cultured on a porous membrane and hydrated gels of collagen and Matrigel did not flatten but formed spheroids of GT cells. The monolayer cultures showed an increase in sulfation with time but a decrease in IRG production. The spheroid cultures maintained a constant level of sulfation over time and, with the exception of Matrigel (gel), also showed a decrease in IRG production. These results indicate that the level of sulfation was unchanged from that of the original tumor when cells were grown in spheroids but increased when cultured as monolayers. It appears that alteration of the cellular milieu alters colony morphology, which in turn alters gastrin processing. ",3 2020,"Use of pulmonary artery catheters in patients with acute myocardial infarction. Analysis of experience in 5,841 patients in the SPRINT Registry. SPRINT Study Group This study analyzes the use of PAC in a registry comprising 5,841 hospitalized patients with AMI. A total of 371 patients received PAC. In-hospital mortality was higher in patients with CHF who received PAC, while there was no difference in patients with cardiogenic shock or persistent hypotension. Mortality in patients receiving PAC was higher irrespective of the presence or absence of ""pump failure."" A separate analysis of discharge summaries of 364 patients with CHF showed that PAC was used more frequently in sicker patients and that when severity of CHF was assessed, no difference in mortality was found in patients with mild or moderate CHF. We conclude that while a higher in-hospital mortality is found in patients receiving PAC, this excess is likely related to difference in severity of CHF, which had not been assessed in every individual. It is unlikely that PAC increases mortality. ",13 2578,"Immunoproliferative small intestinal disease: portrait of a potentially preventable cancer from the Third World. PURPOSE: To review the recent progress in the understanding of clinical and laboratory characterization as well as management of immunoproliferative small intestinal disease (IPSID). DATA IDENTIFICATION: A literature search was conducted using Index Medicus, MEDLINE (1962 to 1989), and bibliographies of identified relevant articles. STUDY SELECTION: All international comprehensive reviews, reported epidemiologic or immunologic studies, and prospective clinical trials published or abstracted in English were selected. RESULTS OF DATA SYNTHESIS: A high incidence of lymphoma primarily in the gastro-intestinal tract in Third World countries has stimulated enormous epidemiologic and pathogenetic interests globally. IPSID, with a distinctive biologic marker (alpha heavy chain para-protein), affects the young underprivileged population of those countries. The initially benign-appearing antibiotic-responsive immunoproliferative lesions often evolve to fatal high-grade lymphomas. Roles of environmental and host factors in this evolutionary course are emerging. Recently demonstrated malignant potentials form the early onset of pathogenesis have given a new dimension to the traditional management strategy of IPSID. CONCLUSIONS: Epidemiologic, immunologic, and pathogenetic data that have emerged over the last 25-year study of IPSID have improved our understanding about the complexity of infection-immunity-cancer interrelationships, comparable to those that have arisen from the study of the acquired immunodeficiency syndrome. Early detection and institution of antimicrobial-based treatment regimens with judicious and consistent follow-up can save the lives of many young patients whose manpower is badly needed in Third World countries. ",19 1773,"Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial The Multiple Risk Factor Intervention Trial (MRFIT) is a randomized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease (CHD) mortality in 12,866 high-risk men aged 35-57 years. Men were randomly assigned to either a special intervention (SI) program, which consisted of dietary advice for lowering blood cholesterol levels, counseling aimed at cessation for cigarette smokers, and stepped-care treatment for hypertension for those with elevated blood pressure, or to their usual sources of health care within the community (UC). Among the 12,866 randomized men, 8,012 (62%) were hypertensive at baseline. For this subgroup, mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15% (p = 0.19) for CHD and 11% (p = 0.13) for all causes. These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years (March 1982 through December 1985) than during the preceding 6-8 years (through February 1982). During the posttrial years, death rates were lower for SI than for UC men by 26% (p = 0.09) for CHD and 23% (p = 0.02) for all causes. For those with diastolic blood pressure equal to or more than 100 mm Hg, this posttrial trend was a continuation of a trend during the trial; therefore, with 10.5 years of follow-up, death rates were markedly lower for SI than for UC by 36% (p = 0.07) for CHD and 50% (p = 0.0001) for all causes. Similarly, for those without baseline resting electrocardiographic abnormalities, the favorable posttrial outcome for the SI group was a continuation of a trend during the trial. In contrast, for those with baseline diastolic blood pressure of 90-99 mm Hg and for those with baseline resting electrocardiographic abnormalities, the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial. Two factors appear to have contributed to this more favorable mortality trend for the SI group: 1) a change in the diuretic treatment protocol for SI men about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg; and 2) a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.(ABSTRACT TRUNCATED AT 400 WORDS). ",13 1972,"Intracoronary urokinase for intracoronary thrombus accumulation complicating percutaneous transluminal coronary angioplasty in acute ischemic syndromes. Intracoronary urokinase was used to treat flow-limiting intracoronary thrombus accumulation that complicated successful percutaneous transluminal coronary angioplasty (PTCA) during acute ischemic syndromes in 48 patients who were followed up through the acute phase of their illness. The study group comprised 10 patients with unstable angina pectoris, 18 patients with an evolving acute myocardial infarction, and 20 patients with postinfarction angina. The initial mean percent coronary diameter stenosis for the entire population was 95 +/- 7% and decreased with initial PTCA to 41 +/- 20% (p less than 0.001), with improved corresponding coronary flow by Thrombolysis in Myocardial Infarction trial (TIMI) grade. However, thrombus accumulation then resulted in a significant increase in percent diameter stenosis to 83 +/- 17% (p less than 0.001); a corresponding significant reduction in coronary flow also occurred by TIMI grade. After administration of intracoronary urokinase (mean dose, 141,000 units; range, 100,000-250,000 units during an average period of 34 minutes), with additional PTCA, mean percent diameter stenosis significantly decreased to 34 +/- 17% (p less than 0.001); a correspondingly significant improvement in mean coronary flow by TIMI grade occurred to 2.9 +/- 0.2. Overall, the angiographic success rate was 90%. There were no ischemic events requiring repeat PTCA and no procedure-related myocardial infarctions or deaths before hospital discharge. One patient was referred for urgent coronary artery bypass graft surgery after a successful PTCA. Plasma fibrinogen levels were obtained in 15 patients, and in no patient was the level below normal for our laboratory. ",13 2060,"Incidence of perioperative myocardial ischemia detected by different electrocardiographic systems To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.5-30 Hz (a typical operating room monitor), a Marquette Electronics MAC II ECG at 0.05-40 Hz and 0.05-100 Hz (a standard ECG), and a Del Mar Holter recorder at 0.1-100 Hz. Relative ST-segment position and incidence of new ischemia compared to the preoperative ECG were determined in 109 sets of preinduction traces and 877 sets of intraoperative traces. ST-segment position on the three recording systems conforming with the American Heart Association (AHA) low-frequency response recommendations (0.05 Hz) were similar. Compared to the standard ECG, ST-segment position on the Spacelabs at 0.5-30 Hz was consistently more negative. Displacement on the Holter was consistently less negative and less positive. By the 0.1-mV displacement criterion for diagnosis of myocardial ischemia on any one ECG system, 16.5% of patients on arrival and 32.1% of patients intraoperatively suffered new myocardial ischemia. Based on the operating room monitor, arrival and intraoperative ischemia were present in 15.6 and 27.5% of patients, respectively. Ischemia at the same periods was less frequent by the standard ECG system (5.5 and 12.8%, respectively) and least frequent by the Holter recorder (4.6 and 8.3%, respectively). ",13 1644,"Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure. The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This article reviews the multiple effects of angiotensin II in target tissues, the evidence for the presence of functional tissue RAS and the data that suggest a role for these tissue RAS in the pathophysiology of heart failure. Activation of circulating neurohormones is predictive of worsened survival in heart failure; however, cardiac and renal tissue RAS activities are also increased in the compensated stage of heart failure, when plasma renin-angiotensin activity is normal. It is hypothesized that the plasma RAS maintains circulatory homeostasis during acute cardiac decompensation, while changes in tissue RAS contribute to homeostatic responses during chronic sustained cardiac impairment. This concept of different functions of circulating and tissue RAS in the pathophysiology of heart failure may have important pharmacologic implications. ",13 167,"Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole. In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates. ",3 893,"Trends in lung cancer, chronic obstructive lung disease, and emphysema death rates for England and Wales 1941-85 and their relation to trends in cigarette smoking Trends in smoking associated respiratory diseases in England and Wales during 1941-85 have been studied, with careful attention to problems caused by changes in classification of cause of death. Three diseases were selected for analysis: lung cancer, emphysema, and chronic obstructive lung disease. During 1971-85 deaths that would previously have been certified under chronic bronchitis have increasingly tended to be classified under chronic airways obstruction. The definition of chronic obstructive lung disease that was used includes both terms to avoid the artificial decline caused by consideration of chronic bronchitis in isolation. Age specific rates for all three diseases show a pronounced cohort (period of birth) pattern, rates for men rising up to the rates for those born shortly after the turn of the century and then declining, and rates for women peaking in the cohort born 20-25 years later. For chronic obstructive lung disease, but not for lung cancer and emphysema, the cohort peak is superimposed on a sharply declining downward trend. In both sexes cohort patterns of cumulative cigarette consumption peak at a time broadly similar to those seen for the three diseases. Trends in cigarette consumption, however, cannot explain the underlying steeply declining rate of chronic obstructive lung disease. Nor can they fully explain the declining trends in lung cancer and emphysema rates in younger men and women. ",7 1352,"Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis. To estimate the renal extraction and de novo production of angiotensin I and to assess the contribution of blood-borne renin to renal angiotensin I production, the aortic and renal venous plasma levels of renin and intact [125I]angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [125I]angiotensin I were measured in subjects with unilateral renal artery stenosis (n = 8) who were treated with captopril (50 mg b.i.d.). Results demonstrated that 80% of angiotensin I delivered by the renal artery was extracted both by the affected and the unaffected kidney and that on both sides a major part of angiotensin I in the renal vein was derived from intrarenal de novo production. Production of plasma angiotensin I was in excess over extraction (p less than 0.01) on the affected side, whereas extraction was in excess over production (p less than 0.01) on the contralateral side. The plasma level of de novo intrarenally produced angiotensin I in the renal vein was seven times higher on the affected side than the contralateral side. This difference was by far too big to be explained by a difference in the transit time of blood between the two kidneys, by an augmented production of angiotensin I in the circulating blood passing through the affected kidney due to the higher level of venous plasma renin activity in that kidney, or by the combination of both. ",11 540,"Immunohistochemical differentiation of basal cell epithelioma from cutaneous appendages using monoclonal anti-glycoprotein antibody TNKH1. Its application in Mohs' micrographic surgery. TNKH1, which was primarily developed to detect differentiated melanocytic tumor cells, was found to recognize basal keratinocytes of hair follicle and some basal keratinocytes of human epidermis. Thus, TNKH1 decorated the basal cells of following structures: epidermis (39 of 54, only part of each specimen [OPES]), upper hair follicle (one of 24, OPES), lower hair follicle (21 of 21, very high rate of each specimen [VHES]), sebaceous duct (14 of 15, VHES), sebaceous gland (ten of 14, germinative cells near duct), eccrine duct (three of 19, OPES). Epithelial tumors, considered to be derived from or differentiating toward hair follicle such as trichilemmoma (one of one, VHES) and basal cell epithelioma (BCE) (32 of 32, VHES) were labeled not only in the peripheral cells but in their entirety. On the other hand, epidermal tumors, such as seborrheic keratosis (ten of 11, OPES), actinic keratosis (two of three, OPES), and squamous cell carcinoma (one of two, OPES), showed an irregular peripheral basal cell staining as in normal epidermis. The apocrine sweat apparatus and eccrine secretory portion were negative. Eccrine ductal tumors such as syringoma (two tested), eccrine acrospiroma (one), and eccrine carcinoma (two) were TNKH1 negative. Taking advantage of this total labeling of BCE versus peripheral labeling of the hair follicle, the authors could distinguish BCE tissue from other structures clearly. Among confusing structures the upper hair follicle and the eccrine duct were excluded easily because of their negative staining with TNKH1. The lower hair follicle was TNKH1 positive but only in the outer basal layer, whereas the BCE was TNKH1 positive in its entire basaloid cells. The result indicated that TNKH1 will be a useful antibody in Mohs' micrographic surgery. ",3 2723,"High HIV risk-taking among young gay men. Previous research has shown younger age to be correlated with greater HIV sexual risk-taking among gay men. The purpose of this study was to identify variables associated with HIV risk-taking among younger gay men. Ninety-nine gay men aged 18-25 in three medium-sized West Coast communities completed self-report questionnaires regarding HIV-related behaviors and attitudes. Of the respondents, 43% reported having engaged in unprotected anal intercourse during the previous 6 months. Men who engaged in unprotected anal intercourse reported greater enjoyment of unprotected anal intercourse, perceived less risk of unprotected anal intercourse, labeled themselves as more at risk for AIDS, reported poorer communication skills with sexual partners, and were more likely to have a boyfriend/lover than men who had not engaged in high-risk sex. In addition, respondents perceived the likelihood of acquiring HIV from unprotected anal intercourse with young gay men to be significantly lower than with older gay men. These findings highlight the need for HIV risk-reduction interventions designed specifically for young gay men and identify critical areas to be targeted in such interventions. ",19 2103,"Hemodynamic influence of LVAD on right ventricular failure. Left ventricular assist device (LVAD) pumping has hemodynamic and anatomic influences on right ventricular performance. A total artificial heart (TAH) model was employed to better understand the hemodynamic influence of an LVAD on the failing right ventricle. Biventricular failure was simulated by reducing both ventricular drive pressures of the TAH. After getting hemodynamic data, LVAD pumping in the case of right ventricular failure was simulated by increasing just the left ventricular drive pressure. In the LVAD-simulating condition, cardiac output increased and right atrial pressure decreased significantly (p less than 0.05) compared with the biventricular failure condition, whereas right ventricular function and minute work were the same in these two conditions. Even though changes were accompanied by adaptive increases in pulmonary resistance, substantially lower pulmonary artery and left atrial pressures resulted in the LVAD-simulating condition. From a hemodynamic perspective, these results indicate that an LVAD can increase right ventricular volume work by decreasing right ventricular pressure work, whereas right ventricular net pressure-volume work is unchanged and right ventricular failure is not worsened. ",13 2401,"The electroretinogram in minimal diabetic retinopathy. The pattern and diffuse flash electroretinograms were measured in 20 normal subjects and 40 diabetic patients who had either normal fundi or microaneurysms only. The amplitudes of the pattern electroretinogram were found to be similar in both normals and diabetics. In the case of the flash electroretinogram the diabetic patients showed a division into two main groups. One group was not dissimilar to the group of normal subjects, while the second group showed hypernormal amplitudes. No explanation could be given, from the data collected, for this subdivision, though it is suggested it might reflect the degree of metabolic disturbance. ",17 1049,"Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program. Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses. We have examined the distribution of three mutations--a 4-nucleotide insertion in exon 11, a G----C transversion at a 5' splice site in intron 12, and a 269Gly----Ser amino acid substitution in exon 7--among individuals enzymatically diagnosed as carriers of Hex A deficiency. Mutation analysis included polymerase chain reaction (PCR) amplification of the relevant regions of genomic DNA, followed by allele-specific oligonucleotide hybridization; another test for heterozygosity of the exon 11 insertion was based on the formation of heteroduplex PCR fragments of low electrophoretic mobility. The percentage distribution of the exon 11, intron 12, exon 7, and unidentified mutant alleles was 73:15:4:8 among 156 Jewish carriers of Hex A deficiency and 16:0:3:81 among 51 non-Jewish carriers. Regardless of the mutation, the ancestral origin of the Jewish carriers was primarily eastern and (somewhat less often) central Europe, whereas for the non-Jewish carriers it was western Europe. Because a twelfth of the Jewish carriers and four-fifths of the non-Jewish carriers of Hex A deficiency had mutant alleles other than the three common ones tested, enzyme-based tests cannot be replaced by DNA-based tests at the present time. However, DNA-based tests for two-carrier couples could identify those at risk for the chronic/adult GM2 gangliosidoses rather than for infantile Tay-Sachs disease. ",9 1768,"Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors. The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced alpha 1-adrenergic receptor-mediated rise in cytosolic calcium, whether a pertussis toxin-sensitive G protein is involved in coupling the alpha 1-adrenergic receptor to changes in intracellular calcium and whether enhanced alpha 1 responsiveness is associated with an increase in the level of expression of the alpha 1-adrenergic receptor or in the pertussis toxin-sensitive G protein or proteins. To test the hypothesis that the cardiomyopathic state is associated with a greater alpha 1-receptor-mediated rise in cytosolic calcium, we studied the effect of phenylephrine (in the presence of propranolol) on time-averaged cytosolic calcium concentration ([Ca2+]i) in isolated cardiac myocytes from cardiomyopathic and age-matched control hamsters. Phenylephrine caused a greater increase both in time-averaged [Ca2+]i (an increase of 48 +/- 8% versus 12 +/- 3%, p less than 0.01) and in contractility (+181 +/- 22% versus +35 +/- 9%, p less than 0.01) in cardiomyopathic than in normal cardiac myocytes. Exposure to pertussis toxin (200 ng/ml for 3 hours) attenuated the alpha 1-adrenergic receptor-mediated increase in contractility and time-averaged [Ca2+]i in both cardiomyopathic and normal cells. The level of pertussis toxin-sensitive G protein, as determined by pertussis toxin-mediated [32P]ADP-ribosylation, was 1.6-fold higher in cardiomyopathic versus normal hamster hearts. The density of alpha 1-adrenergic receptors, as measured by the antagonist radioligand [3H]prazosin and the affinity of the receptor for agonist and antagonist were similar in myopathic and normal heart membranes. Thus, in cardiac myocytes from hamsters, the alpha 1-adrenergic receptor-mediated effects on [Ca2+]i and contractility appear to be mediated by a pertussis toxin-sensitive G protein or proteins. In myocytes from cardiomyopathic hamsters, these alpha 1-adrenergic effects were increased in magnitude, as was the level of pertussis toxin-sensitive G protein, but there was no measurable alteration in the density or ligand binding properties of alpha 1-adrenergic receptors. ",13 830,"Motility changes in primary achalasia following pneumatic dilatation. The changes in esophageal motility after pneumatic dilatation were evaluated prospectively in 51 patients with achalasia. The patients were evaluated for a median of 14 months. Pneumatic dilatation led to a clinical improvement in 41 patients. On manometric evaluation, a significant decrease in lower esophageal sphincter pressure was observed (28.4 +/- 14.9 mmHg vs. 13.5 +/- 7.2 mmHg; p = 0.001); the resting pressure of the esophageal body dropped from 4.8 +/- 4.2 mmHg above gastric baseline to 0.1 +/- 3.9 mmHg below gastric baseline. After therapy, peristaltic activity was present in 10/51 (20%) patients; in 1 case, complete relaxation of the lower esophageal sphincter was recorded. Treatment-induced motility changes could not be predicted by clinical history or the lower esophageal sphincter pressure before or after therapy. However, the resting pressure of the esophageal body before and after therapy was significantly lower in these patients in whom peristalsis recurred after therapy than in patients with an unchanged motility pattern. The reappearance of peristaltic activity after pneumatic dilatation was unrelated to lower esophageal sphincter pressure. In conclusion, motility disturbances of the esophageal body in patients with achalasia do not simply reflect the functional obstruction of the lower esophageal sphincter. These findings support the hypothesis that achalasia is not a distinct motility disturbance but should be regarded as part of a broad spectrum of different interrelated esophageal motility disorders. ",5 213,"Selection of breast-preservation therapy for primary invasive breast carcinoma. Breast-preservation treatment for primary breast cancer should not be used for all women. Women frequently excluded from consideration for such treatment or who choose not to have it may be elderly and not concerned about cosmetic appearance or live at a distance so that 6 weeks of daily trips to radiotherapy would be inconvenient or even impossible. Also, if radiotherapeutic expertise or facilities are not available, a breast-preservation program is difficult. In Massachusetts, a full course of just over 6000 cGy (4500 cGy to the whole breast and a 1600-cGy local boost) costs roughly $6000. Thus, breast preservation is more expensive than mastectomy even with reconstruction, as patients still frequently require a hospital admission with general anesthesia for an axillary dissection. Although insurance policies cover such expenses, patients who do not have insurance or have inadequate coverage may find the extra expense of the breast-preservation technique burdensome or impossible. Women with a small breast and a proportionately large cancer may have an unsatisfactory cosmetic outcome after appropriate lumpectomy. The cosmetic result in such patients frequently cannot be predicted beforehand; this fact adds emphasis to the need for a two-step process of lumpectomy and then re-evaluation of the cosmetic outcome as well as pathologic features for decisions regarding breast preservation. Finally, women may have strikingly different attitudes toward breast preservation than expected by the surgeon. For some women, the urge to preserve the breast is so strong that they will accept virtually any risk to achieve this option, whereas for other women, the constant anxiety about a recurrence or undergoing radiation therapy is traumatic enough that they readily accept mastectomy. In our referral surgical oncology practice, roughly 60% of patients are currently treated with breast-preservation techniques; the remainder undergo mastectomy, with immediate reconstruction in approximately three fourths of the cases. The proportion of patients who elect to have breast preservation depends greatly on local medical customs and attitudes; the radiotherapeutic skills available; women's attitudes, which frequently are dependent on the local press and publicity; and the surgeon's interest and enthusiasm for such a program. There is no appropriate proportion of patients who should be treated by breast-preservation techniques, but clearly, the proportion of patients so treated increases with experience, acceptability, publicity, and availability. Thus, the selection of breast-preserving therapy for individual patients is a result of an extraordinary array of factors that need to be considered in each patient.(ABSTRACT TRUNCATED AT 400 WORDS). ",3 1083,"Surgical technique for implantation of the neurocybernetic prosthesis. The surgical technique for the implantation of the neurocybernetic prosthesis is described in detail. This procedure is straightforward and is easily carried out by surgeons familiar with carotid surgery. ",9 985,"Ventilator dependency in the United Kingdom. There are 24 children who are currently long term ventilator dependent in the UK. Nine of these are cared for entirely at home. An additional 11 children have been long term ventilator dependent since March 1983. The prevalence of these children appears to be increasing. The financial and manpower resources needed for these children whether at home or in hospital is considerable. There are reasons to suppose that the apparent increase in prevalence will continue. ",7 2707,"Monoclonal antibodies to immunogenic lymphoma cell variants displaying impaired neoplastic properties: characterization and applications. Immunogenic, nontumorigenic cell variants derived from the highly tumorigenic mouse lymphoma cell line S-49 were used to raise monoclonal antibodies (MAbs) in syngeneic BALB/c mice. MAbs of the following specifications were derived: (a) MAbs that interacted preferentially with the immunogenic variants, (b) MAbs that interacted with both immunogenic variants and parental tumorigenic cells, and (c) a MAb that interacted with both immunogenic and tumorigenic S-49 cells and the normal BALB/c splenocytes. Six MAbs raised in this way were found to recognize at least five different cell-surface epitopes. Functional analysis of the different MAbs suggested their potential usefulness in passive immunization against parental tumorigenic cells as well as in enrichment of immunogenic cells from a mixed population containing a preponderance of tumorigenic cells. ",19 3225,"Neuropsychological assessment of monozygotic twins discordant for schizophrenia. A comparison of monozygotic twins discordant for schizophrenia controls for genetic variance and reduces variance due to environmental circumstances, thus serving to highlight differences due to phenotypic-related variables. In this study, we assessed 16 such twin pairs on a wide range of neuropsychological tests. The affected twins tended to perform worse than their unaffected counterparts on most of the tests. Deficits were especially severe on tests of vigilance, memory, and concept formation, suggesting that dysfunction is greatest in the frontotemporal cortex. While manifest symptoms were not highly associated with neuropsychological scores, global level of functioning was. To address the issue of genetic liability, we also compared the sample of discordant unaffected twins with a sample of seven pairs of normal monozygotic twins. No significant differences between the groups were found for any neuropsychological test. In fact, the results suggest that neuropsychological dysfunction is a consistent feature of schizophrenia and that it is related primarily to the clinical disease process and not to genetic or nonspecific environmental factors. ",22 66,"Giant basilar aneurysm in the course of subacute bacterial endocarditis. We describe a man aged 42 years with mitral valve regurgitation who suffered from subacute bacterial endocarditis caused by Streptococcus morbillorum. The clinical picture began with a toxic syndrome. Five months later, the patient had an embolic episode and a right rostral pontine stroke, which was followed a few days later by an adversive focal seizure on the right. Despite antibiotic treatment, he suffered complete third nerve palsy. Arteriography, magnetic resonance imaging, and computed tomography of the brain showed a giant aneurysm in the rostral end of the basilar artery; the aneurysm was clipped. We discuss the clinical features, radiology, and characteristics of this aneurysm as a unique case of a giant bacterial aneurysm in the vertebrobasilar system. ",0 2419,"Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. We examined steady-state levels of mRNA encoding type IV collagen, B1 chain of laminin, and the basement membrane heparan sulfate proteoglycan in the kidney cortex of a mouse model (KKAy) of non-insulin-dependent diabetes. mRNAs encoding laminin B1 and the proteoglycan were unchanged in kidneys taken from diabetic mice with demonstrable basement membrane thickening. mRNA levels for type IV collagen, in contrast, were significantly elevated (2-fold) in diabetic mice concurrent with but not preceding morphologically thickened basement membranes. There was a negative correlation between a ratio of proteoglycan/type IV collagen and levels of albuminuria in the diabetic mice. No correlation was noted with laminin. We also examined the effects of inhibiting the synthesis of thromboxane, a potent vasoconstrictor, on the steady-state levels of type IV collagen in the diabetic mice. Inhibition of thromboxane stopped the progression of albuminuria and prevented an increase in type IV collagen mRNA levels. We conclude that basement membrane thickening in diabetes, a hallmark of diabetic nephropathy, is partly a consequence of an unbalanced increase in the production of type IV collagen. The relative decrease in proteoglycan production may contribute to chronic albuminuria. ",17 1396,"Prolonged neuromuscular blockade with vecuronium in a neonate with renal failure. An 11-day-old neonate with renal failure caused by dysplastic kidneys was anaesthetised with thiopentone, vecuronium, nitrous oxide and oxygen, for insertion of a long-term peritoneal dialysis catheter. Complete neuromuscular block of 210 minutes' duration ensued after the initial dose of vecuronium (97 micrograms/kg). Partial block persisted for a further 30 minutes. The prolonged neuromuscular block in this case may have been because of proportionately greater dependence on renal clearance of vecuronium in neonates. ",11 2659,"Asthmatic airways have a disproportionate hyperresponsiveness to LTE4, as compared with normal airways, but not to LTC4, LTD4, methacholine, and histamine. Airways responsiveness to leukotriene (LT) C4, LTD4, LTE4, histamine, and methacholine have been studied in eight asthmatic and six normal subjects. Airways responsiveness to each bronchoconstrictor agonist was assessed by constructing cumulative dose-response curves, and the dose that produced a 35% decrease in specific airways conductance (PD35) was obtained by linear interpolation. Airways of subjects with asthma were approximately 14-, 15-, 6-, 9-, and 219-fold more responsive to histamine, methacholine, LTC4, LTD4, and LTE4, respectively, than were normal subjects. Thus, there was a substantially augmented level of hyperresponsiveness to LTE4 in bronchial asthma, which was not observed for the other bronchoconstrictor agents, when compared to normal subjects. In contrast to LTC4 and LTD4, as histamine and methacholine responsiveness increase, the dose ratio of histamine to LTE4 (PD35 histamine/PD35 LTE4) and the dose ratio of methacholine to LTE4 also tended to increase. This suggests that as the nonspecific airways responsiveness increases, the relative potency of LTE4 also increases, whereas potency of LTC4 and LTD4 decrease. These results suggest that the mechanism of the bronchoconstriction induced by LTE4 may be distinct from that produced by LTC4 or LTD4 in subjects with asthma. This may reflect leukotriene subtype receptor heterogeneity in asthmatic airways. ",19 2433,"Changes in basal and stimulated growth hormone secretion in the aging rhesus monkey: a comparison of chair restraint and tether and vest sampling. We studied basal serum GH and GH responses to iv clonidine and insulin-induced hypoglycemia in a group of four young (5-7 yr old) and four older (10-14 yr old) adult male rhesus monkeys under two restraint conditions, chair adaptation and a tether and vest system, to determine what changes in GH secretion occur with aging. The serum GH response to iv administration of GH-releasing hormone (GHRH) was also studied in the groups under tether and vest restraint. Serum samples were collected every 15 min and assayed for GH using a human GH RIA and for cortisol using an enzyme-linked immunosorbant assay. GH and cortisol concentrations in the young and older groups were analyzed with analysis of variance (ANOVA). In the chaired studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (2.7 +/- 0.8 vs. 3.5 +/- 0.5 micrograms/L; P = 0.0002). Prestimulation GH was lower before clonidine and insulin in the older chaired group (1.1 +/- 0.5 and 2.3 +/- 0.6 micrograms/L, respectively) compared to the younger group (3.6 +/- 0.8 and 3.8 +/- 0.7 micrograms/L, respectively; P less than 0.001). Poststimulation GH was lower after clonidine and insulin in the older chaired group (3.2 +/- 2.4 and 7.1 +/- 2.8 micrograms/L, respectively) compared to the younger chaired group (6.3 +/- 2.2 and 10.3 +/- 3.0 micrograms/L, respectively; P less than 0.05), but the differences in GH increments were not statistically significant. In the tether and vest studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (1.7 +/- 0.4 vs. 3.5 +/- 1.2 micrograms/L; P less than 0.0001). Prestimulation GH concentrations were also lower in the older tethered animals before clonidine (2.1 +/- 0.3 micrograms/L) and GHRH (1.4 +/- 0.2 micrograms/L) compared to levels in the younger animals (3.1 +/- 0.9 and 3.2 +/- 0.7 micrograms/L; P = 0.0023 and P = 0.0001, respectively). The younger tethered animals had greater poststimulation responses to clonidine (8.7 +/- 3.0 micrograms/L), insulin (8.8 +/- 3.6 micrograms/L), and GHRH (6.0 +/- 2.4 micrograms/L) than the older animals (3.8 +/- 0.9, 3.9 +/- 2.5, and 2.9 +/- 0.7 micrograms/L; P less than 0.0001, P = 0.0025, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 400 WORDS). ",17 1150,"Replication patterns of the fragile X in heterozygous carriers: analysis by a BrdUrd antibody method. The replication status of the fragile X chromosomes was studied in short-term cultures of lymphocytes from six female heterozygous carriers. The fragile X was induced by adding 0.1 microM fluorodeoxyuridine during the last 24 h of culturing. The replication status of the X chromosomes was studied using a bromodeoxyuridine (BrdUrd) antibody method. BrdUrd was added (1) at a final concentration of 0.2 micrograms/ml during the early S phase of chromosome replication (16-10 h before harvest), (2) at 0.2 microgram/ml during the late S phase (the last 6 h of culturing), (3) at 20 micrograms/ml during the early S phase, and (4) at 20 micrograms/ml during the late S phase. BrdUrd that was incorporated into replicating chromosomes was detected by using a nuclease and BrdUrd monoclonal antibody. The frequency of the fragile X was reduced by BrdUrd treatment. The degree of reduction was more severe in the 20 micrograms/ml than in the 0.2 microgram/ml series and was more severe with late S than with early S treatment. Of the early- and late-replicating fragile X chromosomes, those which were actively replicating during a BrdUrd treatment were more reduced than the others. Thus, the average rate of early and late S treatment with 0.2 microgram BrdUrd/ml was assumed to be the closest reflection of the situation in vivo. There was no correlation between the average rate of the early replicating, active fragile X and the intelligence of the heterozygous carriers studied. ",9 3297,"Preoperative piroxicam for postoperative analgesia in dental surgery. Fifty patients were allocated randomly to receive placebo or piroxicam 40 mg, 2.5 h before surgical removal of lower third molars under general anaesthesia. A significantly greater number of patients in the piroxicam group did not require opioid analgesia after operation (P less than 0.05). The piroxicam group also required fewer doses of paracetamol in the first 24 h after recovery from anaesthesia (P less than 0.05), and the time from recovery to first postoperative analgesia was longer in those patients who had received piroxicam (P less than 0.05). Piroxicam did not significantly prolong the duration of recovery from anaesthesia. ",22 1508,"The perinatal impact of cocaine, amphetamine, and opiate use detected by universal intrapartum screening. Universal urine testing for cocaine, amphetamines, and opiates was performed on 1643 women admitted to an obstetric service for a 1-year period with 20.5% having positive results. There were 299 patients with positive toxicology results matched for race and discharge date with patients having negative toxicology and drug history. Significant differences in age, prior obstetric history, prenatal care, alcohol history, and smoking were noted between groups. There was a significant decrease in birth weight, head circumference, length, and gestational age for the drug-positive group, which was most marked in cocaine and multiple drug users. These differences persisted after we controlled for smoking, prenatal care, and prior preterm births. Differences in birth weight and head circumference remained after we controlled for gestational age. Rates of congenital anomalies and abruptio placental were similar between groups. Perinatal substance abuse is independently associated with growth retardation and prematurity. Multiple risk factors are frequently present, necessitating a comprehensive approach to prenatal care. ",12 224,"Prognostic indicators in invasive breast cancer. Tumor size and axillary lymph node involvement are the primary determinants of clinical course for most patients. Receptors for estrogen and progesterone are important additional prognostic factors for disease-free survival, overall survival, survival time after initial disease recurrence, and the likelihood of response to hormonal therapy. Histologic grading has merit as a prognostic factor, although poor reproducibility limits its broad application. Promising data have been emerging from the use of flow cytometry to analyze DNA content and proliferative rate. Patients with aneuploid tumors are more likely to have a shorter survival time than patients with diploid tumors. A high S-phase fraction also identifies a subset of patients at increased risk for early relapse. A combined index of ploidy and S-phase may be a more useful guide; together, diploidy and low S-phase identify a subgroup of node-negative patients at very low risk for disease recurrence. A number of oncogenes have been identified in breast cancer; amplification of the HER-2/neu gene or overexpression of the gene product may be an important prognostic indicator for node-positive patients. ",3 894,"Use of biological glue to control pulmonary air leaks. Biological glue is a natural adhesive generated by the interaction between fibrinogen (pre-glue) and thrombin to produce fibrin. The pre-glue is prepared from a single donor (to avoid the problems of pooled plasma) and stored as cryoprecipitate. Before being used it is thawed, dissolved in saline, and activated into an adhesive by the addition of topical thrombin. Biological glue was used prophylactically to prevent air leaks from bronchial suture lines and raw lung surfaces after pulmonary resections in six patients. In addition two new methods of using biological glue have been developed for the control of persisting air leaks. In selective intrabronchial tamponade the glue is instilled into the bronchial tree through a flexible bronchoscope, and in therapeutic pleurodesis it is instilled into the pleural cavity through a chest drainage tube. The air leaks were resolved in all cases. Seven procedures using selective intrabronchial tamponade were carried out in six patients. Four were immediately successful but three were not and required further interventions. Therapeutic pleurodesis alone was successfully carried out in one patient and as an adjunct to selective intrabronchial tamponade on two occasions. A thoracotomy was eventually needed in one of the seven patients. ",7 3004,"An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval. ",22 1573,"Florid pulmonary veno-occlusive disease. A young woman presented with rapidly progressive dyspnea and clinical findings strongly suggestive of primary pulmonary hypertension or possible pulmonary embolism (or both). She died of acute right-sided heart failure. A diagnosis of pulmonary veno-occlusive disease was made at autopsy. Approximately 100 cases of this disease have been reported previously in the literature. We describe a patient with a particularly florid progression of this unusual disease. Death occurred within six weeks of the onset of symptoms. ",13 966,"Search and nonsearch protocols for radiographic consultation. Six radiologists, acting as radiograph reviewers, used two different consultation protocols to differentiate among 292 ambiguous chest radiographic findings: 120 simulated nodules and 172 normal findings (previous readers' false-positive reports of nodules). The nonsearch protocol identified each finding (by film location), and reviewers rated the likelihood of each finding's being a pulmonary nodule. The search protocol asked reviewers to report and rate all locations regarded as possible nodules on each radiograph and assigned a default negative rating to any unreported finding (nodule or normal structure). Receiver operating characteristic analyses demonstrated a significantly higher accuracy for each reviewer's search-protocol discriminations between these nodules and ambiguous normal findings. This superiority-of-search result suggests that radiologists' second opinions about suspected lesions might be more accurate when consultants follow a search protocol, independently reviewing radiographs without prior knowledge of the specific findings that concerned the primary radiograph readers. ",7 1615,"Angioplasty from the contralateral approach: use of a guiding catheter and coaxial angioplasty balloons. An 8-F guiding catheter has been developed for use with coaxial angioplasty balloon catheters in angioplasty of the femoral artery from the contralateral approach when antegrade puncture of the ipsilateral femoral artery is not possible. The catheter may be used for angioplasty of the femoral artery bifurcation and the superficial femoral artery and for arterial stenoses in patients with renal transplants. ",13 1493,"Hypersecretion of luteinising hormone, infertility, and miscarriage The relation between prepregnancy follicular-phase serum luteinising hormone (LH) concentrations and outcome of pregnancy was investigated prospectively in 193 women with regular spontaneous menstrual cycles. The group included 26 nulliparous and 167 multiparous women with various obstetric histories. Of the 147 women with LH concentrations of less than 10 IU/l (normal LH group) 130 (88%) conceived, whereas only 31 (67%) of the 46 women with LH values of 10 IU/l or more (high LH group) did so. In the high LH group, 20 (65%) of the pregnancies ended in miscarriage, whereas only 15 (12%) of pregnancies in the normal LH group did so. The adverse effect of a high prepregnancy LH concentration on fertility and outcome of pregnancy was seen in primigravidae, women with previously successful pregnancies, and women with a history of recurrent miscarriage. These data indicate an important role for hypersecretion of LH before conception in miscarriage. This finding offers the possibility of a simple predictive test for women before pregnancy, and could also be used to identify patients with an endocrine abnormality that can be remedied. ",12 142,"In vitro growth inhibition of Plasmodium falciparum by sera from different regions of the Philippines. Sera from different malaria endemic regions of the Republic of the Philippines were compared for their ability to inhibit growth of Plasmodium falciparum in vitro. Dialyzed serum was added to synchronous cultures containing schizonts for either the total 48 hr test period or only the last 24 hr in order to analyze the effects on erythrocytic invasion and intraerythrocytic growth, respectively. Reduction in 3H-hypoxanthine uptake was used to determine the percent of inhibition compared to nonimmune serum. One hundred seventy sera from Mindanao and Palawan in the South, the centrally located island of Mindoro, and Luzon in the North, were tested against 4 P. falciparum strains from the Philippines and 1 from Africa. Indirect fluorescent antibody titers were not predictive of inhibition. Inhibition of merozoite invasion rather than intraerythrocytic parasite growth is suggested by this study. Generally, sera were more inhibitory to parasite strains from the same geographical area than to those from more remote areas. ",2 854,"Maintaining periodontal treatment. Dental maintenance, or supportive periodontal treatment (SPT), can keep the periodontium and peri-implant tissues healthy after active therapy. Patients who comply to suggested SPT fare better periodontally and keep their teeth longer. Data should be gathered by examinations, talking with patients, and reviewing personal oral hygiene. Then sub- and supra-gingival deposits should be removed. The average SPT visit should last 1 hour and should be scheduled every 3 months. Supportive periodontal treatment for patients with more advanced periodontal or peri-implant destruction should be the responsibility of the periodontist. ",6 2612,"Identification of human immunodeficiency virus hybridizing sequences in the peripheral blood of a patient with systemic lupus erythematosus. Systemic lupus erythematosus, a multisystemic disorder, is considered a prototype of the autoimmune diseases. Although its cause remains unknown, a viral etiology has been proposed. We report that a rapid and sensitive messenger RNA in situ hybridization technique detected hybridizing sequences to the human immunodeficiency virus type in the peripheral blood cells of a woman with systemic lupus erythematosus in whom the presence of acquired immuno-deficiency syndrome was reasonably excluded. ",19 1241,"White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study. T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects. ",9 216,"Adjuvant antiestrogen therapy for breast cancer. Past, present, and future. Laboratory investigations using animal models of breast cancer growth have indicated that the antiestrogenic compound tamoxifen is a tumoristatic agent. It is therefore effective in suppressing, rather than destroying, the breast tumor. Its use as an adjuvant in breast cancer management has been successful, with a proportion of women benefiting from long periods of tamoxifen treatment. All the initial studies recruited postmenopausal women, but tamoxifen is now proposed for the treatment of premenopausal women for an extended time. Naturally, there are many aspects of the toxicology of tamoxifen to consider; however, careful monitoring of clinical trials will determine the safety of the drug for the general patient population. ",3 2055,"Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models. The cardioprotective effect of amlodipine, a long-acting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion. Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and saline-treated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipine-treated group than in the control animals. In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed. A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader. ",13 2499,"Famine in southern Ethiopia 1985-6: population structure, nutritional state, and incidence of death among children. OBJECTIVE--To assess the effects of drought on mortality in children. DESIGN--Prospective epidemiological study forming part of nutritional monitoring during famine relief work. SETTING--24 Food distribution sites in Arero and Borana provinces in southern Ethiopia. PATIENTS--A monthly average of 14,173 and 5,334 children under 5 were examined in 1985 and 1986, respectively. Altogether 148,966 child months (105,872 for 1985 and 43,094 for 1986) were available for analysis. INTERVENTION--The families of all children were supplied with food each month. Basic medical care was also provided. MAIN OUTCOME MEASURE--Mortality in children under 5. RESULTS--A 40% increase in crude mortality was observed among children living in traditional and stable societies. The severe consequences were observed mainly among children living in relief shelters, where a threefold to fourfold increase in crude mortality was recorded among children. Increased childhood mortality was also associated with high prevalence of malnutrition, living in the most arid areas, and the dry season. A long period of food aid was needed to normalise the nutritional state, especially for children living in relief shelters. CONCLUSIONS--The most severe consequences of the widespread famine that occurred in the Arero and Borana provinces of southern Ethiopia during 1985-6 were seen among children living in relief shelters. Early food intervention may decrease the scale of migration and thus also reduce the severe consequences of a famine. ",17 2719,"Reduced cerebral blood flow in early stages of human immunodeficiency virus infection. In order to determine if brain perfusion abnormalities, which are known in patients with acquiredimmunodeficiency syndrome dementia, occur in early stages of human immunodeficiency virus infection, technetium 99m hexamethyl-propyleneamine oxime-single-photon emission computed tomography studies were performed in 20 patients infected with human immunodeficiency virus who belonged to Walter Reed stages I through IV. None of these patients demonstrated signs of dementia or severe neurological dysfunction. Pathological patterns of hexamethyl-propyleneamine oxime uptake were seen in 14 patients, seven of whom had normal results during neurological examination. Only four patients had signs of cerebral atrophy on cranial computed tomographic scan. These data suggest that subtle changes in cerebral perfusion seem to arise early in the course of human immunodeficiency virus infection and may indicate human immunodeficiency virus encephalopathy before neurological symptoms or noticeable structural damage occurs. ",19 326,"Liver transplant for metastatic neuroendocrine tumor. Generally, the results of liver transplantation for metastatic liver disease have not been favorable. One exception has been the unique group of neuroendocrine tumors, the slow growth of which allows liver transplantation to effectively palliate and control symptoms. We report two cases: (a) A 51-year-old man who underwent orthotopic liver transplantation and resection of the pancreatic primary tumor for a nonfunctioning malignant neuroendocrine tumor with features of both carcinoid and islet-cell glucagonoma remains symptom-free and without evidence of tumor recurrence at 13 months follow-up. (b) A 47-year-old man who underwent orthotopic liver transplantation and Whipple resection for a metastatic islet-cell tumor in the head of the pancreas is fully recovered at 5 months follow-up. ",3 2285,"Subacute cutaneous lupus erythematosus lesions progressing to morphea. A women had annular lesions of subacute cutaneous lupus erythematosus that slowly resolved and were replaced by plaques of morphea. The immunologic implications of this unique transitional case of subacute cutaneous lupus erythematosus to morphea are discussed. ",16 414,"Natural history of cardiac rhabdomyoma in infancy and childhood. Although spontaneous regression of cardiac rhabdomyoma has been reported, prognosis is still considered to be poor and surgery continues to be indicated. The experience with rhabdomyoma diagnosed in live infants over a 20-year period was reviewed. Diagnosis by angiography or echocardiography was accepted only if multiple tumors were present or if tuberous sclerosis was also diagnosed. Nine patients (3 diagnosed prenatally and the remaining 6 at age less than 8 months) were identified as having a total of 24 tumors. Measurements in 2 planes demonstrated at least some evidence of regression in 24 patients (100%), with 20 of 24 having complete resolution. One patient required delayed surgery for excision of a subaortic ridge that appeared at the site of a resolved tumor. Our findings suggest that pediatric cardiac rhabdomyoma is most often a benign condition in which spontaneous regression is the rule. Surgery is recommended only for patients with refractory dysrhythmias or severe hemodynamic compromise. ",3 202,"Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society. Years of potential life lost (YPLL) is an indicator of premature mortality that complements traditional incidence and mortality rates and that facilitates comparisons among different cancers. We calculated YPLL from cutaneous melanoma and 11 other cancers routinely recorded and tracked by Surveillance, Epidemiology and End Results (SEER). YPLL from cutaneous melanoma ranked eighth for persons younger than 65 years of age and fourth for those 20 to 49 years of age. An average of 17.1 YPLL per death were due to melanoma, one of the highest rates for adult-onset cancers. The results of our study, the first to apply YPLL to cutaneous melanoma, emphasize the disproportionate impact of this cancer on young and middle-aged adults and reemphasize the importance of this cancer as a public health priority. ",3 2705,"Enhanced percutaneous absorption of a novel topical cyclosporin A formulation and assessment of its immunosuppressive activity. No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadaver stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun) alone (CyA) or with PE (CyA + PE) in olive oil in the donor chamber, the penetration rate (mean +/- SD microgram/cm2/h) into receptor fluid was 53 +/- 43 (n = 13) for CyA and 660 +/- 175 (n = 7) for CyA + PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA +/- PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA +/- PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA + PE compared with vehicle-treated sites (P less than 0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin. ",19 521,"The effect of somatostatin on 5-hydroxytryptamine release from a carcinoid tumor. One of the major manifestations of the carcinoid syndrome is secretory diarrhea thought to be due to overproduction of 5-hydroxytryptamine (5-HT). Synthetic somatostatin analogues have proved to be clinically effective in controlling this diarrhea. We have established a continuous cell line from a human pancreatic carcinoid tumor that secretes 5-HT. We examined the ability of the somatostatin analogue, SMS 201-995, to inhibit 5-HT release in vitro. Tumor cells were exposed to SMS 201-995 (10(-6) mol/L), pentagastrin (10(-9) mol/L), acetylcholine (10(-5) mol/L), and isoproterenol (10(-5) mol/L) alone and in combination; 5-HT release was assayed with high pressure liquid chromatography. We found that pentagastrin (6.43 +/- 0.64 ng/ml), isoproterenol (20.24 +/- 2.17 ng/ml), and acetylcholine (12.39 +/- 1.10 ng/ml) each stimulated release of 5-HT compared to control values (4.38 +/- 0.42 ng/ml). SMS 201-995 significantly reduced release of 5-HT in response to isoproterenol and acetylcholine but did not inhibit the effect of pentagastin. These data suggest that different agents do not act through the same pathway to stimulate 5-HT release from human pancreatic carcinoid cells. ",3 3258,"Late luteal phase dysphoric disorder in young women. The authors determined the prevalence of late luteal phase dysphoric disorder in 217 university women aged 17-29 years. Unaware of the focus on premenstrual syndrome (PMS), the participants rated DSM-III-R symptoms of late luteal phase dysphoric disorder over 90 days. Using a 30% or greater premenstrual change as an index of luteal variation, the authors found that 10 women (4.6%) met the symptom criteria during two menstrual cycles. Compared to 25 young women seeking treatment for PMS who met the same diagnostic criteria, the 10 women from the university sample reported significantly less fatigue and impaired concentration and somewhat less severe depression and overall symptoms. ",22 515,"Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients. Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor alpha (TNF-alpha) in vitro. BF is a protein with a molecular mass of 28 kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-alpha and recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-alpha more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-alpha when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-alpha and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-alpha in clinical trials with human cancer patients. ",3 448,"Erythrocyte stearic acid desaturation in patients with colorectal carcinoma. The erythrocyte stearic:oleic acid ratio (saturation index) was investigated as a means of differentiating between control subjects (n = 146) and patients with benign (n = 48) and malignant (n = 117) colorectal disease and patients undergoing postoperative follow-up after curative resection (n = 49). Erythrocyte fatty acid profiles were determined by gas liquid chromatography. Neither age, sex, Dukes' stage, nor degree of differentiation of the tumors had a significant effect on the erythrocyte saturation index. The erythrocyte saturation index was lower in patients with primary and recurrent colorectal cancer compared with control subjects and patients with inflammatory bowel disease or benign colonic polyps (P less than 0.0001). The erythrocyte saturation index was not found to be useful in the postoperative follow-up of these patients. Using both saturation index and age as a means of differentiating between patients with primary colorectal cancer and control subjects gave a sensitivity of 67 percent and a specificity of 81 percent. ",3 2880,"The loads on the lumbar spine during work at an assembly line. The risks for fatigue injuries of vertebral bodies. This study was performed in an attempt to determine the total spinal compressive load during assembly line work to find a possible association with the many complaints of back pain. A flexion analyzer was used to register trunk movements, and analysis of postures and lifted weights was done from video recordings. The load on the spine at the L3 level was calculated through a biomechanical model, meant for analysis of static, sagittally symmetric postures and lifting tasks. Maximum lift tests were performed before and after a full work day. The peak load on the L3-L4 level when lifting corresponded to an average 22% of the load at the lift test. The mean load during a work cycle was 818 N. It was concluded that the many complaints of back pain could not be attributed to high peak loads, repetitivity of the lifts, or large load doses. Monotony, stress, and low job satisfaction are more likely factors of greater importance. ",20 2154,"Doppler umbilical artery studies in the twin-twin transfusion syndrome. Eleven patients with twin pregnancies were identified as having twin-twin transfusion syndrome on the basis of like-sex twins with monochorionic placentation and umbilical venous blood hemoglobin differences exceeding 50 g/L at delivery. Umbilical artery velocity-time waveform studies had been performed in these pregnancies as part of a large series of 456 twin pregnancies. In all 11 cases, the systolic-diastolic (S-D) ratio differences between the twins were less than 1 unit (mean 0.4 +/- 0.2), indicating that in twin-twin transfusion, umbilical artery S-D ratios are concordant even in the presence of discordancy in fetal size. ",14 1629,"Maximal oxygen uptake in severe aortic regurgitation: a different view of left ventricular function. Respiratory gas exchange was used to assess left ventricular (LV) function in 22 patients with severe aortic regurgitation (19 men and three women, aged 18 and 70 years, mean 49 years). Anaerobic threshold and symptom-limited maximal oxygen consumption (VO2 max) were measured during treadmill exercise, and the results were compared with conventional echocardiographic and radionuclide indices of LV systolic function. The results were considered with respect to the patients' New York Heart Association functional class. Both rest and exercise LV ejection fractions were variable, but the mean results were similar in all classes. The echocardiographic indices of LV cavity dimensions, fractional shortening, radius/thickness ratio, and systolic wall stress also showed a wide range but with similar mean results in each class. In contrast, VO2 max and anaerobic threshold showed a relationship to functional class. VO2 max was 32.4 +/- 3.4 ml/kg/min in age-matched control subjects; in the patients it was 27.9 +/- 4.7 in class I, 24.7 +/- 5.7 in class II, and 14.2 +/- 2 in the combined class III/IV. Results in patients in classes I and II were similar, but both groups were significantly different from control subjects (p less than 0.05) and from patients in class III/IV (p less than 0.01). About half of the patients with moderate LV dysfunction (judged by reduced VO2 max) were asymptomatic, and LV function was impaired in 4 of 10 patients in class I. Thus, unlike conventional indices of LV function, VO2 max appeared capable of distinguishing patients with moderate-to-severe LV dysfunction from those with little or no LV dysfunction. Measurement of respiratory gas exchange appears to be a valid and useful supplementary means of assessing LV function in severe aortic regurgitation. Further long-term evaluation is required. ",13 1854,"Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography [corrected and republished with original paging, article originally printed in J Am Coll Cardiol 1990 Oct;16(4):862-70] Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis. ",13 834,"Failure of hepatitis B immunization in liver transplant recipients: results of a prospective trial. Twenty patients with advanced liver disease, in need of transplantation, were given three injections of 20 micrograms and three injections of 40 micrograms hepatitis B vaccine to see if an antibody response could be obtained. Only 20% of patients developed measurable anti-HBs. One who failed to develop anti-HBs developed chronic hepatitis B after exposure to her infected sexual partner. Type of liver disease in the native liver, age, sex, sexual preference, timing of immunization (before or after transplantation), and dosage of hepatitis B vaccine did not seem to explain the lack of immunologic response to hepatitis B vaccine. It is presumed that immunosuppression, both from the underlying disease and from immunosuppressive medications, best explains our findings. Liver transplantation patients infrequently benefit from hepatitis B vaccine. It is possible that other vaccines given to prevent viral and bacterial illness may also fail to elicit immunologic response in such patients. ",5 1503,"Congenital and perinatal cytomegalovirus infections. Cytomegalovirus is the most common cause of congenital and perinatal viral infections throughout the world. Congenital infection occurs in 1% of all live births in developed countries and in an even higher percentage in developing nations. As a result of transmission during birth, by breast milk, and by blood transfusion, perinatal infections are much more prevalent than congenital infections. The vast majority of these infections are chronic, subclinical forms, but symptomatic infections are sufficiently prevalent and dangerous to represent a major unsolved public health problem throughout the world. In this review the epidemiologic, clinical, immunologic, and therapeutic facets of cytomegaloviral infections in pregnant women and their offspring will be discussed. ",12 2444,"Time course of sprouting during muscle reinnervation in vitamin E-deficient rats. A typical aspect of motoneuron plasticity is the sprouting which occurs during muscle reinnervation, resulting in a transitory multiple innervation of the muscle cells. In order to verify the effect of a decreased protection from free radical attack on the sprouting, the multiple innervation in the extensor digitorum longus muscle, following sciatic nerve crush and regeneration, was studied in vitamin E-deficient rats. Thus, the innervated end-plates and the end-plates with multiple innervation were studied with histochemical and electrophysiological techniques. The percentage of innervated end-plates was similar in both groups at 30 as well as at 60 days after nerve crush. Nevertheless, multiple innervation was found in a larger part of the muscle and it lasted longer in the deficient rats. This finding is discussed in relation to some of the major hypotheses of sprouting; it may be relevant in the treatment of some lesions of peripheral nerve. ",17 2004,"Transesophageal echocardiography during percutaneous balloon mitral valvuloplasty. To ascertain the value of transesophageal echocardiography during percutaneous balloon mitral valvuloplasty, the present study was undertaken in 26 anesthesized patients (21 women and 5 men; mean age, 47 years) with symptomatic rheumatic mitral valve stenosis. In all but one patient the balloon dilation of the mitral valve was successful and Doppler-derived valve area increased (0.9 +/- 0.3 to 1.9 +/- 0.4 cm2). Transesophageal echocardiography provides continuous monitoring, as well as guidance of the procedure. Crossing the arterial septum, as well as delivery of the sheath through the mitral valve orifice and correct positioning of the balloon, was highly facilitated and reduced x-ray exposure time. The degree of mitral regurgitation and the presence of interatrial shunting at the end of the procedure could be readily assessed, making cineangiography not necessary. Complications of the procedure, such as pericardial effusion, could be detected before hemodynamic deterioration had occurred (one patient). The advantages of transesophageal echocardiography for routine monitoring of percutaneous mitral valvuloplasty, however, should be weighted against the added risk and expense of this support. ",13 182,"The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients. Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse-free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome. ",3 1044,"Prevalence and characteristics of multiple analgesic drug use in an elderly study group. With few exceptions, use of multiple analgesic drugs achieves dubious increases in analgesia while placing elders at increased risk of the many potential adverse effects of analgesic drugs. The potential for duplication of analgesic therapy among the elderly is great due to prevalent painful chronic conditions and the variety of prescription and nonprescription analgesic remedies available. The prevalence of multiple analgesic product use and patterns of concurrent use of different analgesic categories was investigated in a geographically defined population of persons 65 years of age and older. The demographic characteristics of users of multiple analgesic drug products were examined, as were their smoking status, alcohol use, lifetime history rates of major illnesses, physical functioning, pain experiences, memory performance, and depressive symptoms. A substantial proportion of analgesic users reported taking multiple products in the preceding 2 weeks (14.4% of female and 10.5% of male analgesic users). Men who reported pain in the preceding year were more likely to use multiple analgesic products. Women who experienced pain or limited physical functioning, or who had higher depressive symptom scores or a life-time history of ulcers were most likely to use multiple analgesic products. Thus, although some users of multiple analgesic products reported significant pain, several other factors were shown to be related to the phenomenon of multiple use. ",9 753,"Microprocessor-assisted solvent-transfer system for gallstone dissolution. In vitro and in vivo validation. To improve the efficacy, safety, and convenience of contact dissolution of gallbladder stones, a microprocessor-assisted solvent transfer system was developed. The system's two pumps simultaneously infuse and aspirate solvent into and from the gallbladder at a high flow rate through a multilumen catheter. The microprocessor controls the pumps using a closed feedback loop control algorithm to regulate intragallbladder pressure to prevent solvent escape into the duodenum. Turbulent solvent flow at the catheter end in the gallbladder is designed to induce rapid stone dissolution and to suspend insoluble residue, thus promoting its aspiration. The system's response and gallbladder emptying capacity was 160-fold faster than the natural gallbladder emptying rate. The rate at which gallstones were dissolved by methyl tert-butyl ether using the system was compared with that achieved with a syringe pump. For 6 of 11 pairs of stones that totally dissolved, the mean dissolution time with the system was 10 +/- 6 minutes compared with 112 +/- 81 minutes for the syringe pump. In the 5 of 11 stone pairs which dissolved incompletely, insoluble residue was completely eliminated by the system in 21 +/- 9 minutes but not by the syringe pump even at 360 minutes. When the system was used in gallstone patients, solvent recovery was 99% +/- 1%, and the concentration of a nonabsorbable marker did not change, confirming the lack of appreciable absorption of methyl tert-butyl ether. These studies suggest that the microprocessor-assisted solvent transfer system is a device capable of safe, complete, and fully automatic contact dissolution of cholesterol gallbladder stones using methyl tert-butyl ether or similar solvents. ",5 194,"HBV-DNA sequences in tumor and nontumor tissue in a patient with the fibrolamellar variant of hepatocellular carcinoma. One patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti-HBe. DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences. Undigested DNA from the tumor gave a high-molecular-weight smear, and restriction-enzyme analysis indicated a single instance of integration. Nontumor liver tissue was analyzed from three separate areas. Hepatitis B virus DNA was detected in two of these; restriction-enzyme digestion suggested they contained different sites of viral integration. As with the typical hepatitis B virus-related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high-molecular-weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor. The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus-related hepatocellular carcinoma. ",3 2572,"Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. Twenty-seven patients were referred for evaluation of anaphylaxis after induction of general anesthesia (GA) in which thiobarbiturates, muscle relaxants, or antibiotics were administered intravenously. Skin testing by the prick and intracutaneous methods was performed with dilutions of the thiobarbiturates and muscle relaxants; beta-lactam reagents were used in patients who had also received these drugs. No skin test reactivity was noted in 16 normal subjects. Skin tests were positive in 13 patients (thiobarbiturates in five, muscle relaxants in six, and antibiotics in two patients). Two patients were dermatographic and yielded indeterminate skin test results. Eleven of the 27 patients subsequently had GA; all patients received a premedication regimen of prednisone and diphenhydramine. Of three patients with negative skin tests, one experienced an arrhythmia, but no other signs attributable to anaphylaxis were noted. One patient with dermatographism had GA without a reaction. Positive skin tests implicated an agent that was avoided in seven patients; one of these patients experienced delayed urticaria/angioedema after the completion of GA. Thus, no patients developed anaphylaxis during subsequent GA for which agents producing positive skin tests were avoided, and a premedication regimen was used. ",19 2703,"Use of inhaled corticosteroids in patients with mild asthma. A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks' treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning. ",19 1390,"Urodynamic tests for female geriatric urinary incontinence. Most urodynamic tests currently in use in the evaluation of female urinary incontinence have not been applied to a community-based sample to determine their specificity. In this study of a random sample of noninstitutionalized elderly, 258 self-reported continent and 198 self-reported incontinent women sixty years and older, who participated in a household survey, underwent a clinic evaluation (history, physical examination, and urinalysis); of these 67 continent and 100 incontinent female respondents underwent urodynamic testing. The uroflowmetry, cystometry, and supine static urethral pressure profilometry (UPP) findings did not differ significantly between continent and incontinent subjects (whether based on a self-report or a clinician's diagnosis of urinary continence status). Standing static and dynamic UPP and lateral cystography showed significant differences between self-reported continent and incontinent respondents. The provocative stress test significantly distinguishes continence from incontinence, and stress incontinence from other types. The sensitivity of the provocative stress test was 39.5 percent, whereas its specificity is 98.5 percent. Urodynamic testing including uroflow study, static UPP, and lateral cystography should not be used as a screening test but rather selectively as a confirmatory test, and to determine the therapeutic approach, and to assess the outcome of therapy. ",11 619,"Arthrodesis of the ankle with cancellous-bone screws and fibular strut graft. Biomechanical analysis. The stability of an arthrodesis with two cancellous-bone screws across the ankle joint was evaluated in eighteen ankles from fresh-frozen cadavera. Tibiotalar motion was recorded in response to the following loading modes: medial-lateral moment, plantar flexion-dorsiflexion moment, and internal-external tibial torque. The series of loading tests was performed with two cancellous-bone screws through the tibia into the talus and a lateral fibular strut graft fixed with a proximal and a distal screw. The tests were repeated after the strut graft was removed, and again after it had been reapplied. The amount of motion at the site of the arthrodesis was greatest with tibial torque and was least with medial-lateral bending; this was true for specimens with or without a fibular strut graft. Removal of the strut graft allowed increased tibiotalar motion for all modes of loading; increases in motion were far greater for specimens of poor bone quality. ",4 3067,"Vertigo after epidural morphine. Severe complications from the use of epidural morphine for analgesia after Caesarean section are rare. A case is reported of extreme prostrating vertigo several hours after epidural morphine injection, where the time of onset of the symptom coincided with the expected time of arrival of the morphine within intra-cerebral cerebro-spinal fluid. ",22 1977,"Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity. The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups. ",13 121,"Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage. Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination. These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas. ",1 161,"HLA class I and class II antigen expression on squamous cell carcinoma of the head and neck. We compared human major histocompatibility (HLA) class I and class II antigen expression on squamous cell carcinoma of the head and neck with that on normal mucosa. Frozen sections of a consecutive series of 30 squamous cell carcinomas were stained with the monoclonal antibodies W6/32 (class I) and anti-DR (class II) using an immunoperoxidase technique. Normal mucosa showed class I and class II expression in the basal layers only. Class I expression on tumors was diffuse in 87%, patchy in 10%, and scattered in 3%. Class II expression on tumors was diffuse in 20%, patchy in 53%, scattered in 20%, and absent in 7%. Patterns of expression did not correlate significantly with clinical parameters, including survival, except that class II diffuse and patchy patterns were found to correlate with more poorly differentiated tumors. ",3 238,"The use of molecular probes to distinguish new primary tumors from recurrent tumors in gynecologic malignancies. This is the first report using DNA molecular probe technology to distinguish between recurrent tumor and a second primary malignancy in a patient. Tumor DNA was extracted from squamous cell carcinoma of the cervix at the time of radical hysterectomy. Eighteen months later a squamous cell cancer was found in a vaginal apex biopsy from which DNA was extracted. Tumor DNA from both lesions was subjected to restriction enzyme digestion and DNA molecular hybridization with human papillomavirus (HPV) probes. Although both lesions were positive for HPV 16, their respective restriction enzyme patterns had different HPV genetic arrangements, thereby demonstrating their distinctness. ",3 2438,"Ten-year follow-up of behavioral, family-based treatment for obese children Using a prospective, randomized, controlled design, we examined the effects of behavioral family-based treatment on percent overweight and growth over 10 years in obese 6- to 12-year-old children. Obese children and their parents were randomized to three groups that were provided similar diet, exercise, and behavior management training but differed in the reinforcement for weight loss and behavior change. The child and parent group reinforced parent and child behavior change and weight loss, the child group reinforced child behavior change and weight loss, and the nonspecific control group reinforced families for attendance. Children in the child and parent group showed significantly greater decreases in percent overweight after 5 and 10 years (-11.2% and -7.5%, respectively) than children in the nonspecific control group (+ 7.9% and + 14.3%, respectively). Children in the child group showed increases in percent overweight after 5 and 10 years (+ 2.7% and + 4.5%, respectively) that were midway between those for the child and parent and nonspecific groups and not significantly different from either. At 10 years, child height was related strongly to the height of the parent of the same sex (r = .78 children were 1.8 cm taller than their parents, with no differences in height between groups. ",17 1025,"Small fenestra stapedotomy using a fiberoptic hand-held argon laser in obliterative otosclerosis. Obliterative otosclerosis has been a challenge since the advent of stapes surgery. ""Drill-out"" procedures have had a generally poorer prognosis than conventional stapes surgery because of excessive bleeding, acoustic trauma from the burr, and reclosure of the oval window by otosclerosis. In this report, we describe our early experience using a hand-held fiberoptic argon laser for small fenestra stapedotomy in 10 cases of obliterative otosclerosis. Closure of the air-bone gap to within 10 dB was seen in 100% of the patients. There was no significant sensorineural hearing loss, vertigo, or facial weakness. Argon-laser stapedotomy using a hand-held fiberoptic system is a safe and effective alternative to drill-out stapedotomy in cases of obliterative otosclerosis. ",8 1231,"Quantifying language development from birth to 3 years using the Early Language Milestone Scale. A point-scoring technique for the Early Language Milestone Scale is described. Normative data based on the original 1982 cross-sectional sample and validation data based on a separate longitudinal sample are presented. Mean Early Language Milestone Scale point scores, standard deviations, and percentile equivalents for raw point scores are presented for all ages from birth to 36 months. Correlations between point scores on the Early Language Milestone Scale and scores on other standardized developmental tests such as the Stanford-Binet Intelligence Scale, the Peabody Picture Vocabulary Test, and the Illinois Test of Psycholinguistic Abilities are presented. The clinical and research advantages of this point-scoring technique are presented and compared with the original pass/fail scoring method. ",9 411,"The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract. Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life. ",3 545,"Fallopian tube cancer. The Roswell Park experience. Sixty-four patients with primary fallopian tube cancer treated at Roswell Park Memorial Institute from 1964 to 1987 underwent retrospective clinicopathologic review. In 40 patients fallopian tube cancer was the only primary, but in 24 patients primary fallopian tube cancer was part of a multifocal upper genital tract malignancy. Of the 40 patients with unifocal fallopian disease, the median survival was 28 months. Only 15% of patients were alive and disease free with follow-up ranging from 22 to 141 months (median, 90.5 months). Survival was not associated with stage of disease, tumor histology, grade, or depth of invasion in this series. Fourteen patients who received cisplatin-based chemotherapy were evaluable for response. Three patients (21%) responded; two complete and one partial. Twelve patients without clinical evidence of disease underwent second-look procedures, ten laparotomy and two laparoscopy. Four of ten second-look laparotomies were negative. Secondary debulking was done in three of four patients with gross disease, one of which had a negative third-look laparotomy. Negative laparotomy, second-look or third-look, was associated with improved survival (P = 0.016). One of the two laparoscopies was negative, but the patient recurred. In the remaining 24 patients cancer of the fallopian tube was part of a multifocal upper genital tract malignancy. In 12 patients tubal disease was invasive, and in 12, it was in situ. Separate primaries occurred in the ovaries (n = 20); uterus (n = 7); and cervix (n = 2). This represents 1.3% of ovarian malignancies treated at Roswell Park Memorial Institute during the study period. Fallopian tube cancer seems as virulent as ovarian cancer with few long-term survivors. It is frequently associated with other sites of upper genital tract malignancy. Second-look laparotomy is an important predictor of survival. Second-look laparoscopy may be useful if positive. ",3 2960,"Injuries in an elderly inner-city population. Even though injuries are a leading cause of morbidity and mortality among the elderly in the United States, no comprehensive population-based study of nonfatal and fatal injuries has been carried out in an elderly minority inner-city population. To study injuries in this population, we developed an active surveillance system as part of a large injury prevention program in a poor urban black community. We report 577 cases of nonfatal and fatal injuries in a community of 12,139 persons 65 years of age and older that resulted in emergency room treatment or death between March 1, 1987, and February 29, 1988. Nearly 5% of the elderly population was treated at an emergency room for, or died as a result of, an injury during the study period; the overall injury rate was 48 injuries per 1,000 persons. Injury rates for older women exceeded those for older men and increased with advancing age in both sexes. Fall injuries accounted for 312 (54%) of all injuries and 75% of all hospitalizations for injury. Motor vehicle incidents and violence were the second and third most common injuries, accounting for 13% and 7% of injuries, respectively. Given the predominance of falls relative to other injuries, prevention of falls should receive major emphasis in injury prevention efforts in inner-city minority populations. ",20 1510,"Direct ultrasonographic measurement of fetal lung length in normal pregnancies and pregnancies complicated by prolonged rupture of membranes. Fetal lung length was measured directly with ultrasonography in 20 patients with prolonged rupture of membranes, commencing before 25 weeks' gestation. Measurements were made weekly and compared with data collected from 310 normal pregnancies. Measurement of fetal lung length by ultrasonography was a good predictor of pulmonary hypoplasia, predicting greater than 90% of cases. There was a good correlation between lung size assessed by the last ultrasonographic examination and lung weight postmortem (r = 0.783, p less than 0.05). Lung length measurements were superior to fetal chest circumference measurements in the identification of pulmonary hypoplasia. There was a significant negative association between the amount of amniotic fluid and pulmonary hypoplasia (p less than 0.05). There were fetuses with pulmonary hypoplasia that had respiratory movements seen at the majority of ultrasonographic examinations. ",12 1197,"Some endorphin derivatives and hydrocortisone prevent EEG limbic seizures induced by corticotropin-releasing factor in rabbits. Corticotropin-releasing factor (CRF) injected into the cerebral ventricles of small mammals induces EEG limbic seizures, behavioral excitability, stereotyped behavior, and tardive enhancement of hippocampal theta voltage and frequency. Because we addressed this phenomenon when we explained the pathogenesis of infantile spasms in children, we wished to study the interference exerted by some gamma-endorphin fragments on EEG epileptiform and behavioral symptoms induced by CRF in the rabbit. Animals were implanted intracerebroventricularly (i.c.v.) with semichronic cortical and hippocampal electrodes, together with a cannula into the left lateral ventricle. When some gamma-endorphin derivatives (DT gamma E, DE gamma E) were injected intravenously (i.v.) for 4 days (or hydrocortisone once), they prevented the EEG ictal seizures induced in the hippocampus of rabbits by CRF injected i.c.v. Hydrocortisone and DE gamma E also prevented the appearance of scattered spiking and partially prevented tardive enhancement of theta voltage in the hippocampal EEG. Finally, DE gamma E also prevented stereotyped behavior and excitability induced by CRF. These results confirm the regulatory role exerted by CRF in limbic structure excitability and suggest that the above peptides may be involved in a regulatory feedback mechanism of CRF metabolism or activity. The possibility that these peptides may also have interesting antiepileptogenic properties should be considered. ",9 2598,"FcR-mediated enhancement of HIV-1 infection by antibody. Although CD4 is a major receptor for human immunodeficiency virus (HIV) infection of cells, studied by ourselves and others clearly show that the Fc receptor (FcR) also plays a role in infection, perhaps in conjunction with other surface receptors. IgG antibodies to HIV-1 will enhance infectivity in cells (such as monocyte-macrophages) that have surface Fc receptors; F(ab')2 fragments of antibodies did not enhance, and blocking of FcR inhibited enhancement. The high-affinity FcR for IgG (Fc gamma RI) appeared to be functional. Sera from HIV-1-infected patients had neutralizing activity at high concentrations, but enhanced infection at low concentrations (i.e., high dilutions). Our studies show that the CD4 receptor is required for antibody-mediated enhancement of infection, as enhancement can be blocked by recombinant soluble CD4 and by Leu3 antibody. Although enhancement can be demonstrated in vitro, the in vivo importance of enhancing antibodies remains to be defined in HIV-1 infection. ",19 2365,"Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes. Vanadate ions, low-molecular-weight phosphate analogues, mimic most of the rapid actions of insulin in various cell types. When administered orally to diabetic hyperglycemic rats, vanadate reaches the circulation, mimics insulin stimulation of glucose uptake and metabolism, and leads to normoglycemic and partial anabolic states. In addition, vanadate restores tissue responsiveness to insulin and hepatic glycogen levels and activates new synthesis of key enzymes for carbohydrate metabolism. This suggests that correcting hyperglycemia is sufficient to correct the typical metabolic alterations found in streptozocin-induced diabetic rats. Several weeks of oral administration of vanadate to diabetic rats has not produced detectable liver or kidney toxicity. The mechanism by which vanadate mimics the actions of insulin is still obscure. Unlike insulin, vanadate does not seem to stimulate the autophosphorylation and endogenous tyrosine phosphorylation of insulin-receptor kinase or other intracellular proteins either directly or by virtue of its known inhibitory effect on protein phosphotyrosine phosphatase. Results from many studies support a model in which vanadate activates glucose metabolism by either utilizing an alternative (insulin-independent) cascade or bypassing the early events of the insulin-dependent cascade. Either of these possibilities is of clinical importance, because early insulin events may become defective, as a result of severe hyperinsulinemia, and may contribute to insulin resistance. Alternative pathways by which vanadate may stimulate glucose metabolism, e.g., by increasing intracellular Ca2+ levels and/or regulating intracellular and intravesicular pH, are discussed. From a clinical perspective, studies should be continued in evaluating the level of vanadate toxicity after prolonged treatment and searching for agents that potentiate its insulin mimetic actions in vitro and in vivo. ",17 1852,"Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy [corrected and republished with original paging, article originally printed in J Am Coll Cardiol 1990 Oct;16(4):839-46] Heart-reactive antibodies are commonly observed in patients with myocarditis or cardiomyopathy. Such antibodies may be important in the pathogenesis of these disorders, yet the specific antigens recognized have not been studied systematically. This report characterizes circulating heart autoantibodies from patients with myocarditis (n = 17) or idiopathic cardiomyopathy (n = 71) and from healthy volunteers (n = 15). Indirect immunofluorescence demonstrated that high titer (greater than or equal to 1:20) immunoglobulin G (IgG) antibody activity occurred in 59% of the myocarditis samples, 20% of the cardiomyopathy samples and none of the normal samples. All samples were tested by Western immunoblotting for IgG activity against a normal human heart extract. The number of antigens recognized by each sample was enumerated and the molecular weight of each antigen estimated; the prevalence of reactivity against antigens in selected molecular weight classes was determined. There was no difference in the mean number of heart antigens recognized by serum from each group. For most weight classes, prevalence either did not differ significantly among the various groups or subgroups or was greatest among samples from healthy volunteers. Prevalence of reactivity with 190 to 199 kilodalton (kd) antigens was greatest (p less than 0.05) among low titer serum samples from patients with myocarditis. High titer cardiomyopathy serum differed from normal serum by an increased (p less than 0.05) prevalence of antibodies to 40 to 49 and 100 to 109 kd antigens. These results suggest that western immunostaining may ultimately contribute substantively to identifying patients with myocarditis or cardiomyopathy. ",13 2077,"Recanalization of chronic, totally occluded coronary arteries by new angioplasty systems. The benefit and safety of new angioplasty equipment as compared with the conventional guidewire approach was evaluated in 154 consecutive patients. with chronic, totally occluded coronary arteries. The protocol followed a stepwise design: first, conventional guidewires and low-profile balloons were used, followed by ""balloon-on-the-wire"" systems (Probe, Ace) or by a shaft-enforced, tip-deflecting catheter (Omniflex). In 97 patients with occlusions of 2 to 12 weeks' duration, recanalization was achieved in 51 patients (53%) with the conventional approach and in 29 patients with the new devices (balloon-on-the-wire [n = 5], Omniflex [n = 24]), thereby raising the success rate to 82%. In 57 occlusions of greater than 12 weeks' duration, the recanalization attempt was successful in 58%, mediated in 16 patients (28%) by the Omniflex catheter and in 5 patients by balloon-on-the-wire systems. There were no life-threatening complications and only 1 (0.6%) emergency bypass operation was necessary. New angioplasty devices are therefore of considerable value in the attempt to improve the results of coronary angioplasty in chronic total occlusions. ",13 2462,"Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East. A common glucose-6-phosphate dehydrogenase (G6PD) variant characterized by severe enzyme deficiency and B-like electrophoretic mobility is called ""G6PD-Mediterranean"" because it is found in different populations around the Mediterranean Sea. Sequence analysis of Italian subjects has revealed that the molecular basis of G6PD-Mediterranean is a single C-T transition at nucleotide position 563, causing a serine phenylalanine replacement at amino acid position 188. Most G6PD-Mediterranean subjects also have a silent C-T transition (without amino acid replacement) at nucleotide position 1311. Twenty-one unrelated individuals from Saudi Arabia, Iraq, Iran, Jordan, Lebanon, and Israel with both severe G6PD deficiency and B-like electrophoretic mobility were tested for both mutations by using amplification followed by digestion with appropriate restriction enzymes. All but one had the 563 mutation, and, of these, all but one had the 1311 mutation. Another 24 unrelated Middle Eastern individuals with normal G6PD activity or not known to be G6PD deficient were similarly tested. Four had the silent mutation at position 1311 in the absence of the deficiency mutation at position 563. We conclude that (1) the large majority of Middle Eastern subjects with the G6PD-Mediterranean phenotype have the same mutation found in Italy, (2) the silent mutation is an independent polymorphism in the Middle East, with a frequency of about .13, and (3) the mutation leading to the G6PD-Mediterranean deficiency has probably arisen on a chromosome that already carried the silent mutation. ",17 1875,"Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease BACKGROUND. The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS. To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS. The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS. The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment. ",13 3049,"Urgent care center pediatric telephone advice. Pediatric telephone advice is sought frequently by members of the community. This study was undertaken to evaluate the quality and accuracy of pediatric telephone advice given by free-standing urgent care centers. One hundred such facilities were telephoned and advice was requested by a research assistant. A case was presented that could have represented a pediatric medical emergency. Overall only 17 centers gave adequate advice. The data suggest that under some circumstances free-standing urgent care center pediatric telephone advice may be inaccurate and inappropriate. Workable policies and protocols for pediatric telephone advice should be instituted by these facilities. ",22 3014,"Kidney transplantation in patients aged sixty years and older. Outcomes of renal transplantation were reviewed for 26 transplants performed in 25 patients 60 years of age or older between 1985 and 1989. Three grafts were from family donors and 23 were from cadaver donors. Twenty-one were first transplants and five were retransplants. Cyclosporine was used as primary immunosuppression and azathioprine and prednisone were administered to most patients. Overall patient and graft actuarial survival rates were 79% and 71%, respectively, at both 1 and 3 years. Patients (n = 14) free of both diabetes and cardiac disease (low risk) had 1- and 3-year patient and graft survival rates of 91% and 84%, respectively. Conversely, high-risk patients (n = 12) had patient and graft survival rates at 1 and 3 years of 67% and 58%, respectively. Early deaths (less than or equal to 6 months) were caused by sepsis (two patients) or cardiac events (three patients), and four of the five were in high-risk patients. Irreversible rejections and serious infectious complications were not as common as steroid-induced diabetes, which occurred in five patients. This experience suggests that kidney transplantation can be done safely and successfully in patients older than 60 years of age and should be the treatment of choice for low-risk patients in this category. ",22 2675,"Suppressive effects of morphine pellet implants on in vivo parameters of immune function. Chronic morphine treatment elicits a variety of immunosuppressive effects in mice. Most of the work describing this immuno-suppressive activity of the opioid is based on in vitro assessments of the performance of certain components of the immune system in morphine-treated animals. Relatively little has been done by way of tracking the effects of chronic morphine treatment on immunologic parameters in the intact animal. Therefore, this study used several classic in vivo determinations of immune function in mice treated chronically with morphine. Morphine pellet (75 mg) implantation led to a significant inhibition (91%) of paw swelling in a picryl chloride-induced delayed type hypersensitivity response. Uptake of iododeoxyuridine in an in vivo lymphocyte proliferation assay and splenomegaly in a graft vs. host reaction were also significantly suppressed by morphine pellet implantation (34 and 52%, respectively). Coimplantation of a naltrexone pellet (10 mg) completely reversed the suppressive responses to morphine in each assay. Naltrexone alone had no significant effect in any of the assays. The suppressive effects of morphine were less pronounced in adrenalectomized mice in the graft vs. host assay (51% vs. 9% reduction in morphine-pelleted shams relative to morphine-pelleted adrenalectomized mice). These findings indicate the pathophysiologic significance of the previously reported suppression of in vitro correlates of immune function in morphine-pelleted mice. The results further demonstrate that the immunosuppressive effects observed after morphine pellet implantation are naltrexone reversible and suggest that activation of the adrenal is one potential mechanism for this effect. ",19 497,"Increasing incidence of cecal and sigmoid carcinoma. Data from the Connecticut Tumor Registry. We have studied both the distribution and incidence of colorectal cancer using The Connecticut Tumor Registry, the oldest tumor registry in the United States. During the time period 1973 to 1985, left-sided colon cancers accounted for 63% of the cancers, right-sided cancers 33%, and cancers with unspecified sites 4%. Indeed, this pattern of distribution has remained constant for 25 years. For the period 1935 to 1985, we calculated the sex-specific, age-adjusted (normalized to the 1970 U.S. Census) incidence. Age-adjusted incidence of rectal cancer has remained stable for 50 years: for men, 22.8 cases/100,000/year, and for women, 13.9 cases/100,000/year. During these 50 years, the age-adjusted incidence of cecal carcinoma for men has increased from 3.6 to 16.7 cases/100,000/year, while for women, it has increased from 4.9 to 14.2 cases/100,000/year. Sigmoid carcinoma for men has increased from 8.8 to 18.7 cases/100,000/year, and for women, it has increased from 7.7 to 12.8 cases/100,000/year. The incidence of colon cancer at each site has been and continues to be increasing at a constant rate. Age-adjusted incidence for all colorectal cancers has increased from 35.2 to 70.2 cases/100,000/year for men and from 32.1 to 49.2 cases/100,000/year for women. Thus, distribution of colorectal cancers by site in Connecticut has remained stable for 25 years. More importantly, however, the age-adjusted incidence of colon cancer has continued to increase for 50 years, whereas that of rectal cancer has remained relatively stable. ",3 3215,"Prehospital prophylactic lidocaine does not favorably affect outcome in patients with chest pain. STUDY OBJECTIVES: The purpose of our study was to determine the morbidity and mortality in initially stable patients presenting to paramedics with chest pain; to examine possible beneficial effects of its use, including reduction of sudden death syndrome in the prehospital and emergency department setting; and to determine if prophylactic lidocaine is associated with adverse effects in this patient population. DESIGN AND SETTING: This was a randomized, prospective study using prophylactic lidocaine in patients complaining of chest pain who presented to our paramedic system between January 1984 and January 1988. TYPE OF PARTICIPANTS: All patients aged 18 years or older with chest pain of suspected cardiac origin who presented to paramedics during the study period were included. Excluded were patients presenting with warning arrhythmias, second- or third-degree heart block, bradycardias of less than 50, hypotension of less than 90 mm Hg systolic, or known allergy to lidocaine. INTERVENTIONS: Patients were randomized into two groups, the lidocaine-treated group and the control group. An initial bolus of 1 mg/kg IV lidocaine was administered to the lidocaine-treated group. A simultaneous 2 mg/min IV drip was established. Ten minutes after the first dose of lidocaine, a second bolus of 0.5 mg/kg was administered. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,427 patients were entered; 704 received lidocaine, and 723 did not. Discharge diagnoses included acute myocardial infarction (31%), unstable angina (33%), other cardiac problems (7%), and noncardiac problems (29%); overall mortality rate was 7.4%. There was an equal distribution of deaths between the lidocaine-treated group (57) and the control group (48). Six patients had a cardiac arrest in the prehospital setting, and 15 had a cardiac arrest in the ED. Malignant ventricular arrhythmias as the precipitating arrest rhythm in patients with acute myocardial infarctions were similar for the lidocaine-treated and control groups. The incidence of adverse effects, including hypotension, bradycardias, second- or third-degree heart blocks, tinnitus, and altered mental status, was similar in both groups. CONCLUSION: There are no benefits from the administration of prehospital prophylactic lidocaine in stable patients with chest pain; therefore, routine use in this setting appears unwarranted. ",22 732,"Management of the acute abdomen complicating oral anticoagulation therapy. Acute abdominal pain in the patient receiving oral anticoagulants poses a difficult diagnostic and therapeutic challenge. We describe two cases of peritonitis requiring laparotomy in anticoagulated patients, and review 49 similar case reports from the world literature. These patients were usually explored for signs of bowel obstruction. At operation, the intestine often appeared infarcted, but pathologic examination commonly revealed intramural hematomata. In contrast, we present microscopic evidence of hemorrhagic cecal infarction complicating oral anticoagulation therapy in one patient. Intramural intestinal hemorrhage is the most common cause of acute abdominal pain in the anticoagulated patient who undergoes laparotomy. In addition to intramural hemorrhage, 14 per cent of patients had coexistent volvulus, appendicitis, intestinal wall disruption or intestinal infarction. We conclude that anticoagulated patients with suspected intramural intestinal hemorrhage may have severe intraabdominal pathology requiring operation. Therefore, operation is mandatory for patients who fail to improve after a short course of expectant management. ",5 2045,"New calcium antagonists: relevance of vasoselectivity. The calcium antagonists are a heterogeneous class of drugs used to treat a number of cardiovascular disorders. A new generation of calcium antagonists under development have a higher degree of selectivity for vascular smooth muscle and coronary vasculature compared with verapamil, nifedipine, and diltiazem. The clinical relevance of vasoselectivity and its impact on drug selection are discussed. The newer calcium antagonists are important alternatives to older agents and may be associated with improved tolerance and a reduced incidence of adverse effects. Their place in therapy has yet to be defined by comparative studies of efficacy and safety. ",13 413,"Constitutional symptoms in patients with germ cell neoplasms. A patient with a mediastinal germ cell neoplasm evidenced fever, weight loss, pruritus, and painful adenopathy on ingestion of alcohol. Retrospective review revealed that 9 percent of 104 patients with advanced germ cell neoplasm evidence constitutional symptoms at presentation. ",3 1748,"Does blood rheology revert to normal after myocardial infarction? After myocardial infarction there is an acute deterioration of the flow properties of blood. The present study was designed to test whether the abnormality persists. Blood and plasma viscosity, red cell aggregation and deformability, haematocrit, erythrocyte sedimentation rate, white cell count, cholesterol, and triglycerides were measured in 51 patients who had had a myocardial infarction 5.4 (mean) years before. Results in patients and controls were compared and matched pairs with identical cardiovascular risk factors were also selected. Blood viscosity and red cell aggregation were increased and red cell deformability was decreased in the 51 patients. The abnormalities were independent of the interval since infarction and persisted for years. The rheological abnormalities present after myocardial infarction are at least partly independent of the acute event and acute phase reactions. They contribute to the reduced perfusion of the microcirculation of the heart. ",13 2445,"Temporary amelioration of hyperlipidemia in low density lipoprotein receptor-deficient rabbits transplanted with genetically modified hepatocytes. Familial hypercholesterolemia is an inherited disease in humans that is associated with coronary artery disease and is caused by a deficiency of the receptor that mediates the internalization of low density lipoprotein (LDL). We have used an animal model for familial hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit, to design a therapeutic approach for this disease, which attempts to correct the hepatic defect in LDL receptor expression. Hepatocytes were harvested from WHHL rabbits, plated in primary cultures, and exposed to recombinant retroviruses capable of efficiently transferring a functional human LDL receptor gene. Genetically modified cells were harvested and infused into the portal vein of WHHL recipients, who were analyzed for metabolic consequences of human LDL receptor expression. Each animal exhibited a statistically significant decrease in total serum cholesterol 2-6 days after transplantation, with an eventual return to pretreatment levels. Proviral DNA sequences and virus-directed transcripts were detected in liver tissue 24 hr after transplantation. In situ hybridization demonstrated provirus expression in a small population of hepatocytes distributed in periportal sections of the liver. This study illustrates the potential of somatic gene therapy in ameliorating hyperlipidemia associated with familial hypercholesterolemia. ",17 2961,"Effects of nonparticipation in trauma center system on emergency department utilization. The University of Illinois Hospital (UIH) serves an inner-city urban population in one of the highest crime rate districts in Chicago. On May 20, 1986, the city's Level I Trauma ordinance took effect with the University of Illinois Hospital declining to participate. To measure the impact of the ordinance on a nonparticipating hospital, we undertook a retrospective analysis of our trauma patient utilization statistics. Consecutive monthly patient census data of 71 months was compiled with emphasis on patient presenting complaints and related subspecialty evaluation. We observed significant decreases of patients presenting with head injuries, fractures, and animal bites as well as with major trauma, minor trauma, and general surgery hospital admission. The final disposition of the patients arriving by ambulance was consistent with the observed decrease in major traumatic conditions and in minor traumatic conditions. However, the mean number of patient presentations per day (ppd) admitted to regular medical or surgical beds decreased from 2.70 ppd to 2.30 ppd while the mean number of ppd sent home increased from 2.64 ppd to 3.49 ppd. These data suggest that loss of trauma center status designation has a profound effect on utilization of emergency departments not participating in the trauma system. Nonparticipation appears to be associated with a significant decrease in utilization rates for major and minor trauma patients and a significant increase in the number of patients discharged who had arrived by the Chicago Fire Department Paramedic System (CFD). This effect on the emergency department extends to utilization of inpatient services. ",20 3051,"Systemic pattern of free radical generation during coronary bypass surgery. Diffuse impairment of ventricular function after cardiac surgery may be related to the generation during reperfusion of the myocardium of free radicals derived from oxygen. Fifteen patients undergoing elective coronary bypass surgery were studied by previously described assays for peroxidised lipids and for isomerised lipids which were used as indices of free radical activity. Serial blood samples were obtained from systemic arterial, mixed venous, and coronary sinus catheters before, during, and after the ischaemic period. The patients underwent coronary artery surgery on cardiopulmonary bypass with a membrane oxygenator, relative hypothermia 30-34 degrees C, and intermittent cross-clamping of the aorta. During the ischaemic periods there were no significant changes in the indices of free radical activity. During the reperfusion phase there was a significant increase in free radical indices in arterial and mixed venous blood. A small rise in free radical indices in coronary venous blood was not statistically significant. These data indicate that free radical activity is increased in patients shortly after the cessation of cardiopulmonary bypass. The pattern of distribution between the different sampling sites suggests that much of the observed increase in isomerised and peroxidised lipids originates from tissues other than the myocardium. ",22 3187,"Color Doppler diagnosis of mechanical prosthetic mitral regurgitation: usefulness of the flow convergence region proximal to the regurgitant orifice. In prosthetic or paravalvular prosthetic mitral regurgitation, transthoracic color Doppler flow mapping can sometimes fail to detect the regurgitant jet within the left atrium because of the shadowing by the prosthetic valve. To overcome this limitation, we assessed the utility of color Doppler visualization of the flow convergence region (FCR) proximal to the regurgitant orifice in 20 consecutive patients with mechanical prosthetic mitral regurgitation documented by surgery and cardiac catheterization (13 of 20 patients). In addition, we studied 33 patients with normally functioning mitral prostheses. Doppler studies were performed in the apical, subcostal, and parasternal long-axis views. An FCR was detected in 95% (19 of 20) of patients with prosthetic mitral regurgitation. A jet area in the left atrium was detected in 60% (12 of 20) of patients. In 18 of 19 patients with Doppler-detected FCR, the site of the leak was correctly identified by observing the location of the FCR. A trivial jet area was detected in eight patients with a normally functioning mitral prosthesis; in none was an FCR identified. Thus color Doppler visualization of the FCR proximal to the regurgitant orifice is superior to the jet area in the diagnosis of mechanical prosthetic mitral regurgitation. Moreover, FCR permits localization of the site of the leak with good accuracy. ",22 1401,"Effect of calcium entry blocker nitrendipine on renal function after renal vascular occlusion. The ability of the Ca entry blocker nitrendipine to improve postischemic renal function was studied in nine groups (n = 70) of rats. After anesthesia, nitrendipine was administered for 15 min through the femoral vein. The dose administered depended on the group. Group 1 (n = 7), the control, received only 0.9% NaCl, group 2 (n = 12) 0.25 mg/kg; group 3 (n = 10) 0.50 mg/kg; group 4 (n = 8) 0.75 mg/kg; group 5 (n = 6) 1.00 mg/kg; group 6 (n = 7) 1.50 mg/kg; group 7 (n = 7) 2.00 mg/kg; group 8 (n = 6) 2.50 mg/kg; and group 9 (n = 7) 3.00 mg/kg. After the administration of nitrendipine, the kidneys were rendered ischemic for one hour by cross-clamping the renal vessels. Comparison of 24-h creatinine clearances for 72 h after reversal of ischemia demonstrated that nitrendipine was capable of providing a degree of protection against renal ischemia and the protective effect was dose dependent (p less than .05). ",11 3283,"Defective dystrophin in Duchenne and Becker dystrophy myotubes in cell culture. We examined normal and dystrophic human myotubes in cell culture for expression of dystrophin, the protein product of the Duchenne muscular dystrophy locus. Dystrophin levels in developing myotubes detected by Western blotting increased after 24 hours and reached maximum levels after 10 days in fusion medium. We did not detect dystrophin in myotubes cultured from Duchenne myoblasts (7 cases). Myotubes from a Becker muscular dystrophy patient's biopsy produced a lower molecular weight (approximately 408 kd) dystrophin, which was the same size in a whole muscle preparation from the same biopsy. This 408-kd dystrophin was the expected size for this Becker patient whose DNA was deleted for exons 45-48 of the Duchenne gene. This cell culture system will allow a detailed analysis of the effects of potential pharmacologic agents on steady-state dystrophin levels. ",22 375,"Ampullary carcinoma in patients under 50 years of age with a poor prognosis. Clinicopathologic features of 145 Japanese patients with ampullary carcinoma were compared among three age groups. The 145 patients were divided into three groups by the patient's age at the time of operation; there were 24 patients in group I (younger) aged less than or equal to 50 years, 99 in group II (ordinary) aged 51-69, and 22 in group III (elderly) aged greater than or equal to 70. The three groups showed no significant difference in sex, icterus, duration of icterus, size of the tumor, year of operation, macroscopic type, histopathologic type, tumor margin, lymphatic permeation, venous invasion, or pancreatic invasion. The survival curve of group I was worse than those of groups II and III. Multivariate regression analysis using 11 prognostic variables failed to reveal that the age of the patient at the time of operation was an independent factor. The younger patients aged less than or equal to 50 fared worse than the elderly patients aged greater than or equal to 70, because the group I tumors included a significantly greater number of advanced ampullary carcinoma with more frequent perineural invasion than did the group III tumors. ",3 2881,"Traumatic disruptions of the thoracic aorta: treatment and outcome. Of 27 patients admitted to our level I trauma center with acute disruption of the thoracic aorta, two patients died of exsanguination before aortic repair. One patient had massive leakage from the aneurysm after aortography and died during surgery. All patients suffered from multiple injuries. Eighty-three percent of the patients had major operations in addition to the aortic repair. ""Clamp and sew"" technique was used in 18 patients (75%), two of whom had multiple tears of the aortic arch. Heparin-coated shunts were used in five patients (20.8%), and a cardiopulmonary bypass was performed in one patient who had multiple tears. Three postoperative deaths were related to polytrauma, cardiogenic shock, and sepsis. Paraplegia developed in three patients, two of whom had multiple aortic lesions necessitating longer ischemia time during the repair. Only one patient had complete neurologic deficit at the 1-year follow-up. In our series, neither surgical procedure proved superior. We conclude that the ""clamp and sew"" technique for repair of the disrupted thoracic aorta may allow for a more favorable outcome. ",20 2963,"Blunt trauma to the heart: the pathophysiology of injury. Blunt injuries to the heart are common and potentially lethal. These injuries often go undetected while more obvious problems are treated. A cardiac injury should be suspected in any patient who sustains severe chest trauma. The spectrum of cardiac trauma ranges from injuries with no actual cellular damage (myocardial concussion) to cardiac chamber rupture. The pathophysiology, diagnosis, and treatment of these injuries are discussed. ",20 2776,"Alcohol protects the diaphragm during dietary restriction. We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress-stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different. ",20 2019,"Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia. The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine. ",13 2609,"Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma. The efficacy of nebulized glycopyrrolate compared with metaproterenol was evaluated in 46 patients with acute asthma. In a double-blinded, randomized fashion, patients received, as sole therapy, either 2 mg of glycopyrrolate or 15 mg of metaproterenol every 2 h over a 6-h study period. Of the 35 patients completing the study, analysis of variance demonstrated no difference in percentage of change in FEV1 between glycopyrrolate and metaproterenol. Two hours after the initial dose, there was a 30 percent increase in FEV1 for glycopyrrolate compared with a 25 percent increase for metaproterenol (p greater than 0.05, NS). In contrast to the comparable bronchodilator activity, the side effects profile of the two agents were markedly dissimilar. Not only were subjective complaints of tremor, palpitations, and paresthesias increased for metaproterenol, but the heart rate response was significantly elevated (p less than 0.05) compared with glycopyrrolate. Based on these data, administration of the aerosolized anticholinergic agent, glycopyrrolate, is a reasonable therapeutic alternative for acute asthma. ",19 1784,"Clinical evaluation of single versus multiple mammary artery bypass. The superior patency and clinical advantages of internal mammary artery (IMA) grafting are well established. However, the relative benefits of routine multiple IMA grafting remain uncertain. To determine whether routine multiple compared with single IMA utilization improved survival of patients undergoing coronary bypass procedures, 1,063 patients were prospectively allocated, beginning in 1984, to divergent management strategies of single (group 1, n = 420) versus multiple IMA grafting (group 2, n = 643). Subsequent analysis of anatomical extent of disease and preoperative baseline risk factors showed no differences (p = NS) between the two groups. All variables reflecting operative technique were similar (p = NS) for the two groups, except 74% of group 1 patients with multivessel disease received a single IMA graft, whereas 71% of group 2 patients with multivessel disease received multiple IMAs (p less than 0.05). By multivariate analysis, impairment of left ventricular ejection fraction, acute evolving myocardial infarction, advanced age, and unstable angina were incremental risk factors for mortality (all p less than 0.03), but group assignment (p = 0.4) and ultimate therapy were not (p = 0.6). Survival probabilities (expressed as 30-day group 1/group 2; 4-year group 1/group 2) were overall (0.97/0.98; 0.93/0.90), elective (0.98/0.99; 0.97/0.92), acute (0.95/0.97; 0.89/0.88), age of less than 65 years (0.98/0.99; 0.97/0.93), age of 65 years or older (0.93/0.97; 0.84/0.89), ejection fraction of 0.40 or more (0.97/0.99; 0.95/0.94), ejection fraction of less than 0.40 (0.95/0.96; 0.87/0.82), nondiabetic (0.98/0.98; 0.94/0.91), and diabetic (0.92/0.97; 0.88/0.87). No differences in survival were significant (p = NS). ",13 1392,"In treating impotence, urology and sex therapy are complementary. Urologists and mental health professionals are neither competitors nor adversaries. The principles of sex therapy represent a thoughtful and sensitive way to approach patients with almost any clinical problem so that they are more comfortable with the recommended tests or treatments. Sex therapy may be very helpful as an adjunct in treating ""organic"" as well as primarily emotional erectile dysfunction. We believe that with information we can help build a bridge between urologists and mental health professionals. ",11 2008,"Transient myocardial ischaemia after acute myocardial infarction. The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications. ",13 909,"Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients. The effect of changing the rate of infusion of propofol for induction of anaesthesia was studied in 60 elderly patients. Propofol was administered at 300, 600 or 1200 ml h-1 until loss of consciousness (as judged by loss of verbal contact with the patient) had been achieved. The duration of induction was significantly longer (P less than 0.001) with the slower infusion rates (104, 68 and 51 s), but the total dose used was significantly less (P less than 0.001) in these patients (1.2, 1.6 and 2.5 mg kg-1, respectively). The decrease in systolic and diastolic arterial pressure was significantly less in the 300-ml h-1 group at the end of induction and immediately after induction (P less than 0.01). The incidence of apnoea was also significantly less in the slower infusion group. ",7 47,"A large outbreak of antibiotic-resistant shigellosis at a mass gathering. In July 1987, a large outbreak of shigellosis occurred among attendees at a mass gathering in a national forest, the annual Rainbow Family Gathering. Sanitation in the campsite was poor, allowing widespread transmission of disease, probably by food, water, and person-to-person spread. The attack rate may have been greater than 50% among the estimated 12,700 attendees. The outbreak was caused by Shigella sonnei, resistant to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole; the organism was of colicin type 9 and contained a 90-kilobase plasmid not found in non-outbreak-related strains. The dispersal of the group resulted in nationwide dissemination of the organism, and outbreaks in three states were linked to transmission from attendees at the Gathering. This outbreak demonstrates the potential for rapid dissemination of disease in such a setting and the necessity for careful planning of mass gatherings. ",0 1914,"Effect of beta-adrenergic blocking agents on the circadian occurrence of ischemic cardiovascular events. Clinical observations suggest that beta-adrenergic blocking agents can modify the circadian occurrence of a variety of ischemic events. Morning awakening is associated with a rapid increase in blood pressure and pulse, serum catecholamine content and platelet activation, at a time of decreased blood thrombolytic activity. Beta-adrenergic blocking agents have the potential to modify many of these events. Current data indicate that these agents modify blood pressure and pulse, but do not prevent their early morning increase. In addition, beta-adrenergic blocking agents decrease ventricular ectopy and its circadian variation. Recent studies in humans indicate, however, that metoprolol does not affect the circadian increase in platelet activity or serum catecholamines. The specific mechanism by which beta blockers affect the circadian occurrence of ischemic events remains uncertain. ",13 3031,"Plasma norepinephrine in chronic schizophrenia. Several lines of evidence indicate altered noradrenergic function in schizophrenia. The authors examined resting, standing, and change (standing minus resting) in plasma norepinephrine levels in 14 drug-free patients with chronic schizophrenia or schizoaffective disorder and in 33 age- and sex-matched healthy volunteers. Schizophrenic patients had significantly higher resting and standing plasma norepinephrine levels and significantly greater change. Resting and standing levels were significantly related to positive and negative symptoms. There was a significant positive correlation between resting plasma and CSF norepinephrine levels and a significant negative correlation between CSF homovanillic acid and resting, standing, and change in plasma norepinephrine levels. ",22 262,"Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases. We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence. ",3 1223,"Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment. ",9 2308,"Growth factor and proto-oncogene expression in psoriasis. The expression of several proto-oncogenes and growth factors was analyzed in normal skin and psoriatic lesions by RNA blot hybridization. Isolation of intact RNA from frozen biopsy samples required immediate exposure to denaturants during tissue homogenization. Lipocortin II and cyclophilin transcripts were used as internal controls. These transcripts were abundant and slightly but significantly elevated in psoriatic lesions. When results were normalized according to these reference transcripts, there was no increase in the expression of c-myc, c-Ha-ras, c-erbB (EGF receptor), c-jun, or transforming growth factor-beta (TGF-beta) transcripts in psoriatic lesions, and lesional c-fos transcripts were decreased relative to normal skin. In contrast, expression of TGF-alpha mRNA transcripts were markedly increased in psoriatic lesions even after normalization. Placement of normal or psoriatic tissue in organ culture for 2 to 4 h resulted in strong induction of c-fos, c-jun, and c-myc transcripts, but not of the other genes studied. Thus, overexpression of proto-oncogenes may be more characteristic of the epidermal response to acute injury than of the steady-state hyperplasia characteristic of psoriasis. Interferon-gamma (IFN-gamma) increased TGF-alpha mRNA levels in cultured human KC at long time intervals (24-48 h). However, of various cytokines tested, only EGF and TGF-alpha induced TGF-alpha mRNA after short time intervals (2-4 h). These results as well as the selective overabundance of TGF-alpha mRNA in psoriatic lesions among various cytokines tested suggest that activation of the EGF receptor tyrosine kinase by TGF-alpha is important in the pathogenesis of psoriatic epidermal hyperplasia. ",16 858,"Needle aspiration biopsy in salivary gland lesions. The value of needle aspiration biopsy in the evaluation and management of salivary gland pathology is controversial. The major reasons for this controversy are the difficulty in cytologic evaluation and the fact that the extent of surgery can be easily defined based on clinical judgement. However, a preoperative diagnosis is helpful in discussions with patients regarding the extent and type of surgery. Apart from the fact that needle biopsy can distinguish benign from malignant conditions, it is also very useful in distinguishing between salivary and other nonsalivary pathology. Over the past 7 1/2 years, we have performed 160 needle aspirations of parotid, submandibular, and submucosal lesions. Adequate specimens for cytologic evaluation were obtained in 155 patients (97%). A total of 84 parotid lesions, 70 submandibular lumps, and 6 submucosal abnormalities were detected. A cytologic diagnosis of benign pathology was made in 120 patients. Twelve patients had lymphoma and the diagnosis was suspected based on needle aspiration. There were 10 patients with tuberculosis and 30 patients with hyperplastic lymph nodes or benign lymphoepithelial disease of the parotid. There were three false-positive and two false-negative reports. No complications such as hematoma, nerve injury, or infection developed. The major difficulty was in distinguishing between malignancy and obstructive sialadenitis in the submandibular region. Needle aspiration was helpful in evaluating lesions in the tail of the parotid and submandibular area. The cytologic distinction between salivary and nonsalivary pathology was useful in planning the appropriate surgery and the extent of surgical resection. From a clinical standpoint, the distinction between benign and malignant salivary and nonsalivary pathology was very helpful. Preoperative diagnosis of Warthin's tumor, lymphoma, or benign lymphoepithelial disease was essential to the correct management of these patients. ",6 2453,"Cholesterol-lowering effect of skim milk from immunized cows in hypercholesterolemic patients. The effect of skim milk from cows immunized against a variety of human intestinal bacteria on serum cholesterol concentrations was examined in 11 patients with primary hypercholesterolemia in a 24-wk, randomized, double-blind, placebo-controlled, crossover study. After a 4-wk baseline period, patients were treated for 8 wk either with skim milk from immunized cows (active) or with control skim milk (placebo) followed by an 8-wk period with the treatment order reversed. Eight weeks of active treatment with skim milk from immunized cows reduced serum total cholesterol concentrations by 0.52 +/- 0.59 mmol/L (mean +/- SD; P less than 0.025), or 8%, LDL cholesterol by 0.16 +/- 0.59 mmol/L (NS), or 4%, and the atherogenic index (total cholesterol/HDL cholesterol) by 0.42 +/- 1.85 (P less than 0.05), or 8%, compared with the placebo treatment. Reversal of the favorable development occurred upon cessation of active treatment. We conclude that daily supplementation of a normal diet with skim milk from immunized cows can result in a significant reduction of elevated blood cholesterol concentrations. ",17 667,"Eosinophilic granuloma of the cervical spine. A case report and review of the literature. This is a report of a case of eosinophilic granuloma involving the second cervical vertebra in a 33-year-old woman. There have been 32 case reports in the literature describing eosinophilic granuloma presenting as cervical spine disease. Due to its intimate relation to the central nervous system, the opportunity for neurological sequelae and neurosurgical intervention is common in cervical eosinophilic granuloma. In this report a brief history of eosinophilic granuloma is reviewed and case histories from the literature with cervical spine involvement are summarized. The therapeutic options are described and a recommended protocol for management is outlined. ",4 2699,"Influence of human immunodeficiency virus infection on reproductive decisions. This article discusses the role of the practitioner in the pregnancy decision-making process of the HIV-infected woman. Literature on women's decisions is reviewed, and variables that influence decisions are discussed. The author concludes that HIV infection does not have a significant impact on pregnancy decisions. Other cultural and psychosocial variables may have more importance. ",19 762,"Stasis syndromes following gastric surgery: clinical and motility features of 60 symptomatic patients. We retrospectively reviewed the records of 60 patients who had been referred for gastrointestinal manometry because of stasis after gastric surgery. Nausea, vomiting, bloating, abdominal pain, and weight loss were the most common symptoms. Two thirds of these patients had a well-documented history of peptic ulcer before their initial operations; in others, surgery was performed for other reasons, such as obesity (5%) or reflux esophagitis (8%). Twelve patients had undergone truncal vagotomy and a ""drainage operation"" and 48 had received a partial gastrectomy with a gastroenterostomy: Billroth I (n = 8), Billroth II (n = 11), Roux-en-Y (n = 29). All patients had recordings of gastrointestinal manometry; 16 also had a scintigraphic measurement of gastric emptying. Measurements were compared with data from healthy controls. Gastric manometry, which could be assessed only in the group with an intact antrum, was characterized by antral hypomotility (p less than 0.05). Gastric emptying studies showed rapid early emptying of liquids and delayed emptying of solids (both p less than 0.05). In the whole group, fasting jejunal motility was characterized by absence of phase II in 13, presence of bursts of phasic activity in 18, and abnormal propagation of phase III in 8. A significantly increased frequency of phase III of MMC was noted in the patients after Billroth II and Roux-en-Y operations. Postprandially, 19 patients failed to develop a ""fed pattern."". ",5 2636,"HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Cells of the mononuclear phagocyte system are the predominant cell producing HIV-1 in most tissues including the central nervous system (CNS), spinal cord, lung and skin; infection is associated with dementia, neuropathy, pneumonitis, and dermatitis respectively. Different HIV-1 isolates vary markedly in their ability to infect mononuclear phagocytes productively. Here we describe molecular clones of a CNS-derived isolate, HIV-1(JR-FL), which can replicate efficiently in mononuclear phagocytes. Analysis by polymerase chain reaction of early events after infection indicates that the early phase of viral replication before reverse transcription determines tropism. Genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates that mononuclear phagocyte infectivity can be determined by a 157-amino-acid region of the gp 120 glycoprotein of HIV-1(JR-FL). Significantly, this region is upstream from the previously defined CD4-binding domain. We propose that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain. ",19 2273,"Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. The expression of B-type receptors for platelet-derived growth factor (PDGF) was investigated in skin biopsy samples from patients with systemic sclerosis (SSc), by immunohistochemical staining using monoclonal antibodies specific for the receptor. Whereas skin from healthy individuals lacked expression of PDGF-B receptors, receptor expression was seen in sclerodermatous skin lesions from 13 of 14 patients. Increased receptor expression was observed in dermal vessels, as well as on many stromal fibroblast-like cells close to these vessels. PDGF-B receptor expression was most pronounced within and around dermal vessels in which perivascular infiltrates of Leu-4-positive T lymphocytes and HLA-DR-positive, RFD7-positive activated macrophages were present. Both perivascular inflammatory cell infiltrates and PDGF-B receptor expression were generally also seen in macroscopically normal areas of the skin of the SSc patients, indicating that the observed phenotypic alterations may precede the macroscopically observable features of scleroderma in the skin. The observed induction of PDGF-B receptors, together with indirect indications of increased synthesis and release of PDGF, would be compatible with altered PDGF-mediated control of connective tissue cell growth as part of the molecular basis for development of the skin lesions in SSc. ",16 2370,"Absence of brown product FFI in nondiabetic and diabetic rat collagen. Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2-(2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L-proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry. ",17 3025,"Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. Altogether, 750 cases of spontaneous abortion between the fifth and 25th week of gestation were analyzed cytogenetically by the direct-preparation method using chorionic villi. The majority of cases (68%) were derived from early abortions before the 12th week of gestation. The frequency of abnormal karyotypes was 50.1%; trisomy was predominant (62.1%), followed by triploidy (12.4%), monosomy X (10.5%), tetraploidy (9.2%), and structural chromosome anomalies (4.7%). Among trisomies, chromosomes 16 (21.8%), 22 (17.9%), and 21 (10.0%) were prevalent. The frequency of chromosomally abnormal abortions increased with maternal age but only because of an increase of trisomy. Polyploidy and monosomy X, however, decreased. Mean maternal age was significantly increased for trisomies 16, 21, and 22 and was highest for trisomies 18 and 20. The results obtained are within the range of variability reported earlier from tissue culture-type studies. A consistent feature during our study is the excess of females in chromosomally normal abortions (male:female sex ratio 0.71). According to the methodology applied, maternal cell contamination and undetected 46,XX molar samples cannot have influenced the sex ratio. However, a bias introduced by social status or maternal age cannot be excluded. With the more rapid and convenient direct preparation of chorionic villi, reliable cytogenetic data on causes of spontaneous abortions can be obtained. ",22 3015,"The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common. ",22 702,"Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations. Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms. ",5 715,"Albumin absorption and protein secretion by the gallbladder in man and in the pig. To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders. ",5 1437,"One year of rHuEPO therapy prolongs RBC survival and may stabilize RBC membranes despite natural progression of chronic renal failure to uremia and need for dialysis. rHuEPO was administered to eight patients with chronic renal failure (CRF) and uremia (U) for 1 year. Creatinine Clearance (GFR) averaged 14.3 (9-25) ml/min at an Hct of 28% (26-30). Baseline RBC survival by 51Cr T1/2 was highly correlated with GFR (r = 0.66), p less than 0.05 (2), average 21.6 days. Repeat 51Cr T1/2 at 3 months with GFR 10 ml/min at Hct 38% was prolonged by 7 days to 28.6 (p less than 0.005), and at 1 year remained increased to 28 days (p less than 0.001) with Hct 39%, despite further decreased GFR to less than 4 ml/min and need for dialysis. Reticulocytes varied from 1.6% to 7.4 (3-6 weeks) to 3.1 (3 months) and 1.5% (1 year). Bone marrow cellularity increased from 36% to 47% (3 months) and 44% (1 year). M:E ratio decreased from 3.9:1 to 1.7:1 (3 months) to 1.6:1 (1 year). Marrow iron decreased from 4.1/6 to 2.4/6 (3 months) to 1.8/6 (1 year). Doses of rHuEPO had to be reduced to avoid polycythemia. rHuEPO stimulates erythropoiesis in pts with progressive CRF and U for 1 year. The initial increase in hematocrit is due to the early peak of reticulocytes. At 3 months, rHuEPO maintains the increased hematocrit by three mechanisms: 1) increased reticulocytosis, 2) a trend to increased bone marrow erythroid cellularity, and 3) lengthened RBC survival. At 1 year of rHuEPO therapy, the trend to increased marrow cellularity persists, however, the maintenance of target hematocrit is via a lengthened RBC survival. Despite progression of CRF and U, rHuEPO produced RBCs with longer survival than expected. RBC membranes may have been stabilized by rHuEPO. ",11 2813,"The development of medical education on alcohol- and drug-related problems at the University of Toronto. Medical education on alcohol- and drug-related problems at the University of Toronto covers undergraduate, residency and graduate programs, a result of collaboration since 1959 between the university and the Addiction Research Foundation of Ontario. An undergraduate core curriculum, developed in the early 1970s, is offered in year 2; it has been supplemented by electives, selectives and comprehensive clinics. The undergraduate program is rated highly by students; since 1978, 3024 have completed the core program. Residency training started in 1974 and is available through electives lasting from 1 to 12 months in internal medicine, psychiatry, and family and community medicine. To date, 370 residents have completed one of these electives; 129 have completed graduate programs in which their theses concerned alcohol- and drug-related topics, and there have been an additional 13 research and postdoctoral fellows. Despite the progress, there is still a need to improve and expand the undergraduate and residency programs and to develop an effective program of continuing medical education. The goals should be to ensure that, as far as possible, all medical graduates from the University of Toronto have the knowledge, attitudes, skills and behaviours needed to contribute effectively to the prevention and treatment of alcohol- and drug-related problems in their chosen field of practice and to avoid problems from their personal use of alcohol and other drugs. ",20 183,"Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma. Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series. The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution. Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01), identified smaller lymph nodes (P less than 0.001), and identified more histologically involved nodes of significantly smaller size (P less than 0.001). Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens. Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas. ",3 1360,"The urethral plug: a new treatment modality for genuine urinary stress incontinence in women. A new modality, the urethral plug, was used to treat 22 women with genuine urinary stress incontinence. The plug is made of thermoplastic elastomer (Kraton G), and consists of a meatal plate, a soft stalk and 1 or 2 spheres along the stalk. The spheres were located according to the result of the urethral pressure profile. The midpoint of the proximal sphere was placed at the bladder neck and the distal sphere was placed just above the maximum urethral pressure point. At voiding the plug was removed and afterwards a new plug was inserted. The plug with 2 spheres was tested in week 1 (period 1) and the plug with only the distal sphere was tested in week 2 (period 2). A total of 22 patients completed period 1. Eight patients did not complete period 2, mostly due to either unchanged incontinence during period 1 or a repeated loss of the plug with 1 sphere. In periods 1 and 2, 73 and 79% of the patients were subjectively and objectively continent or improved. A total of 14 patients completed both periods. Eight patients preferred the plug with 2 spheres, 1 preferred the other plug and 5 had no preference. The side effects were few. This preliminary study shows that the urethral plug seems to be a promising alternative treatment for female genuine urinary stress incontinence. ",11 2152,"Improvement of brain function in hemodialysis patients treated with erythropoietin. To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I-V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment. ",14 1251,"Vision screening in a primary care setting. A missed opportunity? To determine the effectiveness of vision screening in a primary care setting, we administered a questionnaire and a vision test to 458 patients from a general medical clinic. Subjects were referred for complete ophthalmologic evaluation if they failed the vision test or met other ""high-risk"" criteria based on information contained in the questionnaire. Patient-initiated requests for eye examinations were also honored. A total of 169 patients were scheduled for eye examinations, and 148 actually underwent ophthalmologic evaluation. One hundred one of those examined were referred on the basis of the study criteria. ""Serious eye disease"" (cataract, glaucoma, diabetic retinopathy, or age-related macular degeneration) was diagnosed in 96 (95%) of these patients. Prompt surgical intervention was recommended in 27 (27%), and medical treatment was begun in 21 (21%). Of those with serious eye disease, 59% met the criteria by failing the vision test, while 69% met the high-risk criteria determined by the questionnaire. Of the 148 subjects who received ophthalmologic evaluations, 47 requested them. Serious eye disease was diagnosed in 23 (50%) of the 47 patients. None of these individuals required immediate surgery, and medical treatment for glaucoma was begun in eight (17%). These data suggest that screening for serious eye disease in a primary care setting is an efficient mechanism to use for the identification of patients with undetected ocular disorders that require follow-up or treatment. ",10 1809,"Abnormal hemodynamic response to Valsalva maneuver in patients with atrial septal defect evaluated by Doppler echocardiography. Hemodynamic responses to the Valsalva maneuver were studied in eight healthy subjects (group 1) and eight patients with ASD (group 2) using Doppler echocardiography. The acute changes of aortic blood flow profiles during the Valsalva maneuver were investigated on a basis of beat-to-beat estimation. During the active strain phase (phase 2), group 1 showed a significant decrease in systolic blood pressure, SV and CO with reflex tachycardia; in group 2, there was a significant decrease in SV and CO with reflex tachycardia, but not systolic blood pressure. The percentage decreases in SV and CO in group 2 were significantly less than those in group 1 (23 +/- 16 percent vs 48 +/- 10 percent for SV, p less than 0.01; 17 +/- 12 percent vs 40 +/- 13 percent for CO, p less than 0.05). After release of strain phase (phase 4), group 1 showed significant reversed changes in systolic blood pressure, SV and heart rate, indicating an overshoot effect which was, however, not observed in group 2. Thus, patients with ASD presented abnormal Valsalva response which was characterized by the absence of phase 4 overshoot and a less marked phase 2 change. The findings suggest that the decremental effect of impaired venous return on stroke output during active strain may be attenuated by the increased pulmonary blood volume due to left-to-right shunt. In patients with ASD, the lesser decrement of CO during phase 2 may not provoke sufficient sympathetic activity to induce overshoot response in phase 4. ",13 3276,"Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood. In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO. ",22 498,"Bronchogenic carcinoma in situ on the carina eradicated by endobronchial biopsy. Squamous cell carcinoma in situ of the bronchus is a rare disorder in an isolated clinical setting. We present a case of carcinoma in situ located on the carina with excisional biopsy via a fiberoptic bronchoscope and no recurrence after five years. To our knowledge, this represents the only case of carcinoma in situ treated solely with excisional biopsy. This case further emphasizes the importance of securing biopsy specimens for all mucosal abnormalities and raises the possibility of limited excision as sole therapy for carcinoma in situ. ",3 2430,"Increased overnight growth hormone concentrations in diabetic compared with normal adolescents. To determine the extent to which spontaneous plasma GH concentrations are abnormal in adolescents with insulin-dependent diabetes mellitus we performed 12-h overnight plasma GH profiles in 21 diabetic adolescents (11 males and 10 females; aged 9.8-16.5 yr; median, 13.6 yr) and 34 healthy adolescent controls (17 males and 17 females; aged 9.1-20.9 yr; median, 13.1 yr). Data were analyzed using the pulse detection program Pulsar and time series analysis, and are presented with respect to age and puberty stage. Mean and maximum GH concentrations, sum of the peak amplitudes, and mean calculated baseline concentrations in the normal children were higher during puberty; highest levels were seen in girls at puberty stages 2-3, and in boys at stages 4-5. A similar pattern was observed in the diabetic adolescents, but all measures of pulse height and mean calculated baseline concentrations were significantly greater than those in the normal subjects (multivariate analysis, P less than 0.001). Pulse frequency did not change during puberty in the normal or diabetic subjects, and the dominant pulse periodicity in both groups was about 180 min. We conclude that the predominant change in GH release during puberty is in pulse amplitude, and that this is increased in diabetes, whereas pulse frequency remains constant in both normal and diabetic adolescents. ",17 1816,"Calcitropic hormones, platelet calcium, and blood pressure in essential hypertension. Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathyroid hormone were positively correlated with mean arterial pressure (r = 0.58, p less than 0.001; r = 0.54, p less than 0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r = -0.60, p less than 0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathyroid hormone was positively correlated to platelet cytosolic calcium (r = 0.43, p less than 0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r = -0.44, p less than 0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism. ",13 2916,"Knee function after complex femoral fractures treated with interlocking nails. Twenty-three complex femoral fractures were treated with interlocking nails. After fracture healing, knee function was analyzed, including alignment, quadriceps and hamstring strength, thigh atrophy, and range of motion (ROM). Similar to previous studies in the preinterlocking nail era, knee function was impaired in comparison with the contralateral limb. Seventy-three percent of patients had decreased quadriceps strength, and 60% had decreased hamstring strength. Sixty-five percent had thigh atrophy. The ROM and alignment were satisfactory. Despite the advantages of early ROM with femoral fractures treated with interlocking nails, knee function is often unsatisfactory once fracture union has occurred. Therefore, a formal knee rehabilitation program is recommended to achieve an optimal result. ",20 3335,"Maintenance of circulation during ventricular fibrillation with the simultaneous use of two ""counterpulsation"" devices. Two valveless, single orifice counterpulsation devices, with pumping stroke volumes of 65 ml each, were implanted on the ascending aorta and pulmonary artery of seven open chest anesthetized dogs. After completion of the preparation, ventricular fibrillation was induced. The devices were synchronized to pump simultaneously at a rate of 85-100 bpm. The combined use of the counterpulsation devices provided maximal aortic pressure of 111.4 +/- 25.1 mmHg during ventricular fibrillation for a period of 15-60 min. The mean left ventricular pressure was 17.7 +/- 4.4 mmHg, and the cardiac index 64.5 +/- 23.6 ml/kg/min. Cardioversion of ventricular fibrillation to sinus rhythm restored normal hemodynamics. The counterpulsation device implanted on the ascending aorta was not able to maintain circulation for more than 5 min after the induction of ventricular fibrillation, if used alone. In conclusion, the use of two counterpulsation devices implanted on the ascending aorta and pulmonary artery was able to maintain circulation in experimental animals during ventricular fibrillation. ",22 3081,"Massive allografts in salvage revisions of failed total knee arthroplasties. Ten patients with failed total knee arthroplasties and severe bone loss were treated with massive whole distal femur and proximal tibial allografts in combination with prosthetic implants. Fourteen allografts were inserted either as invaginated or segmental grafts and were rigidly fixed to the host bone. Clinically and roentgenographically, 12 of 14 grafts (86%) seemed to have united to the host bone. The average range of motion was 92 degrees. Five patients developed complications; two of these involved the allograft (nonunion and fracture) and two were caused by inadequate healing at the ligament-allograft junction. One patient had a late infection. With careful planning and improved surgical techniques, these complications can be avoided. The massive allograft-prosthesis composite techniques is a viable reconstructive alternative worthy of further clinical trials. ",22 1146,"Symptomatic carotid endarterectomy trials. The possible benefit of carotid endarterectomy in stroke prevention is being evaluated in three major clinical trials. To date, the European Carotid Surgery Trial has randomized 2,200 patients, 30% of whom have a carotid stenosis of greater than 70% appropriate to their symptoms. The North American Symptomatic Carotid Endarterectomy Trial has randomized 1,000 patients, of whom more than half have this severity of appropriate stenosis. Quality control and the evaluation of outcome events in this trial is achieved by a three-tier review, including review by medical and surgical adjudicators who are blinded to the treatment arm of each patient. Baseline characteristics of the patients eligible but not randomized are similar to those of patients who have been randomized. Two percent of the patients randomized to the surgical arm have declined surgery and crossed over to the medical arm, and 3% have elected surgery after randomization to the medical arm. Both of these studies, as well as a Veterans Administration trial, are continuing to randomize patients. ",9 745,"Pancreatitis. Pancreatitis is a common but rather poorly understood entity most often associated with alcohol abuse or biliary tract disease. Despite the availability of a variety of diagnostic tests and imaging techniques, the diagnosis of pancreatitis continues to be primarily a clinical one. Of major concern to the emergency physician is distinguishing pancreatitis from other, potentially lethal, causes of abdominal pain, and identifying those patients with severe pancreatitis who are at risk for a complicated course secondary to the remote systemic effects of the disease. ",5 1715,"Subaortic obstruction: intraoperative echocardiography as an adjunct to operation. Fourteen patients undergoing operation for subaortic obstruction (membranous obstruction in 11 patients, tunnel obstruction in 2 patients, obstruction due to reduplicated mitral valve tissue in 1 patient) were evaluated by intraoperative epicardial echocardiography. In all 9 patients with ""discrete"" obstruction who underwent prebypass epicardial echocardiography, the septal and lateral attachments of the lesion were correctly demonstrated. The precise extent of tunnel stenosis was seen in both patients. The lateral attachment of the membrane in 4 patients and multiple extensions in another 2 were identified by the epicardial study (having been missed on precordial echocardiography). The discrete membrane was enucleated in 10 of the 11 patients and was partially resected in 1. One tunnel obstruction was completely relieved; the other was partially relieved. Reduplicated mitral valve tissue in the remaining patient was completely resected. Epicardial imaging after bypass showed remnants of the membrane in 2 patients. Intraoperative Doppler echocardiography and color flow imaging confirmed the absence of clinically significant residual gradients (less than 20 mm Hg) in all but 1 patient with tunnel obstruction. Epicardial imaging provided excellent morphological information about obstructive lesions of the left ventricular outflow tract and enabled immediate assessment of surgical repair. ",13 324,"Cutaneous melanoma and bilateral retinoblastoma. We report the case of an otherwise healthy 37-year-old man who had had bilateral enucleation during early childhood for bilateral retinoblastomas, in addition to two cutaneous melanomas (the first appearing at age 27 years). He also had dysplastic melanocytic nevi and a history of cutaneous melanoma in his mother. Retinoblastoma may aggregate in families and is associated with DNA abnormalities of chromosome 13. Recent reports have emphasized the appearance of second malignancies in retinoblastoma survivors. The second malignancies include osteosarcoma, soft tissue sarcoma, and cutaneous melanoma. Cutaneous melanoma also may aggregate in families, usually in the setting of dysplastic melanocytic nevi. The features of this case and of similar reported cases suggest that there may be a greater than expected association between retinoblastoma and cutaneous melanoma. ",3 2125,"Are blood pressure levels increasing in Denmark? The Copenhagen City Heart Study is a prospective cardiovascular population study designed to evaluate the incidence of and risk factors for cardiovascular disease. A random population sample comprising approximately 20,000 individuals was invited to participate. Blood pressure was measured, and information regarding the use of antihypertensive medication was collected in an initial survey during the period 1976-1978 (attendance rate 74%) and from a second survey during the period 1981-1983 (attendance rate 70%). A significant increase in systolic and diastolic blood pressure between survey 1 and survey 2 was found among both men and women greater than 40 years of age and not using antihypertensive medication. The increase in blood pressure in the follow-up survey could not be explained by changes in methods, changes in the prescription of antihypertensive medication, or selection bias. Factors associated with changes in systolic and diastolic blood pressure were examined by multiple linear regression analysis. Both increase in body mass index and increase in alcohol consumption were positively correlated with changes in systolic and diastolic blood pressure, while use of antihypertensive medication, a high value of body mass index at survey 1 and a high level of education were negatively correlated with changes in systolic and diastolic blood pressure. Female sex and advanced age were also negatively correlated with changes in diastolic blood pressure. Consumption of tobacco and alcohol, income and changes in consumption of tobacco were not significantly correlated with changes in systolic and diastolic blood pressure. ",13 2463,"Behavioral covariates of waist-to-hip ratio in Rancho Bernardo. We examined lifestyle and dietary habits in 685 men and 943 women (mean age 67 years) who completed an interview, examination, and food frequency questionnaire in 1984-87. Waist-to-hip ratio increased with age and body mass index in both men and women. In multiple regression, waist-to-hip ratio was independently associated with smoking, alcohol consumption, and exercise in men, and with smoking and alcohol consumption in women. The data suggest that waist-to-hip ratio is affected, at least in part, by behavioral, and potentially modifiable, factors. ",17 657,"Determinants of vertebral mineral density in patients receiving long-term glucocorticoid therapy. This study addresses the impact of clinical and biochemical factors on the bone density of patients receiving glucocorticoid therapy. Vertebral mineral density was measured by quantitative computed tomography in 35 patients aged 17 to 77 years who had received therapeutic glucocorticoid drugs for 0.1 to 22 years. The mean (+/- SEM) vertebral mineral density z score in the subjects was -1.7 +/- 0.2. z score was unrelated to underlying diagnosis, sex, or age but was significantly related to the duration of previous steroid therapy (r = -.38) and to the total cumulative glucocorticoid dose (r = -.50). The rate of change of bone density in 16 of these subjects followed up over a period of 12 months was -8.9% and was significantly greater in subjects taking more than 12.5 mg of prednisone per day. Bone loss was not influenced by sex, age, duration of previous steroid treatment, or diagnosis and was not predictable from biochemical measures of calcium metabolism. ",4 2686,"Effect of inhaled methacholine on inspiratory flow. One hundred consecutive outpatients with symptoms suggestive of asthma who came to the Pulmonary Function Laboratory for a methacholine challenge test were studied. In addition to the forced expiratory maneuvers, forced inspiratory maneuvers were performed before and after the maximal response to methacholine. In 24 patients, the methacholine challenge suggested that they had asthma (forced expiratory volume in 1 s [FEV1] decrease greater than or equal to 20 percent). Six of these 24 patients also had a decrease in maximal forced inspiratory flow (FIFmax) greater than or equal to 20 percent and nine had a decrease in forced inspiratory flow at 50 percent of vital capacity (FIF50) greater than or equal to 20 percent, suggesting that bronchoconstriction can cause decreased inspiratory as well as expiratory flows. In 76 patients, the methacholine challenges were ""negative"" (FEV1 decrease less than or equal to 20 percent), suggesting that they did not have asthma. Nevertheless, in 11 of these 76 patients the FIFmax decrease was greater than or equal to 20 percent, and in 14 patients the FIF50 decrease was greater than or equal to 20 percent, suggesting that intermittent central airway obstruction is responsible for these patients' symptoms. ",19 2163,"Bioavailability of iron in hemodialysis patients treated with erythropoietin: evidence for the inhibitory role of aluminum. The dose of recombinant human erythropoietin (r-HuEPO) required to correct the anemia of end-stage renal disease (ESRD) varies among patients. The response to r-HuEPO is impaired if absolute or relative iron deficiency exists. Aluminum may cause a microcytic anemia in patients with ESRD, but the mechanism remains incompletely defined. Twenty-two patients in the Canadian Multicentre EPO trial were studied for 6 months. In this randomized double-blind placebo-controlled trial, free erythrocyte protoporphyrin (FEP) was used as an indicator of iron-deficient deficient erythropoiesis. The relationship of FEP to the estimates of iron availability (serum iron, transferrin saturation, ferritin) and iron utilization (corrected reticulocyte count, hemoglobin) was evaluated by multiple linear regression analysis. The effect of aluminum on FEP was evaluated by adjusting the statistical model for this variable. All patients were iron replete as assessed by serum ferritin. FEP was not related to serum aluminum before administration of r-HuEPO, but it was significantly correlated with aluminum in the treated group. In hemodialysis patients treated with r-HuEPO, the proportion of the variability explained by the parameters of iron utilization and iron availability was 0.27. The effect of aluminum increased this to 0.59. In hemodialysis patients not receiving r-HuEPO, the proportion of variability in FEP explained by the model increased from 0.16 to 0.28 by adjusting for aluminum. The data support the hypothesis that aluminum interferes with the bioavailability of stored iron for erythropoiesis and thus may result in a microcytic anemia in patients with ESRD or may blunt their response to r-HuEPO therapy. ",14 81,"Postneonatal infectious disease mortality: the French situation. Mortality caused by infectious and parasitic diseases represents a limited part of all postneonatal deaths in France, which have been stable for the past decade. This component is worthy of careful analysis because it is at least partially preventable. Statistics are presented and interpreted, with discussion on which disorders should be included in assessing the impact of infection on morbidity and mortality. Figures and international rankings change according to the inclusiveness of the definition chosen. There is need for epidemiologic and statistical research to make comparisons of mortality more clear. Morbidity is also important because of high incidence, frequent hospitalization, and a heavy social cost. Policy and services in France that relate to control and treatment of infection are described, as are shortcomings that call for further efforts. ",0 1228,"Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies. Transcutaneous cranial electrical stimulation (TCES) with high frequency (166 kHz) intermittent current (100 Hz: Limoge current) has been used for several years in cardiac, thoracic, abdominal, urological and micro-surgery. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long-lasting postoperative analgesia. We have confirmed these clinical observations in rats using the tail-flick latency (TFL) test to measure pain threshold. TCES was not found to modify the pain threshold in drug-free rats, but it potentiated morphine-induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 h before the drug injection and be maintained throughout the duration of its pharmacological action. TCES potentitation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. These findings were confirmed by blind tests of the efficiency of TCES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide). The analgesic effect of these 4 opiates (TFL as % of baseline without or with TCES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 micrograms; analgesic effect 152%, 207% with TCES) suggesting that TCES potentiation of opiate-induced analgesia is centrally mediated. ",9 860,"Long-term fate of the vascularized iliac crest bone graft for mandibular reconstruction. Vascularized bone grafts, such as the iliac crest, have become a major tool for mandibular reconstruction. Due to the growing trend toward immediate bone replacement followed by implant osseointegration and dental rehabilitation, further understanding of the long-term characteristics of these grafts is essential. Early postoperative bone scans demonstrate increased activity within the vascularized graft relative to surrounding bone. This study addressed the use of bone SPECT (single photon emission computed tomography) scintigraphy as a long-term method of evaluating the integrity of vascularized bone grafts. ",6 2464,"The delta (delta) gap: an approach to mixed acid-base disorders The anion gap (AG) is a helpful, yet underused, clinical tool. Not only does the presence of a high AG suggest a certain differential, but knowledge of the relationship between the rise in AG (delta AG) and the fall in bicarbonate (delta HCO3) is important in understanding mixed acid-based disorders. Simple arithmetic converts this relationship into a numerical value, the delta gap (delta gap). The delta gap = delta AG - delta HCO3. If the delta gap is significantly positive (greater than +6), a metabolic alkalosis is usually present because the rise in AG is more than the fall in HCO3. Conversely, if the delta gap is significantly negative (less than -6), then a hyperchloremic acidosis is usually present because the rise in AG is less than the fall in HCO3. Familarity with the relationship between the changes in AG and HCO3 can be useful in unmasking occult metabolic disorders. ",17 2051,"Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha-2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta-ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A-mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous ""down-regulation"" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta-2 ARs are nearly normal. ",13 3312,"Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. The receptors for erythropoietin and other cytokines constitute a new superfamily. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we describe two classes of activating mutations in the erythropoietin receptor (EPOR). A single point mutation in the exoplasmic domain enables it to induce hormone-independent cell growth and tumorigenesis after expression in nontumorigenic, interleukin-3-dependent haematopoietic cells. A C-terminal truncation in the cytoplasmic domain of the EPOR renders the receptor hyperresponsive to erythropoietin, but is insufficient to induce hormone-independent growth or tumorigenicity. The activating point mutation retards intracellular transport and turnover of the receptor. These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein. ",22 2528,"Defective fasciculata zone function as the mechanism of glucocorticoid-remediable aldosteronism. Glucocorticoid-remediable aldosteronism is characterized by unusual sensitivity of aldosterone secretion to ACTH. Suppressibility by glucocorticoid and continued stimulability by exogenous ACTH has provided the basis for diagnosis and treatment of the disorder. A qualitative biochemical abnormality consisting of marked overproduction of the products of the cortisol C-18 oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, has been examined in 10 patients with the disorder and compared to the normal C-18 oxidation products of corticosterone, aldosterone, and 18-hydroxycorticosterone. The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18-hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18-hydroxycortisol. All 4 C-18 oxygenated corticosteroids were markedly elevated in the untreated state and showed rapid parallel suppression with low doses of glucocorticoid. The proportional changes in C-18 oxygenated cortisols together with aldosterone and 18-hydroxycorticosterone suggested the mechanism of a common catalytic site of a cytochrome P450 methyl oxidase serving both cortisol and corticosterone substrates. The ACTH-dependent secretion of the C-18 oxidation products of both corticosterone and cortisol in the disorder is attributed to the acquisition of methyl oxidase activity by the fasciculata zone, where there are abundant pools of these precursors. ",18 1303,"A portable digital data recorder for long-term monitoring of scrotal temperatures The application of a new, miniaturized portable digital data recorder ""Thermoport"" (Institute for Reproductive Medicine, Munster, West Germany) for continuous determination of scrotal temperatures revealed great variations of scrotal temperature during 24 hours in normal men. Maximum temperatures approached body core temperatures. Mean scrotal temperatures of 10 normal men rose during sauna from 32.72 +/- 0.23 degrees C to 37.53 +/- 0.38 degrees C. During treadmill running, scrotal temperatures increased by more than 2.5 degrees C. Minimal scrotal temperatures were increased in some men with varicocele compared with normal fertile men indicating impaired cooling mechanisms. The continuous temperature measurements facilitate assessment of temperature dynamics. The miniaturized design of the Thermoport makes it suitable for routine use in outpatients of infertility clinics, in occupational medicine for evaluation of heat hazards, and for investigations of body temperatures under various experimental conditions. ",11 1074,"Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane. The cerebral effects of sevoflurane were compared in dogs with those of enflurane and isoflurane. Initially, the minimum alveolar concentrations (MAC) of sevoflurane and enflurane were determined and the electroencephalographic (EEG) responses to increasing doses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5 and 2.0 MAC) in unparalysed animals were examined. Administration of sevoflurane was not associated with seizure activity at any concentration either during normocapnia (PaCO2 5.3 kPa) or hypocapnia (PaCO2 2.7 kPa), even in the presence of intense auditory stimuli. All dogs anaesthetized with enflurane demonstrated sustained EEG and motor evidence of seizure activity induced by auditory stimuli at concentrations of enflurane greater than 1 MAC, particularly during hypocapnia. In a separate group of dogs, the effects of increasing concentrations of sevoflurane and isoflurane (0.5, 1.5 and 2.15 MAC) were compared directly on arterial pressure, cardiac output and heart rate, cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2) using the venous outflow technique. Sevoflurane, in common with isoflurane, had minimal effects on cerebral blood flow at the concentrations studied, but significantly reduced the CMRO2 at end-tidal concentrations sufficient to produce a burst suppression pattern on the EEG (approximately 2.15 MAC). Both sevoflurane and isoflurane significantly decreased arterial pressure in a dose-dependent manner, but neither drug significantly altered cardiac output. ",9 3226,"Bilateral phrenic nerve palsy associated with open-heart surgery. The incidence of phrenic nerve palsy after open-heart surgery has been estimated at 10%, but it is usually unilateral and does not cause symptoms. Bilateral phrenic nerve injury after coronary artery bypass surgery is a rare complication. This case report describes a patient who developed bilateral phrenic nerve palsies and required prolonged ventilatory support. Denervation of both hemidiaphragms was documented by needle electromyography four weeks after bypass surgery. The patient required total ventilatory support for three months and partial ventilatory support for an additional three months. This case demonstrates the usefulness of electromyographic screening for documentation and prognostication after phrenic nerve injury. The cause of the lesion was unclear, but hypothermia and stretch were leading hypotheses. This patient developed the phrenic nerve palsies despite using a cardiac insulation pad. ",22 1423,"Sterile versus non-sterile dialysis fluid in chronic hemodialysis treatment. As the quality of water in the dialysis fluid varies considerably, and in view of the fact that endotoxin or active derivatives can cause acute side effects in patients, the dialysis fluid must be sterile. Therefore, we introduced ultrafiltration of dialysis fluid before entering the dialyzer. Fifteen patients, (ten women, five men) were treated for 4 weeks with nonsterile, and then with sterile dialysis fluid. The bacterial loading in the dialysis fluid before hemodialysis was 1.34 X 10(5)/ml, and after hemodialysis 2.9 X 10(3)/ml; the endotoxin concentration was high and varied between less than 1 EU/ml and greater than 10 EU/ml before and after hemodialysis. After ultrafiltration of the dialysis fluid by a polyamide hollow fiber membrane, all samples were free of bacteria and the concentration of endotoxin was lower than the detectable limit (less than 0.03 and less than 0.5 EU/ml). With ultrafiltration of dialysis fluid we can obtain sterile dialysate, which is endotoxin free. Interleukin-1 and tumor necrosis factor in the patients with ultrafiltration was significantly lower than without ultrafiltration. ",11 754,"Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones. Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic duct's tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure. ",5 1926,"Subnormal parasympathetic activity after cardiac transplantation. Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6. ",13 3273,"Stress adaptation and low-frequency impedance of rat lungs. At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency. ",22 2063,"Preanaesthetic medication with clonidine. The purpose of this study was to evaluate oral clonidine in a dose of 0.3 mg as a routine premedicant. Sixty-nine normotensive female patients were studied in a randomized double-blind investigation in which clonidine was compared with an inert treatment. Clonidine produced a significant reduction in anxiety (P less than 0.05) and sedation and a reduction in the sleep dose of methohexitone (P less than 0.05). Tachycardia in response to intubation was attenuated by clonidine (P less than 0.05). However, the magnitude of the increase in arterial pressure after intubation was not affected. Intraoperative and postoperative hypotension were common after premedication with clonidine 0.3 mg and caution is urged in its use as a premedicant. ",13 2345,"Nature, nurture, nutrition: interdisciplinary programs to address the prevention of malnutrition and dehydration. Malnutrition and dehydration are common problems in nursing home patients. One explanation for this may be the large number of patients requiring feeding assistance. The Dysphagia Team at the Department of Veterans Affairs Medical Center in Miami, Florida served as the primary source in the expansion of a nutritionally supportive environment to assist in the prevention of malnutrition and dehydration in patients with feeding/swallowing disorders. ""Silver Spoons,"" a program in which volunteers provide supervised feeding, ""Happy Hour,"" a time each day during which an atmosphere is provided that encourages socialization and hydration, and ""Second Seating,"" during which lunch is provided for patients who require modification of eating style, food texture, or timing are described. Analysis of the program's outcomes show it to be timely, pleasing to patients, and cost-effective. ",17 2599,"Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3-year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse. ",19 1706,"Hemodynamic effects of nebivolol at rest and on exertion in patients with heart failure. Nebivolol is a novel B-1-adrenoceptor-blocking drug with an unusual hemodynamic profile unlike classical B-blockers. In dogs and in healthy volunteers it decreases blood pressure and heart rate but improves left ventricular function. The authors studied 10 male patients with coronary artery disease and heart failure (ejection fraction mean = 46%). A Swan-Ganz catheter was placed into the pulmonary artery, and the mean blood pressure, the heart rate, the pulmonary artery pressure, the pulmonary wedge pressure, the right atrial pressure, the cardiac output, and the stroke volume were measured at rest and on exertion before and after seven days' treatment with oral nebivolol (5 mg/day). While the blood pressure and the heart rate decreased significantly, the pulmonary artery and wedge pressures, as well as the right atrial pressure and the cardiac output, did not change during treatment. The stroke volume increased significantly. The maintained cardiac output cannot be explained by any changes in preload or afterload; instead a positive inotropic mechanism must be assumed. Unlike other B-blockers it seems to be possible to treat patients with heart failure with nebivolol without causing the hemodynamic situation to deteriorate. ",13 1362,"The management of posterior urethral valves by initial vesicostomy and delayed valve ablation. We managed 32 neonates and infants with temporary vesicostomy and delayed valve ablation. The criterion on which successful management was gauged was estimated creatinine clearance. Renal failure or death occurred in 30% of the patients and 7% required transplantation. There was no apparent difference between our patients managed initially with vesicostomy and other series managed initially with valve ablation in preventing the complications of posterior urethral valves. ",11 2002,"Biplane transesophageal echocardiography: technique, image orientation, and preliminary experience in 131 patients. Transesophageal echocardiography with use of a uniplane phased-array transducer with a transverse or horizontal scanning plane has become a well-established tool for evaluating cardiovascular diseases. Recent introduction of biplane probes has enhanced the diagnostic capability of this imaging technique. This article discusses the technique of biplane transesophageal echocardiographic examination and image orientation. The diagnostic value and advantages of various biplane transesophageal images of the heart, aorta, and aortic arch from various esophageal positions are described. ",13 323,"Buschke-Loewenstein tumor: verrucous carcinoma of the penis. The Buschke-Loewenstein tumor is an anogenital tumor of characteristic clinical and histologic pattern best considered as a low-grade, well-differentiated squamous cell carcinoma. This remarkable neoplasm and its features are reviewed in detail, stressing salient advances in our understanding of it. ",3 2422,"Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants. It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg-1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover. ",17 419,"Immunophenotypic aberrancy in adult acute lymphoblastic leukemia. Some recent reports indicate a high frequency of immunophenotypic aberrancy in acute lymphoblastic leukemia (ALL). To investigate this issue with regard to adult ALL, the authors reviewed the immunophenotyping data from 39 cases analyzed in their clinical laboratory. Flow cytometric analysis of peripheral blood and/or bone marrow was performed with the use of a panel of 21 B-cell, T-cell, and myeloid monoclonal antibodies (MoAbs). The surface antigen profiles of the leukemic cells were compared with those of normal bone marrow and thymic counterparts, as defined by current models. Twenty-six cases were B-precursor ALL, 8 were T-ALL, and 3 were B-ALL (Burkitt's leukemia). Only two cases coexpressed lymphoid and myeloid antigens. In contrast, intralineage aberrancy was quite common. Immunophenotypes from 13 of 26 B-precursor ALL cases deviated from normal B-lineage marrow cells as defined by a recent classification. The T-ALL cases were also immunophenotypically heterogeneous. This high incidence of aberrant antigen expression in adult ALL suggests that leukemogenesis also involves aberrant differentiation rather than purely a process of maturational arrest. ",3 3182,"Molecular biology of circulatory shock. Part III. Human hepatoblastoma (HepG2) cells demonstrate two patterns of shock-induced gene expression that are independent, exclusive, and prioritized. During shock and resuscitation, parenchymal cells of solid organs are exposed to a rapidly changing microenvironment, which may include a reduced oxygen tension and an increased concentration of certain cytokines including tumor necrosis factor alpha and interleukin-1. In vivo experiments that testedl iver biopsied from pigs undergoing cardiogenic shock and resuscitation demonstrated several patterns of gene expression. To study the independent and additive influences of hypoxia and of cytokines in vitro, human hepatoblastoma (HepG2) cells were perturbed by hypoxia/reoxygenation (H/R), by heat shock, and by the cytokines interleukin-1 and tumor necrosis factor alpha alone and in combination. H/R induces new patterns of protein synthesis and secretion that are indistinguishable from those induced by heat shock and independent of the acute-phase response mediated by the cytokines. The H/R (heat-shock) response has priority over and will extinguish gene expression supported by the cytokines. This previously unrecognized hierarchy of stress gene expression could well form the molecular basis of shock-related cell and organ failure. ",22 1128,"Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. We found anti-GM1 IgM antibodies in 23% of 56 patients with motor neuron disease (MND), in 19% of 69 patients with neuropathy, and in 7% of 107 controls with other neurologic and nonneurologic diseases. Most of these patients had anti-GM1 IgM antibody titers of 1:80 or less; slightly higher antibody titers (up to 1:640) were found in 3 patients, 1 with MND and 2 with neuropathy, and very high titers (1:20,480) in a patient with MND and an IgM kappa M protein that reacted with GM1, GD1b, and asialo GM1. Six other patients with anti-GM1 IgM that also bound to GD1b. Reactivity with GD1b did not correlate with anti-GM1 titers but was only present in patients with MND or neuropathy. Anti-GM1 IgM antibodies may be a normal constituent of the human antibody repertoire but their frequency and, in some cases, their levels are higher in patients with MND and neuropathy. The origin and the pathogenetic role of these antibodies in neural impairment remain to be established. ",9 428,"Immediate versus delayed shoulder exercises after axillary lymph node dissection. A total of 144 evaluable patients with breast cancer were enrolled in a multicenter, randomized, prospective study to establish the role of delayed shoulder exercises on wound drainage and shoulder function after axillary lymph node dissection. Patients in group 1 (n = 78) started active shoulder exercises 1 day postoperatively. Patients in group 2 (n = 66) started on the eight postoperative day, following 1 week of immobilization of the arm. Patients in group 2 had 14% less wound drainage volume than those in group 1 (600 +/- 436 mL versus 701 +/- 398 mL); this difference, however, was not significant. Also, no differences could be established between the two groups when duration and volume of wound drainage, number and volume of seroma aspirations, wound complication rates, and shoulder function were compared 6 months after surgery. ",3 1911,"Mental stress as an acute trigger of ischemic left ventricular dysfunction and blood pressure elevation in coronary artery disease. Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients. ",13 223,"Trends in primary breast cancer management. Where are we going? The treatment of cancer during any period has been based not on the whim of a clinician but on the therapeutic consequences of the dominant biologic model of the disease. Until the 1960s, the dominant model of breast cancer was of a disease that spread centrifugally along anatomic pathways, with time being the only determinant of prognosis. An alternative model, that of biologic determinism, posits that the outcomes of treatment are determined by the extent of microscopic dissemination that occurred before the tumor became detectable. This model, too, has flaws, and the author suggests that it is time for a Kuhnian paradigm shift. Breast cancer exhibits a heterogeneity of phenotypes resulting from one or perhaps two mutations. The multiple prognostic variables may be epiphenomena, expressing different degrees of amplification of a limited domain of the genome. ",3 184,"Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas. Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors. ",3 2039,"Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease. The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars-Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system. ",13 2967,"Antibiotics and the postburn hypermetabolic response. Severe burn injury has been documented to significantly increase resting metabolic energy expenditure. This increase in metabolic rate appears to be possibly correlated with the degree of burn wound colonization and infection with bacteria. Prevention of such colonization and infection through the use of topical antimicrobial agents appears to decrease the metabolic alterations resulting from burn injury. These findings indicate that appropriate use of topical antibacterial agents may decrease the metabolic demands seen in burned patients. Burn-induced translocation of intestinal bacteria has also been hypothesized to contribute to the postburn hypermetabolic response. Attempts at preventing this entity in a burned guinea pig model through the use of selective decontamination of the digestive tract by the administration of enteral antibiotics have failed to demonstrate any measurable effect. ",20 3203,"Metaplastic change in mesenchymal stem cells induced by activated ras oncogene. 3T3 T murine mesenchymal stem cells have the potential to differentiate into a variety of different cell types even though they show a predilection to undergo adipocyte differentiation in vitro. The possibility that the activated c-Ha-ras (EJras) oncogene might influence the pathway of differentiation of these stem cells is investigated in the current study. Activated ras oncogene was transfected and stably expressed in 3T3 T cells; assays then were performed to determine its effect on differentiation. The results show that all EJras-transfected cell lines lose their ability to differentiate to adipocytes and instead differentiate into cells that express many characteristics of macrophages. Such cells contain numerous cytoplasmic granules, extensive nonspecific esterase activity, and anchorage-independent growth. The modulation of differentiation pathway from an adipocyte lineage to a macrophagelike cell lineage does not result from the transforming effect of EJras, because a nontransformed cell clone that expresses p21EJras protein also exhibits this modified differentiation pathway. These data suggest that the EJras oncogene specifically modulates the differentiation pathway of 3T3 T mesenchymal stem cells. This experimental system should therefore provide an excellent model to evaluate the mechanistic role of EJras in the process of metaplasia. ",22 2036,"Warm induction blood cardioplegia in the infant. A technique to avoid rapid cooling myocardial contracture. The use of profound hypothermia and total circulatory arrest for repair of heart defects in neonates usually involves a period of systemic and myocardial bypass cooling. Rapid cooling of muscle (skeletal, smooth, and myocardial) can result in contracture through elevation of cytosolic calcium levels. The increased myocardial tone caused by cooling might render the heart more vulnerable to a subsequent period of cardioplegic ischemic arrest. Infants may be more susceptible to contracture because their small body mass allows more rapid myocardial temperature change when prearrest bypass cooling is used. The influence of avoiding rapid myocardial cooling before induced cardioplegic arrest was analyzed in a group of infants weighing less than 6 kg at the time of open cardiac operation. Myocardial ischemic arrest by warm (37 degrees C) induction blood cardioplegia was used in 57 infants and compared with results in 440 infants treated with standard blood cardioplegia. Multivariate logistic regression analysis revealed that patient diagnosis, weight, and age at operation were significant risk factors for operative mortality. The use of warm induction blood cardioplegia had a strongly positive independent effect on survival (p = 0.0003) for any patient weight, age, or diagnostic group. We recommend the avoidance of rapid myocardial cooling on bypass in all patients before induction of cardioplegic ischemic arrest. ",13 1792,"Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome. From June 1980 to April 1989, 72 of 401 (18%) adult recipients of orthotopic heart transplantation developed prolonged (greater than 24 hours) bradyarrhythmias (less than 60 beats/min) within 5 days after transplantation. Junctional bradycardia occurred in 50 (69%) recipients, sinus bradycardia in 18 (25%), and slow ventricular response during atrial fibrillation in four (6%). Fifty-five of 72 (76%) patients had bradyarrhythmias of less than 20 days' duration (less than 7 days, 50 patients; 7-20 days, five patients). Fifty patients returned to sinus rhythm (greater than 60 beats/min) by the time of discharge. Five patients expired within 20 days. Seventeen of 72 (24%) patients had bradyarrhythmia for more than 20 days, which was symptomatic in 11. All 17 patients (junctional bradycardia, 13 patients; sinus bradycardia, four patients) received a permanent pacemaker within 40 days after transplantation. Between 1 and 12 months (mean, 4 +/- 3 months) after pacemaker implantation, 12 patients recovered sinus rhythm (greater than 70 beats/min). The other five patients had intrinsic rates of 32-57 beats/min (mean, 48 +/- 10 beats/min) during 1-9 months (mean, 4 +/- 3 months) of follow-up. The donor ischemic time in bradyarrhythmia patients was 202 +/- 34 minutes, which was significantly longer (p less than 0.01) than the 173 +/- 43 minutes for those patients without bradyarrhythmia. Conclusively, the incidence of posttransplantation bradyarrhythmia is relatively high. It is usually temporary, however, even in patients with a prolonged duration of bradyarrhythmia. A relation appears to exist between donor ischemic time and the incidence of bradyarrhythmia. ",13 1133,"Confusion. The term confusion describes a plethora of possible cognitive deficits and behavioral manifestations. A subjective assessment of confusion must be followed by an objective systematic evaluation to develop the cognitive-behavior profile. Because of age-associated physiologic and pathologic changes, elderly patients are at high risk for developing acute confusion. The management of confusion presents a challenge to nursing. Nursing can play a significant role in the prevention and the early detection of acute confusion. Preventing or identifying confusion early will decrease the physical and psychological stress of the patient as well as decrease the cost of hospitalization by shortening length of stay. Additional research is needed to determine the efficacy of present nursing activities and to identify new approaches for management. ",9 1336,"Sedoanalgesia in urology: a safe, cost-effective alternative to general anaesthesia. A review of 1020 cases. Sedoanalgesia is a technique developed to provide safe and satisfactory operating conditions for a wide range of patients independent of age and overall level of fitness (although its use in children remains to be established). It is suitable for both endoscopic and open procedures, day-cases and in-patients. When used in day-case surgery it significantly improves overall efficiency. It is recognised that day-case surgery is an important and cost-effective element in surgical care. With increasing restraints being imposed upon hospital finances, patient beds and staffing levels, any strategies designed to improve efficiency in this sphere of surgical activity are to be welcomed. That 93% of patients prefer sedoanalgesia to conventional general anaesthesia attests to its high degree of acceptability. The technique of sedoanalgesia, its applications and potential impact for urology are detailed. ",11 922,"Real and pseudo late asthmatic reactions after submaximal exercise challenge in patients with bronchial asthma. A new definition for late asthmatic responses after exercise challenge. The late asthmatic reaction after exercise challenge remains a controversial issue. In this study, 21 patients recorded peak expiratory flow rate (PEFR) on two control days without performing exercise. There was no difference between both control days when PEFR at 1 h was compared with baseline PEFR and when PEFR at 4 to 13 hours was compared with baseline PEFR. After analyzing variation coefficients of baseline PEFR on a control day and exercise day, PEFR was not allowed to differ more than 15.3 percent in the same patient when comparing exercise day and control day for the late fall in PEFR in the study. In 17 of 81 patients, a late asthmatic reaction after exercise challenge was present when PEFR fall was greater than or equal to 20 percent compared with baseline PEFR value. In eight of the 17 patients, a real late asthmatic reaction to exercise challenge was present with a PEFR fall greater than or equal to 20 percent on at least three successive time points and who had a PEFR fall greater than or equal to 20 percent compared with corresponding clocktime on a control day. The late asthmatic reaction to exercise challenge is characterized not as a nonspecific epiphenomenon, but as a fall in PEFR of greater than or equal to 20 percent compared with baseline PEFR value and with corresponding clocktime on a control day on at least three successive time points. Graphic illustration of airway responses following exercises may facilitate the detection of a late asthmatic response. ",7 2608,"Effect of facial cooling on mucosal blood flow in the mouth in humans. 1. To determine the effects of facial cooling on intraoral thermal events, we placed a thermal conductivity sensor on the buccal surface of the left cheek in six normal and six asthmatic subjects. Room temperature and cold stimuli were then applied to the integument surface of both sides of the face while mucosal surface temperature and thermal conductivity, as an index of blood flow, were recorded. 2. The room temperature challenge had no effect. Application of the cold stimulus to the exterior of the left cheek caused a monotonic decrease in temperature in the mouth in all subjects and was associated with a change in thermal conductivity in which blood flow increased and then fell to baseline despite a continued drop in temperature. These responses were purely local in that cooling of the right side of the face did not change the temperature or blood flow on the left side. No differences were noted between the asthmatic and normal subjects. 3. The data indicate that lowering the temperature of the skin of the face produces significant alterations in the thermal environment within the mouth. With facial cooling, buccal temperature falls and mucosal blood supply transiently rises. This effect appears to be a purely local thermally mediated event. Facial pressure and cutaneous reflexes do not play a role. The above changes may contribute to the conditioning of inspired air during oral breathing. ",19 264,"Left superior vena cava: a pitfall in computed tomographic diagnosis with surgical implications. We report 2 cases in which computed tomography of the mediastinum demonstrated an abnormality originally misinterpreted as lymphadenopathy but subsequently shown to represent a left superior vena cava. Misinterpretation may result in errors in optimum treatment and may complicate surgical exploration of the mediastinum. These 2 cases are presented to remind radiologists and surgeons of the possibility of this unusual anatomy. ",3 1866,"Intraoperative peripheral Nd:YAG laser-assisted thermal balloon angioplasty: short-term and intermediate-term follow-up. Laser-assisted thermal balloon angioplasty was performed in 48 arteries (iliac, superficial femoral, and popliteal). Indications for surgery were limb salvage (25%), rest pain (38%), and claudication (38%). Patients were categorized into three groups: lesions less than 5 cm, greater than 5 to 10 cm, or greater than 10 cm in length. Demographic characteristics, risk factors, and outcome measures were compared by use of Fisher's exact test and Student's t test. The time for vascular patency failure was compared by use of a standard Kaplan-Meier survival analysis for the three groups. Initial failure to recanalize was noted in 14% in lesions less than 5 cm, 40% in lesions greater than 5 to 10 cm, and 73% in lesions greater than 10 cm. The overall success rate was 38%, with a mean follow up of 1 year. The less than 5 cm lesion group had a significantly higher rate of overall success (59%, p = 0.005) than the other two groups combined. The greater than 10 cm lesion group did significantly worse (9%) than the other two groups combined (p = 0.028). Patients in the less than 5 cm group had significantly longer patency than the other two groups (p less than 0.01). Iliac lesions had a higher overall success rate (73%) than superficial femoral and popliteal artery lesions (35%) (p = 0.038). In conclusion, the widespread application of laser-assisted thermal balloon angioplasty cannot be justified without further long-term clinical and laboratory investigation. Conversely, the potential of this technique should not be dismissed out of hand. Proper patient selection, length and nature of the lesion to be treated, and the appropriate forms, doses, and method of delivery of laser energy, remain to be defined. ",13 682,"Investigation of mode of action of biofeedback in treatment of fecal incontinence. A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence. ",5 2367,"Absence of angiogenesis-inhibitory activity in aqueous humor of diabetic rabbits. We studied inhibitory activity of angiogenesis in the eye to explore the formation of new blood vessels in diabetic microvascular diseases. When we examined the effects of extracts from various ocular tissues of nondiabetic rabbits on the proliferation of bovine aortic endothelial cells, potent inhibitory activity was found in lens and aqueous humor. Aqueous humor inhibited both angiogenesis on chorioallantoic membrane in vivo and promotion of endothelial cell growth in vitro, which were induced by retinal extracts. However, in diabetic rabbits, aqueous humor lost the ability to inhibit the growth of endothelial cells. The loss of activity became evident 1 mo after the alloxan injection and lasted while the animals were hyperglycemic. In addition, diabetic aqueous humor failed to suppress retinal extract-induced angiogenesis promotion and endothelial cell growth. The absence of the inhibitory activity of angiogenesis in diabetic aqueous humor might be involved in promotion of neovascularization in diabetic ocular disease. ",17 17,"hemofiltration reverses left ventricular dysfunction during sepsis in dogs. Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration. ",0 724,"Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa. One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock-wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner. ",5 1673,"Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome. Antidromic circus movement tachycardia was documented in 36 of 345 consecutive patients with Wolff-Parkinson-White syndrome undergoing detailed electrophysiologic evaluation. Twenty-six patients were men and 10 were women (mean age +/- standard deviation 26 +/- 12 years [range 12 to 45]). Multiple accessory pathways were identified in 12 of these 36 patients (33%). Ten of the patients (67%) with clinically documented antidromic tachycardia had multiple accessory pathways. Dizziness and syncope occurred in 61 and 50% of patients with antidromic circus movement tachycardia. Six patients had clinical documentation of atrial fibrillation, and 4 patients (11%) were resuscitated from ventricular fibrillation. In the 36 patients, 56 distinct antidromic tachycardias were recorded and several different pathways were observed. Orthodromic tachycardia was the most frequently associated arrhythmia (72%). Dual atrioventricular nodal pathways were present in 12 patients (33%); however, atrioventricular nodal tachycardia could be initiated in only 2 of them. Interruption of the accessory pathway was successfully performed in all 20 patients undergoing surgery. ",13 3091,"Progressive functional deterioration of bioprostheses assessed by Doppler ultrasonography. Doppler echocardiography was used to study the function of bioprosthetic heart valves by noninvasive means in 32 patients aged 29 to 72 years at various postoperative intervals. There were 24 Ionescu-Shiley, four Hancock, and four Carpentier-Edwards prostheses, 19 in the aortic and 13 in the mitral position. Initial studies were performed at a mean of 2.3 years after implantation and were repeated one, two, and three years thereafter. Flow velocities in the mitral orifice, left ventricular outflow tract, and ascending aorta, as well as mitral pressure half-time, were measured from pulsed-wave or continuous-wave Doppler recordings. Mitral and aortic valve areas and aortic pressure gradients were calculated. In aortic prostheses the valve area decreased and pressure gradient increased progressively in relation to the time from implantation. The mean value (+/- SD) of the aortic valve area was 67 +/- 17 percent of the manufacturer's nominal value at the first examination and 57 +/- 20 percent one year later, 51 +/- 14 percent two years later, and 46 +/- 11 percent three years later (overall differences, p less than 0.01). In mitral prostheses, reduction of the valve area was not related to the time from implantation. The mean mitral valve area was 45 +/- 12 percent of the nominal value at rest and increased to 68 +/- 18 percent during exercise at a mean of 45 months after implantation. There was no change in these values at the one-year repeat study. It is concluded that in a population with predominantly pericardial bioprostheses, (1) aortic tissue prostheses showed a progressive functional deterioration demonstrable by Doppler echocardiography, most probably due to degenerative changes; and (2) in mitral tissue prostheses, there was no significant reduction of orifice area in relation to time from implantation. Reduction of mitral valve areas may, to some extent, reflect a less than full opening at rest. ",22 2677,"Silk-induced asthma in children: a report of 64 cases. A total of 64 children less than 15 years of age with asthma caused by silk were studied. The diagnosis was based on a history of wheezing, positive skin tests to silk, positive conjunctival or nasal provocation tests, or serum IgE-Sw (silk waste). The average age of onset was 4 years 2 months. Sex ratio (M:F) was 3.6:1. A positive skin test is essential for the diagnosis. Conjunctival provocation tests were performed in 80% of cases because of reliability, safety, and convenience. The first symptom appeared an average of 10 months after initial exposure to silk. In 61% of patients, asthma was accompanied by allergic rhinitis but in only 14% of cases by conjunctivitis. In most cases, asthma occurred in winter, due to seasonal use of bed quilts or clothes filled with silk. Silk is a highly potent allergen. The average mean wheal diameter elicited by silk in prick testing was larger than two histamine equivalent prick tests. A cross reactivity exists among mulberry silk, and silkworm cocoons, batryticated silkworms, and silkworm chrysalis. ",19 385,"Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism. Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. We studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14-eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also became more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA-treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distention and disruption of the cristae along with an increase in cytoplasmic vacuolization. We conclude that the inhibitors of eicosanoid biosynthesis, NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also induce increased astrocytic differentiation. ",3 2427,"Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin-treated type II diabetic patients. To determine the contribution of skeletal muscle to fasting hyperglycemia in noninsulin dependent type II diabetes (NIDDM), the forearm balance of glucose, lactate, and alanine was quantified in 25 control subjects, 21 hyperglycemic (blood glucose: 11.6 mmol/L), and 19 insulin-treated patients with NIDDM (blood glucose: 5.8 mmol/L). Forearm glucose uptake was similar in controls (4.6 +/- 0.6 mumol L-1 min-1) and in hyperglycemic diabetic patients (4.5 +/- 0.9 mumol L-1 min-1). In spite of this, in the diabetic patients lactate (5.1 +/- 0.8 mumol L-1 min-1) and alanine (2.6 +/- 0.4) release by the forearm was 3- and 2-fold higher than in the control group (lactate: 1.7 +/- 0.8, P less than 0.005; and alanine: 1.3 +/- 0.2, P less than 0.05, respectively). The ratio of lactate release to glucose uptake was 57% and 18% in diabetic and control subjects, respectively. Insulin administration did not affect either glucose uptake or the release of gluconeogenic substrates by the forearm. It is concluded that: 1) in fasting patients with NIDDM, glucose is taken up by the skeletal muscle in normal amounts but preferentially used nonoxidatively with lactate formation. This suggests that, although the muscle does not contribute directly to fasting hyperglycemia, it may play an indirect role through an increased delivery of glucose precursors; and 2) insulin-induced normoglycemia is maintained by mechanisms that do not involve the exchange of glucose and gluconeogenic substrates by the skeletal muscle. ",17 583,"The importance of calcium regulation in toxic cell injury. Studies utilizing the technology of digital imaging fluorescence microscopy. The regulation of ions within the cell is of critical importance in both acute and chronic toxicology. Recently, new methods have been developed for measuring such changes in living cells and correlating them with studies of structure, function, and biochemistry. A major revolution has occurred from the linkage between the computer and the light microscope, which has resulted in the use of digital imaging fluorescence microscopy and video intensification microscopy coupled with image analysis. These methods have already yielded much additional information and it is anticipated that their further application by pathologists and toxicologists will continue to uncover the important role of ion deregulation and toxic cell injury. ",3 2779,"Ethanol-inducible cytochrome P-450: assessment of substrates' specific chemical probes in rat liver microsomes. The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol-inducible cytochrome P-450 was studied in rats treated with different xenobiotics such as 3-methylcholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p-nitrophenol hydroxylation (283 +/- 19% and 304 +/- 21%), N-nitrosodimethylamine (NDMA) demethylation (280 +/- 105% and 228 +/- 95%), benzene hydroxylation (258 +/- 60% and 236 +/- 61%), butanol oxidation (173 +/- 34% and 154 +/- 32%), aniline hydroxylation (147 +/- 22% and 95 +/- 8%), and ether de-ethylation (95 +/- 17% and 83 +/- 17%) and a not significant increase of N-nitrosodiethylamine (NDEA) de-ethylation (34 +/- 11% and 9 +/- 8%) in rat microsomes, respectively, versus control animals (mean +/- SD, values expressed as nmol/min/nmole P-450). All of these activities significantly decreased after 3-MC treatment, except for the p-nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de-ethylation, p-nitrophenol, and benzene hydroxylations (106 +/- 38%, 109 +/- 14%, and 153 +/- 62%, respectively) versus controls. These results suggest that NDMA and especially 1-butanol are the most specific and useful probes of alcohol-inducible cytochrome P-450 in crude liver microsomes. ",20 303,"Familial occurrence of gastric cancer in the 2-year experience of a population-based registry. The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with ""diffuse"" carcinoma (52%) than in subjects with ""intestinal"" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a ""family history"" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients. ",3 3300,"Effect of motion artefact on pulse oximeters: evaluation of four instruments and finger probes. The ability of the Ohmeda 3700, Nellcor N200, Datex Satlite Plus and Simed S100 pulse oximeters to detect induced hypoxaemia in the presence of motion artefact was assessed, under conditions of controlled vibration using an industrial vibration facility. Vibration at 4 Hz and 8 Hz induced increases in detection time for hypoxaemia and spurious decreases in the displayed SaO2 in some of the oximeters tested. Finger-dependent differences in oximeter performance and pulse rate registration were noted especially in those oximeters without ECG linkage (Ohmeda 3700 and Simed S100). Subsequently, eight different pulse oximeter finger probes were assessed for those characteristics that may predispose to motion artefact. There were marked differences in the mass of the probes, the forces exerted on the test finger and in the force required to displace the probes from the subject's finger. Differences in both the microprocessor programmes and the physical characteristics of the finger probes may explain the observed differences in function. Similar studies should form part of the standard evaluation of new pulse oximeters. ",22 636,"Estrogen therapy during menopause and the treatment of osteoporosis. Estrogen remains the single most effective agent in the treatment of menopausal symptoms and prevention of bone loss. This article focuses on the use of estrogen therapy during menopause and the pharmacotherapy of osteoporosis. Risks and benefits of hormonal therapy and regimen selection for menopausal women are discussed. The second section of the article focuses on current treatment strategies for osteoporosis. ",4 2031,"Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats. Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient. ",13 1996,"Circumferential quantitative analysis of planar 201T1 myocardial scintigraphy in the diagnosis of coronary artery disease. Methodology for the computer analysis of 201T1 myocardial perfusion images has been developed by several laboratories. Substantial evidence of the advantage of this approach over visual inspection alone has been reported. The currently available computer analyses use different algorithms to analyze 201T1 kinetics in the myocardium. The authors evaluated and compared two widely used software programs, Medical Data System (MDS): a mean-count profile, and the Cedars Sinai (CS): a maximal-count profile, of planar 201T1 scintigraphy for their ability to detect coronary artery disease (CAD). ",13 3345,"Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning. Biliary tract obstruction or anastomotic leakage are common problems following liver transplantation. In a sequential study, 31 patients with a liver transplant were investigated by 99mTc-IODIDA (IODIDA) scanning and T tube cholangiography (TTC) and the results were compared with clinical outcome. Seven patients had an extrahepatic biliary obstruction and one patient had a biliary leak. In the detection of biliary complications TTC and IODIDA scanning were similar in terms of sensitivity (63 per cent for both) but TTC had a better specificity (79 per cent versus 60 per cent) and accuracy (74 per cent versus 60 per cent) than IODIDA scanning. When liver function was taken into account, the diagnostic efficacy of both tests in patients with bilirubin levels of less than 200 mumol/l was similar. With levels greater than 200 mumol/l there was a greater number of false positive results with IODIDA scanning (12 per cent versus 54 per cent). The only significant biliary leak was clearly detected by TTC but not IODIDA scanning. TTC remains the more effective way of evaluating the biliary tract after transplantation. IODIDA scanning has limited value when bilirubin levels are elevated, but may provide additional information about blood supply, hepatocyte function and intrahepatic cholestasis. ",22 3103,"Desmopressin and antifibrinolytics. Desmopressin appears to be a safe and effective hemostatic agent for use during surgery in patients with mild to moderate hemophilia or von Willebrand disease. Uremic patients also benefit from substitution of desmopressin for cryoprecipitate to control bleeding. The highly variable response to desmopressin by individual patients with hemophilia or von Willebrand disease dictates that each patient receive a trial administration prior to surgery; surgery should proceed only following verification of a therapeutically effective increase in Factor VIII and vWF after desmopressin. Use of desmopressin in patients with normal baseline hemostatic function is not clearly advantageous, although certain patient subgroups might benefit, and prospective studies have documented the drug's safety in these cases. Data are lacking to clarify a role for desmopressin during surgery in patients taking aspirin. Antifibrinolytic therapy appears to decrease bleeding without increased risk after cardiac surgery. In addition, specific use after urological surgery may be beneficial in the absence of upper urinary tract bleeding. In the last ten years, other applications for antifibrinolytic therapy have been found--both surgical (intracranial aneurysms, oral and lacrimal surgery) and nonsurgical (in cancer patients and for gastrointestinal bleeding). Although anecdotal reports have fueled fears of increased thrombosis with antifibrinolytics, controlled studies indicate no increased risk. ",22 645,"Mother-daughter pairs: spinal and femoral bone densities and dietary intakes. Bone mineral density (BMD) of the lumbar spine (L1-L4) and femur (femoral neck, Ward's triangle, and trochanter) was measured in 37 healthy, white mother-daughter pairs by dual-photon absorptiometry. Mothers and daughters were aged 52 +/- 7 and 25 +/- 4 y (mean +/- SD), respectively. Three-day dietary intakes were evaluated. Significant correlations between mother-daughter pairs for BMD of all lumbar and femoral areas [except for L2 (r = 0.26, P = 0.054)] indicated familial resemblances in bone mineralization. Total calcium intake was significantly correlated with three BMD values for the daughters (L2, femoral neck, and trochanter) but not for the mothers. When mothers were classified as pre- (n = 20) or postmenopausal (n = 17), correlation coefficients for BMD were higher for premenopausal mothers and their daughters and lower for postmenopausal mothers and their daughters, except for the trochanter. The results suggest that the nature of inheritance of bone mass of women may have at least two components, one influencing the level of peak bone mass and one related to bone loss at menopause. ",4 2235,"Development of a new transvenous patent ductus arteriosus occlusion technique using a shape memory polymer. A novel percutaneous patent ductus arteriosus (PDA) occlusion technique, without the potential problems associated with conventional techniques, has been long awaited. The development of a novel transvenous PDA occlusion technique using a temperature-shape changeable occluder device, and the verification of its in vitro performance, were demonstrated in this study. The principles of this technique are: 1) the bar form device was inserted into the PDA transvenously by a guide wire and a pushing catheter, 2) the device was dashed with hot water through catheters, 3) the device was expanded by hot water in the PDA, and the PDA was occluded. The occluder device, made of a shape memory polymer (polynorbornene), was designed to have the monobloc configuration of a thin disk with a hole for a guide wire in the center and a cone. The barlike device by hot press was fully expanded within 10 sec upon immersion into 45 degrees C water. The mock-circulation test with the ""great arteries"" and a specially designed ""PDA"" showed 1) the introduction of hot water (45 degrees C) through the catheters caused expansion of the device which stayed in the ""PDA"" without any support, 2) the ""aortic"" pressure and the distal ""aortic"" flow increased rapidly, and the ""pulmonary"" flow reduced promptly. This resulted in a drastically reduced shunt ratio at the PDA from 68% to 30%. Thus, the novel PDA occlusion technique developed here functioned well to occlude the PDA in a great arteries model. ",15 3043,"Urinary tract re-functionalization after long-term diversion. A 20-year experience with 177 patients. From 1969 to 1990, previously diverted urinary tracts were 'undiverted' in 177 patients whose ages ranged from 1 to 31 years. Fifty-six of the patients (32%) had been diverted for 10 years or longer. There were 67 female and 110 male patients. Forty-four patients had only one kidney and in two of those patients it was a previous renal transplant. One patient was anephric at the time of reconstruction, having had two unsuccessful transplants. Most of the diversions had been considered permanent. Types of diversions that were reversed include ileal loop, colon conduit, loop ureterostomy or pyelostomy, end ureterostomy, cystostomy or vesicostomy, long-term nephrostomy, and ureterosigmoidostomy. ",22 2546,"Oral calcium load test: diagnostic and physiologic implications in hyperparathyroidism. An oral calcium load test (CLT) (1 gm Ca/50 kg) was administered to 11 control subjects and 35 patients with overt hyperparathyroidism to assess its efficacy in diagnosis of hyperparathyroidism. All participants were placed on a low-calcium diet 3 days before the CLT. Intact parathormone and ionized calcium (Cai) levels were measured 0, 1, 2, and 3 hours after CLT. Initial Cai and parathormone (mean +/- SE) were 1.22 +/- 0.01 mmol/L and 2.94 +/- 0.03 pmol/L in the control group compared with 1.43 +/- 0.02 mmol/L and 10.6 +/- 2.2 pmol/L in the group with hyperparathyroidism. Both groups had a similar percent increase in Cai values (control, 5.9% +/- 0.8%; hyperparathyroidism, 6.3% +/- 0.6% (p greater than 0.1). A decline in parathormone levels of 47.6% +/- 2.8% in patients with hyperparathyroidism was significantly less than the 75.3% +/- 5.3% decline observed in control subjects (p less than 0.025). Three hours after CLT, parathormone was suppressed in control subjects, whereas a rebound occurred in patients with hyperparathyroidism. Postoperative CLT demonstrated a higher mean percent Cai increase and percent parathormone decline (Cai, 8.9% +/- 1.1%; parathormone, 67.9% +/- 1.8%) compared with preoperative values (Cai, 6.0% +/- 1.0%; PTH, 49.6% +/- 4.3%) (p less than 0.025), and 3 hours after calcium intake, parathormone remained suppressed, similar to control subjects. After surgery, three patients had elevated parathormone and low normal Cai levels and parathormone response to a CLT confirmed the diagnosis of secondary hyperparathyroidism. In conclusion, a CLT (1) can confirm the diagnosis of hyperparathyroidism and successful parathyroidectomy, (2) distinguished postoperative secondary from persistent primary hyperparathyroidism, (3) demonstrated nonautonomy of abnormal parathyroid glands with a parathormone response to a calcium load characterized by an earlier nadir, decreased suppressibility, and more rapid recovery, and (4) produced dynamic changes that did not distinguish patients with hyperparathyroidism from control subjects or hyperplasia from adenoma. ",18 2573,"Determinants of in vivo histamine release in cutaneous allergic reactions in humans. To determine host factors influencing the magnitude of mediator release during ongoing cutaneous allergic reactions in humans, we compared, in 22 subjects, the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release to (1) the in vitro reactivity and sensitivity of basophils to antigen for histamine release and (2) skin test sensitivity and reactivity to antigen, histamine, and codeine. There was no significant correlation between the first-hour and second- to fifth-hour histamine release. With a combination of basophil, antigen, histamine, and codeine skin sensitivity and reactivity, 64% to 75% of the magnitude of the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release could be accounted for. We conclude that antigen-induced in vivo allergic responses are a complex phenomenon dependent, in part, on antigen sensitivity, basophil and mast cell reactivity, and end organ responsiveness to mediators. ",19 1373,"A dose titration study evaluating terazosin, a selective, once-a-day alpha 1-blocker for the treatment of symptomatic benign prostatic hyperplasia. The efficacy and safety of terazosin, a selective long-acting alpha-1-adrenergic blocker, were evaluated in 45 normotensive patients with symptomatic benign prostatic hyperplasia ranging from 50 to 76 years old. All patients underwent a complete urodynamic evaluation and transrectal prostatic ultrasonography before enrollment into the study. The dose of terazosin was titrated to 5 mg. per day for a 1-month interval, provided adverse drug reactions were not observed. Of the patients 39 (87%) completed the dose titration study. The parameters used to assess the effectiveness of terazosin included peak and mean urinary flow rates, micturition symptom scores and the global assessment by the patient of symptomatic improvement. Over-all, the mean systolic and diastolic blood pressures changed by less than 1%. The peak and mean urinary flow rates increased by 42 and 48%, respectively. The obstructive and irritative symptom scores improved by 63 and 35%, respectively. Over-all, 30 of the 45 participants (67%) indicated that the voiding symptoms were markedly improved while on terazosin. Five patients did not complete the dose titration study due to development of adverse drug reactions, including erectile dysfunction (7%), tiredness (7%), light-headedness (4%), palpitations (4%), nasal congestion (2%) and asymptomatic hypotension (2%). There were 25 patients (55%) followed on terazosin for 4 to 10 months (mean 6.5 months). The improvements in urinary flow rates and symptom scores were maintained for this interval. Although this preliminary experience with terazosin is encouraging, the ultimate role of terazosin for the long-term treatment of benign prostatic hyperplasia needs further evaluation. ",11 2173,"Alterations in pulmonary mechanics after transfusion in anemic preterm infants. Pulmonary mechanics were studied in ten anemic preterm infants using an esophageal balloon and mask, before and after transfusion with 10 ml/kg of packed RBC. Their mean birth weight was 1212 +/- 323 g and gestational age was 29.27 +/- 2.4 wk. Transfusions were carried out at a mean postnatal age of 41.9 +/- 21.8 days. The mean Hct increased from 28 +/- 3.1 to 38.3 +/- 3.3%. Dynamic lung compliance decreased in all infants after transfusion. There was a 33.8% increase in resistance; the work of breathing increased after transfusion. These changes might be due to volume overload or increased lung water content. ",14 2754,"Tricyclic antidepressant overdose: conservative management in a community hospital with cost-saving implications. Reports of late-onset cardiovascular complications following tricyclic antidepressant (TCA) overdose have led to a very conservative approach to these patients. Many patients have been hospitalized for continuous cardiac monitoring, regardless of the clinical presentation. Management algorithms based on clinical predictors of outcome have recently been proposed. We used the algorithm developed by Tokarski and Young to retrospectively evaluate the care of 33 TCA overdose patients admitted to our hospital over a 3-year period. We then identified 11 patients who could have been treated on an outpatient basis had the algorithm been employed. Ten were admitted to a monitored unit and spent a mean of 31.6 +/- 15.64 hours on the unit. None of the 11 patients developed complications during their hospital stay. Use of the algorithm would have resulted in an estimated cost savings of 13 hospital days and $14,000. ",20 2910,"Flumazenil: a benzodiazepine antagonist. Although benzodiazepines have been proven safe and effective for the induction and maintenance of sedation, some instances require the reversal of these events prior to the natural process of metabolism and elimination. Flumazenil, a 1,4-imidazobenzodiazepine, is an antagonist that can reduce or terminate benzodiazepine effects in a dose-dependent manner. The antagonist acts by the competitive inhibition of benzodiazepines at their central nervous system receptor sites. When administered intravenously in incremental doses, flumazenil allows for optimal patient response on an individual basis. Despite its short elimination half-life, small doses of flumazenil are usually effective in producing benzodiazepine reversal. Flumazenil's short duration of activity is due to its rapid hepatic metabolism and elimination. Intravenous antagonist doses of 0.2 mg followed by 0.1 mg/min to a total dose of 1 mg have produced significant results in reversing benzodiazepine sedation. As much as 5 mg of flumazenil have been necessary when treating benzodiazepine or mixed-agent intoxications. In such situations, response rarely exceeds a duration of one hour. If resedation occurs, additional doses or an infusion of the antagonist may provide the desired response. Flumazenil is well tolerated locally as well as systemically. Nausea and vomiting occurring after anesthesia is the most documented adverse effect in both placebo and treatment populations. However, there has been no significant difference in the occurrence of vomiting in placebo compared with flumazenil-treated subjects. Careful observation and slow reversal of central nervous system depression is crucial in the avoidance of benzodiazepine withdrawal in those patients dependent upon these agents. Flumazenil appears to provide a mechanism for the safe and effective reversal of benzodiazepine-induced sedation. ",20 1793,"Factors affecting survival in total artificial heart recipients before transplantation. To identify factors affecting the successful bridge to transplantation, experience with 32 recipients of the Jarvik-7 artificial heart was reviewed. Between patients with and without a successful bridge, there were no significant differences in preoperative hepatorenal function or postoperative hemodynamics, but there were significant differences in body size. When recipients were divided according to body surface areas of less than or greater than 1.8 m2, the smaller patients more frequently developed respirator dependence (73% vs. 18%, p less than 0.01), renal failure (53% vs. 18%, p less than 0.05), and hepatic failure and sepsis, resulting in less frequent qualification for transplantation (20% vs. 65%, p less than 0.05). There were no successful bridge operations in seven patients with body surface areas of less than 1.7 m2, and only one success in nine patients who were less than 170 cm in height, despite use of a smaller stroke volume model. The smaller patients had poorer ventricular filling, which was largely compensated for by the drive controls set for significantly longer diastole and higher vacuum, resulting in similar hemodynamics between the groups. The results suggest that device fitting as manifested by body size is an important factor affecting major organ recovery and subsequent transplantation in recipients of the Jarvik-7 artificial heart. A paracorporeal device may be advisable for patients with body surface areas of less than 1.8 m2 or who were less than 175 cm in height until an even smaller model with a better fit in the thorax becomes available. ",13 1716,"Use of the variable-length intraluminal sutureless graft. From August 1987 to May 1988 we treated 4 patients with acute ascending aortic dissections with a variable-length intraluminal aortic prosthesis. This operation uses profound hypothermic circulatory arrest and represents a refinement of existing techniques. There was no mortality, and morbidity was minimal. Modifications of this technique can be used in performing proximal aortic root reconstruction with a composite valved conduit. The use of a variable-length intraluminal prosthesis and hypothermic circulatory arrest is illustrated. This is a safe and useful technique in select cases of acute ascending aortic dissection. ",13 1340,"Familial testicular cancer in five members of a cancer-prone kindred. Of a family of 13 siblings, four brothers have developed testicular neoplasms, one embryonal cell carcinoma and three testicular seminomas. A first cousin once removed on their mother's side of the family (fourth-degree relative) has developed an embryonal carcinoma. After treatment they are all alive and well. Their mother is a dizygous twin and one of ten siblings. Multiple other cancers have been diagnosed among her siblings and their offspring including breast carcinoma at age 30 years in monozygous twin nieces. Associated urogenital abnormalities, concordance of age, and discordance of pathology in the five males with testicular cancer is discussed. Further identification and reporting of this risk factor is encouraged. ",11 280,"Surgical treatment of brain metastases in malignant melanoma. The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. The 30-day mortality was zero. The 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). The seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2-4 months), and those treated with chemotherapy alone (median, 2-4 months). The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases. ",3 1041,"Dementia, depression, or grief? The differential diagnosis. Depression, grief, and dementia are conditions frequently encountered among the community-living elderly. This review offers a primary care perspective of the distinguishing features for each and discusses the special issues of managing the elderly. Major depression in the elderly usually responds to antidepressant medication, whether the depression occurs alone (endogenous) or as a response to another condition (reactive). ",9 1610,"Mitral stenosis: evaluation with MR imaging after percutaneous balloon valvuloplasty. To evaluate the pathoanatomic findings of mitral valve stenosis and changes after percutaneous balloon valvuloplasty (PBV), magnetic resonance (MR) imaging was performed in 23 patients. The patients were imaged with a 2.0-T system within 1 week before and 3-10 days after PBV. The angle of the interatrial septum was measured on the transverse image to facilitate a successful transseptal puncture. On MR images, the mean transverse and anteroposterior diameters of the left atrium at the level of the aortic root in the ventricular diastolic phase decreased significantly after PBV. Areas of flow-related intraluminal signal intensity detected in the left atrial cavity of 17 patients (74%) before the procedure disappeared in 15 patients after the procedure. Other MR imaging findings after PBV were the disappearance of intraluminal signal intensity in the pulmonary artery, normal curvature of the interatrial and interventricular septa, and pericardial effusion as a complication. MR imaging was thought to provide useful information before and after PBV in patients with mitral stenosis. ",13 1756,"Conservative management of asymptomatic popliteal aneurysm. Historical review shows that the treatment of popliteal aneurysm has developed by trial and error and there is disagreement about the proper management of the symptomless patient. In 1981 a policy of conservative management for asymptomatic popliteal aneurysm was adopted in this unit. Since that time we have also managed nine patients with thrombosed popliteal aneurysms by arteriography and low-dose intra-arterial streptokinase. Six patients treated within 72 h of occlusion achieved significant (70-100 per cent) lysis, but streptokinase was ineffective in those treated 10 or more days after the thrombosis. Of the six patients with significant lysis, three were treated by elective reconstruction and two by anticoagulation. One patient who had significant lysis died. Vascular patency of all five successfully treated limbs was maintained and no limb loss occurred in those who presented late and failed to achieve significant lysis. These results reinforce the view that thrombolysis is the treatment of choice for thrombosed popliteal aneurysms. The low complication rate for asymptomatic popliteal aneurysms and the advent of safe, effective thrombolysis indicate that operation for symptomless popliteal aneurysm is no longer required. ",13 2234,"Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions. ",15 1221,"Quantitative assessment of extradural bupivacaine analgesia. Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection. ",9 2555,"Angiotropic (intravascular) large cell lymphoma. A clinicopathologic study of seven cases with unique clinical presentations. The authors recently reported the antigenic phenotypes of three cases of so-called ""malignant angioendotheliomatosis"" and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement, the second with lytic bone lesions and thickened nasal sinus mucosa, the third had diffuse myalgia, the fourth had dyspnea and pulmonary infiltrates, the fifth had gangrene of the lower extremities, total-body skin involvement, and pancytopenia, the sixth had a lesion of the foreskin mimicking squamous cell carcinoma, and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with, in two cases, extravascular spread into soft tissue. Immunohistologic studies showed a B-cell phenotype in five cases and a T-cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma, and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long-term follow-up is available. These data indicate that, although ALCL affects predominantly the central nervous system and skin, unusual clinical presentations may occur, and patients with ALCL may respond to combination chemotherapy for large cell lymphoma. ",19 475,"Magnetic resonance imaging of vertebral osteoblastoma: a report of two cases. Two patients with vertebral osteoblastoma evaluated with computed tomography and magnetic resonance imaging are presented. A literature review revealed that cases of osteoblastoma originating within the vertebral body are exceedingly rare. ",3 1242,"Primary progressive aphasia. Longitudinal course, neuropsychological profile, and language features. Four patients with the clinical syndrome of primary progressive aphasia and a nonfluent aphasia profile were followed up over a period of 3 to 5 years. Extensive neuropsychological data for three patients revealed a progressive, quantitative decline of language with relative stability of memory, visuospatial skills, and reasoning. Comportment and most activities of daily living were preserved even when speech was unintelligible. Although several aphasia types may be associated with primary progressive aphasia, a nonfluent aphasia profile and phonemic paraphasic errors are most useful in differentiating it from the much more common clinical syndrome, ""probable Alzheimer's disease."" The clinicopathological correlates of probable Alzheimer's disease differ from those associated with primary progressive aphasia. Therefore, the clinical distinction between the two syndromes may be important for predicting the underlying pathophysiologic changes during the life of the patient. ",9 2816,"Treatment of juxtaarticular nonunion fractures at the knee with long-stem total knee arthroplasty. A retrospective study of ten patients with juxtaarticular nonunions at the knee treated with long stem total knee arthroplasty was performed. The average age of the patients was 76 years old, with an average follow-up of 36 months. The nonunions were present for an average of 36 months. There were six patients in the series with prior total knee arthroplasty. Clinical union was achieved in all ten patients. All patients improved their ambulatory status. Range of motion improved from an average preoperative range of 40 degrees to an average postoperative range of 85 degrees. Complications occurred in three of ten patients, with one being a postoperative infection. Surgical techniques are described to aid in treatment of difficult juxtaarticular nonunion fragments. ",20 3088,"Effect of amiodarone on erythrocyte shape and membrane properties. 1. Amiodarone is a potent anti-arrhythmic drug with lipophilic properties. The intercalation of such a drug into the membrane of erythrocytes may alter their shape and have an impact on the flow properties of blood. We therefore studied the influence of amiodarone on erythrocyte shape and deformability in vitro and in vivo. 2. Incubation in vitro with increasing amiodarone concentrations led to a progressive stomatocytic shape transformation and a decreased deformability of the erythrocytes. 3. Amiodarone treatment in eight patients did not affect erythrocyte morphology and deformability. However, an increase in the membrane cholesterol/phospholipid ratio was found. 4. The stomatocytic shape transformation of erythrocytes in vitro indicates that amiodarone intercalates in the inner hemileaflet of the lipid bilayer leading to membrane internalization. These results shed light on the interaction of amiodarone with biomembranes. ",22 1387,"Prognostic implications of disappearance rate of biologic markers following radical prostatectomy. Six patients with localized prostatic carcinoma undergoing radical prostatectomy were studied by serial sample collection from the time of surgical removal of the prostate up to one week in the postoperative period. Of the three markers studied (PAP, PSA, LASA), half-life of specific prostatic markers were calculated. Half-life of PAP was found to be 7.25 hours +/- SE of 0.7 hours. For PSA the half-life could be obtained in 4 of 6 patients and was found to be 45.5 hours +/- SE 4.9 hours. In 2 patients PSA did not fall in a regular fashion and half-life could not be obtained. In both patients metastatic disease has developed within six months of surgery. LASA demonstrated progressive increase following surgery, most likely due to associated inflammatory reaction. These studies confirm previous observations that PSA is a more sensitive marker than PAP, and that the presence of an elevated PSA after radical prostatectomy denotes the presence of residual disease. ",11 1000,"Aqueous beclomethasone diproprionate nasal spray: regular versus ""as required"" use in the treatment of seasonal allergic rhinitis. OBJECTIVE: to determine the effect of alternative regimens of nasal steroid administration on symptoms and quality of life. DESIGN: randomized, double-blind, parallel-group comparison. SUBJECTS: sixty ragweed-sensitive adults recruited from participants of previous studies and through media advertising. INTERVENTIONS: 200 micrograms of aqueous beclomethasone diproprionate nasal spray, twice daily, from 1 week before until 1 week after the ragweed-pollen season (regular) or 100 micrograms of the spray, taken as required, up to 400 micrograms daily; troublesome nasal symptoms were treated, in both groups, by increasing the daily dose to 800 micrograms until symptoms were controlled. If this treatment was insufficient, 120 mg of terfenadine, daily, was added. RESULTS: One subject in the ""as required""-treated group withdrew with uncontrolled nasal symptoms. In the remaining subjects, sneezing, stuffy nose, and rhinorrhea, measured by a daily diary, were significantly better controlled in the regular-treated group (p less than 0.025). Impairment of quality of life, including sleep disturbance, nonhay fever symptoms, practical problems, and uncomfortable emotions were greater in the as required-treated group (p less than 0.001). Subjects in the regular-treated group required less additional terfenadine (0.27 tablets per subject versus 1.40; p = 0.022). Eye symptoms and eye-drop use were similar in the two treated groups. CONCLUSION: In patients with seasonal allergic rhinitis, regular use of inhaled steroids results in fewer symptoms and better quality of life than when the spray is taken only as required. ",8 64,"Infectious diseases as a Canadian subspecialty, with projections to the year 2000. Infectious diseases is a relatively new subspecialty in Canada. During the past decade, however, important advances have been made. These include the formation of the Canadian Infectious Diseases Society and the development of the first Royal College of Physicians and Surgeons examinations in the subspecialty of infectious diseases. The majority of Canadians training for practice in the field of infectious diseases are now enrolled in programs in Canada. Despite predictions in the United States of an excess of physicians who specialize in infectious diseases, such a situation has not occurred in Canada. More physicians with training in infectious diseases will be required in Canada in the next decade to fill positions in patient care, microbiology (for individuals with both clinical and laboratory training), research, epidemiology and infection control, programs related to human immunodeficiency virus infections, geographic and international medicine, the pharmaceutical industry, and education and administration. In Canada, the extent to which infectious diseases physicians are involved in these areas varies from that in the United States. This review suggests a continued need for physicians with appropriate training in infectious diseases. ",0 2272,"Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid. We administered borage seed oil (9 capsules/day) for 12 weeks to 7 normal controls and to 7 patients with active rheumatoid arthritis. The therapy provided 1.1 gm/day of gamma-linolenic acid (GLA). GLA administration resulted in increased proportions of its first metabolite, dihomo-gamma-linolenic acid (DGLA), in circulating mononuclear cells. The ratios of DGLA to arachidonic acid and DGLA to stearic acid increased significantly in these cells. Significant reductions in prostaglandin E2, leukotriene B4, and leukotriene C4 produced by stimulated monocytes were seen after 12 weeks of GLA supplementation. The antiinflammatory effects of GLA administration observed in animal models, and the apparent clinical improvement experienced by 6 or 7 rheumatoid arthritis patients given borage seed oil in this open, uncontrolled study may be due in part to reduced generation of arachidonic acid oxygenation products. ",16 3264,"Intrathoracic current flow during transthoracic defibrillation in dogs. Transcardiac current fraction. To achieve transcardiac threshold current during transthoracic defibrillation, a considerably larger current must be delivered to the thorax to compensate for the shunting effect of the lungs, the thoracic cage, and other elements of the torso. This shunting effect is thus an important determinant of transthoracic defibrillation threshold and can be quantified by the transcardiac current fraction (FC, the ratio of transcardiac to transthoracic threshold currents). Previous estimates of FC have ranged from as low as 3% to as high as 45%. The purpose of of this study was to quantify both FC and the major intrathoracic current pathways. Transthoracic and intrathoracic voltages and currents were simultaneously measured during high-voltage transthoracic shocks in 20 dogs. With correction factors determined from another set of 12 dogs, these raw data were corrected to compensate for field distortion caused by the presence of the intrathoracic electrodes, and the adjusted data were fit to a resistive network model. The results showed that 82% of the transthoracic current was shunted by the thoracic cage, while 14% was shunted by the lungs. The remaining 4% (FC) is the portion that passed through the heart. There was good agreement between the two independent methods used to calculate FC. Analysis based on the model indicated that FC was 3.7%, whereas FC determined by direct measurement with calibrated electrodes was 4.2%. Therefore, the results of this study, in contrast to earlier estimates of FC, show that defibrillation in dogs is achieved by only 4% of the total transthoracic current. ",22 431,"The single-breath nitrogen test, mortality, and cancer. The relationship between indices of the single-breath nitrogen test and mortality, overall cancer incidence, and respiratory cancer incidence was examined in a cohort of 876 men, 46 to 69 yr of age, examined in 1974 and followed until June 1985. Closing volume, closing capacity, and slope of phase III were not related to mortality or cancer. In contrast, FEV1 was related to mortality, with an estimated relative mortality risk of 1.37 (95% confidence interval, 1.11 to 1.70) per liter under the expected FEV1, given height, age, and smoking, but FEV1 was not related to cancer. Inability to perform acceptable single-breath nitrogen test tracings was related to mortality with a relative mortality risk of 2.03 (1.45 to 2.85), but not to cancer. We conclude that indices of the single-breath nitrogen test have no predictive value concerning overall mortality and cancer incidence. ",3 208,"Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2. ",3 2237,"Changes in circulating alphafetoprotein following administration of mifepristone in first trimester pregnancy. The occurrence of fetomaternal haemorrhage was investigated in 30 women by measuring maternal serum alphafetoprotein (AFP) levels before and after the administration of mifepristone (RU 486) for termination of first trimester pregnancy. A significant rise in AFP levels was seen in 21 women (70%), the increase ranging from 6 to 660% of baseline levels. The apparent frequency of fetomaternal haemorrhage was similar to that reported previously for surgical termination of first trimester pregnancies. ",15 1564,"A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients. ",13 2061,"Effect of halothane and isoflurane on postischemic ""stunned"" myocardium in the dog. Short periods of coronary artery occlusion are known to produce prolonged periods of ventricular dysfunction. The effects of halothane or isoflurane on contractility and metabolism in postischemic ""stunned"" myocardium were studied in an open-chest canine model in which the left anterior descending artery (LAD) was occluded for 15 min and then reperfused. Regional function in the LAD and circumflex artery (CIRC) areas were measured with sonomicrometry, and metabolic data were determined from simultaneous arterial and venous measurements of oxygen and lactate. Halothane and isoflurane produced equivalent decreases in systolic shortening in both normal (CIRC) and stunned (LAD) areas of the heart. Furthermore, the amount of depression was similar with either halothane or isoflurane. Halothane 0.75 MAC significantly decreased systolic shortening in both the LAD region (from 38.8 +/- 25.9% to 11.0 +/- 21.8%) and in the CIRC region (from 116.7 +/- 24.7% to 87.5 +/- 23.3%). At equivalent MAC concentrations of isoflurane, the values were 42.5 +/- 45.7 to -7.0 +/- 49.9% in the LAD region and 91.5 +/- 11.9% to 66.9 +/- 23.9% in the CIRC area. At 1.5-MAC halothane, systolic shortening in the LAD region decreased from 47.9 +/- 47.2% to -0.6 +/- 20.3% and in the CIRC area from 114.6 +/- 16.8% to 76.0 +/- 18.7%. Isoflurane at 1.5 MAC produced significant decreases, from 23.4 +/- 54.5% to -15.6 +/- 27.1% in the LAD region and from 94.4 +/- 33.2% to 61.3 +/- 28.2 in the CIRC area. ",13 585,"Function after amputation, arthrodesis, or arthroplasty for tumors about the knee. We studied the function of twenty-two patients who had had a malignant skeletal tumor adjacent to the knee. An above-the-knee amputation was done in seven; a resection arthrodesis, in nine; and a replacement arthroplasty, in six. The patients all walked at a similar speed (sixty-one to sixty-six meters per minute), which is slower than normal (eighty meters per minute). They all walked with comparable efficiency at three velocities: the mean consumption of oxygen was 0.210 milliliter per kilogram of body weight per meter at free velocity, 0.215 milliliter per kilogram of body weight per meter when they walked 25 per cent faster, and 0.211 to 0.240 milliliter per kilogram of body weight per meter when they walked 50 per cent faster. The three groups of patients and a normal control group consumed oxygen at similar rates. The patients who had had an amputation were very active, and they were the least worried about damaging the affected limb, but they had difficulty walking on steep, rough, or slippery surfaces. The patients who had had an arthrodesis had a more stable limb and performed the most demanding physical work and recreational activities, but they had difficulty sitting. The patients who had had an arthroplasty led sedentary lives and were the most protective of the limb, but they were the least self-conscious about the limb. ",3 299,"Increased expression of the multidrug-resistance gene in undifferentiated sarcoma. We analyzed multidrug-resistance gene (mdr1 gene) expression in a patient with undifferentiated sarcoma of the liver using the cloned cDNA for the mdr1 gene. Tissue samples were available at the time of initial diagnosis and of two intracranial relapses after chemotherapy with a regimen including doxorubicin and teniposide. The level of mdr1 gene expression was increased sevenfold in the intracranial tumor at the time of first relapse and 11-fold at the second relapse. This case may be an example of acquired multidrug resistance associated with overexpression of the mdr1 gene. ",3 757,"Witzel pneumatic dilation for achalasia: safety and long-term efficacy Forceful dilation of the lower esophageal sphincter is considered primary therapy for achalasia. The Witzel pneumatic balloon dilator, unlike fluoroscopically placed dilators, is placed over a standard gastroscope allowing positioning and dilation under direct vision. We report our experience with the Witzel dilator in 45 patients with achalasia over a 5-year period. All patients had at least one major symptom score of 8 out of 10 for dysphagia and/or regurgitation before dilation. After Witzel dilation, symptomatic response was graded as excellent (score 0 to 2), good (score 3 to 5), fair (score 6 to 8), and poor (no improvement). Symptom response was assessed after 1 week, 1 month, 6 month, 1 year, and present. The mean period of follow-up was 25 months (range, 3 to 85 months). Passage of the balloon across the gastroesophageal junction was technically unsuccessful in three patients. Esophageal perforation occurred in two patients (4%) and transient chest pain greater than 2 days in three patients (7%). There was no bleeding or death. Symptomatic long-term improvement was excellent in 25 patients (63%), good in 6 patients (15%), fair in 4 patients (10%), and poor in 5 patients (12%). A repeat Witzel dilation was performed in five patients but resulted in good/excellent improvement in only one patient. We conclude that pneumatic dilation with the Witzel balloon is a safe, effective procedure for achalasia. ",5 2513,"Management of primary hypothyroidism. Primary hypothyroidism is a common condition requiring lifelong treatment and monitoring. The type and amount of thyroid hormone replacement, selection of laboratory tests, and timing of office visits are all important for optimizing patient well-being and reducing the costs of medical care. The aim of treatment is to bring the patient to the euthyroid state. Currently this is defined as a normal serum concentration of TSH by recently developed sensitive and specific immunometric assays, and is accomplished by titrating the dose of levothyroxine and changing it not more often than at 4- to 6-week intervals. As an indicator of euthyroidism, the sensitive TSH assay has advantages over tests of serum T4, FT4I, T3, FT4, and TSH by RIA because it is independent of TBG changes that result from pregnancy, birth-control pills, and estrogen replacement, is not spuriously elevated by the levothyroxine treatment itself, and is the only test that detects both subclinical hypothyroidism and subclinical hyperthyroidism. Additional serum tests are not usually necessary but have advantages under special circumstances. Once the optimal replacement dose is determined, monitoring can be done yearly or even bi-yearly, depending on the adequacy of patient education and patient compliance. ",18 1191,"Osseointegration of titanium implants in total hip arthroplasty. Osseointegration is defined as direct contact on the light microscopic level between living bone tissue and the implant. Using titanium screw dental implants in the jaw, a lasting interface under loaded conditions extending over a 20-year follow-up period has been demonstrated. This demonstration brings up the question whether a similar interface can be achieved in total hip arthroplasty (THA) between living bone and a titanium alloy implant under necessitated conditions of immediate loading. Two series of cases are reported. The first series used a femoral, press-fit, titanium alloy component and the second used a press-fit titanium acetabular component and redesigned femoral, press-fit, titanium alloy component. Both demonstrated a high percentage of good to excellent results. Roentgenograms showed that the geometrical changes in the redesigned femoral component gave early indications of a better fixation with loading in valgus, less subsidence, and less evidence of distal stress transfer. A two-and-one-half-year postoperative anatomic specimen study confirmed osseointegration to the press-fit titanium alloy femoral component. Multiple areas of contact between bone and metal without fibrous interposition were seen. Examination by electron microscopy supported the light microscopic findings. These findings support further use of smooth, press-fit titanium components in THAs without the need for porous coating, mesh, or other surface modifications. ",9 336,"Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases. ",3 1575,"Severe aortic regurgitation as a late complication of temporal arteritis. Two patients with a remote history of pathologically documented giant cell arteritis developed severe regurgitation. The first patient developed severe aortic regurgitation five years after the pathologic documentation of giant cell arteritis of the temporal arteries. Giant cell arteritis involvement of the aortic root was confirmed. The second patient developed aortic regurgitation seven years after pathologic documentation of giant cell arteries of the temporal arteries. Although pathologic confirmation of the aortic root process was not obtained, this case strengthens the clinical association between giant cell arteritis of the temporal arteries and subsequent aortic root dilatation and severe aortic regurgitation. Observation for signs of de novo severe aortic regurgitation is indicated in follow-up of patients with temporal arteritis. ",13 2153,"Molecular defect of the band 3 protein in southeast Asian ovalocytosis BACKGROUND. Southeast Asian ovalocytosis is a form of hereditary elliptocytosis in which the red cells are rigid and resistant to malaria invasion. The underlying molecular defect is unknown. METHODS AND RESULTS. We studied the red cells of 54 patients with ovalocytosis and 122 normal controls. We found that ovalocytes contain a structurally and functionally abnormal band 3 protein, the principal transmembrane protein of red cells. The structural lesion of ovalocyte band 3 was revealed by limited proteolytic cleavage of the protein, which produced fragments of abnormal size that were derived from the cytoplasmic domain of the protein. The structural lesion was present in all the subjects with ovalocytosis but none of the controls. This region of band 3 serves as the principal binding site for the membrane skeleton, a submembrane protein network composed of ankyrin, spectrin, actin, and protein 4.1. The structural defect is dominantly inherited, being tightly linked with the inheritance of ovalocytosis (the probability of linkage is in excess of 10 million to 1). Ovalocyte band 3 bound considerably more tightly than normal band 3 to ankyrin, which connects the membrane skeleton to the band 3 protein. This tight binding of ovalocyte band 3 to the underlying skeleton containing ankyrin was directly confirmed in intact cells by the finding that ovalocyte band 3 had markedly reduced lateral mobility in the membrane. CONCLUSIONS. The red cells in Southeast Asian ovalocytosis carry a structurally and functionally abnormal band 3 protein. This molecular defect may underlie the increased rigidity of the red cells and their resistance to invasion by malaria parasites. ",14 101,"Thoracic empyema: causes, diagnosis, and treatment. Thoracic empyema is a disease that has been recognized for centuries. The principles of management as stated by Hippocrates remain more or less unchanged. Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases. With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis. When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay. The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered. If the original infection is adequately treated, empyema rarely occurs. Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention. These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment. Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management. ",0 2972,"Isolation of Tete serogroup bunyaviruses from Ceratopogonidae collected in Colorado. Two viruses were isolated from ceratopogonid midges collected in northern Colorado. Electron microscopy indicated that both isolates were bunyavirus-like. Indirect fluorescent antibody and serum dilution-plaque reduction neutralization tests showed that these isolates were members of the Tete serogroup, most closely related antigenically to Tete and Batama viruses but distinguishable from both and from each other. We suggest the name Weldona virus for these isolates. Antibody in both waterfowl and passerine birds in northern Colorado indicates the enzootic presence of these viruses in northern Colorado and raises unanswered questions about the introduction and establishment of Tete serogroup viruses in the Americas. ",21 392,"Expression of murine renin genes in subcutaneous connective tissue. A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue. ",3 626,"Electrophysiological spectrum of inclusion body myositis. We present electrodiagnostic data on 30 patients with inclusion body myositis (IBM) in order to better delineate its electrophysiological features. Comprehensive electromyography (EMG) and nerve conduction studies (NCS) were performed in all cases. Twelve patients had single fiber electromyography (SFEMG). EMG showed abundant short-small motor unit potentials (MUP) with fibrillations and positive sharp waves in 56.6% of patients, and a mixed pattern of large and small MUP in 36.7%. In 6.7%, only ""neurogenic"" features were seen. NCS were slow in 33.3%. SFEMG revealed a mildly abnormal jitter and a slightly increased fiber density. IBM demonstrates a heterogeneous EMG profile. A pattern of large and small MUP is highly suggestive of IBM but is seen in only about one third of cases. ",4 2035,"Studies of myocardial protection in the immature heart. II. Evidence for importance of amino acid metabolism in tolerance to ischemia. This study tests the importance of amino acid transamination in determining the tolerance of immature hearts to ischemic damage. Amino acid transamination was inhibited metabolically by pretreatment with aminooxyacetic acid. The aminooxyacetic acid dose and duration were determined by incubating in vitro tissue homogenate and showing that an 8 mmol/L AOA dose for 5 minutes blocked 90% of alanine aminotransferase and aspartate aminotransferase activity. Control studies in nonischemic hearts showed that coronary perfusion with aminooxyacetic acid for 5 minutes did not impair myocardial performance. In contrast, pretreatment of immature puppies with aminooxyacetic acid severely impaired recovery after 45 minutes of normothermic global ischemia (30% versus 85% recovery in untreated hearts, p less than 0.05). Biochemical analyses of hearts undergoing ischemia showed aminooxyacetic acid to limit lactate production, impair glutamate utilization, prevent alanine production, and limit succinate accumulation (p less than 0.05). These data suggest that amino acid transamination is an important adaptive process in the immature heart that improves its resistance to ischemic damage. ",13 2663,"Profile of bronchospastic disease in Puerto Rican patients in New York City. A possible relationship to alpha 1-antitrypsin variants. A high prevalence of asthmalike symptoms was noted among patients of Puerto Rican descent attending Beth Israel and North Central Bronx Medical Centers in New York City, as compared with other ethnic groups. An evaluation of family and medical histories, pulmonary function data, and alpha 1-antitrypsin phenotypes was undertaken in such Puerto Rican patients and control subjects without asthma. The patients showed a higher proportion of MS and MV phenotypes. All the patients in both MM and variant phenotype groups, with the exception of four MM patients, had features indicative of asthma, with labile airway obstruction, and elevated serum immunoglobulin E and eosinophil levels. The latter was significantly higher in the patients with variant phenotypes than in MM patients. Patients with alpha 1-antitrypsin variants also had much shorter smoking histories as compared with the MM group, and all reported histories of asthma in first-degree relatives, as compared with 66% among the MM patients. We conclude that there is an increased incidence of asthma among Puerto Ricans in New York City, and that the antitrypsin variant phenotypes (specifically S and V) play a role in this incidence and its expression. ",19 3047,"The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity. The purpose of this study was to (1) evaluate the relative cost effectiveness of the central venous pressure and flow-directed pulmonary artery catheters used to maintain normal hemodynamic values as therapeutic goals in the control groups vs supranormal values empirically observed in critically ill postoperative survivors in the protocol groups, and (2) to evaluate tissue perfusion and oxygenation in relationship to organ failure and mortality. In two prospective clinical trials there were no significant differences in outcome between the central venous pressure and pulmonary artery control groups that used normal values as therapeutic goals. However, there were marked and significant reductions in morbidity and mortality of the protocol groups using the supranormal cardiac index, oxygen delivery, and oxygen consumption values as goals. The cumulative oxygen debt was less and organ failures were fewer and less severe in the protocol groups than in the control groups. ",22 2190,"Natural and modified history of complete atrioventricular septal defect--a 17 year study. We reviewed 103 cases of isolated complete atrioventricular septal defect. These cases represented 4.4% of the cases of congenital heart disease diagnosed in our hospital by catheterisation and angiography during 1971-88. Most children (n = 76) had Down's syndrome. Banding of the pulmonary artery was performed in seven cases and complete repair in 67 cases. In the period 1971-82 the complete correction was performed at a mean age of 23 months with a surgical mortality of 88.8%. In the period 1983-8 the mean age at complete correction was 13 months, the mortality 43.2%, and the five year actuarial survival was 46.8%. The 22 patients that survived after complete correction were in functional classes I and II of the New York Heart Association classification. After a mean follow up of 10 years only eight (36%) of the 22 who were followed up and treated medically survived; all had developed pulmonary vascular obstructive disease and were in functional classes III or IV. Our findings stress the importance of early complete surgical repair. ",15 2584,"Bronchoconstriction induced by spirometric maneuvers in patients with bronchial asthma. We analyzed forced expiration maneuver-induced bronchoconstriction in 14 asthmatic patients and in seven normal subjects by breaking down the forced expiration maneuver of spirometry (the FVC maneuver) into two phases: a slow, deep inspiration to the total lung capacity (TLC) (the DI maneuver) and a forced expiration to the residual volume (RV) (the PFV maneuver). Specific airway conductance (sGaw) was measured at functional residual capacity (FRC) after each of the three maneuvers. All of the maneuvers caused the greatest bronchoconstriction immediately after completion of the maneuver. The mean decreases in the sGaw immediately after the FVC, DI, and PFV maneuvers were 45.0 +/- 6.6 (SD)% (P less than .001), 29.6 +/- 5.3% (P less than .001), and 16.7 +/- 5.3% (P less than .03), respectively. The decrease in sGaw by the FVC maneuver was very close to the combined algebraic sum of the DI maneuver and the PFV maneuver. The normal subjects did not show any changes in the sGaw by any of the maneuvers. The inhalation of albuterol almost abolished the response of bronchoconstriction to any of the three maneuvers, but inhalation of an anticholinergic agent, ipratropium bromide, did blunt the response. This study suggests that forced expiration maneuver-induced bronchoconstriction in asthmatics can be caused not only by deep inspiration to the TLC but also by forced expiration to the RV, and that the bronchoconstriction may be brought about mainly by an increase in parasympathetic activity. ",19 1317,"The case for no initial treatment of localized prostate cancer. This contribution summarizes the evidence from the natural history and pathology of this disease that, given the high incidence of latent cancer, a policy of radical treatment at diagnosis will represent over-treatment in the majority of cases. As yet, neither radical prostatectomy nor radical radiotherapy has been shown to be effective in managing the poorly differentiated tumor in the patient with ""localized"" disease. For the patient with well-differentiated disease, there is little evidence that early treatment is mandatory, because the majority of these patients will not die of prostatic cancer. The adoption of a policy of diagnosis followed by active surveillance would spare many patients the hazard and discomfort of a major operation or of a course of radiotherapy, would minimize expenditure, and would ensure that treatment was given only to those patients in whom progression had been demonstrated. Such an approach is almost certain to be as effective as treatment at diagnosis. Confirmation of this view is likely to be obtained from the existing studies of immediate versus delayed orchiectomy or LHRH therapy currently being undertaken by the Urological Working Party of the Medical Research Council in the United Kingdom and the Urological Group of the EORTC within Europe. ",11 1404,"Hyaluronic acid (Sperm Select) improves retention of sperm motility and velocity in normospermic and oligospermic specimens. The effects of Sperm Select (Pharmacia AB, Uppsala, Sweden), a hyaluronic acid medium, on the motility and membrane integrity properties of sperm were studied. In 15 normospermic specimens after overnight incubation, the motility parameters in the control versus the Sperm Select group were as follows (mean +/- SEM): motility, 18.8% +/- 2.8% versus 27.4% +/- 2.9%; velocity, 21.5 +/- 2.4 versus 27.2 +/- 2.2 microns/s; linearity, 3.8 +/- 0.3 versus 4.4 +/- 0.2; lateral head displacement, 1.5 +/- 0.2 versus 1.9 +/- 0.1 microns; and tail beat/cross frequency, 8.8 +/- 1.3 versus 10.8 +/- 1.4 Hz. The density of motile sperm was 10.8 +/- 2.3 versus 18.5 +/- 2.5 X 10(6) sperm/mL. Finally, the velocity coefficient, the multiple of the sperm motility and linear velocity, was 4.6 +/- 1.1 versus 8.1 +/- 1.4. However, we found no Sperm Select related differences when testing sperm membrane integrity with hypoosmotic swelling and supravital staining. Thus, Sperm Select improves the retention of sperm motility (most prominently velocity) apparently due to a direct action of hyaluronic acid on sperm metabolism or contractility rather than to preservation of sperm membrane integrity. In 20 oligospermic specimens, Sperm Select caused similar improvements in sperm motility, and the duration of motility could be predicted from the degree of enhancement in sperm velocity after short-term Sperm Select exposure. A modified Sperm Select protocol is described that further increases motile sperm yield without a centrifugation step. ",11 3178,"Cytomegalovirus in a macerated second trimester fetus: persistent viral inclusions on light and electron microscopy. The macerated stillborn fetus represents at least one third of all perinatal deaths. Microscopic examination of these specimens is often unrewarding. We have reported a clinically unsuspected cytomegalovirus infection in a second trimester macerated fetus. Cells suggestive of CMV inclusions were identified by light microscopy, but electron microscopy confirmed the presence of viral infection and proved valuable in making the diagnosis even though necrosis was severe. ",22 1984,"Carotid endarterectomy: a ten-year analysis of outcome and cost of treatment. Between 1978 and 1988, 215 patients with an average age of 67 years, underwent 246 carotid endarterectomies. Two hundred ten (85.4%) patients were symptomatic, and 36 (14.6%) were asymptomatic. Six patients (2.4%) had a postoperative stroke, and all had immediate reoperation. One of these patients died (30 day mortality rate, 0.4% for the series), and two (0.8%) recovered completely, whereas three (1.2%) had a mild permanent neurologic deficit. Two patients (0.8%) had nonfatal myocardial infarction. Mean follow-up of 42.2 months (range, 1 to 126 months) was achieved. At 5 and 8 years actuarial survival rates of 82% and 66% and stroke-free survival rates of 67% and 37% were observed. Actuarial stroke free rates of 90% at 5 and 8 years were noted. By introducing and observing guidelines that required preoperative study of most clearly defined classes of patients before admission for surgical treatment, the average length of stay for carotid endarterectomy was lowered from 9.5 days in the first 5 years of the study to 5.8 days in the second 5 years (p = 0.001). Average hospital charges, expressed in constant dollars, decreased from $3113 in the first 5 years to $2620 in the second 5 years (p = 0.02) despite an 88% inflationary increase in medical consumer price index. This experience shows that the length of hospitalization of patients with carotid endarterectomy can be reduced and the cost of admission lowered without untoward effect on perioperative morbidity and mortality rates. ",13 1007,"Hearing aids for high-frequency hearing loss. This cross-over study compares the relative benefits of a standard NHS contracted hearing aid with a high-frequency emphasis commercial aid in subjects with high-frequency hearing loss. Disability questionnaires and free-field speech-in-noise (FAAF II) tests were used to assess subjects unaided and after 6 weeks of wearing each aid. Total FAAF II test scores showed no significant difference with either aid, but analysis of frequency-specific subscores demonstrated less use of low-frequency information when using the high-frequency emphasis aid. Overall questionnaire responses relating to conversation showed more benefit with the high-frequency emphasis aid. Subjects generally preferred this aid, possibly due to less low-tone gain than the standard NHS aid. ",8 1292,"Posterior horizontal and vertical tightening to treat combined punctal ectropion with medial canthal tendon laxity. The classical operations to treat either medial canthal tendon laxity or punctal aversion occurring alone possess drawbacks if they are used to treat these conditions when they occur simultaneously. A simplified procedure is described whereby tissue is removed via a posterior eyelid approach so that the eyelid may be tightened both horizontally and vertically, thus inverting the punctum and fixating it in the lacrimal lake. This procedure is quite easy to perform and can be done under local anesthesia in the office. ",10 2397,"Use of Doppler flow velocity waveform analysis in detection of initial diabetic microangiopathy. Doppler flow velocity waveform analysis (FVWFA), recorded from the dorsalis pedis artery (DPA) and the radial artery (RA), was performed on 36 women in attempting to detect an initial diabetic microangiopathy (DM). The study comprised two groups of women affected by non-insulin-dependent diabetes mellitus, 6 patients (pts) of reproductive age (1), 12 pts in menopause (II), and two groups of age-matched healthy controls (C) (III and IV). Clinical signs of initial DM were present in group I. All the examined pts were nonsmokers and normotensive and without cardiopathy, signs of diabetic macroangiopathy, collagen vascular disease and/or Raynaud's phenomenon, and renal failure. Four waveform dimensions capable of separating different degrees of peripheral obstructive arteriolar disease were determined on velocity tracing and the results used in a single best discriminant equation. The resultant discriminant score (DS), derived by FVWFA on DPA, showed a highly accurate rate of separating the young pts with DM from both C and the pts in menopause without DM. Furthermore, the resultant DS was statistically not different in groups II, III, and IV. In conclusion, FVWFA on DPA, in this experience, has proved to be an accurate and sensitive method in the detection of initial DM. ",17 1179,"Cerebral hemodynamics in patients with normal pressure hydrocephalus: correlation between cerebral circulation time and dementia. Regional cerebral blood flow and regional cerebral circulation time were measured in 13 demented patients with chronic hydrocephalus, mostly normal pressure hydrocephalus. The average hemispheric, frontal, and temporal cerebral blood flows were significantly reduced. The average regional cerebral circulation time values were significantly prolonged in the frontal, temporal, and thalamic regions, most markedly in the frontal white matter, where periventricular lucency was observed on computed tomography. Clinical improvement was obtained in all patients after operation. While postoperative regional cerebral blood flow values did not change compared with preoperative ones, postoperative regional cerebral circulation time values were significantly reduced in all the regions measured, and most markedly in the frontal white matter. The present results suggest that microcirculation in the frontal lobe is closely correlated with dementia in association with pressure exerted on the nerve fibers in the frontal white matter in patients with normal pressure hydrocephalus. ",9 1676,"Value of carvedilol in congestive heart failure secondary to coronary artery disease. Despite considerable interest in the use of beta-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction less than or equal to 45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean +/- standard deviation exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than 0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31 +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7 mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than 0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less than 0.0005). These hemodynamic changes were mediated partly by vasodilation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease. ",13 1702,"Hindbrain ischemia produced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats. Hindbrain ischemia was induced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats (SHRs). Mean arterial blood pressure was lowered to 80 mmHg in SHRs and to 50 mmHg in Wistar-Kyoto rats (WKYs) by a controlled hemorrhage, and then the vertebral artery was bilaterally occluded through alar foramina of the first cervical vertebra. Following vertebral occlusion, blood flow of the cerebellum was significantly decreased to 9.4 +/- 2.0 mL/100g/min (+/- SEM) while flow of the cerebrum remained at 32.1 +/- 5.4 in SHRs. In contrast, cerebellar blood flow in WKYs was preserved at 24.2 +/- 2.9 mL/100g/min. Brain lactate, pyruvate, and adenosine triphosphate (ATP) were determined in SHRs after sixty minutes of hypotension with or without vertebral occlusion. Although infratentorial metabolites were actually unaltered in rats with hypotension alone, infratentorial lactate and lactate/pyruvate ratio significantly increased to 14.38 +/- 3.61 mmol/kg and 67.7 +/- 12.1, respectively, with a concomitant decrease in ATP in SHRs with hypotension and vertebral occlusion. Bilateral vertebral artery occlusion, together with moderate hypotension, was shown to produce a marked reduction of cerebellar blood flow and to induce ischemic metabolic changes in the infratentorial brain in SHRs. ",13 2361,"Biguanides and sulfonylureas as combination therapy in NIDDM. Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy. ",17 3158,"Premenstrual syndrome: an update for the clinician. Premenstrual syndrome is a complex disorder in which a variety of symptoms can occur in the luteal phase of the menstrual cycle. The symptoms should occur each cycle only from the time near ovulation to soon after the onset of menses. There should be at least 1 week in follicular phase that is symptom-free. Symptoms should be severe enough to significantly interfere with the ability of the patient to function within her normal lifestyle. Diagnosis is based on clinical information from prospective charting of symptoms. Up to 50 per cent of patients who think they have PMS really suffer from another type of mental illness, usually a depressive disorder. Laboratory tests are not generally helpful in the diagnosis. Treatment is based on the type(s) of symptom(s). Available treatments are reviewed with documentation of results from double-blind placebo-controlled experimental designs. The etiology of PMS is not known. However, there are good empiric therapies available that can help most PMS patients. ",22 174,"Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response. ",3 941,"Breathing exercises for the medical patient: the art and the science. The art of breathing exercises can be traced to the late 1800s. In the past 10 years, the increased demand for treatment for respiratory muscle failure of dysfunction has resulted in numerous studies evaluating methods of treatment or training. This article provides an overview of research and practice, focused on treating the medical patient experiencing dyspnea or loss of respiratory muscle strength and endurance. ",7 2587,"Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 micrograms daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p less than 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improvements occurred during the first 3 months but, in some, were still progressing slowly at 1 yr. Improvements in responsiveness were accompanied by significant improvements in asthma symptoms, bronchodilator use, and number of asthma exacerbations. The results show that regular, prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness, sometimes with full resolution, and these improvements are accompanied by clinically significant improvements in clinical asthma. ",19 3212,"Chloroprocaine antagonism of epidural opioid analgesia: a receptor-specific phenomenon? Sixty healthy patients scheduled for elective cesarean delivery under epidural anesthesia were randomized to receive either lidocaine or 2-chloroprocaine as the primary local anesthetic agent. When patients first complained of postoperative pain in the recovery room, they were given either fentanyl 50 micrograms or butorphanol 2 mg, epidurally, in a randomized, blinded fashion. Postoperative analgesia, quantitated on a visual analogue scale, as well as time elapsed until first request for supplemental opioid, did not differ for patients receiving butorphanol after either 2-chloroprocaine or lidocaine anesthesia. In contrast, epidural fentanyl produced a shorter and lesser degree of sensory analgesia after 2-chloroprocaine use, whereas epidural fentanyl after lidocaine anesthesia provided pain relief similar to that seen in the butorphanol groups. Side effects were limited to somnolence with butorphanol and pruritus with fentanyl. No evidence of respiratory depression was seen in any patient. We conclude that 2 mg of butorphanol epidurally provides approximately 2 to 3 h of effective analgesia after cesarean delivery with either lidocaine or 2-chloroprocaine anesthesia. Epidural fentanyl seems to be antagonized when 2-chloroprocaine, but not lidocaine, is used as the primary local anesthetic agent. We suggest a possible mu-receptor-specific etiology for this effect. ",22 3316,"Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency. Deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a common inherited defect in energy metabolism. Characterization of the mRNA encoding MCAD in a Dutch MCAD-deficient patient revealed an A----G change at nucleotide position 985 of the MCAD mRNA coding region. This point mutation results in the substitution of a glutamic acid for a lysine at amino acid position 304 of the mature protein. The single base change was not found in any wild-type MCAD mRNAs. A mutant allele-specific oligonucleotide probe was used in a hybridization analysis of amplified genomic DNA of MCAD-deficient family members, a carrier, and normal individuals. The hybridization analysis specifically identified individuals who were heterozygotes or homozygotes. In addition to the point mutation, a significant proportion of the index patient's MCAD mRNA contained a variety of deletions and insertions as a result of exon skipping and intron retention. The missplicing occurred in multiple regions throughout the MCAD mRNA. Analysis of the patient's MCAD gene in the regions where the missplicing occurred most frequently did not reveal a mutation in the splicing acceptor or donor sites. Therefore, the molecular characterization of this family revealed a crucial point mutation in the MCAD gene and an unusual abnormality in MCAD pre-mRNA splicing. ",22 1959,"The relationship between sex hormones and high-density lipoprotein cholesterol levels in healthy adult men. The objective of this study was to clarify the complex and uncertain relationship between endogenous sex hormones and high-density lipoprotein (HDL) cholesterol levels in healthy men. Fifty-five healthy adult men were consecutively recruited from an ongoing cross-sectional study of cardiovascular disease risk factors from a lipid research clinic at the University of Washington, Seattle. Subjects receiving medication were excluded. Multiple linear regression analysis identified several factors that correlated highly significantly with HDL cholesterol levels, including alcohol intake; frequency of strenuous exercise; age; levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride; and carbohydrate intake. Nearly 80% of the heterogeneity in HDL cholesterol levels could be accounted for by these factors. Despite finding significant correlations with factors known to influence HDL cholesterol levels, no correlation with estradiol level, testosterone level, or the ratio of estradiol to testosterone levels was apparent. In conclusion, endogenous sex hormones do not appear to influence HDL cholesterol levels in healthy adult men. Alternatively, a large proportion of the heterogeneity in HDL levels in this group of men can be accounted for by environmental factors. The disparity between this conclusion and others may be partially due to differences in accounting for these confounding variables. ",13 1930,"Molecular biology in cardiology: recent developments and opportunities for clinical applications. The revolution in molecular biology that has taken place in the last decade has provided powerful research methods that are changing our understanding of cardiovascular physiology and disease. This editorial commentary will highlight several areas of current research activity within the broad and expanding field of molecular cardiology, with a special emphasis on prospects for clinical applications in cardiovascular medicine. ",13 3010,"A comparison of hospital costs and morbidity between octogenarians and other patients undergoing general surgical operations. The hospital costs and clinical results of 304 patients who were more than 80 years old and who underwent general surgical procedures were evaluated. The over-all mortality rate was 14 per cent; 19.9 per cent occurred in patients admitted under emergency conditions as compared with 8.9 per cent that occurred in patients undergoing elective procedures (p less than 0.001). Seventy-nine per cent of the patients were discharged and 7 per cent required care in a skilled nursing facility. Survival rates were as good or better than standard life table survival rates for 80 year old patients. Costs were higher in those who were admitted under emergent conditions or who died in the hospital. Deaths were a result of complications of the primary disease rather than associated disease in most groups. Neither costs nor length of stay could accurately predict survival of individual patients. We concluded that health resources should be directed at treating problems, such as cholelithiasis, hernia or carcinoma, early before complications develop. ",22 109,"Parents' vs physicians' utilities (values) for clinical outcomes in potentially bacteremic children. Our previous analyses of decision strategies in children 3-24 months with acute-onset fever greater than or equal to 39 degrees C and no evident bacterial focus of infection indicated that the risks of routine blood cultures (the unnecessary hospitalization and treatment of children who clear their bacteremia spontaneously) outweigh its benefits (the prevention of a few cases with major infectious sequelae). Because those analyses were based on parents' values for beneficial and adverse clinical outcomes, we wished to examine whether those values differed in physicians and, if so, whether the differences were sufficient to change the results of the decision analysis. Using a pre-tested linear analog utility (value) scale, we evaluated eight potential clinical outcomes in potentially bacteremic children by surveying 121 parents of healthy 3-24-month-old children attending a private pediatric group practice and 57 attending physicians of a tertiary-care children's hospital emergency room. Utilities were based on a 0-1 normalization, where 0 is the utility of the worst outcome (meningitis or other major bacterial infection, plus venipuncture), and 1 the utility of the best outcome (complete recovery without venipuncture or hospitalization), and were analyzed using a recently developed statistical model of utility. The majority of parents and physicians combined the imputed components of the outcomes (disease, pain of venipuncture, and stress of hospitalization) in a nonlinear fashion. Parents assigned substantially lower utility (i.e. greater disutility) to venipuncture, minor infection, and hospitalization than did physicians, and these utilities were even lower in parents with other children at home. ",0 808,"Physicochemical determinants of in vitro shock-wave biliary lithotripsy. Human gallstones were studied by visual inspection, computerized tomographic imaging, and chemical analysis to assess physicochemical characteristics that may determine the outcome of in vitro shock-wave fragmentation. Eighty-five stones (mean diameter: 13.2 +/- 5 mm) were each collected from different patients. Fifty-five (65%) calculi were angular and 30 (35%) round or oval-shaped. Three easily obtained measures were derived from each stone's optimal computerized tomographic image including the mean stone density, a measure corresponding to the standard deviation of the mean stone density value which we termed the stone density distribution index and which may reflect the physicochemical heterogeneity of a given gallstone, as well as the density range. After the administration of 2500 shock waves using an electrohydraulic generator, fragmentation was noted in 68 calculi (80%) and was satisfactory in 27 (32%) (where the largest resulting fragment diameters were all less than or equal to 5 mm). Strong determinants of satisfactory fragmentation on multivariate analysis included a stone diameter of less than or equal to 15 mm, the presence of an angular stone shape, and a stone density distribution index of greater than or equal to 60 Hounsfield units. The other parameters did not independently determine satisfactory fragmentation. Prospective clinical trials are needed to assess whether these findings result in a better prediction of the success of extracorporeal biliary lithotripsy and a broadening of its indications. ",5 1733,"Blood pressure response to dietary calcium intervention in humans. Epidemiological and experimental studies have suggested that dietary calcium deficiency may lead to the development of hypertension. This article reviews findings in human trials on calcium intervention with special reference to the responses of blood pressure and biochemical variables. Calcium supplementation consistently resulted in decreased blood pressure in a subset of hypertensive and normotensive subjects, but led to increased blood pressure in some hypertensive patients. The variable blood pressure responses to calcium supplementation could not be predicted on the basis of routine biochemical parameters and appeared to be due to differences in the backgrounds of the subjects and/or the design and size of the trials. It is concluded that further studies are required on the hypotensive effect of calcium supplementation. ",13 3097,"Late onset adrenal hyperplasia: mutation at codon 282 of the functional 21-hydroxylase gene is not ubiquitous. Ten patients affected with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia were studied to determine the prevalence of a mutation at codon 281 of the functional 21-OH gene (CYP21B) that results in a valine to leucine amino acid shift. This mutation has been reported in eight unrelated late-onset adrenal hyperplasia patients of Ashkenazi Jewish descent possessing the human leukocyte antigen-B14,DR1 haplotype. Normally, there are two 21-OH genes; a pseudogene (CYP21A) and a functional gene (CYP21B). The aberrant codon 281 sequence is normally present only in CYP21A. In all of our late-onset adrenal hyperplasia patients, hybridization of an oligonucleotide probe specific for this mutation was demonstrated to CYP21A but not to CYP21B. The mutation at codon 281 of CYP21B does not appear to be a ubiquitous genetic marker for 21-OH deficient late-onset adrenal hyperplasia, suggesting that this disorder may demonstrate the same molecular heterogeneity as congenital adrenal hyperplasia. ",22 3199,"Postmortem chorionic villus sampling is a better method for cytogenetic evaluation of early fetal loss than culture of abortus material. In utero chorionic villus sampling at the time of diagnosis of intrauterine fetal death is compared with more traditional use of cultured fetal skin, products of conception, or amniocentesis. A total of 102 specimens from early fetal losses were evaluated for success in karyotyping and chromosomal results. We found postmortem chorionic villus sampling is technically possible, offers the highest likelihood of getting a cytogenetic result, and is a rapid, reliable, and safe technique. The extraembryonic component of intrauterine fetal deaths appears to remain viable and continues to grow long after the embryo has died. Samples obtained at the time of diagnosis of fetal death offer the greatest changes of successfully obtaining a karyotype. The incidence of chromosome abnormalities associated with fetal loss, particularly trisomies, is higher than previous data suggested. ",22 488,"Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes? The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer. ",3 3181,"Rejection of multivisceral allografts in rats: a sequential analysis with comparison to isolated orthotopic small-bowel and liver grafts. Multivisceral isografts and allografts were transplanted to Lewis rats, and the histopathologic changes were studied in the liver, intestine, and other constituent organs. Rats receiving isografts had indefinite survival with maintenance of weight. With multivisceral allografts (from Brown-Norway donors), the intestinal component was rejected more severely than the companion liver and with about the same severity as when intestinal transplantation was performed alone. Intestinal rejection in either circumstance was a lethal event, causing death in 10 to 12 days. The earliest (by day 4) and most intense cellular rejection was in the Peyer's patches and mesenteric lymph nodes. This was associated with or followed by cryptitis, epithelial cell necrosis, focal abscess formation, mural necrosis, and eventual perforation. Liver allografts transplanted alone or as part of multivisceral grafts also had histopathologic evidence of rejection, but this was self-limiting and spontaneously reversible when the liver was transplanted alone. Thus the Achille's heel of multivisceral grafts is the intestinal component that is not protected by the presence of the liver in the organ complex. Better immunosuppression should permit successful experimental and clinical transplantation of such grafts. ",22 787,"Esophageal reflux before and after isolated myotomy for achalasia. Four patients with achalasia underwent 24-hour esophageal pH measurements as ambulatory patients before and after limited myotomy without fundoplication. Resting lower esophageal sphincter pressure was reduced from 24.3 +/- 1.3 mm Hg to 7.5 +/- 4.3 mm Hg. No significant differences (p greater than 0.05) were found before and after operation in the total 24-hour pH data distribution (pH 6.24 +/- 0.84 vs 5.75 +/- 1.03), the fraction of time below pH 4.0 (4.8% +/- 5.3% vs 8.0% +/- 6.9%), or the mean duration of reflux episodes greater than 5 minutes (22.8 +/- 18.8 minutes vs 23.0 +/- 10 minutes), all +/- SD. Effective relief of esophageal obstruction in achalasia is feasible by isolated limited myotomy without producing gastroesophageal reflux. ",5 1293,"Learning curve for radial keratotomy. I prospectively evaluated my own learning curve for radial keratotomy (RK) by comparing the results achieved in two groups: 20 consecutive eyes on which I performed RK without having had previous experience with the procedure (group 1); and 20 other eyes, matched for age, sex, and preoperative refractive error, on which I performed RK after I had performed the procedure 250 times (group 2). Although there were nine microperforations in group 1 and none in group 2, the postoperative refractions and uncorrected visual acuities were similar in both groups. Since the microperforations had no adverse effect on the visual results, it is reasonable to conclude that there was, in effect, no learning curve involved in my experience with RK. ",10 2940,"Anterior cruciate ligament injury: evaluation of intraarticular reconstruction of acute tears without repair. Two to seven year followup of 155 athletes To evaluate the effectiveness of our treatment regimen, we retrospectively studied the surgically treated knees of 155 athletes, aged 15 to 42 years, who had sustained acute ACL tears. All were treated with ligament excision and intraarticular bone-patellar tendon-bone reconstruction followed by early motion with emphasis on full extension. The follow-up period ranged from 2 to 7 years. Of the 155 patients, 140 were available for final followup at a minimum of 2 years after reconstruction. The patients were evaluated by objective measures (KT-1000, Cybex, Lachman test, range of motion, and postoperative competition level) and subjective assessment scores (pain, swelling, stability, activity level, walking, stair climbing, running, jumping, or twisting). The subjective scores were tabulated for stability level, total score, and activity level. After the patients achieved full range of motion, the KT-1000 measurements at a 20 pound force revealed an average difference of 1.3 mm between the injured and noninjured knees. All but 3 of the 140 patients had a firm endpoint on the Lachman test, and the Cybex tests showed a mean hamstring strength of 98% and mean quadriceps strength of 90%. Sixty of the 69 varsity athletes who were eligible to play returned to preinjury competition level the following season. One had reconstruction failure and eight chose not to continue competition for academic reasons. The questionnaire score average was 92.7 (maximum, 100 points, normal athletic knee score 93.5). We concluded that the surgical procedure, with emphasis on early full extension postoperatively, achieved excellent results and provided a stable knee. ",20 933,"Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study. We designed an intensive, weekly treatment regimen for patients with small-cell lung cancer (SCLC) using six of the most active chemotherapeutic agents for this disease (doxorubicin [DOX], cyclophosphamide [CTX], vincristine [VCR], etoposide [VP-16], cisplatin [CDDP], and methotrexate [MTX]). The goal of this program was to gain rapid, repetitive exposure to multiple, active drugs. Treatment was administered weekly for a total of 16 weeks. Seventy-six SCLC patients (limited disease, 34; extensive disease, 42) were treated. The overall complete plus partial response rate was 82%. Complete response rates of 47% and 38% were observed in patients with limited (LD) and extensive disease (ED), respectively. The median survivals for patients with LD and ED were 16.6 and 11.4 months, respectively. Toxicities were tolerable and were primarily hematologic. Twenty-six patients had one or more transient life-threatening toxicities, but only one patient developed a fatal toxicity. Eighty-four percent of the patients received 80% or greater of the intended protocol dosages over the entire 16-week treatment period. We conclude that this intensive, short-duration treatment regimen is at least as good as other ""standard"" regimens, and we are encouraged aged by the complete response rate and median survival in patients with ED SCLC. ",7 74,"The inactivation of antithrombin III by serum elastase in patients with surgical infections. The relationship between serum elastase and antithrombin III was determined in septic surgical patients as a possible mechanism for intravascular thrombosis and hypercoagulability during sepsis. Eighteen patients with surgical infections and elevated white blood cell counts had their blood assayed daily for white blood cell count, serum elastase, and antithrombin III, until the patient's white blood cell count returned to normal. Antithrombin III was significantly lower (0.87%) when elastase was above the normal range (greater than 14.2 micrograms/ml). Elastase was significantly higher (30.6 micrograms/ml), when antithrombin III was less than normal. These data indicate that elevated serum elastase is associated with a significant reduction in circulating antithrombin III. Stimuli that increase serum elastase, i.e. surgery, trauma, or sepsis may promote intravascular thrombosis by the inhibition of antithrombin III at the blood-endothelial cell interface. ",0 466,"Hepatic tumors: signal enhancement at Doppler US after intravenous injection of a contrast agent. Experiments were carried out to detect and establish the origin of Doppler and echo signal enhancement in small vessels of the systemic circulation and of tumors after intravenous injection of a contrast agent. Eight woodchucks (Marmota monax) were studied; each woodchuck had naturally occurring hepatocellular carcinoma. Injections of 0.1-4.0 mL of air-filled human serum albumin microspheres were administered into a hind limb or jugular vein. Ultrasound (US) examination included transabdominal duplex scanning, color Doppler imaging, placement of a Doppler transducer on the exposed tumor, and surgical implantation of pulsed Doppler cuffs. Doppler signals were assessed by recording color Doppler images and results of spectral analysis. While subjective echo level was unaffected within the tumors, dramatic Doppler signal enhancement was recorded in both normal and tumor vessels. At optimum dose levels, a signal gain of approximately 10 dB was recorded from the tumor. Analysis showed that the echo enhancement was due to the presence of the contrast agent in branches of the hepatic artery. These results suggest that tumor detection may be enhanced by intravenous administration of a US contrast agent. ",3 718,"""Healed"" experimental gastric ulcers remain histologically and ultrastructurally abnormal. The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence. ",5 3346,"Patterns of dyspepsia in patients with no clinical evidence of organic diseases. We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between ""related"" and ""associated"" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis. ",22 231,"Local recurrence after curative resection of colorectal adenocarcinoma. A total of 853 patients with 861 colorectal adenocarcinomas were operated on at our institution between 1965 and 1981. Complete follow-up information was obtained in all but six patients (99.4%), and all available histologic slides were reviewed to determine pathologic stage and characteristics. Six hundred fifty-one patients (76.3%) underwent a potentially curative procedure, and their operative mortality rate was 2.8%. Of the 627 patients available for analysis, 50 (8%) had a local recurrence. The median time to local recurrence was 18 months, and only 16% of local recurrences were diagnosed 5 years after the original resection. Median survival of patients with a local recurrence was 3 1/2 years from the original resection, and 16 patients (32%) survived 5 years or longer. A multivariate logistic regression analysis was conducted to examine the influence of several clinical and pathologic characteristics on local recurrence among Dukes' stages B and C adenocarcinomas (n = 539) after exclusion of patients with synchronous tumors (n = 8), postoperative deaths (n = 18), loss to follow-up (n = 6), or incomplete data (n = 11). This analysis revealed that the local recurrence rate was significantly related to depth of invasion (B1 + C1 = 0%; B2 + C1 = 10%; p less than 0.01), site of origin (right plus transverse colon = 6%; left plus rectosigmoid colon = 10%; rectum = 12%; p less than 0.05), and lymphatic or capillary microinvasion (absent, 6%; present, 14%; p less than 0.05). This analysis attempts to identify patients at high risk for development of local recurrent disease to select candidates for postoperative adjuvant therapy. ",3 761,"Crohn's disease: what about the pancreas? [editorial] Crohn's disease (CD) is now accepted as a systemic illness. The importance of extraintestinal manifestations is underlined by the fact that such ""complications"" can be more prominent and even more difficult to control than the intestinal disease itself. Lately, evidence for a more than accidental association of pancreatitis and exocrine pancreatic insufficiency with CD is growing. This might have a significant impact on the treatment of abdominal pain and diarrhea in CD, symptoms which have so far been attributed exclusively to the intestinal rather than the extraintestinal manifestations of the disease. ",5 2932,"Foley catheter balloon puncture and the risk of free fragment formation. The incidence of free fragment formation following balloon puncture or spontaneous bursting was examined in 294 Foley catheters immersed for 48 h in urine. The catheters were divided into 3 groups: 100 were inflated to the manufacturer's recommended volume, 100 to twice the volume and 94 to 3 times the recommended volume. The catheter balloons were punctured by pricking with a hypodermic needle. The overall incidence of free fragment formation was 27.3%. For both types of catheter examined, increasing balloon volume was not associated with an increased risk of free fragment formation following puncture. However, increasing volume was associated with increased free fragment formation when the balloon burst spontaneously. In view of the high risk of free fragment formation, cystoscopy should be performed in all cases of spontaneous catheter balloon rupture or after percutaneous balloon puncture. ",20 2376,"Insulinomimetic properties of trace elements and characterization of their in vivo mode of action. Lithium and vanadate have insulinomimetic actions in vitro. In this study, we examined the in vivo effects of lithium and vanadate on glucose metabolism in diabetic (90% partial pancreatectomy) rats. Four groups of chronically catheterized rats were studied: control, diabetic, diabetic treated with lithium (plasma concn 1.0 +/- 0.1 meq/L) and vanadate (0.05 mg/ml in drinking water), and diabetic treated with lithium, vanadate, zinc, and magnesium. Postmeal plasma glucose was increased in diabetic versus control rats (18.7 vs. 7.7 mM, P less than 0.01) and was normalized by addition of lithium and vanadate (8 mM) or lithium, vanadate, zinc, and magnesium (7.4 mM). Euglycemic insulin-clamp studies were performed 2 wk posttreatment; insulin-mediated glucose uptake was reduced in diabetic compared with control rats (142 +/- 4 vs. 200 +/- 5 mumol.kg-1.min-1, P less than 0.01), returned to normal with lithium and vanadate (206 +/- 6 mumol.kg-1.min-1), or increased to supranormal levels with lithium, vanadate, zinc, and magnesium (238 +/- 6 mumol.kg-1.min-1). During the insulin clamp, muscle glycogenic rate was severely impaired in diabetic versus control rats (18 vs. 70 mumol.kg-1.min-1) and was normalized by lithium and vanadate (91 mumol.kg-1.min-1) or lithium, vanadate, zinc, and magnesium (93 mumol.kg-1.min-1). ",17 835,"Increasing prevalence of gallstones in male veterans with alcoholic cirrhosis. Cases of alcoholic cirrhosis identified at necropsy were studied for the prevalence and type of gallstones, compared with age- and race-matched autopsy controls. Data were examined from 1970-1977 and 1980-1987. In the early sample of 460 cirrhotic patients, 33% had gallstone disease, contrasted with 12% in the controls. In the 1980s, among 299 patients, 46% had gallstone disease, whereas it was present in 13% of the controls. The prevalence of stones was significantly greater in the patients than in the controls for both time periods and, among the patients, was significantly greater in the 1980s than in the 1970s (p less than 0.05). A comparison of cirrhotic patients with and without gallstones indicated a significantly higher incidence of ascites in the patients with gallstones. The gallstones in cirrhotics were more frequently pigmented than in the controls in both time periods. In 100 living patients with advanced cirrhosis studied by sonography during 1987 and 1989, the prevalence of gallstones was 43%, almost the same as the autopsy sample from 1980-1987. In these cirrhotics, ascites, encephalopathy, and varices were more prevalent in the patients with stones than those without. We conclude that pigmented gallstones are increasing in cirrhosis of the liver related to the severity of the liver disease. ",5 957,"The rise of tuberculosis in America before 1820. Bills of mortality, newspaper and gazette articles, journals, and other records with specific references to ""consumption,"" ""phthisis,"" and other terms for tuberculosis were reviewed to determine the occurrence and importance of tuberculosis in the American colonies before 1820. Review of these sources indicates a marked increase in the proportional mortality from tuberculosis in the United States in the 18th century. ""Consumption"" may have been the leading cause of death in adult American colonists. ",7 3310,"Loss of photosynthetic and chlororespiratory genes from the plastid genome of a parasitic flowering plant. Photosynthesis is the hallmark of plant life and is the only plastid metabolic process known to be controlled by plastid genes. The complete loss of photosynthetic ability, however, has occurred on several independent occasions in parasitic flowering plants. Some of these plants are known to lack chlorophyll and certain photosynthetic enzymes, but it is not known to what extent changes have occurred in the genes encoding the photosynthetic apparatus or whether the plants even maintain a plastid genome. Here we report that the nonphotosynthetic root parasite Epifagus virginiana has a plastid chromosome only 71 kilobases in size, far smaller than any previously characterized land plant plastid genome. The Epifagus plastid genome has lost most, if not all, of the 30 or more chloroplast genes for photosynthesis and most of a large family of plastid genes, the ndh genes, whose products may be involved in a plastid respiratory chain. The extensive changes in Epifagus plastid gene content must have occurred in a relatively short time (5-50 x 10(6) yr), because Striga asiatica, a related photosynthetic parasite, has a typical complement of chloroplast genes for photosynthesis and chlororespiration. The plastid genome of Epifagus has retained transcribed ribosomal RNA and ribosomal protein genes, suggesting that it expresses one or more gene products for plastid functions not related to photosynthesis. ",22 338,"Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding. ",3 593,"The influence of growth hormone on the reversibility of articular cartilage degeneration in rabbits. Growth hormone has chondrogenic affects on normal as well as on damaged articular cartilage. In this study, the influence of growth hormone is investigated on early degenerative changes in the articular cartilage in 72 New Zealand white rabbits. Cartilage lesions were created in femoral condyles using an immobilization model. Cartilage damage was assessed using biochemical, histologic, and biomechanical criteria. Growth hormone had no influence on prevention of immobilization abnormalities but had a significant affect on healing of established lesions. ",4 2432,"Impaired growth hormone (GH) response to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH. ",17 597,"Open transpedicular biopsy of the vertebral body. We describe a method of obtaining a biopsy from the body of a vertebra by an open transpedicular route. This minimises the danger of contamination of tissue planes and spaces. ",4 456,"The melanocyte and melanoma. This paper reviewed some of the interesting biological aspects of melanocytes and their relationship to the nevus and to melanoma. It also proposed a rationale for ""adequate"" surgery in the management of melanoma according to level, depth, margins, and trends in treatment. These propositions were derived from an analysis of 995 cases of melanoma of the head and neck. ",3 926,"A placebo-controlled trial of immunotherapy with two extracts of Dermatophagoides pteronyssinus in allergic rhinitis, comparing clinical outcome with changes in antigen-specific IgE, IgG, and IgG subclasses. A double-blind, placebo-controlled trial of immunotherapy was conducted in patients with Dermatophagoides pteronyssinus rhinitis. Thirty patients received an extract with a high content of Der p I (Pharmalgen), 20 received a conventional mite extract (Allpyral), and 30 patients received histamine chloride (placebo). Specific IgG and subclasses were measured before and after 3 and 12 months of treatment by RIA and/or ELISA, and specific IgE by RAST. Clinical outcome was assessed by skin prick tests, nasal challenge, visual analogue, and diary-card symptom and drug scores; from these findings, a clinical index was derived. An IgG response occurred only in the Pharmalgen-treated group: D. pter IgG and IgG1 increased by 3 months (p less than 0.05) and then plateaued to 12 months (p less than 0.05). IgG4 levels increased throughout treatment (p less than 0.05 and p less than 0.01), as did the IgG/IgE ratio. A subclass switch from IgG1 to IgG4 occurred. D. pter IgE rose at 3 months (p less than 0.05). Clinical improvement occurred at 3 and 12 months in the Pharmalgen-treated group only. Pretreatment levels of IgE, IgG1, or IgG4 did not predict clinical outcome. Our findings are compatible with the hypothesis that IgG subclasses may modulate antigen-IgE interactions, although the antibody response to this potent extract need not be causally related to improvement. ",7 781,"Interventional radiology of the biliary tract. Transcholecystic intervention. Diagnostic and therapeutic biliary intervention by percutaneous access to the gallbladder is an important new area in interventional radiology. The anatomy of the gallbladder, biliary tree, and surrounding viscera is reviewed in this article as a preliminary to discussion of the diagnostic techniques of aspiration, cholangiography, biopsy, and the therapeutic techniques of gallbladder drainage and cholelithotomy. Recently there has been a bewildering proliferation of procedures aimed at removal, fragmentation, and dissolution of gallbladder stones. Several of these are discussed in this article. Removal of common bile duct stones by percutaneous cholecystostomy also is discussed. ",5 3011,"Effects of medical and surgical treatment on cerebral perfusion and cognition in patients with chronic cerebral ischemia. The effects of medical treatment with and without cerebral revascularization procedures on cognition and cerebral blood flow were compared among 36 patients with extracranial occlusive cerebrovascular disease and cognitive impairments. Three comparable groups were studied. The first group (N = 18) received only medical treatment by control of risk factors for stroke (including hypertension, diabetes, and hyperlipidemia) and antiplatelet aggregant medication. The second group (N = 10) had the same medical treatment plus superficial temporal-to-middle cerebral artery bypass, and the third group had the same medical treatment plus carotid endarterectomy. Regional cerebral blood flow and cognition were monitored in all three treatment groups over a 3-year interval. All groups showed stabilization without expected rates of decline for both cerebral blood flow and cognition, but no statistically significant differences emerged among the treatment groups. ",22 1933,"The Framingham Disability Study: relationship of various coronary heart disease manifestations to disability in older persons living in the community. The relation between coronary heart disease and disability was examined in 2,576 community-dwelling women and men ages 55-88 years. These Framingham Study participants were originally recruited in 1948-51 for an examination of cardiovascular disease. Twenty-seven years later, remaining members of the cohort were interviewed to ascertain physical abilities, and a score on a disability scale was assigned. Multivariate logistic analyses examined disability in relation to uncomplicated angina pectoris (AP), complicated AP, and coronary heart disease other than AP, controlling for possible confounders. In younger and older women and men, uncomplicated and complicated AP were associated with disability. Coronary heart disease other than AP was associated with disability only in the younger men. Congestive heart failure predicted disability only in the women. These results suggest that onset of AP should be recognized as a critical point in the development of disability and that AP is a better predictor of disability than is myocardial infarction or coronary insufficiency. ",13 20,"Congenital insensitivity to pain with neuroparalytic keratitis. Congenital insensitivity to pain is a well-defined entity in the group of sensory deficiency syndromes. To the best of our knowledge, unilateral neuroparalytic keratitis associated with congenital insensitivity to pain has not been reported. We report such a case to alert clinicians to this potentially blinding problem. ",0 629,"Radical osteoclastic craniectomy in sagittal synostosis We report our experience in the surgical treatment of sagittal synostosis using radical osteoclastic craniectomy in 60 consecutive patients. After surgery in children aged 6 months or younger (Group I), reossification usually started 2 weeks postoperatively and was complete within 6 months, resulting in an optimal skull contour. In children aged 7 to 12 months (Group II), reossification was prolonged and lasted for 12 months or longer. The skull contour normalized in its biparietal width and improved in sagittal diameter, remaining, however, slightly abnormal. In children older than 12 months (Group III), the skull contour partly improved in the biparietal diameter but did not change in the sagittal direction. Reossification was incomplete with persistent pseudosutures. Enlarged frontal subarachnoid spaces were reversible or improved in all patients independent of age at the time of surgery. We encountered no complications in our series. In our opinion, radical osteoclastic craniectomy is the simplest, most efficient, and most physiologically sound method for the treatment of sagittal synostosis in patients up to 6 months of age. This procedure allows the rapidly growing brain to form its skull vault, thus providing optimal cosmetic results. In older children, osteoplastic morcellation procedures should be the treatment of choice. ",4 3035,"Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs. We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299). ",22 1596,"Natural history of hypertrophic cardiomyopathy in the elderly. The prognosis of patients diagnosed as having hypertrophic cardiomyopathy at advanced age has not been well defined. This study details follow-up information obtained for 95 patients initially diagnosed as having hypertrophic cardiomyopathy at age greater than or equal to 65 years. Seventy-five percent of patients were symptomatic, as defined by the presence of chest pain, dyspnea or syncope, and the mean ventricular septal thickness was 20 mm. The median duration of follow-up study was 4.2 years. The survival rate at 1 and 5 years was 95% and 76%, respectively, which was not significantly different from that an age- and gender-matched control group. Of patients presenting with New York Heart Association functional class I or II dyspnea, only 18% progressed to class III or IV during the follow-up period. However, patients presenting with class III dyspnea had a 1 year mortality rate of 36%, significantly higher than that of control subjects (p less than 0.003). Of the echocardiographic variables, indexed left atrial size was most strongly associated with reduced survival (p less than 0.008). These results suggest that the prognosis of elderly patients with hypertrophic cardiomyopathy is generally favorable. Certain clinical and echocardiographic variables appear to be of use in identifying patients with a less favorable prognosis. ",13 1909,"Application of time series analysis to circadian rhythms: effect of beta-adrenergic blockade upon heart rate and transient myocardial ischemia. Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to beta blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal. ",13 1873,"Intraoperative transesophageal color-coded Doppler echocardiography for evaluation of residual regurgitation after mitral valve repair. Because mitral valve competence after mitral valve reconstruction is awkward to assess during this procedure, we evaluated in this respect transesophageal color-coded Doppler echocardiography in 23 patients undergoing mitral valve reconstruction for severe mitral regurgitation. Transesophageal echocardiographic examinations were performed after induction of anesthesia but before sternotomy (baseline), after mitral valve repair before decannulation, and at sternal closure, all at similar mean aortic pressure and echocardiographic instrument settings. The degree of mitral regurgitation by transesophageal color Doppler flow mapping was visually quantified on a 5-point scale (0 to 4), pending the left atrial extent of the regurgitant jet. This was compared with the degree of mitral regurgitation by left ventricular cineangiography performed within several weeks after operation and also visually quantified on a 5-point scale (0 to 4), with use of the right anterior oblique projection. There was good correlation between the two methods (r = 0.83; p less than 0.001). We conclude that residual mitral regurgitation, as assessed by transesophageal color flow mapping in the operating room, highly correlates with the ultimate mitral regurgitation by cineangiography. Therefore transesophageal echocardiography can be helpful for evaluation of mitral valve competence during mitral valve reconstruction, and hence, in case of repair failure, allow valve replacement in the same surgical session, thus avoiding reoperation. ",13 897,"External detection of pulmonary accumulation of indium-113m labelled transferrin in the guinea pig. Accumulation of radioisotope labelled transferrin in the lungs of guinea pigs was determined with an external detection system. The method is based on the intravascular and extravascular distribution of indium-113m labelled transferrin compared with the intravascular distribution of technetium-99m labelled red blood cells. Guinea pigs were given iloprost, a prostacyclin analogue and potent pulmonary vasodilator, and noradrenaline, a pulmonary vasoconstrictor, in an attempt to increase and decrease respectively the blood volume in the lungs. Neither agent altered transferrin accumulation in the lung by comparison with a saline infusion. Iloprost infused before and after oleic acid infusion reduced macro-molecular leakage when compared with oleic acid alone. These data suggest that the double isotope method can distinguish between hydrostatic and injury induced pulmonary oedema. ",7 1485,"Adenomyosis in Pakistani women: four year experience at the Aga Khan University Medical Centre, Karachi. As part of a quality assurance programme at the Aga Khan University Medical Centre, Karachi, Pakistan, all hysterectomy specimens were reviewed from January 1986 to December 1989. Adenomyosis was found in 237 of the 419 (56.5%) specimens studied. Of these 237 patients, 232 (97.9%) were parous and 196 (82.8%) were in the fourth and fifth decades of life. This high prevalence in parous women aged 40-59 years was significant. Fibroids, cervicitis, and endometrial hyperplasia were the most common associated diagnoses. Of all the associations studied, only endometrial hyperplasia was significantly more prevalent in the group with adenomyosis. Adenomyosis was stated as an indication for surgery in 69 patients and was confirmed by histopathology in 49 (71%). Preoperative suspicion of adenomyosis was present in 49 (20.6%) patients of all those ultimately found to have the disease. There is a high prevalence of adenomyosis in the population studied, which indicates that the condition may have been underdiagnosed in the past, especially as it is difficult to diagnose without surgery and hysterectomy is currently the only treatment. ",12 3318,"Inactivation of human alpha-globin gene expression by a de novo deletion located upstream of the alpha-globin gene cluster. Synthesis of normal human hemoglobin A, alpha 2 beta 2, is based upon balanced expression of genes in the alpha-globin gene cluster on chromosome 16 and the beta-globin gene cluster on chromosome 11. Full levels of erythroid-specific activation of the beta-globin cluster depend on sequences located at a considerable distance 5' to the beta-globin gene, referred to as the locus-activating or dominant control region. The existence of an analogous element(s) upstream of the alpha-globin cluster has been suggested from observations on naturally occurring deletions and experimental studies. We have identified an individual with alpha-thalassemia in whom structurally normal alpha-globin genes have been inactivated in cis by a discrete de novo 35-kilobase deletion located approximately 30 kilobases 5' from the alpha-globin gene cluster. We conclude that this deletion inactivates expression of the alpha-globin genes by removing one or more of the previously identified upstream regulatory sequences that are critical to expression of the alpha-globin genes. ",22 2321,"Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. Uroporphyrinogen decarboxylase (URO-D) is a cytosolic heme-biosynthetic enzyme that converts uroporphyrinogen to coproporphyrinogen. Defects at the uroporphyrinogen decarboxylase locus cause the human genetic disease familial porphyria cutanea tarda. A splice site mutation has been found in a pedigree with familial porphyria cutanea tarda that causes exon 6 to be deleted from the mRNA. The intron/exon junctions on either side of exon 6 fall between codons, so the resulting protein is shorter than the normal protein, missing only the amino acids coded by exon 6. The shortened protein lacks catalytic activity, is rapidly degraded when exposed to human lymphocyte lysates, and is not detectable by Western blot analysis in lymphocyte lysates derived from affected individuals. The mutation was detected in five of 22 unrelated familial porphyria cutanea tarda pedigrees tested, so it appears to be common. This is the first splice site mutation to be found at the URO-D locus, and the first mutation that causes familial porphyria cutanea tarda to be found in more than one pedigree. ",16 2245,"Autologous mixed lymphocyte reaction is reduced in patients with psoriasis. The autologous mixed lymphocyte reaction (auto-MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto-MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto-MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast, the allogeneic lymphocyte reaction (allo-MLR) in psoriatics was similar to that in normal controls. ",16 1023,"Epstein-Barr virus-related antibody. Changes in titers after therapy for nasopharyngeal carcinoma. Using long-term follow-up data from a prospective, collaborative study of 182 North American patients, we evaluated the significance of various serologic tests for antibody to Epstein-Barr virus in predicting outcome after treatment in patients with nasopharyngeal carcinoma. We restudied these patients by examining repeated measurements of each titer at various times after diagnosis and treatment. We looked for associations between trends of titers, measured as the slope of log(titer) against time, and titer level, measured as the mean of log(titer), with the outcome: alive and no evidence of disease; alive with recurrence; or dead of nasopharyngeal carcinoma. We found that posttreatment sequential measurements do not predict outcome. ",8 2718,"Stereotactic biopsy of an active multiple sclerosis lesion. Immunocytochemical analysis and neuropathologic correlation with magnetic resonance imaging. Stereotactic biopsy of an active multiple sclerosis lesion in a 23-year-old patient with unilateral symptoms and an isolated high-signal-intensity magnetic resonance abnormality yielded 10 serial tissue cores (1.0 x 0.5 cm) spanning 40 mm within and around the lesion. We performed semiquantitative analysis of lymphocyte phenotype, using antisera to CD3, CD4, CD8, and CD22 molecules, in 11 separate perivascular cuffs in three tissue sections from the lesion edge. Total cells in the cuffs varied from 10 to 100; ratios of CD4+/CD8+ cells in individual cuffs varied from 1.3 to 4.7. Although intense parenchymal infiltrates bordered the least cellular cuffs, parenchymal and perivascular cell phenotypes were indistinguishable, arguing against selective trafficking of lymphocytes into tissue. Individual microfoci of cells displaying CD45RA, CD25, and TQ1 antigens were present. The remarkable phenotypic heterogeneity of T lymphocytes in the multiple sclerosis lesion border is consistent with exposure in situ to a diversity of differentiating stimuli. Histologic demyelination correlated very closely with the signal-intensity abnormality observed on magnetic resonance imaging. These studies provide unusual insight into the histologic and immunocytochemical morphologic appearance of the active multiple sclerosis plaque. ",19 2629,"Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma. Durable complete remissions (CRs) can be achieved in patients with diffuse large-cell lymphoma (DLCL) with multidrug chemotherapy. The length of time to reach CR may be predictive of treatment outcome. However, defining CR by chest radiograph or computed tomography (CT) is often difficult since residual abnormalities do not always indicate residual disease. We have prospectively evaluated the ability of gallium-67 citrate (Ga-67) imaging to define residual disease and predict outcome in 37 consecutive patients with DLCL. Patients received 296 to 370 megabecquerels (MBq) Ga-67 and were imaged prior to, following cycles 4 to 6, and at completion of intensive chemotherapy. Ga-67 scan results were correlated with radiographic studies. Seventeen of 37 patients (46%) showed persistent, abnormal Ga-67 uptake halfway through chemotherapy. Of these, four were in CR, 11 were in partial remission (PR), and two showed no change in tumor size. At follow-up, 10 (59%) have died (three who were scored as CR and seven who were in PR halfway through therapy), two are alive with active tumor, one relapsed and survives following bone marrow transplant, and four (three in PR and one in CR at the therapeutic halfway point) are without disease at a median of 28 months from presentation. Of the 20 patients who were Ga-67-negative halfway through therapy, 11 were in CR and nine were in PR. Five of 20 patients (25%) have died. Three, in radiographic CR died at 11, 26, and 28 months, and two in radiographic PR died at 15 and 17 months. One patient is alive with active tumor, and 14 patients (70%) are alive without disease at a median of 34 months from presentation. Ga-67 imaging proved to be an excellent indicator of residual viable tumor; a positive scan halfway through therapy predicted for a poor outcome and may well justify a change in treatment. ",19 3099,"Intravenous but not intracolonic epidermal growth factor maintains colonocyte proliferation in defunctioned rat colorectum. The role of epidermal growth factor in the proliferation of normal and premalignant colonocytes in vivo is not fully understood. In particular, the relative importance of its possible systemic and intraluminal routes of action has not been fully clarified. Rats with surgically defunctioned distal colorectums were used, and mini osmotic pumps were implanted to study the effects of intraluminal and IV administration of epidermal growth factor on colonocyte proliferation. Within 2 weeks of bypass, colonocyte proliferation in defunctioned colorectum has decreased to about one third the rate in normal colorectum or in colorectum proximal to the defunctioning colostomy. Intraluminal epidermal growth factor, infused from the time of operation did not reverse this hypoplasia, whereas IV epidermal growth factor maintained colonocyte proliferation at approximately the normal rate in bypassed colorectum. This model is suitable for testing other putative colonic mitogens for possible intraluminal and systemic effects. ",22 937,"Current epidemiology of pertussis in Japan. Since the introduction of whole cell pertussis vaccine into general use as part of the routine immunization in 1947 under the Preventive Immunization Law, a steady decrease in reported cases of pertussis was noted until 1974. At that time the number of reported cases reached an all time low and no deaths caused by pertussis were reported. The vaccine (diphtheria-tetanus-whole cell pertussis vaccine) had been given to infants 12 weeks old or older in a 0.5-ml dose by deep subcutaneous injection; three doses were given at intervals of 3 to 8 weeks and the fourth dose (booster) was given 12 to 18 months after the third dose. The immunization was completed with those four doses. Because whole cell vaccine appeared to be associated with severe neurologic illnesses, it was temporarily suspended in 1975. The vaccine was resumed soon thereafter but the age of administration was raised to 24 to 48 months. Under these circumstances acceptance rates of pertussis occurred, reaching a peak in 1979. Although whole cell vaccine was used even after temporary suspension, it was considered to be unacceptable by the public. As a result the acellular pertussis vaccine was developed and has totally replaced whole cell vaccine since 1981. A steady decrease in reported cases of pertussis as well as the number of deaths has been noted since 1979 in accordance with increase in vaccine acceptance rates. The national surveillance system begun in 1981 demonstrated also a steady decrease in the incidence of pertussis during the past 9 years. ",7 947,"Treatment of atelectasis of upper lung lobes. Selective bronchial suctioning with J-shaped catheter tip and guide mark. We developed a technique for blind bronchial suction using a curved-tip catheter with a guide mark, for the treatment of atelectasis of the lower and middle lobes of the lung. Suction of the upper lobe bronchi could not be performed because of the combination of the peculiar anatomy of the upper lobe bronchi with catheter design. We treated successfully two cases of atelectasis of the right upper lobes using a Rusch Metras bronchography catheter with a guide mark which is not readily available. Therefore we devised a J-shape tipped catheter with a guide mark. We have successfully treated 13 episodes of atelectasis of the right upper lobe in 10 patients and one episode in the left upper lobe in one patient with this new catheter. ",7 3353,"Short-term and long-term changes in renal function after donor nephrectomy. We retrospectively examined the effect of nephrectomy on renal function in 55 living related donors. Renal function was measured with 131iodine-orthoiodohippurate scans. All patients were studied preoperatively, and 1 week and 1 year postoperatively. In 20 patients 10-year followup was available. Compensatory hypertrophy was complete 1 week postoperatively: effective renal plasma flow of the remaining kidney was 32.5% higher than preoperatively. The increase remained stable for at least a year. The degree of compensatory hypertrophy was significantly greater in male patients (46.9% after 1 week) than in female patients (26.7%). Compensatory hypertrophy occurred in all age groups studied and it was most pronounced in patients less than 30 years old. In the patients followed for 10 years effective renal plasma flow decreased from 387.7 ml. per minute 1 week after nephrectomy to 367.4 ml. per minute at 10 years. This result is similar to the decrease seen in the normal population. According to our results, renal donation by living related persons does not lead to long-term decrease in renal function. ",22 2246,"Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity. ",16 2354,"Impact of intensive educational approach to dietary change in NIDDM. The aim of this study was to compare the effects of an intensive educational approach incorporating longer time, greater simplicity, repetition, and cognitive motivational techniques with a conventional one in subjects with established non-insulin-dependent diabetes mellitus (NIDDM) whose weight, glycemic control, and diet were not optimal. Subjects were randomly allocated to intensive or conventional education. Of 350 subjects, 70 met the study criteria, which included established NIDDM (greater than or equal to 3 mo), suboptimal recent glycemic control, dietary fat intake greater than or equal to 35% of total energy intake, and body mass index greater than or equal to 25 kg/m2. The intensive approach was associated with significantly greater improvements in dietary compliance, dietary intake (complex carbohydrate, [P = 0.013], legumes [P less than 0.0001], fiber [P less than 0.0001], total fat [P less than 0.004], saturated fat [P less than 0.004]), and total cholesterol level (P = 0.007). The transient improvement in glycemic control was similar in both groups. An intensive education program can improve dietary compliance in established NIDDM subjects more than a conventional one. These recommended dietary improvements achieve better improvement in total cholesterol but do not necessarily improve glycemic control. ",17 1298,"Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients. ",11 2709,"AIDS, minority patients, and doctors: what's the risk? Who's talking? We asked 39 physicians providing primary care for a mostly minority patient population to respond to a questionnaire concerning their attitudes and behavior toward AIDS risk assessment and preventive counseling and to indicate their beliefs concerning patients' knowledge and behavior. Most of the 36 physicians who responded (92%) agreed that physicians must educate their patients about AIDS. They also reported that patients who engage in risk-taking behavior may not know much about AIDS transmission and prevention. Despite these beliefs, these doctors reported that they gave advice to only 11% of their male patients and 14% of their female patients. More than one third of physicians reported feeling uncomfortable talking about patients' sexual preferences and practices. To identify patients at risk and to help prevent AIDS, methods must be found to make physicians more comfortable discussing sexual issues with their patients, especially their minority patients. ",19 2593,"Macrophage tropism of HIV-1. Both in vivo and in vitro studies clearly demonstrate that cells of the mononuclear phagocyte lineage are major hosts for human immunodeficiency virus type 1 (HIV-1) replication. Presumably these cells play a key role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). To further delineate the interactions between HIV-1 and host cells, the susceptibility and permissivity of normal human peripheral blood-derived monocyte/macrophages (M/M) and T lymphocytes, and neoplastic monocytoid and lymphoid cell lines to various HIV-1 isolates was assessed. The results suggest: (1) ""fresh"" isolates recovered from patients and propagated only in normal host cells exhibit a dual tropism for both M/M and T cells, regardless of their tissue of origin or the cell type from which they were isolated; (2) the repeated passage of an HIV-1 isolate through normal M/M does not generally result in the loss of the ability to infect normal T cells nor vice versa; (3) the majority of fresh HIV-1 isolates do not infect neoplastic cells of either origin, and those that do show no preference for monocytoid or lymphoid targets, regardless of their cell origin. ",19 1728,"From the parallel group design to the crossover design, and from the group approach to the individual approach. The consequences of heterogeneity in response to antihypertensive drugs for the clinical development programs of new antihypertensive drugs and for the care of the individual hypertensive patient have not previously been sufficiently recognized. They play a role in the inappropriate choice of too-high daily doses of some antihypertensive drugs at the end of extensive international development programs. They are also implicated in the insufficient control of blood pressure observed in the long-term multicenter trials in hypertension, where some patients have been treated for several years with drugs that were not the most appropriate for their disease and which did not adequately control their blood pressure. In addition to the parallel group studies, the use of double-blind two-period or multiple period crossover designs can provide valid data for the dose-finding of new antihypertensive drugs and their comparative evaluation. At the end of the trial, these designs also offer each patient the opportunity to be treated with the right dose of the drug most appropriate for his or her disease. ",13 2789,"Mortality following hip fracture before and after implementation of the prospective payment system. Recent studies of patients with hip fractures from two hospitals have suggested that the marked reduction in length of stay that occurred following implementation of the Medicare prospective payment system (PPS) resulted in decreased quality of care for these patients. To assess whether this change influenced mortality, we studied patients with hip fractures aged 65 years or older from a 20% sample of Michigan Medicare enrollees. There were 2130 such patients in the 2 years preceding (October 1981 through September 1983) and 2238 in the 2 years following (October 1984 through September 1986) implementation of PPS. Although the demographic characteristics of patients with hip fractures did not change after PPS, the mean length of stay (95% confidence interval) decreased by 4.4 (4.1 to 4.7) days. However, mortality in the year following the fracture did not change: 23.2% before PPS, 23.7% after PPS; rate difference of 0.5% (-2.0 to 3.0). This finding was consistently present within subgroups defined by patient demographic characteristics. Furthermore, when the analysis was restricted to patients treated in those hospitals with the greatest reduction in average length of stay following PPS (7.5 days, or 35%), there was no significant change in 1-year mortality. For those patients who were enrolled in Medicaid and not in a nursing home at the time of the fracture, there was no increase in the rate of nursing home residence 1 year after the fracture. Thus, the findings of this population-based study suggest that the key outcomes of postfracture mortality and nursing home residence were not affected by the implementation of PPS. ",20 2676,"Virologic and immunologic aspects of acquired immunodeficiency syndrome. From the initial clinical descriptions of the acquired immunodeficiency syndrome (AIDS) in 1981 to the present time, much has been discovered concerning the epidemiologic factors, pathogenesis, treatment and prevention of this disease. Recent advances in epidemiology have included a better understanding of the occupational risk of human immunodeficiency virus (HIV) infection after percutaneous exposure (responsible for approximately 0.4 per cent of instances), an appreciation of the potential variability in the time interval between infection and seroconversion (generally on the order of three months but occasionally longer) and establishment of the need for intimate contact to transmit infection. Following the discovery of HIV-1 as the etiologic agent of AIDS, many rapid advances have been possible including the development of screening tests, elucidation of the HIV-1 genome and the discovery that the CD4 T lymphocyte is the predominant cell destroyed by HIV-1. Progressive destruction of CD4 T cells results in a progressive decline in immunologic function that may take a variety of clinical forms, ranging from no symptoms to severe opportunistic infections. The delineation of the life cycle of HIV-1 has helped in the development of antiretroviral therapies, including agents that interfere with reverse transcription (nucleoside analogues, such as zidovudine, dideoxycytidine, dideoxyinosine and azidodideoxyuridine) and agents that interfere with viral assembly (protease inhibitors and interferon alpha). A more precise understanding of the nature of the immune response elicited after HIV-1 infection has resulted in the development of several candidate HIV-1 vaccines, including recombinant vaccinia viruses expressing the HIV-1 envelope and recombinant envelope proteins. ",19 3323,"Flumazenil in ketamine and midazolam anaesthesia. A double-blind, parallel group study using flumazenil and placebo was carried out to determine whether patients who received flumazenil would awake more quickly and whether this drug would reverse the protection conferred by midazolam on the psychic sequelae of ketamine. Fifty female patients were studied. The results showed that there was a significant reduction in awakening time (p = 0.02) and a very significant increase (p = 0.001) in the incidence of dreams in the flumazenil group. ",22 1682,"Mechanical factors in large artery disease and antihypertensive drugs. Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis. ",13 1745,"Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats. This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats. ",13 1979,"Increased endothelin in experimental heart failure. Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced. ",13 2619,"Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. Ten aspirin (ASA)-sensitive patients with asthma underwent double-blind, placebo-controlled oral challenges with salsalate followed by ASA-sensitive confirmatory challenges. All 10 patients sustained asthmatic reactions to ASA, but only two developed respiratory reactions to 2 gm of salsalate. In these two patients, repeat confirmatory challenges with 2 gm of salsalate reproduced the same asthmatic reactions. Both patients were desensitized to ASA, and cross-desensitization with 2 gm of salsalate was then achieved. We conclude that salsalate, a weak inhibitor of cyclooxygenase in vitro, is less likely than ASA to induce asthma in known ASA-sensitive patients with asthma but may occasionally cross-react in these patients. Such reactions were mild and easily treated with beta 2-agonists. ",19 1796,"Is adenosine 5'-triphosphate derangement or free-radical-mediated injury the major cause of ventricular dysfunction during reperfusion? Role of adenine nucleoside transport in myocardial reperfusion injury. The aim of this study was to determine the dual role of ATP as an energy substrate and as a major source of oxygen-derived free-radical-mediated reperfusion injury by using adenine nucleoside blocker, p-nitrobenzylthioinosine (NBMPR), and adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA). In a randomized study, 16 dogs were instrumented with minor-axis LTZ-piezoelectric crystals and intraventricular pressure transducers to monitor, off bypass, left ventricular performance by using a sensitive and load-independent index of contractility (slope of the stroke work-end-diastolic length relation). Hearts were subjected to 60 minutes of normothermic global ischemia and 120 minutes of reperfusion. Normal saline without (Group 1, n = 8) or with (Group 2, n = 8) NBMPR and EHNA was infused in three boluses into the cardiopulmonary bypass reservoir before ischemia and reperfusion. Transmural serial biopsies were obtained before and during ischemia and reperfusion and analyzed for myocardial adenine nucleotide pool intermediates by using high-performance liquid chromatography. In the control group, three hearts developed ischemic contracture and another three hearts exhibited cardiogenic shock during reperfusion. In the EHNA/NBMPR-treated group, left ventricular performance recovered within 30 minutes of reperfusion (p less than 0.05 vs. control). Myocardial ATP was depleted to 20% of normal in both groups by the end of ischemia (p less than 0.05). Intramyocardial adenosine in the EHNA/NBMPR-treated group was 12-fold greater (15.09 +/- 1.6 nmol/mg protein) than the control group at the end of the ischemic period (p less than 0.05). Inosine was about fourfold higher in the control group (19.07 +/- 1.50 nmol/mg protein) compared with the drug-treated group (p less than 0.05). During reperfusion, myocardial ATP levels increased to approximately 50% of normal in the EHNA/NBMPR group while remaining depressed (20% of normal) in the control group. Thus, despite the dramatic loss of myocardial ATP during ischemia, complete recovery of ventricular performance and significant repletion of ATP during reperfusion were observed when adenosine transport and deamination were modulated during ischemia and reperfusion. These results suggest that 1) the myocardium may have more ATP than is needed for basic cardiac functions and 2) washout of ATP diffusible catabolites is detrimental to ventricular performance during reperfusion. Specific blockade of nucleoside transport resulted in complete functional recovery despite low but critical ATP levels.(ABSTRACT TRUNCATED AT 400 WORDS). ",13 2600,"Zidovudine (Retrovir) update. Zidovudine (AZT) is the first antiretroviral agent to be licensed for the treatment of human immunodeficiency virus (HIV) infection. Since the initial placebo-controlled trial showing improved survival among patients with acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection (AIDS-related complex [ARC]) zidovudine has been evaluated in other stages of HIV infection. This review offers physicians who treat patients with HIV infection a comprehensive analysis of the current data on the clinical efficacy of zidovudine in various stages of HIV infection and on zidovudine's adverse effects. After a search of MEDLINE for pertinent articles published since 1985, controlled studies and studies of long-term zidovudine therapy, of zidovudine therapy for HIV-related conditions and of the incidence and management of adverse reactions were evaluated. In addition, abstracts from international meetings were reviewed. No significant difference in clinical outcome was found between high-dose and low-dose zidovudine therapy, but there were significantly fewer toxic effects in the low-dose group. In two other studies zidovudine was found to delay disease progression in patients with asymptomatic or mildly symptomatic HIV infection who had an absolute CD4 count of less than 0.5 x 10(9)/L; the low incidence of adverse reactions may have been due to either the early stage of the infection or the low dose used. The demonstration of zidovudine-resistant isolates after at least 6 months of therapy has yet to be correlated with clinical deterioration. When to begin zidovudine therapy among asymptomatic patients with a CD4 count of less than 0.5 x 10(9)/L remains unclear. Zidovudine can be used safely to delay progression to AIDS or ARC in certain patients with asymptomatic or mildly symptomatic HIV infection and can prolong survival in those with more severe infection. Further studies are necessary to identify indicators that could better define when to start treatment and how to alleviate toxic effects. Combination therapy with such agents as interferon alpha may become the preferred choice of therapy to prevent toxic effects and zidovudine resistance. Zidovudine prophylaxis has been used after HIV exposure. Although studies with animal models have had encouraging results infection has occurred despite immediate prophylaxis and thus further investigation is required. ",19 2169,"Sickle erythrocytes inhibit human endothelial cell DNA synthesis. Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling. These results indicate that interaction between sickle erythrocytes and the endothelium may result in altered endothelial function. This altered endothelial function may contribute to the development of vascular occlusive phenomena in patients with sickle cell anemia. ",14 513,"Human recombinant GM-CSF in allogeneic bone-marrow transplantation for leukaemia: double-blind, placebo-controlled trial. In a randomised, double-blind trial 20 patients with leukaemia received human recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and 20 received placebo, for 14 days after allogeneic, matched sibling, bone-marrow transplantation. The neutrophil count recovered to 0.5 x 10(9)/l 3 days earlier in the GM-CSF group than in the placebo group (not significant), and the median neutrophil count at 14 days was significantly higher in the GM-CSF group (1.90 vs 0.46 x 10(9)/l). The lymphocyte count was significantly higher in the GM-CSF than in the placebo group between days 10 and 15 after transplantation, but this difference was not associated with a higher incidence of graft-versus-host disease. There was no evidence that GM-CSF was associated with a greater incidence of leukaemic relapse. The GM-CSF group had lower haemoglobin concentrations and platelet counts and higher plasma urea, creatinine, and bilirubin than the placebo group. The duration of hospital stay was the same for both patient groups. Further studies are now indicated to assess the overall effect of GM-CSF on outcome after allogeneic bone-marrow transplantation. ",3 1572,"Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy. Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction. ",13 108,"Prevention of infection in a porous tracheal prosthesis by omental wrapping. The ideal tracheal prosthesis has to permit complete incorporation by epithelialization of the luminal surface. This is not possible with the currently available impermeable solid silicone tube. The authors developed a reinforced, porous polyurethane tubular prosthesis which has the potential for complete incorporation. However, because these prostheses are implanted in a contamined area such as the airway, they all become infected. In order to prevent infection, the authors evaluated the effect of omental wrapping in guinea pigs. The authors' tubular prosthesis was implanted subcutaneously in the abdominal area with the ends open to the air. Ten prostheses were wrapped with omentum and 10 prostheses were not. In 4 weeks, all control prostheses were infected and marsupialized. All the wrapped prostheses remained in place and were macroscopically not infected. Microscopically, all wrapped prostheses were well vascularized and were incorporated by granulation tissue, which did not occur in the prostheses of the control group. From these results the authors conclude that omental wrapping would be an effective way to prevent infection of porous tracheal prostheses in an open-to-the-air situation, and allow rapid tissue ingrowth and incorporation in the host. ",0 140,"Ascariasis. Ascaris lumbricoides is the most common helminth to infect humans. Infection occurs when contaminated soil containing mature eggs is swallowed. Clinically, infection ranges from the asymptomatic carrier state to life-threatening pulmonary disease or intestinal obstruction. Diagnosis is most frequently established by identification of the eggs in stool specimens. Treatment with antiparasitic drugs is effective in preventing serious complications and eradicating the parasite from all members of the household. ",2 2418,"Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans. We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM. ",17 330,"Lymphokine-activated killer (LAK) cells. V. 8-Mercaptoguanosine as an IL-2-sparing agent in LAK generation. Guanine ribonucleosides, substituted at the C8 position with either a bromine or a thiol group, have recently been shown to regulate several immunologic responses. We have previously shown that 8-mercaptoguanosine (8MG) can replace the requirement for cytokines in the generation of MHC-restricted CTL. In this paper, we examined the ability of 8MG to induce MHC-nonrestricted killer cells. We found that 8MG did not induce significant lytic activity from normal resting lymphocytes. However, 8MG was able to synergize with minimal amounts of IL-2 in inducing lytic activity similar to lymphokine-activated killers (LAK) in that both NK-sensitive and NK-resistant tumor cells were killed. Both the precursors and effectors of 8MG-LAK activity were similar to NK cells and were CD4- CD8- asialo-GM1+ NK1.1+. Similar to IL-2-induced LAK, 8MG-LAK were B220+. 8MG appeared to ""stage"" these precursor lymphocytes to become more responsive to IL-2 because optimal induction of 8MG-LAK required preincubation with 8MG before the addition of IL-2. This ""staging"" appeared to be due to the release of a ""second signal"" since it was readily inhibited by cyclosporine A. Anti-IFN-alpha beta was as efficient as cyclosporine A in inhibiting 8MG-LAK generation, whereas anti-IFN-gamma and anti-IL-1 did not exhibit significant inhibition. These findings suggest that 8MG can be of possible utility as an IL-2-sparing agent in LAK generation from NK cells. ",3 1310,"Epidemiology of prostate cancer. Available epidemiologic data do not allow targeting of specific populations for prostate cancer screening or early detection programs. Although certain strong factors have been identified (age, race, location), none sufficiently defines high-risk groups in whom recommendations should differ from those of other age-matched patients. Certainly, a strong familial tendency has been identified, but the relative contribution of genetic and environmental factors in these patients remains unclear. Some hypotheses on the pathogenesis of prostate cancer are possible based on the available data. Genetic factors appear to be permissive, as are hormonal influences, which are partially regulated by genetics. Environmental factors appear to be promotional in genetically susceptible men. Dietary fat may also be an important promotional factor in genetically susceptible men. Dietary factors appear to exert some influence by modulating sex hormone concentration. Several factors demand more investigation and understanding of the epidemiology of prostate cancer. The relative frequency of the disease and the increasing death rate from prostate cancer are of concern. The similarities in the incidence of latent prostate cancer among various groups with strong differences in the rate of clinically apparent disease raise significant issues regarding potential lifestyle or environmental promotional factors. Further understanding of the pathogenesis of prostate cancer may allow a refinement and definition of programs for prevention and early detection of the disease. ",11 387,"Basement membrane of cervical adenocarcinoma: an immunoperoxidase study of laminin and type IV collagen. The basement membrane components type IV collagen and laminin were examined immunohistochemically in 14 cases of adenocarcinoma of the cervix. The patterns of staining in adenocarcinoma in situ, invasive adenocarcinoma, and early invasive adenocarcinoma were compared to see whether characteristic patterns could be delineated. Adenocarcinoma in situ had a uniform intact basement membrane, whereas the basement membrane of invasive adenocarcinoma was fragmented and irregular. Cases of early stromal invasion showed early gland buds and outpouchings with defective basement membrane staining. The degree of histologic differentiation of the tumor was not clearly related to the amount of basement membrane component staining. The concept of early stromal invasion in cervical adenocarcinoma, as supported by our immunohistochemical studies, is discussed as it relates to a possible pathogenic mechanism in early invasion and infiltration of adenocarcinoma of the cervix. ",3 2545,"Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. Diabetes and aging are commonly accompanied by arterio- and atherosclerosis. Infiltration of the arterial subendothelial intima by macrophages/monocytes is an important early event preceding the development of atheromatous lesions; these macrophages are known to produce mitogenic factors in early atherosclerotic lesions. It has been previously shown that, over time, vascular matrix accumulates proteins nonenzymatically modified by advanced glycosylation end products (AGEs). In view of the fact that macrophages/monocytes have AGE-specific receptors associated with the expression of several growth factors, we investigated the possibility that AGEs mediate initial monocyte-vessel wall interactions that occur before overt formation of vascular lesions. This study demonstrates that (i) in vitro- and in vivo-formed AGEs are chemotactic for human blood monocytes, (ii) sub-endothelial AGEs can selectively induce monocyte migration across an intact endothelial cell monolayer, and (iii) subsequent monocyte interaction with AGE-containing matrix results in the expression of platelet-derived growth factor. These results support the existing hypothesis that in vivo-forming glucose-derived protein adducts can act as signals for the normal turnover of senescent tissue protein by means of the AGE-specific receptor system. Time-dependent glucose-induced deposition of AGEs on matrix proteins may promote monocyte infiltration into the subendothelium. Subsequent AGE-triggered macrophage activation and consequent elaboration of proliferative factors may normally coordinate remodeling but may also lead to the diverse pathogenic changes typical of arterio- and atherosclerosis in diabetic or aging populations. ",18 873,"The role of herpes simplex virus in the development of oral mucositis in bone marrow transplant recipients. Herpes simplex virus (HSV) has been implicated as a major etiologic factor in the development of ulcerative mucositis in bone marrow transplant (BMT) recipients. In this study, 60 patients who received BMTs were evaluated for at least 30 days post-transplant for ulcerative mucositis and the presence of culturable HSV. Fifty-nine patients received prophylactic acyclovir. Forty-six patients developed ulcerative lesions and 45 of these were culture negative for HSV. Neither the source of transplant (autologous versus allogenic) nor the HSV antibody status of the patient affected the frequency of mucositis. The conditioning regimen appeared to be the most significant factor contributing to the severity of ulcerative mucositis. While the majority of ulcers occurred on movable nonkeratinized mucosa in BMT recipients, the usual sites of reactivation of intraoral HSV are nonmovable, keratinized mucosa. We conclude that HSV is probably not a major etiologic agent of mucositis in BMT recipients and that acyclovir is an effective agent in preventing HSV reactivation. ",6 3238,"Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction. The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers. ",22 638,"Computer-assisted tomography of scoliosis operated with or without Harrington's rod. Biomechanics aspects of the fusion. Forty-eight cases of posterior vertebral arthrodesis for scoliosis, performed with or without instrumentation, were examined using computed tomography (CT) scanning to study the evolving fusion mass. The authors observed that the fusion mass area is more voluminous in the cases performed without instrumentation than in the ones performed with instrumentation, and that 2 years after fusion the bone mass shows already a considerable increase. For the cases operated with Harrington's technique, the increase of the fusion mass is very slow and becomes considerable 5 years after operation. In both series, the section of the fusion masses at the apex of the curve is asymmetric (with prevalence on the concave side), with an area of central resorption that shows the structure of a long bone (box section). ",4 283,"Cell lineage markers in human pancreatic cancer. The normal pancreas consists of three major cell types or lineages that share a common embryologic origin from pluripotent endodermal precursors. The type of cell that undergoes neoplastic transformation to form a pancreatic carcinoma is controversial and may influence the phenotype and biologic behavior of the tumor. In this study, immunohistologic techniques were used to determine the cell lineage differentiation expressed in 29 primary exocrine pancreatic adenocarcinomas, five metastatic exocrine pancreatic adenocarcinomas, and five islet cell neoplasma. Specimens of normal pancreas and chronic pancreatitis were used for comparison. The cell lineage markers consisted of monoclonal and polyclonal antibodies against trypsin and lipase (acinar cells); secretory component, carbonic anhydrase II, and pancreatic cancer mucin SPan-1 (ductal cells); and chromogranin-A and somatostatin (islet cells). The expression of carcinoembryonic antigen (CEA) and lysozyme were also determined. This collection of markers allowed the differentiation between acinar, ductal, and islet cells of normal pancreas and chronic pancreatitis specimens. The expression of cell lineage markers in islet cell tumors was homogeneous and restricted to chromogranin-A. In contrast, the expression of these markers in primary and metastatic exocrine pancreatic adenocarcinomas was variable. Reactivity with monoclonal anti-CEA was absent in normal pancreas, and was present in 83% of chronic pancreatitis specimens as well as 90% of exocrine pancreatic adenocarcinomas. In addition, lysozyme reactivity was absent in normal pancreas; however, lysozyme was expressed in one case of chronic pancreatitis, 17 cases of primary carcinoma, and three cases of metastatic carcinoma. These findings support the concept that the original transformed cell type in many pancreatic exocrine carcinomas resemble endodermal ""stem cells"" that retain the capability of differentiation along more than one cell lineage pathway. ",3 2482,"Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis. ",17 1338,"Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, cernilton. A double-blind, placebo-controlled study. Whilst prostatectomy remains the ""gold standard"" for the treatment of outflow tract obstruction due to benign prostatic hyperplasia, medical treatment--if only for symptomatic relief--appears to be an attractive alternative. Most of the pharmacological agents in use block the hormonal or the sympathetic neurological pathways that influence prostate growth and function. All of these drugs are known to have side effects. Sixty patients with outflow obstruction due to benign prostatic hyperplasia (BPH) were entered into a double-blind, placebo-controlled study to evaluate the effect of a 6-month course of the pollen extract, Cernilton. There was a statistically significant subjective improvement with Cernilton (69% of the patients) compared with placebo (30%). There was a significant decrease in residual urine in the patients treated with Cernilton and in the antero-posterior (A-P) diameter of the prostate on ultrasound. However, differences in respect of flow rate and voided volume were not statistically significant. It is concluded that Cernilton has a beneficial effect in BPH and may have a place in the treatment of patients with mild or moderate symptoms of outflow obstruction. ",11 1545,"Ultrasonic integrated backscatter two-dimensional imaging: evaluation of M-mode guided acquisition and immediate analysis in 55 consecutive patients. We have shown previously that cardiac cycle-dependent integrated backscatter characterizes the physical state of myocardium in patients with ischemic heart disease and cardiomyopathy. In the present study the clinical applicability of M-mode guided two-dimensional integrated backscatter imaging was defined in evaluation of 55 nonselected patients. The mean amplitude of cyclic variation of integrated backscatter in normal segments (long-axis view) was as follows: basal septum, 4.2 +/- 1.3 dB (mean +/- SD; n = 27), mid-septum, 4.5 +/- 1.0 dB (n = 26), basal posterior, 4.8 +/- 1.0 dB (n = 30), and mid-posterior, 4.8 +/- 1.2 decibels (n = 27). The respective mean delay values (R wave to nadir) were as follows: 0.89 +/- 0.09, 0.84 +/- 0.09, 0.86 +/- 0.09, and 0.85 +/- 0.12. At least one cardiac cycle could be analyzed fully in 62% of patients. Limitations included technically difficult two-dimensional echocardiography, inadequate M-line orientation, technically remediable errors, or poor quality integrated backscatter images. In abnormal segments (n = 13) cyclic variation was reduced and delay was prolonged (1.2 +/- 1.1 dB and 1.21 +/- 1.1, respectively). Intraobserver and interobserver variability for amplitude measurements were modest, with respective correlation coefficients of r = 0.93; r = 0.72. The findings demonstrate that M-mode--assisted integrated backscatter is a practical approach for characterization of regional myocardial properties promptly and at the bedside in a large portion of patients with cardiac disease. ",13 2236,"A total artificial heart for neonates allowing bridging to transplantation. Since the early 1980s, a rapid increase in successful pediatric heart transplantation has improved the chance of survival for many children suffering from otherwise fatal cardiomyopathies or congenital cardiac defects. During the last 5 years, heart transplantation in neonates and infants (0-28 days and 1-12 months, respectively) has been the most rapidly growing area within the pediatric patient population. No adequate mechanical circulatory support system, designed to be used as a bridge to transplantation, is available for many of these pediatric patients. Neonates are the smallest candidates to potentially benefit from heart transplantation, and their often acute need for either heart transplantation or temporary circulatory support indicates that any new development of a pediatric bridging device should focus on this youngest group. Subsequently, such a device may be modified to any weight or age group. An innovative total artificial heart design was developed in an attempt to meet the anatomic and physiologic requirements of neonates and infants. This report discusses the rapidly growing pediatric heart transplantation patient population, as well as an innovative total artificial heart design. ",15 369,"Mutagen sensitivity in patients with head and neck cancers: a biologic marker for risk of multiple primary malignancies. Eighty-four patients with head and neck cancers were evaluated for in vitro sensitivity to mutagens and then followed longitudinally for development of multiple primary malignancies. We assessed mutagen sensitivity by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromosomal breaks per cell. The mutagen-hypersensitive patients, ie, those who expressed greater than 1.0 break per cell, were significantly more likely to develop multiple primary cancers than were patients who were less sensitive (less than or equal to 1.0 break per cell) (relative risk = 4.4; 95% confidence limits = 1.2, 15.8). This relationship was independent of age, sex, site, and treatment of first primary cancer and tobacco or alcohol exposures. Sensitivity to bleomycin-induced chromosomal damage serves as an indicator of genetic susceptibility to multiple primary malignancies in patients with head and neck cancers. ",3 547,"Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. Breast tumor cell lines have been shown to secrete several distinct polypeptide growth factors, although conflicting results exist for the insulin-like growth factors (IGFs). In contrast a limited number of breast tumor cell lines have definitely been shown to secrete the high affinity IGF binding proteins (IGFBPs) that modify IGF actions. To characterize the types of IGFBPs that are secreted by breast tumor cell lines, conditioned medium was collected from seven separate tumor cell lines, three of which were estrogen receptor (ER) negative, and four of which were ER positive. All three of the ER negative cell lines, MDA-231, MDA-330, and HS578T, secreted binding proteins of 49,000 and 43,000 Mr (IGFBP-3) as well as 29,000 (IGFBP-1) and 24,000 Mr. In contrast, all four ER positive cell lines secreted 34,000 (IGFBP-2) or 24,000 Mr forms, and none secreted the 49,000 and 43,000 or 29,000 Mr forms. BT-20, a cell line that is positive for ER messenger RNA (mRNA) but negative for ER protein, secreted predominantly a 34,000 Mr protein. The amount of total IGFBP activity released in 24 h ranged between 0.4 and 5.6 nM equivalents of IGFBP-1, and there was no significant difference between the ER positive and negative cell lines. The MCF-7 cells that produced predominantly 34,000 and 24,000 Mr forms showed a 1.8-fold increase in IGFBP secretion after estrogen stimulation. Immunoblotting and a specific RIA for IGFBP-1 showed that only the ER negative lines MDA-330, MDA-231, and HS578T secreted this form. Northern blotting analysis for the mRNA encoding this protein showed that both MDA-330 and MDA-231 contained a single 1.6 kilobase mRNA species that hybridized with an IGFBP-1 complementary DNA (cDNA) probe. Immunoblotting analysis of the other cell lines showed that only the 34,000 Mr form secreted by the ER positive cell lines reacted with IGFBP-2 antisera. Exposure of the conditioned media from the three ER negative cell lines to N-glycanase revealed that the 49,000 and 43,000 Mr forms of IGFBP were glycosylated and therefore probably represent IGFBP-3. We conclude that ER negative cell lines secrete three forms of IGFBPs, IGFBP-1, IGFBP-3, and a 24,000 Mr form. In contrast, the ER positive cell lines secrete predominantly IGFBP-2 and the 24,000 Mr form but do not secrete IGFBP-3 or 1.(ABSTRACT TRUNCATED AT 400 WORDS). ",3 1584,"Role of angiotensin-converting enzyme inhibitors in congestive heart failure. Conventional therapy for congestive heart failure (CHF) includes sodium-restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival. ",13 2474,"Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors. The current studies were designed to determine whether chronic overexpression of low density lipoprotein (LDL) receptors in the liver would protect mice from the increase in plasma LDL-cholesterol that is induced by high-fat diets. A line of transgenic mice was studied that express the human LDL receptor gene in the liver under control of the transferrin promoter. When fed a diet containing cholesterol, saturated fat, and bile acids for 3 weeks, the transgenic mice, in contrast to normal mice, did not develop a detectable increase in plasma LDL. The current data indicate that unregulated overexpression of LDL receptors can protect against diet-induced hypercholesterolemia in mice. ",17 3285,"Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. The lumbar and cervical spinal dorsal horns of adult rats with a chronic (8 days) constriction injury of the sciatic nerve on one side (and a sham operation on the other) were examined for signs of transsynaptic degeneration. The incidence of neurons with signs of degeneration (pyknosis and hyperchromatosis; 'dark neurons') was significantly increased in the lumbar dorsal horn on both sides. The ipsilateral lumbar increase was significantly greater than the contralateral increase. There was no increase in the incidence of dark neurons in the cervical dorsal horns of the same rats. The distribution of lumbar dark neurons was similar bilaterally. The majority of the dark neurons were found in the sciatic nerve's territory in laminae I-II. A second group of rats received the same surgery but in addition received a series of 7 daily subconvulsive doses of strychnine. Dark neurons were again found bilaterally (with ipsilateral predominance) in the sciatic nerve's territory in lumbar laminae I-II, but the incidence was significantly greater than that found in the group that did not receive strychnine. The same result was obtained in a third group of strychnine-treated rats when the sham operation was omitted. Thus the appearance of contralateral dark neurons is not dependent on unintentional nerve damage created by the sham procedure. An additional group of rats was sacrificed 8 days after receiving a unilateral sciatic nerve transection, a contralateral sham operation, and the 7 daily strychnine injections. There was no increase in the incidence of dark neurons in any of these rats. ",22 1414,"Treatment with desmopressin in severe nocturnal enuresis in childhood. A series of 22 patients with severe nocturnal enuresis were treated with desmopressin in a randomised double-blind cross-over study. Treatment with 20 and 40 micrograms was highly effective compared with placebo. No difference in dry nights was found between the 2 dosages. Desmopressin proved to be a safe and effective treatment. ",11 1504,"Human oocyte and preembryo donation: an evolving method for the treatment of infertility. The utilization of oocyte and preembryo donation in the treatment of infertility has recently expanded. Since 1983, modifications in the retrieval of donated female gametes have enhanced both the safety and the efficacy of the procedure. Pregnancy rates in women receiving donated preembryos are remarkably high, with success occurring in 25% to 50% of transfer cycles. The technology used for preembryo donation continues to evolve, and the current and future role ovum donation in the treatment of infertility. ",12 3017,"Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions. Febrile nonhemolytic transfusion reactions (FNHTRs) are associated with white cell (WBC) antibodies. The purposes of this study were to determine the frequency of WBC antibodies, to associate the severity of reactions with antibody specificity, and to distinguish FNHTRs from infection and postoperative fever. By using the granulocyte indirect immunofluorescence test in conjunction with lymphocytotoxicity testing, it was found that 70 percent of FNHTRs in 24 patients involved WBC antibodies. The remaining 30 percent of apparent FNHTRs were associated with infections and postoperative fever. Granulocyte-specific antibodies were as prevalent as HLA antibodies and were associated with the severest reactions. Because FNHTRs occur with granulocyte-specific antibodies, HLA antibodies, and possible monocyte-specific antibodies (untested in this and other studies), these reactions could be grouped together as WBC-associated reactions. ",22 2603,"Immune deficiency in family members of patients with Hodgkin's disease. Indirect data supporting a preexisting immunologic impairment in patients with Hodgkin's disease (HD) have been presented in recent years. These immunologic defects are supposed to be related to genetic and/or environmental factors. In this study, 65 first-degree relatives and 12 spouses of 21 consecutive patients with HD were studied immunologically. Furthermore, seven twin pairs in which one partner had HD and four additional nonmatched healthy co-twins were also included in the study. A decreased lymphocyte DNA synthesis induced by Concanavalin A, a high spontaneous DNA synthesis, or a low CD4+/8+ ratio was found in 21 (32%) consanguineous, two (17%) nonconsanguineous relatives, and five (50%) healthy co-twins. The corresponding figures for the untreated patients with HD and the control series were 14 of 21 (65%) and 21 of 127 (16%), respectively. Total lymphocyte counts or lymphocyte subpopulations did not differ between HD relatives and controls. The increased frequency of blood lymphocyte defects among consanguineous first-degree relatives favors the existence of a genetically determined immune deficiency in at least a proportion of apparently healthy relatives of patients with HD. However, nongenetic factors such as age and environment may add to the defect. ",19 3337,"Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia-reperfusion injury in liver transplantation. This study evaluated the effects of a prostaglandin I2 analogue (aPGI2), superoxide dismutase (SOD), and catalase (CAT) on hepatic injury after warm ischemia and reperfusion in terms of survival, mitochondrial function, serum enzymes, and histology. Hepatic ischemia was created in rats by clamping the hepatoduodenal ligament for 90 min with splenofemoral bypass. Reperfusion was induced by unclamping the vessels and disconnecting the splenofemoral bypass. Then aPGI2 (350 ng/kg/min) was infused for 60 min just before hepatic ischemia, and SOD and CAT (5,000 units/kg each) were administered immediately before the start of reperfusion. Serum enzyme and mitochondrial function assessments of livers were made just after ischemia, and after 2 hr of reperfusion. Survival rate was also assessed in a separate group of rats. Liver enzymes such as SGOT, SGPT, and LDH showed no correlation to liver viability. The administration of aPGI2 alone showed no effect on ischemically injured mitochondria; however, the free radical scavengers (SOD, CAT), in combination with aPGI2, showed significant improvement of mitochondrial function together with extension of survival. The ultrastructure of hepatocytes was better preserved in the treated groups. These agents improved the viability of ischemic-reperfused injured livers. ",22 738,"Pharmacokinetics of propofol infusions in patients with cirrhosis. We have compared the pharmacokinetics of propofol as an infusion in 10 control and 10 patients with cirrhosis. Anaesthesia was induced within 3-4 min during administration of an infusion of propofol 21 mg kg-1 h-1. After 5 min, the infusion was decreased in a stepwise manner to 12 mg kg-1 h-1 and subsequently 6 mg kg-1 h-1. The mean recovery time after discontinuation of the infusion was significantly longer in the cirrhotic group; however, when patients opened their eyes, blood concentrations of propofol were similar in both groups (1 micrograms ml-1). Pharmacokinetic analysis was performed from the beginning of infusion to 8 h after termination. Total body clearance was not reduced significantly in cirrhotic (1.56 (SD 0.48) litre min-1) compared with control (1.75 (0.32) litre min-1) patients. The volume of distribution at steady state was significantly greater in patients with cirrhosis than in control patients (202 (82) litre vs 121 (49) litre). However, this difference did not change terminal elimination half-life. The pharmacokinetics of propofol given by infusion to maintain general anaesthesia were not affected markedly by moderate cirrhosis. ",5 1581,"Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats. It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats. ",13 3191,"Neurodevelopmental performance of very-low-birth-weight infants with mild periventricular, intraventricular hemorrhage. Outcome at 5 to 6 years of age. The neurodevelopmental outcome of 38 very-low-birth-weight neonates (birth weight, less than 1501 g) was followed up prospectively from birth to 5 to 6 years of age to assess the neurodevelopmental sequelae of mild periventricular, intraventricular hemorrhage (grades I and II). All neonates were screened for periventricular, intraventricular hemorrhage at 5 to 10 days of age. Eleven incurred a mild periventricular, intraventricular hemorrhage (group 1) and 27 had no periventricular, intraventricular hemorrhage (group 2). Each of the infants was neurodevelopmentally normal at 1 to 2 years of age. The 38 children were matched by race, age, sex, and socioeconomic status with control children (group 3) who had been born at term. On outcome measurements at 5 to 6 years of age, groups 1 and 2 scored significantly lower than group 3 on the combined test measurements and on three of the four individual measurements. Group 1 scored significantly lower than group 2 on the combined test measurements only. These data indicate that very-low-birth-weight infants are at risk for learning problems. Although children with mild periventricular, intraventricular hemorrhage did not demonstrate a significant deficit on individual test scores, the significant difference on the combined battery suggests that mild periventricular, intraventricular hemorrhage has an adverse effect on global performance. ",22 2883,"Effects of individually motivating smoking cessation in male blue collar workers. Adverse demonstrable health effects linked to the individual's smoking were shown to 2,689 American workers to motivate cessation during routine examinations to detect asbestosis. This intervention was evaluated six to 25 months later by a mailed questionnaire and by telephone to non-responders. Results were compared to yearly quit rates of 2.5 percent to 5 percent for 736 workers who were ex-smokers at the initial examination. Of the 504 men who responded by mail, 29.8 percent had quit smoking, 35.9 percent had cut down from a mean of 28 to 13 cigarettes per day, and 34.3 percent were smoking as before. Subsequent follow-up at one year showed that 25.6 percent remained quit, and that 23 percent of those who cut down had quit, for an overall quit rate of 34 percent. Of 101 non-responders contacted by telephone, 17 percent had quit and 53 percent had reduced smoking. In both samples, those who quit were more likely to have had lower alveolar carbon monoxide (COa) levels, to be older, and to have had asbestosis. Responders by mail were the same age as non-responders but had smoked longer, had higher prevalences of asbestosis, emphysema, chronic bronchitis and higher COa. Demonstration of the adverse personal effects of smoking appear to have contributed to the quit rates or reduced smoking rates in 65 percent of the responding workers. ",20 856,"Premolarization of a fractured maxillary first molar: a multidisciplinary treatment. The diagnosis and treatment of a fractured maxillary first molar are described in this case report of a 28-year-old male. Successful treatment of the retained palatal root of the fractured molar, referred to as premolarization, ensued from integration of endodontic, orthodontic, periodontic, and fixed prosthodontic care. ",6 296,"Impaired production of tumor necrosis factor in breast cancer. Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired. ",3 2250,"Contact allergy due to colophony (VI). The sensitizing capacity of minor resin acids and 7 commercial modified-colophony products. 3 minor resin acids and 7 commercial modified-colophony products of different origins were studied by experimental sensitization by means of a modified FCA method. All 3 resin acids were almost negative. The commercial products gave different results. While the maleic-modified product of Greek origin showed a strong sensitizing power, the fumaric-modified, terpene-phenol-modified and a disproportioned rosin were only moderate. A remarkable difference was obtained with the Swedish and Finnish tall oil rosins, which, in contrast to the previously studied French product, exhibited only a weak sensitizing capacity. ",16 1194,"A limited diagnostic investigation for obstructive sleep apnea syndrome. Oximetry and static charge sensitive bed. A simplified sleep apnea investigation consisting of combined oximetry and respiration movement monitoring was compared with conventional polysomnography. These two types of recordings were performed simultaneously during one night in 77 patients with suspected obstructive sleep apnea syndrome (OSAS). A static charge sensitive bed (SCSB) was used in the simplified recording because it provides a comfortable and reliable means of recording respiration movements. Periods of obstructive apneas gave a diamond-shaped periodic respiration movement pattern in the SCSB, usually accompanied by repetitive oxygen desaturations. The average number of desaturations greater than or equal to 4 percent per sleeping hour was termed the oxygen desaturation index (ODI) and compared with the apnea index (AI). In the whole population they were well correlated (p less than 0.0001, R2 = 0.41), but in individual cases there were considerable discrepancies. Patients with periodic respiration movements less than 18 percent of total sleeping time and ODI less than 2 never had AI greater than or equal to 5, whereas patients with periodic respiration greater than 45 percent and ODI greater than 6 always had AI greater than or equal to 5. Fifty-one of the 77 patients fulfilled these criteria. A bradycardia response to apneas was absent in 29 percent of patients with AI greater than or equal to 5. A combination of respiration movement and oximetry recording thus seems to give sufficient information to confirm or negate a diagnosis of OSAS in a majority of patients with clinical symptoms. In borderline patients, further investigations should be performed. ",9 1046,"Acute and long-term changes in serum lipids after acute stroke. We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors. ",9 2620,"Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice. IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down-regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways. ",19 2925,"The use of intestinal antibiotics to delay or prevent infections in patients with burns. Bacterial colonization and infection of wounds in seriously burned patients often comes from the patient's indigenous bowel flora. A prospective randomized clinical trial that involved 30 patients with 20% or greater total body surface area burns was undertaken to evaluate the use of a standard antibiotic bowel preparation in the delay or prevention of bacterial colonization of the burn wound and sepsis. Certain enteric bacteria were seen less frequently in the treated group (Enterobacter organisms), but other bacteria appeared more often in the treated group (Proteus organisms and enterococci). The average time of colonization of the burn wounds was 6.1 days in the treated group and 6.7 days in the control group. Blood cultures were positive for enteric organisms earlier in the treatment group. Pseudomonads appeared earlier in the wound and blood cultures of the treated group than in the control group. The effect of antibiotic bowel suppression in patients with burns is varied and unpredictable. The bowel preparation may select certain organisms and lead to earlier colonization of the wounds. Overall outcome and survival was not improved by the use of an antibiotic bowel preparation in these patients. ",20 2254,"Cultured epidermal autografts and allografts: a study of differentiation and allograft survival. Cultured epidermal sheets were examined before and at various times after grafting on skin ulcer beds. Before grafting, the sheet consisted of four to five layers of keratinocytes with incomplete differentiation. Ten days after grafting, graft recipient sites showed compact hyperkeratosis, a normal-appearing epidermis, and a flat dermoepidermal junction. At 6 months, the stratum corneum had a basket-weave appearance but the dermoepidermal junction remained flat. Monoclonal antibodies to keratins 14 and 10 showed normal basal and suprabasal localization, respectively. Electron microscopy showed a normal basement membrane with anchoring fibrils. LH7:2, a monoclonal antibody that binds to the type VII collagen molecule, stained the dermoepidermal junction in all biopsy specimens. AE-1, an antibody that stains suprabasal cells in hyperproliferative skin, was expressed suprabasally for up to 12 weeks after healing (16 weeks after grafting), but expression was confined to the basal layer at 18 weeks after healing (6 months after grafting). Anti-involucrin staining was found in the deeper layers of the epidermis up to 12 weeks after healing (16 weeks after grafting) but had receded to a normal distribution in upper spinous and granular layers at 18 weeks (6 months after grafting). Overall, the histologic patterns observed in recipient sites during the first 4 months after grafting resembled those observed for 10 to 14 days in newly healed epidermis and in hyperproliferative states such as psoriasis. In four sex-mismatched graft sites, specimens were reacted with a biotinylated probe to the Y chromosome by in situ hybridization. Lack of Y chromosome-positive cells suggested that host keratinocytes had replaced the allografts. Multilocus DNA analysis in one patient confirmed this observation. Our data suggest that an altered state of epithelial maturation persists for several months after culture grafting, with restoration of the normal pattern by 6 months. No differences were detected between autografted and allografted sites. ",16 1774,"Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40% had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79% vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long-term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery. ",13 1732,"Calcium and blood pressure. An epidemiologic perspective. We reviewed the research literature on the epidemiologic relationship between blood pressure levels and calcium, with an emphasis on dietary intake. A conceptual framework for causal inference is summarized; then the designs and results of observational and intervention studies are presented. Of 25 reports of observational studies relating intake of calcium or calcium-rich foods to blood pressure, the majority found some evidence of an inverse association. However, many analyses did not support this relationship, and only two studies have confirmed the inverse association with a prospective design. Nineteen randomized controlled clinical trials of calcium supplementation have been reported, excluding those exclusively in pregnant women. Eleven of these showed no significant effects on blood pressure; in two trials, both systolic and diastolic pressure were significantly reduced; and in the remainder results were equivocal. Pooled analyses yielded estimates of a small (1.8 mm Hg), significant reduction in systolic blood pressure, but no effect on diastolic pressure. Epidemiologic relationships with serum and urinary calcium, and the possible mechanisms of these effects, are also discussed. We conclude that the evidence from studies in humans is suggestive, but not conclusive, regarding a role for calcium in hypertension. Recommendations for further epidemiologic studies are presented. ",13 2142,"Social integration of the older thalassaemic patient. Because social policy favours the fullest possible social integration of chronically ill patients, we have evaluated the facilities that are needed to achieve this for patients with beta thalassaemia major in the light of the therapeutic advances that now permit them to survive into adulthood. We have investigated the social integration of adolescent and young adult thalassaemic patients, 171 from Greece and 112 from Ferrara in Italy. Patients in both areas show a good level of social integration and favourable self image, indicating what may be achieved by providing psychosocial support as part of a comprehensive approach to treatment. ",14 2403,"Low-dose lovastatin safely lowers cholesterol after cardiac transplantation. Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients. ",17 1263,"Unusual exudative retinal detachment 9 months after scleral buckling surgery. A 49-year-old man developed exudative retinal detachment 9 months after uncomplicated scleral buckling surgery in the left eye. The subretinal exudates were strictly localized along the buckle and showed remarkable response to steroid. The cause would be noninfectious inflammation like posterior scleritis, triggered by the buckle itself or its associated factors. It is important to note that subretinal exudates long after scleral buckling can occur in consequence of steroid-responsive inflammation as well as insidious bacterial or fungal infection described previously. ",10 2597,"The effect of interleukin 4 (BSF-1) on infection of peripheral blood monocyte-derived macrophages with HIV-1. The effects of various cytokines were examined in an in vitro model of human immunodeficiency virus type 1 (HIV-1) infection of human peripheral blood monocyte-derived macrophages (MDM). Monocytes were obtained from blood of normal donors by Ficoll/hypaque gradient centrifugation and adherence. These cells were allowed to mature in the presence of varying concentrations of cytokines. After five days in culture, cells were harvested, counted, and inoculated with S5G7, an HTLV-IIIB subclone. The cells were replated in the presence of the same concentrations of cytokines. Culture supernatants were sampled over 28 days for p24 antigen (Ag) as measured by Ag capture assay. In repeat experiments, the following observations were made: 1. MDM from some donors could be infected only in the presence of tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin 4 (IL-4); 2. The effect of GM-CSF was variable; TNF alpha also enhanced HIV replication above controls; 3. IL-4 was the most potent enhancer of HIV-1 replication in MDM of the cytokines tested, inducing p24 Ag levels 75-230 times those seen in control cultures run simultaneously. This effect was dose dependent. Ag production was not observed until Day 14 postinfection in most experiments. Multinucleated giant cell formation was observed only in the presence of IL-4. ",19 1550,"Evolution of the continuity equation in the Doppler echocardiographic assessment of the severity of valvular aortic stenosis. The use of Doppler techniques has greatly enhanced the noninvasive ultrasound technique for evaluation of valvular aortic stenosis. M-mode and two-dimensional echocardiography could not reliably distinguish patients with severe aortic stenosis from those with milder obstructions. The hemodynamic information offered by Doppler complemented echocardiographic imaging and provided an alternative modality for evaluation of patients with aortic stenosis. By application of the modified Bernoulli equation, the pressure gradient across the stenotic aortic valve could be estimated by Doppler echocardiography. Though helpful and widely used, the information provided by the pressure gradient across the valve about the severity of the obstruction was not complete. The assessment of valvular aortic stenosis therefore includes an estimation of the valve area by application of the continuity equation. This review examines the maturation of the continuity equation by Doppler techniques and discusses the implications of the procedure. ",13 487,"Diffuse sclerosing variant of papillary carcinoma of the thyroid. Clinical importance, surgical treatment, and follow-up study. A diffuse sclerosing variant is not very rare among papillary carcinomas of the thyroid when the patients are female and younger than 30 years of age. The variant is characterized by diffuse involvement of one or both thyroid lobes, with dense sclerosis, patchy lymphocytic infiltration, and abundant psammoma bodies. Controversy still exists concerning its prognosis. We reviewed our experience with 14 patients treated between 1958 and 1988. All patients were young females, their age being from 10 to 28 years with a mean of 19.6. Hashimoto's thyroiditis had been suspected in nine patients before they came to our clinic. Nowadays the diagnosis of this cancer is possible when we have this entity in mind and detect abundant psammoma bodies either by ultrasonography or by soft-tissue roentgenography of the neck. Total thyroidectomy with modified neck dissection was carried out in eight patients, subtotal thyroidectomy with neck dissection in five, and lobectomy with neck dissection in one. All of them are alive and well without distant metastasis at a mean follow-up of 16 years. Because most of the patients with this variant of papillary carcinoma are young women and the prognosis is favorable, a complete resection without causing later recurrence, but also cosmetic and complication-free surgery, should be considered. ",3 1314,"Laboratory studies for the detection of carcinoma of the prostate. Acid phosphatase and prostate-specific antigen are extremely useful markers for the management of patients with prostatic carcinoma. Prostatic acid phosphatase, because of its relatively low sensitivity and specificity, as well as analyte instability and diurnal variability, is unsuitable for prostate cancer screening. Improved performance characteristics, stability, the lesser diurnal variation, and the association of elevated prostate-specific antigen with prostatic intraepithelial neoplasia make prostate-specific antigen possibly a better candidate for early detection of this common malignancy. Further investigations in this area are clearly indicated before we can recommend screening with prostate-specific antigen. ",11 522,"Intraatrial extension of thyroid cancer: technique and results of a radical surgical approach. An occlusion of the superior vena cava by a tumor thrombus extending into the right atrium was diagnosed in three patients with a follicular thyroid cancer. All patients showed the typical clinical picture of the superior vena cava syndrome. A right parasternal thoracotomy was performed for preparation of the major vessels. The superior vena cava was opened and the entire intravascular tumor thrombus was removed. The cavotomy was closed directly in two patients. In the third patient the left brachiocephalic trunk was resected and reconstructed with a vascular (polytetrafluoroethylene) graft. This patient had bone and brain metastases and an occlusion of the graft 3 months after surgery after anticoagulation was stopped. The other two patients were clinically symptom free without local recurrence 13 and 50 months after surgery. An aggressive surgical approach is justified in grossly invasive thyroid cancer to decrease local recurrence and death rates, to correct the disturbing clinical symptoms of superior vena caval occlusion, and to prevent tumor embolism and the development of distant metastases. By reducing tumor mass, an even better basis for radioiodine treatment can be prepared. ",3 694,"Effect of ulcerative colitis and smoking on rectal blood flow. Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history. ",5 2092,"In vitro and in vivo testing of a new valved intravascular catheter design. Long-term intravascular catheterization carries a finite risk of catheter occlusion. A catheter tip valve design is presented (Buchwald-Wigness, Strato Medical Corporation, Beverly, MA) which incorporates features designed to decrease the risk of thromboembolism and reduce the need for maintenance procedures. Aspiration and infusion are controlled by separate valves, making it possible to engineer optimized inlet and outlet parameters. The outlet valve is an elastic sleeve expanded around the sidewall outlet ports which opens under injection pressure. The inlet valve is a tubular elastic element compressed against the inlet port from within the lumen, opening under aspiration pressure. A series of valves were prototyped with outlet pressures ranging from 2 to 100"" H2O, and inlet pressures ranging from -40-70"" H2O, and flowrates at 36"" H2O of greater than 1,400 ml/hr. Dog implants of two prototypes with outlet valve pressures of 10"" H2O, and inlet pressures of -40"" H2O, demonstrated that dormant periods of up to 7.5 weeks could be achieved without detectable blood cell entry into the lumen. No significant hemolysis was observed in blood samples aspirated with a 6 cc syringe (8% scored ""slightly hemolyzed"" vs. 44% with the nonvalved controls) indicating that a hemodialysis application is likely. ",13 892,"MR imaging of the bird's nest filter. The appearance of the Bird's Nest inferior vena cava filter on magnetic resonance (MR) images of 11 patients is described. No complication or symptomatic filter displacement was encountered as a result of MR imaging performed at 1.5 T. The filters created significant local artifact and distortion on MR images. However, diagnostic MR images of the pelvis, spine, and brain may still be obtained. ",7 2352,"Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms. A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes. ",17 298,"Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease-free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms. ",3 2542,"Genetic evidence equating SRY and the testis-determining factor. The testis-determining factor gene (TDF) lies on the Y chromosome and is responsible for initiating male sex determination. SRY is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for TDF. Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes or by other deletions. If SRY is TDF, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in SRY. We have tested human XY females and normal XY males for alterations in SRY using the single-strand conformation polymorphism assay and subsequent DNA sequencing. A de novo mutation was found in the SRY gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the SRY gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. ",18 1313,"Transrectal ultrasonography for the early detection and staging of prostate cancer. Relatively recent changes and improvements in equipment have vastly increased image resolution for transrectal ultrasonography of the prostate. The expanded use of transrectal ultrasonography has greatly furthered knowledge of prostate zonal anatomy and permitted clinical evaluation of internal prostate architecture. The technique is operator dependent, as the quality of the results is related directly to that person's knowledge and experience. The significant majority of prostate cancers originate from the peripheral zone. Palpable stage B nodules characteristically have a hypoechoic appearance. There is disagreement about the tumor characteristics that cause hypoechogenicity, but large tumors may obscure the normal prostate anatomy and appear isoechoic because of the lack of contrast with surrounding prostate tissue. The transition zone of the prostate is the origin of benign prostatic hyperplasia and almost 20 per cent of prostate cancers. These tumors probably correspond to most stage A lesions. Transrectal ultrasonography is less accurate in identifying transition zone tumors because of the mixed echogenicity of the transition zone, interference from prostatic calculi or calcified corpora amylacea, and poorer image resolution in this area. Studies evaluating the use of transrectal ultrasonography for early detection of prostate cancer generally have shown a twofold increase in the detection rate compared with digital rectal examination. However, the decreased morbidity and expense of transrectal prostate biopsy using an automatic gun device have increased the frequency of biopsy in ultrasound-examined patients compared with those historically evaluated by digital rectal examination. The increased detection rate may in part be a function of the increased use of biopsies, independent of other factors. Transrectal ultrasonography rarely detects cancer in patient with normal digital rectal examination and a normal serum prostate-specific antigen level. Transrectal ultrasonography may be capable of identifying early capsular penetration or seminal vesicle invasion in some patients with known prostate cancer. However, its superiority to digital rectal examination for this purpose has not been demonstrated unequivocally. Ultrasonography does allow directed biopsies of the seminal vesicles or other suspect areas, and this may be helpful in staging the disease. The use of transrectal ultrasonography in prostate cancer has evolved rapidly, and changes in technology antiquate reports within a few years.(ABSTRACT TRUNCATED AT 400 WORDS). ",11 2566,"Amyloid deposition in intrahepatic large bile ducts and peribiliary glands in systemic amyloidosis. Amyloid deposition in the hepatic parenchyma and portal tracts in the liver is well known in systemic amyloidosis. We recently experienced an autopsy case of systemic amyloidosis presenting the amyloid deposits in the intrahepatic biliary tree. This experience prompted us to survey 19 autopsy cases of systemic amyloidosis. Amyloid deposition was found just under the lining epithelium of the intrahepatic large bile duct in 10 of 19 cases and around the peribiliary glandular acini in 7 of the 19 cases, respectively. Amyloid deposition in the intrahepatic large bile duct and peribiliary glands was positively correlated with the degree of amyloid deposition in the liver but not with type of amyloid protein. Double-staining of amyloid and vascular endothelium disclosed that amyloid deposition was more closely related to the inner part of the peribiliary vascular plexus and to the vascular plexus encircling the peribiliary glands than the lining biliary epithelium and peribiliary glandular acinar cells themselves. The exact pathogenesis of amyloid deposition in these anatomical components, however, remains unclear. Although our cases failed to show any overt clinical symptomatologies related to amyloid deposition in these biliary components, it seems conceivable that more massive amyloid deposition in these anatomical components could give rise to some clinical symptoms. ",19 175,"Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. Potentially curative radical pancreaticoduodenectomy for ampullary adenocarcinoma was performed in 24 patients over a 35-year period. The overall operative mortality was 12.5%. Actuarial survival rate at 5 years was 61% +/- 13.4 standard error of the mean (SEM) and subsequently remained unchanged. In the same time period, 21 patients underwent potentially curative radical pancreaticoduodenectomy for periampullary tumors of pancreatic origin. Similar analysis showed an overall operative mortality of 23.8% and a survival rate at 5 years of 27% +/- 12.5 SEM. The results of radical pancreaticoduodenectomy for ampullary carcinoma in the most recent years (1976 to 1988) were compared with those of former years (1953 to 1975). There were no statistically significant differences in the 5-year survival rate; however, the operative mortality decreased from 25% in the former period to 6.3% in the recent period. Survival was dependent on nodal status. The 5-year survival rate was 78% +/- 11.5 SEM in the absence of nodal metastasis versus 50% +/- 25 SEM in the presence of regional nodal metastasis. These findings support the concept that radical pancreaticoduodenectomy offers a realistic probability for cure in a selected group of patients with carcinomas of the ampulla of Vater. ",3 3307,"The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer. ",22 3141,"Excess deaths from nine chronic diseases in the United States, 1986 To assess excess mortality from chronic disease in the United States, state age-adjusted combined mortality rates for nine chronic diseases in 1986 were compared with three ""minimum"" rates--two calculated from rates actually achieved in states and a third estimated as the mortality remaining after elimination of one risk factor for each disease. Hawaii had the lowest mortality rate of combined diseases (305/100,000); state excesses ranged from 0% to 37%. The sum of lowest disease-specific rates in any state was 284 per 100,000, indicating excesses of between 7% and 41%. A minimum mortality rate of 224 per 100,000 was estimated to result from elimination of one risk factor for each of the nine diseases, indicating state excesses from 26% to 54%, or 524,000 US deaths. Reduction of US mortality from the nine diseases to the risk factor--eliminated rate is estimated to be associated with an increased life expectancy at birth of 4 years. ",22 1772,"Sex differences in control of cutaneous blood flow. Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1 +/- 2.0 versus 6.2 +/- 1.5 ml/100 ml/min). Likewise, FBF in men surpassed that of women (19.5 +/- 4.1 versus 7.7 +/- 1.8 ml/100 ml/min). Similarly, SP in men was greater than that of women (270 +/- 42 versus 81 +/- 16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF. ",13 378,"Carcinoma of the external auditory canal: an update. This review is a continuation of the series of 35 cases of carcinoma of the external auditory canal originally reported by the senior author and colleagues. Eighteen additional cases have been evaluated and treated since 1976. Preoperative high-resolution computed tomographic scanning has replaced polytomography, and improved surgical skull base approaches have allowed for extended resections of advanced lesions. A revised classification for local and extensive lesions is presented. The prognosis for localized tumors treated by en bloc resection remains excellent, whereas prognosis for extensive lesions might be more dependent on histologic type and grade of tumor. ",3 2958,"Subtle injuries of the Lisfranc joint. In fifteen patients, a subtle injury of the Lisfranc joint (tarsometatarsal articulation) was found. The lesion was defined as a diastasis of two to five millimeters between the bases of the first and second metatarsals, as seen on anteroposterior radiographs. There often was a long delay between injury and diagnosis. Eight patients were treated with a below-the-knee cast only, three had treatment with a cast and then tarsometatarsal arthrodesis, two had no initial treatment but later had arthrodesis, and two had open reduction and internal fixation. The duration of follow-up ranged from two to thirteen years after the diagnosis. There was no correlation between the severity of the diastasis and the patient's functional result. Marked disability and pain persisted in seven patients, and six of them had flattening of the longitudinal arch. Maintenance of the longitudinal arch usually was associated with a better functional outcome. When a patient has a subtle injury of the Lisfranc joint, weight-bearing lateral radiographs of both feet are needed to identify flattening of the longitudinal arch. Such radiographs should be made routinely in the evaluation of all injuries of the foot that may involve the Lisfranc joint. ",20 3085,"Review of the all-polyethylene tibial component in total knee arthroplasty. A minimum seven-year follow-up period. A retrospective analysis of 144 total knee arthroplasties was performed between 1975 and 1981 with a minimum follow-up period of seven years. A posterior cruciate condylar prosthesis was used in each procedure. Patients were followed clinically and roentgenographically, and a set of statistical variables was established based on elevation in joint line, tibial component angular alignment, overall limb alignment, and position of the tibial component on anteroposterior and lateral roentgenograms. Review of the study group found that the Hospital for Special Surgery knee scores improved from a preoperative score of 55 to a postoperative score of 88, with 94.5% having good or excellent results. The mean postoperative range of motion was 106 degrees with a mean extension of -0.3 degrees. Radiolucencies developed in 41% of the knees with 5% of the knees having progressive radiolucencies. Eight knees were considered failures based on clinical and roentgenographic evaluations. Factors found to significantly affect the formation of radiolucent lines included a shift of the tibial component medially by greater than 4 mm, a varus tilt of the tibial component greater than 2 degrees, and the diagnosis of rheumatoid arthritis. The only variable associated with aseptic loosening was an elevation of the joint line by greater than 8 mm. ",22 1560,"Experience with the use of coronary autoperfusion catheter during complicated angioplasty. Between February and July of 1989, 22 patients underwent the use of the Stack autoperfusion catheter following acute occlusion or obstructive dissection during coronary angioplasty; in 20 cases conventional balloon was used in an attempt to correct the angiographic appearance followed by the use of Stack catheter when results were sub-optimal. Only 1 patient (4.5%) required surgical revascularization. Although our study is not prospective or randomized, our observations suggest a significant impact in decreasing the need for emergency surgical revascularization after complicated coronary angioplasty with the use of this approach. ",13 2336,"Multiple keratoacanthomas treated with oral retinoids. Multiple eruptive keratoacanthoma of Witten and Zak is a rare disorder characterized by numerous small, eruptive tumors and larger, more typical keratoacanthomas. Affected patients have features of Grzybowski-type keratoacanthomas and Ferguson Smith type. Two patients with multiple keratoacanthomas were treated with oral retinoids. Both patients had hundreds of follicular papules on the trunk and extremities. Less common lesions included nodules with central horn-filled craters more characteristic of classic keratoacanthomas. Retinoid therapy resulted in regression of the larger, more typical keratoacanthomas in both patients. The small follicular keratoacanthomas remained unaffected. Thus oral retinoids are only partially beneficial for the treatment of the Grzybowski type or the Witten and Zak type of multiple eruptive keratoacanthomas. ",16 1151,"The Woolley and Roe case. A reassessment. In 1953, two patients, Cecil Roe and Albert Woolley, sued their anaesthetist for alleged negligence because they had developed painful spastic paraparesis after spinal anaesthesia. The court found that phenol, which was used to sterilise the outside of the ampoules of local anaesthetic, had percolated the glass through invisible cracks, contaminating the solution, but that the anaesthetist could not have been aware of this risk. The case was important, despite the fact that judgement was in favour of the anaesthetist, because of the fears that it generated over the incidence of paralysis after spinal anaesthesia. The 'invisible crack' theory has been the subject of much scepticism. New information has been obtained, and the case re-examined objectively. The most probable source of contamination, which led to paralysis in the two patients, and in a third who received spinal anaesthesia on the same day, has been identified. A similar explanation may lie behind a number of other episodes of paralysis associated with spinal anaesthesia. ",9 2324,"Health status reports in the care of patients with rheumatoid arthritis. We examined the use of formal health status reports every 3 months over 1 year in the clinical care of patients with rheumatoid arthritis (RA). The reports consisted of single-page, computer-generated summaries of scores derived from either the AIMS (Arthritis Impact Measurement Scales) or the MHAQ (Modified Health Assessment Questionnaire) health status questionnaires. A total of 1920 subjects from 27 community practice sites were randomly assigned to three study groups in each practice: intervention, attention placebo and control. Results showed that 55% of the physicians found the reports to be at least moderately useful as an aid to patient management, primarily for improving the doctor-patient relationship. However, no detectable differences among the three groups were seen in terms of medication compliance, number of physician visits, number of referrals, frequency of major medication changes, attitudes towards the physician, patient satisfaction or change in health status over 1 year. The failure to demonstrate objective benefits of health status reports in this study may be due to physician unfamiliarity with health status scores, failure to link the report with an office visit, the relative stability of clinical status in the subjects over 1 year and the relatively short time-frame of the study. ",16 36,"Treatment of tinea cruris with topical terbinafine. Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream versus its vehicle (placebo) in the treatment of tinea cruris. One patient had a negative initial culture and was excluded, and two patients were dropouts, one because of poor study compliance (terbinafine) and one because of an adverse event (placebo). Twenty patients were examined for efficacy of treatment (9 terbinafine-treated, 11 placebo-treated). Both groups were similar in age, sex, duration of disease, prior therapy, size and location of lesion, infecting organism, and predisposing factors. Terbinafine 1% cream was more effective than vehicle cream in the reduction of the signs and symptoms of tinea cruris. In addition, there was a higher conversion rate to negative culture and normal microscopy findings in the terbinafine-treated group. Clinical results combined with evaluation of mycologic tests at end of therapy showed terbinafine to be a rapid and significantly more effective treatment for tinea cruris than placebo (78% vs 18% cure rate, respectively). Follow-up cure rates confirmed these findings (89% and 18%, respectively). No significant adverse events occurred during terbinafine treatment. ",0 2912,"Dyskinetic movements, cognitive impairment, and negative symptoms in elderly neuropsychiatric patients. The presence or absence of tardive dyskinesia, cognitive status, and psychopathology were assessed in a group of elderly male psychiatric patients (N = 49) in a nursing home setting. Twenty-five patients were found to have tardive dyskinesia, which was associated with a greater degree of cognitive impairment and negative symptoms. This finding was not related to obvious macroscopic organic pathologies, which were less prevalent in the dyskinetic patients. In fact, patients with frontal lesions (primarily lobotomies) had a significantly lower prevalence of tardive dyskinesia. ",20 1507,"Corpus luteum function in early pregnancies is primarily determined by the rate of change of human chorionic gonadotropin levels. Regulation of human corpus luteum activity was studied with radioimmunoassays and bioassays of sera drawn serially from women suspected of having ectopic pregnancies. Progesterone values exhibited considerable overlap in pregnancies that were subsequently classified as normal intrauterine (n = 21), ectopic (n = 35), or spontaneous abortion (n = 14). The rate of change of human chorionic gonadotropin concentration was significantly correlated with progesterone levels in ectopic (r = 0.64) and all pregnancies (r = 0.70). There was no correlation (r = -0.18) between the rate of change of human chorionic gonadotropin and the bioactivity produced per volume of serum. Ectopic pregnancies and normal intrauterine pregnancies did not differ in their ratio of in vivo bioactivity to immunoactivity. From these data we conclude that corpus luteum activity is primarily regulated by the rate of change of human chorionic gonadotropin concentration, without the involvement of other serum factors. We also conclude that reduced corpus luteum function in ectopic pregnancies is not a result of biochemical modification of the human chorionic gonadotropin molecule. Finally, we discourage the use of single progesterone values in screening for ectopic pregnancies because of the considerable overlap in progesterone values among these and normal intrauterine pregnancies. ",12 2522,"Circadian rhythmicity of rate-normalized QT interval in hypothyroidism and its significance for development of class III antiarrhythmic agents. Lengthening of repolarization and refractoriness occurs in hypothyroidism; it is associated with a reduced probability of arrhythmias, with the converse occurring in hyperthyroidism. Because the QT interval and its circadian rhythmicity relative to heart rate is poorly defined in man, we used our new computer-assisted technique to measure QT interval in our analysis of 24-hour Holter tapes before and after (8 to 12 weeks) thyroxine (T4) replacement in 10 patients with hypothyroidism; the findings were compared to those in 6 normal control subjects. QTc interval was prolonged (p less than 0.02) and heart rate decreased (p less than 0.005) during the hypothyroid state. Data were analyzed for circadian rhythmicity by repeated-measures analysis. Circadian variation in QTc and heart rate was statistically significant during hypothyroid and euthyroid states (p less than 0.001) as well as in control subjects, but the circadian rhythmicity of QTc interval and heart rate were out of phase; the maximum prolongation of QTc occurred between midnight and 6 A.M., at a time when heart was at its lowest. QTc interval remained significantly prolonged after 8 to 12 weeks of T4 replacement, when biochemical indexes of hypothyroidism had returned to normal values. The computer-assisted QTc interval determination technique that we used, and our data on the circadian rhythmicity of QTc and heart rate, have significant implications for the development of new class III antiarrhythmic agents. ",18 3308,"Systolic wall stress and ventricular arrhythmia: the role of acute change in blood pressure in the isolated working rat heart. 1. The effect of a sudden acute change in blood pressure upon arrhythmia provocation has been studied in an isolated working heart model from the Wistar-Kyoto strain of rat. Twenty-four hearts were studied. 2. They were perfused with two different, modified, Krebs-Henseleit solutions at a fixed left atrial pressure. 3. Acute changes in pressure, both increases and decreases, were arrhythmogenic. Whilst ectopic activity was more predictably produced by pressure reductions, this consisted of simple ventricular ectopics only. Pressure increases, in contrast, were capable of provoking more complex and sustained arrhythmias. 4. The effect of pressure changes were highly dependent upon electrolyte concentrations in the perfusate. Low potassium and magnesium concentrations increased the amount of arrhythmia provoked by pressure increases but tended to reduce that provoked by pressure reductions. 5. We conclude that the direct effect of an acute change in pressure upon the myocardium is arrhythmogenic. However, the myocardial response to a pressure change is interdependent upon prevailing electrolyte concentrations. ",22 3354,"Treatment of idiopathic retroperitoneal fibrosis by immunosuppression. Idiopathic retroperitoneal fibrosis is exceedingly uncommon in childhood and its etiology is uncertain. Support for an immunological basis for the disease is given by a report of a 14-year-old girl with severe retroperitoneal fibrosis causing progressive azotemia in whom azathioprine and prednisolone were used successfully. This case supports the efficacy of immunotherapy in the treatment of idiopathic retroperitoneal fibrosis. ",22 1123,"Fractures of the clivus: classification and clinical features. Fractures of the clival complex were diagnosed in a series of 17 patients admitted to the Maryland Institute for Emergency Medical Services System and the University of Maryland Medical System over a 30-month period. These fractures were divided pathologically into three types based upon their appearance on computed tomography: longitudinal, transverse, and oblique. The mechanisms of injury were similar in all groups, and the Glasgow Coma Scale scores at admission were comparable, regardless of fracture type, in survivors and nonsurvivors. Longitudinal fractures were associated with severe injury to the central nervous system and with brain stem infarction, and 4 of 6 (67%) of these patients died. Transverse fractures of the clival complex were found in 6 patients, 3 of whom (50%) died. All of these patients had fractures of the petrous ridge; 2 of the 3 survivors had multiple cranial nerve deficits, and one patient developed a carotid-cavernous fistula. Of the 5 patients with oblique clival fractures, 2 survived (40%), both of whom had multiple cranial nerve palsies; in addition, one of these patients developed a carotid-cavernous fistula. Using the present generation of computed tomographic scanners, fractures of the clival complex can be reliably diagnosed; they are probably more common than previously believed and can be separated into three groups based on the characteristics on computed tomographic scans and clinical findings. ",9 549,"Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human retinoblastoma cells after exposure to phorbol ester. Pyroglutamyl peptidase II (EC 3.4.19.-), a membrane-bound metalloproteinase, is a highly specific TRH-degrading enzyme. Exposure of Y-79 human retinoblastoma cells to 12-0-tetradecanoyl phorbol 13-acetate (TPA) decreased the activity of this enzyme in a time- and concentration-dependent manner (IC50 5 x 10(-9) M). After 15 min of TPA treatment, only 10% of pyroglutamyl peptidase II activity remained. TPA treatment did not affect the activity of the cytosolic enzyme pyroglutamyl peptidase I (EC 3.4.19.3) or the membrane-bound enzyme dipeptidyl peptidase IV (EC 3.4.19.3). Pretreatment of the cells with the protein kinase C inhibitors H-7 or sphingosine prevented the inactivation of pyroglutamyl peptidase II by TPA. The time course of the TPA-mediated effect paralleled the time course of translocation and activation of protein kinase C in this cell line. Immunoblot analysis demonstrated that inactivation of pyroglutamyl peptidase II was not due to dissociation or internalization of this enzyme molecule. Incubation of TPA-activated Y-79 cell membranes with gamma-[32P]-ATP followed by immunoprecipitation revealed a time-dependent phosphorylation of a 48 kilodalton subunit of pyroglutamyl peptidase II. These studies indicate that the phorbol ester effect is mediated by protein kinase C, and reveal a mechanism of potentiation of the action of TRH at its target sites. ",3 2643,"Laboratory methods in the diagnosis and prognostic staging of infection with human immunodeficiency virus type 1. Laboratory evaluation of infection with human immunodeficiency virus type 1 (HIV-1) may involve detection of antibodies to HIV-1, direct detection of HIV-1 itself, and measurement of an individual's immunologic status at the time of presentation. The ELISA is currently the preferred initial screening test, although a variety of other rapid immunoassays have also been developed. Methods defining the antigenic specificity of the antibody response, such as the western blot, have become standard confirmatory tests in this setting. CD4+ cell enumeration and the HIV-1 antigen capture assay are useful in predicting the course of HIV-1 infection and in monitoring antiretroviral therapies. Newer techniques of HIV-1 co-cultivation permit the characterization of viral isolates and the stratification of patients and facilitate monitoring of the effects of antiretroviral agents. The polymerase chain reaction is of value in identifying HIV-1 infection in individuals with inconclusive serologic results. Judicious use of other laboratory tests, including surrogate markers such as beta 2-microglobulin, also provides prognostic information potentially useful in clinical management of HIV-1-infected patients. ",19 1730,"Alarm reaction and serum K+ in hypertensive patients. The effect of serum K+ of the alarm reaction induced by the participation to an experimental noninvasive study was evaluated in 35 subjects with borderline hypertension and in 18 essential hypertensives. A group of 44 inpatients undergoing routine blood sampling served as a control. Serum K+, blood pressure and heart rate were measured before (casual) and after (baseline) 20 min of rest in the recumbent position. Baseline serum K+ values were significantly higher than casual values in patients participating to the experimental protocol while no change was observed in inpatients undergoing routine blood sampling. The increase in serum K+ induced by relaxation was significantly related to heart rate decrease (r = 0.73). After relaxation 75% of patients had an increase in serum K+ with a change greater than 10% in about 35% of patients. In a subgroup of patients who repeated the same test three times, the alarm reaction was still evident and not reproducible within each patient. These data suggest that when potassium levels are measured in outpatients undergoing diagnostic or experimental procedures falsely reduced levels can be found in a large proportion of subjects. ",13 1969,"Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension. Epoprostenol sodium (prostacyclin) administered intravenously is considered the standard for assessing the ability of the pulmonary circulation to vasodilate. At present, epoprostenol sodium is an investigational drug that has limited availability. In contrast, acetylcholine, also a pulmonary vasodilator, is readily available. Therefore, we assessed the feasibility of using acetylcholine as an alternative to prostacyclin in testing for the capacity of the pulmonary vasculature to vasodilate. Twenty-three patients with primary pulmonary hypertension (mean pulmonary arterial pressure, 58.5 +/- 13.4 mm Hg) received incremental infusions of prostacyclin and acetylcholine to predetermined maximal infusion rates as part of a battery of vasodilator agents administered according to standard protocols (mean, 5.4 +/- 1.2 agents/patient; range, 3-8 agents/patient); the administration of the different agents was timed to avoid synergistic effects. Of all the agents tested, prostacyclin and acetylcholine were most consistently effective in evoking acute pulmonary vasodilation, and both seemed to distinguish patients capable of manifesting acute pulmonary vasodilation from those who were not. However, at maximal doses set by protocol, prostacyclin generally elicited a greater vasodilator response than acetylcholine. The difference in magnitude of response may have been due to use of prescribed dosages of acetylcholine that were submaximal. In other respects, the two agents were similar; both were equally well-tolerated, and side effects were mild and resolved rapidly when the vasodilator infusions were stopped. We conclude that in the majority of patients with primary pulmonary hypertension, acetylcholine appears to be an effective and available substitute for prostacyclin in screening for pulmonary vasodilator responsiveness. ",13 1332,"Effects of calcium antagonists on renal hemodynamics. Recent attention has been focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do markedly alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate but produce only a modest improvement in renal perfusion. Studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the augmentation of the glomerular filtration rate is attributable to a preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations are not fully delineated, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by an acute impairment of renal hemodynamics. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension. ",11 454,"Quality control practices in centralized tumor registries in North America. A survey of quality control practices was mailed to 73 central registries in the U.S. and Canada. The response rate was 88%, with respondents representing a wide range of registry characteristics and reporting strategies. While registries expressed different priorities in data use, 80% of respondents felt quality control data were important in the identification of problems. The most common method of quality control was acceptance sampling (used by 97% of respondents), and took the form of visual review, recoding and edit checking. Computer-based edit checks were almost universally used (95%). Process control methods of any sort were used by only 22% of respondents with less than 4% of registries reporting formal quantitative criteria. Sixty-one percent of respondents reported conducting one or more designed studies (e.g. reabstracting or casefinding studies) but only 20% of those made the results public. Greater emphasis should be placed on development of quantitative process controls, experimental design of quality control studies, and formal analyses and reporting of study results. ",3 2302,"Cytotoxic and immunologic effects of methotrexate in psoriasis. Based on recent experience that Cyclosporin A, an immunosuppressive drug, produces marked improvement in psoriasis, possible immunomodulatory activities of methotrexate (MTX) have been reviewed to look for alternate mechanisms of MTX action in psoriasis. It is generally considered that the therapeutic results of MTX in psoriasis are related to a direct effect on epidermal cell hyperplasia through inhibition of DNA synthesis. Several studies in the literature now suggest possible effects of MTX on the immune system of psoriatics as well as in animal models that may have some pathogenic similarities to psoriasis. In psoriatics receiving MTX, neutrophil chemotaxis is suppressed, resulting in a possible alteration in the potential pathologic activity of neutrophils commonly found in lesional skin. MTX does improve both psoriatic and rheumatoid arthritis. Animal studies of the latter using adjuvant arthritis and graft vs host disease (GVHD) have indicated several possible mechanisms for MTX that affect these processes. In GVHD, MTX selectively destroys cycling CD8+ cells, and in adjuvant arthritis the activation of macrophages is prevented by inhibition of T-cell function. While MTX generally has not been clinically utilized as an immunomodulatory drug for immunologically related diseases, it may, nonetheless, have selective actions that could be specific for some diseases. MTX and Cyclosporin A could work mechanistically in similar ways but at different steps in the activation of T cells and macrophages. It may be that the major direct effect of MTX on epidermal cell proliferation is complemented or even mediated by subtle immunoregulatory effects on the melange of cells in the affected skin and the systemic immune response. ",16 1802,"Quality of life among hypertensive patients with a diuretic background who are taking atenolol and enalapril. The cardioselective beta-blocker atenolol and the angiotensin-converting enzyme inhibitor enalapril were compared for efficacy, safety, and quality-of-life factors in 30 patients with hypertension whose hypertension was inadequately controlled with diuretic alone. Atenolol (50 to 100 mg once a day) and enalapril (2.5 to 40 mg once a day), combined with hydrochlorothiazide (25 mg once a day), had similar levels of efficacy and safety. A comprehensive battery of psychologic assessments for quality of life was administered, including measures of anxiety, depression, psychiatric symptoms, memory, and psychomotor function. These five conceptually based clusters were first analyzed by multivariate analysis of variance procedures, followed by univariate analyses of the individual variables composing each domain. In general, neither atenolol nor enalapril was associated with major changes in psychologic functioning. The only data cluster with a statistically significant change was memory function, primarily as a result of lower scores of the digit span (backward) test, for atenolol relative to enalapril. These preliminary findings suggest that atenolol and enalapril have comparable degrees of efficacy and safety, with no major disparities in quality-of-life effects, for hypertensive patients with a history of taking diuretics and this sort of quality-of-life assessment can be performed during trials of antihypertensive drugs. ",13 2393,"Definitive prenatal diagnosis for type III glycogen storage disease. Prenatal diagnosis for type III glycogen storage disease was performed by using (1) immunoblot analysis with a polyclonal antibody prepared against purified porcine-muscle debranching enzyme and (2) a qualitative assay for debranching-enzyme activity. Cultured amniotic fluid cells from three pregnancies (three families in which the proband had absence of debrancher protein) were subjected to immunoblot analysis. Two unaffected and one affected fetus were predicted. In addition, cultured amniotic fluid cells from nine pregnancies (eight families) were screened with a qualitative assay based on the persistence of a polysaccharide that has a structure approaching that of a phosphorylase limit dextrin when the cells were exposed to a glucose-free medium. This qualitative assay predicted six unaffected and three affected fetuses. All predictions by either method were confirmed postnatally except for one spontaneously aborted fetus. Our data indicate that a definitive diagnosis of type III glycogen storage disease can be made prenatally by these methods. ",17 1569,"Effect of hemodilution on capillary and arteriolovenous shunt flow in organs after cardiac arrest in dogs. The purpose of this study was to observe the changes in capillary and arteriolovenous shunting blood flow after cardiac arrest and subsequent resuscitation by venous return occlusion produced by inflation of an intra-atrial balloon and cross-clamping of the ascending aorta, and to determine how hemodilution might modify such changes. Organ capillary blood flow and the fractional distribution of cardiac output were measured by the microsphere (9-microns diameter) trapping method in dogs. Simultaneously, the arteriolovenous shunt rate was measured by continuous collection of venous blood drained at 4.8 ml.min-1 for 2 min from the brain, kidney, liver, splanchnic organs, skeletal muscle of the pelvic limb, and all of the systemic circulatory organs. The capillary blood flow of the brain, thyroid gland, pancreas, and stomach decreased after circulatory arrest in five nonhemodiluted dogs (group C); arteriolovenous shunt rate was unchanged after circulatory arrest in this group. However, with hemodilution, which was induced either before (pre group, n = 5) or after (post group, n = 5) circulatory arrest, no change occurred in the shunt rate in any of the organs, with the exception of an increase in the systemic arteriolovenous shunt rate in the pre group. Capillary blood flow was maintained at almost the same level as before circulatory arrest in the pre group, but increased significantly in several organs of the post group. The data indicated that hemodilution might be effective for prevention of organ ischemia after cardiac arrest. ",13 1645,"Neuroendocrine activity in congestive heart failure. The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients. ",13 1929,"Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension. Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization. ",13 1947,"Normal angiograms and carotid pathology. Nonstenotic ulcerated atherosclerotic plaques of the carotid arteries may be associated with symptoms of transient ischemic attacks, amaurosis fugax, and stroke. Preoperative evaluation of patients with these symptoms has traditionally included ultrasound and arch aortography angiograms of the area of the carotid bifurcation. Recent evidence has shown that ultrasound is more accurate in detection and morphologic delineation of these nonstenotic lesions. We analyzed the hospital records of 21 patients with ultrasonographic evidence of disease in whom arteriograms were negative. The patient group comprised 15 men and six women, with an average of 66 years. All patients had symptoms of hemispheric transient ischemic attacks and were evaluated with B-mode ultrasound and arteriography. Ultrasound was positive and arteriogram ""negative"" in all of the patients (i.e., described by the radiologist as without hemodynamic significant disease or ulceration, or as normal). The ultrasound diagnosis was confirmed at operation with findings of 20 to 50 per cent stenosis and ulcerative plaques. At retrospective review of the arteriograms, three ulcerations were found in the 21 patients. We conclude that B-mode ultrasound better defines nonstenotic ulcerative lesions and decisions to perform carotid endarterectomy may be based on either positive test. An ulcerative plaque by B-mode ultrasound and appropriate symptoms, therefore, may not require angiography before operation. ",13 355,"Breast cancer screening: who should be included? The recommendations of the U.S. Preventive Services Task Force are reviewed in regard to screening for breast cancer. In contradistinction to those issued by some other national organizations, screening for breast cancer using mammography at ages 40-49 is not recommended. It is concluded that the scientific evidence is insufficient at present to recommend mammography screening for women aged 40-49. The recommendations of the task force are: all women over age 40 should receive an annual breast examination; all women should have mammography every one or two years beginning at age 50 and concluding at approximately age 75 unless disease has been detected; and it may be prudent to begin mammography at an earlier age for women at high risk of breast cancer. These recommendations are appropriate in light of the available evidence; though at present there is no evidence that clinical examination of the breasts at any age reduces breast cancer mortality; the upper age beyond which breast cancer screening no longer has a significant effect in reducing breast cancer mortality is unknown; and there is no evidence that women at high risk for breast cancer benefit to a different degree from screening than women not at high risk. ",3 3078,"The reversibility of canine vein-graft arterialization. We assessed the reversibility of functional and morphological changes of arterialized vein segments by returning them to the venous circulation. Thirteen dogs underwent right carotid and femoral veno-arterial grafting. After 12 weeks, veno-arterial grafts were removed for contractility (norepinephrine [NE] and 5-hydroxytryptamine [5-HT]), luminal prostacyclin (PGI2), and morphometric analyses; the remaining segments were used as left jugular and femoral veno-venous grafts. After another 12 weeks, the veno-venous grafts were harvested. To NE, veno-arterial grafts (ED50, 5.4 +/- 0.1 [-log M]) were less sensitive than control veins (ED50, 6.0 +/- 0.2) or veno-venous grafts (ED50, 6.4 +/- 0.2) but were more sensitive than control arteries (ED50, 4.0 +/- 0.1); the maximum tension of veno-arterial grafts (6.2 +/- 0.6 g) was greater than that of veins, less than that of arteries (9.8 +/- 1.0 g), and comparable with that of veno-venous grafts (5.1 +/- 1.1 g). To 5-HT, veno-arterial (ED50, 7.5 +/- 0.1) and veno-venous (ED50, 7.3 +/- 0.2) grafts were more sensitive than arteries (ED50, 6.0 +/- 0.3), while the vein was unresponsive; the maximum tension of veno-arterial grafts (5.0 +/- 0.7 g) was less than that of arteries (6.9 +/- 0.9 g) and greater than that of veno-venous grafts (1.4 +/- 0.3 g). PGI2 production in veins (3.6 +/- 0.8 ng/ml), veno-arterial grafts (3.9 +/- 0.8 ng/ml), and veno-venous grafts (3.3 +/- 0.9 ng/ml) was comparable and less than that of arteries (6.4 +/- 0.9 ng/ml). Veno-arterial graft intimal thickness (127 +/- 8 microns) and intimal area (15.6 +/- 1.8 x 10(3) microns 2) tended to be greater than that in the veno-venous graft (113 +/- 9 microns and 12.4 +/- 1.8 x 10(3) microns 2); also, the veno-arterial graft medial area (103.0 +/- 7.3 x 10(3) microns 2) was greater than that of the veno-venous graft (80.3 +/- 6.9 x 10(3) microns 2), thereby resulting in a similar relative intimal area (13 +/- 1%). Therefore, some changes associated with arterialization, for example, adrenergic sensitivity, maximum tension to 5-HT, medial thickening, and perhaps intimal hyperplasia, reverted toward venous values when replaced in the venous environment, possibly due to variations in pressure, flow, shear stress, and/or graft preparation techniques. Luminal PGI2 was unchanged in the grafts, implying that graft contractility was not modulated by luminal PGI2. ",22 1694,"Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis. ",13 281,"Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure and an immunoperoxidase (avidin-biotin peroxidase complex) staining technique. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., tumor spread. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features regarding the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors and that loss of H-antigen expression is related to the stage of the tumor and invasion of carcinoma cells. ",3 2100,"Hemodynamic effects of a new right ventricular assist device. A right ventricular assist device (VAD) based on the principle of counterpulsation has been developed at our institution. The device is a valveless, pneumatically actuated, 40 cc, sac-type pump, with a single inlet-outlet port. For right ventricular support, the ""Uniport"" pump is anastamosed end-to-side to the pulmonary artery. In previous experimental trials, the device has been shown to impart minimal trauma to blood components. In this study, biventricular failure was induced in eight Holstein calves by normothermic ischemia during cardiopulmonary bypass. A Pierce-Donachy left VAD (LVAD) was used for left ventricular support following the ischemic insult. Hemodynamic measurements were obtained throughout the study, and each animal served as its own control. A significant increase in post injury cardiac output (33.5 +/- 11.4%) was obtained with use of the Uniport and LVAD, as compared to use of the LVAD alone (p less than or equal to 0.005). Other hemodynamic parameters of right heart failure, including right atrial pressure (RAP), pulmonary artery pressure (PAP), and left atrial pressure (LAP) were not significantly affected. These data suggest that the Uniport right ventricular assist device significantly improves cardiac output in this model of moderate right ventricular failure. Additional studies are required, however, to optimize pump stroke volume, and to further define the performance envelope of the device. ",13 967,"Potential usefulness of an artificial neural network for differential diagnosis of interstitial lung diseases: pilot study. An artificial neural network approach was applied to the differential diagnosis of interstitial lung diseases. The neural network was designed to distinguish between nine types of interstitial lung diseases on the basis of 20 items of clinical and radiographic information. A data base for training and testing the neural network was created with 10 hypothetical cases for each of the nine diseases. The performance of the neural network was evaluated by means of receiver operating characteristic analysis. The decision performance of the neural network was high; it was comparable to that of chest radiologists and superior to that of senior radiology residents. The preliminary results strongly suggest that the neural network approach has potential utility in the computer-aided differential diagnosis of interstitial lung diseases. ",7 1145,"Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats. We sought to determine whether high spatial resolution magnetic resonance imaging is useful for noninvasive quantitation of the ischemic infarct produced by occlusion of the middle cerebral artery and for detection of reduced infarct volume elicited by electric stimulation of the cerebellar fastigial nucleus. Male rats of the spontaneously hypertensive strain were anesthetized, the middle cerebral artery was occluded, and the fastigial nucleus was stimulated for 1 hour. Twenty-four hours later, rats were reanesthetized and T1- and T2-weighted images were obtained. Rats were killed and the volume and distribution of the lesion was established by histopathology. Magnetic resonance imaging estimates of the lesion volume were 271 +/- 41.0 mm3 (middle cerebral artery, n = 5) and 148 +/- 8.4 mm3 (middle cerebral artery + fastigial nucleus stimulation, n = 6; 45% reduction, p less than 0.05). Histopathological analysis revealed a lesion of 229.8 +/- 15.4 mm3 involving somatosensory cortex, lateral caudate putamen, and lateral hippocampus. Fastigial nucleus stimulation resulted in a 36% reduction in infarct volume to 146.0 +/- 10.3 mm3. The retrieved zone was largely in the cortex dorsal and ventral to the lesion and mostly posterior to the lesion. The estimates of lesion volume by magnetic resonance imaging and histopathology did not differ and were highly correlated (r = 0.90; p less than 0.001). This study confirms our previous finding that fastigial nucleus stimulation reduces the volume of a focal ischemic infarct and demonstrates that magnetic resonance imaging not only accurately estimates the volume of the lesion but also can detect changes as small as 50-100 mm3. ",9 132,"Human immunodeficiency virus and the primary care physician. As the scope and size of the human immunodeficiency virus (HIV) epidemic grows, the primary care physician will need to assume a greater role. A knowledge of HIV risk factors and the ability to perform pretest and posttest counseling for HIV testing is essential. Counseling patients on HIV risk reduction should be part of the HIV risk interview. An understanding of the benefits and contraindications of testing, as well as a respect for the impact of testing, is important. All HIV-seropositive individuals should undergo a complete history and review of symptoms as soon as test results are known. Judicious use of laboratory testing, including monitoring of CD4 cell counts, is recommended. Pneumocystis carinii prophylaxis and zidovudine therapy should be offered to patients with appropriately low CD4 counts. ",1 3289,"Fascinating rhythm: a primer on chaos theory and its application to cardiology. Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible. ",22 2124,"Early readmission of elderly patients with congestive heart failure. Repetitive hospitalizations are a major health problem in elderly patients with chronic disease, accounting for up to one fourth of all inpatient Medicare expenditures. Congestive heart failure, one of the most common indications for hospitalization in the elderly, is also associated with a high incidence of early rehospitalization, but variables identifying patients at increased risk and an analysis of potentially remediable factors contributing to readmission have not previously been reported. We prospectively evaluated 161 patients 70 years or older that had been hospitalized with documented congestive heart failure. Hospital mortality was 13% (n = 21). Among patients discharged alive, 66 (47%) were readmitted within 90 days. Recurrent heart failure was the most common cause for readmission, occurring in 38 patients (57%). Other cardiac disorders accounted for five readmissions (8%), and noncardiac illness led to readmission in 21 cases (32%). Factors predictive of an increased probability of readmission included a prior history of heart failure, four or more admissions within the preceding 8 years, and heart failure precipitated by an acute myocardial infarction or uncontrolled hypertension (all P less than .05). Using subjective criteria, 25 first readmissions (38%) were judged possibly preventable, and 10 (15%) were judged probably preventable. Factors contributing to preventable readmissions included noncompliance with medications (15%) or diet (18%), inadequate discharge planning (15%) or follow-up (20%), failed social support system (21%), and failure to seek medical attention promptly when symptoms recurred (20%). Thus, early rehospitalization in elderly patients with congestive heart failure may be preventable in up to 50% of cases, identification of high risk patients is possible shortly after admission, and further study of nonpharmacologic interventions designed to reduce readmission frequency is justified. ",13 3234,"Background review and current concepts of reperfusion injury. We define the concept of reperfusion injury, and we present a background chronology of experimental work supporting and questioning this concept. We identify several new influences, such as current clinical interest in thrombolytic therapy for acute ischemia of heart and brain and the growing recognition of endothelium as a regulator of homeostasis. We propose that these influences will encourage a reexamination of reperfusion injury as a factor in the ultimate outcome of tissue exposed to reversible ischemia. We briefly discuss the major mechanisms presently implicated in reperfusion injury--loss of calcium homeostasis, free radical generation, leukocyte-mediated injury, and acute hypercholesterolemia. ",22 1931,"Clustering of atherogenic behaviors in coffee drinkers. We studied the clustering of coffee consumption and selected atherogenic behaviors in older adults living in a southern California community. Men were somewhat more likely to drink caffeinated coffee while women were more likely to drink decaffeinated coffee. In men, but not women, caffeinated coffee drinking decreased with age and decaffeinated coffee drinking increased. Caffeinated coffee drinkers drank more alcohol, consumed more dietary saturated fats and cholesterol, were more likely to be current smokers and less likely to be current exercisers than were non-coffee drinkers. Smoking and exercise also showed a dose-response relationship to the amount of caffeinated coffee consumed. Risk factor levels among drinkers of decaffeinated coffee were more like those of caffeinated coffee than non-drinkers. These data illustrate the clustering of atherogenic behaviors with coffee drinking and highlight their potential importance in interpreting the growing body of literature about coffee and health. ",13 2310,"The epidemiology and natural history of pressure ulcers in elderly nursing home residents We analyzed prospective data from 19,889 elderly residents of 51 nursing homes from 1984 to 1985 to determine the prevalence, incidence, and natural history of pressure ulcers. Among all residents admitted to nursing homes, 11.3% possessed a stage II through stage IV pressure ulcer. For those residents admitted to the nursing home without pressure ulcers during the study period, the 1-year incidence was 13.2%. This increased to 21.6% by 2 years of nursing home stay. People already residing in a nursing home at the start of the study had a 1-year incidence of 9.5%, which increased to 20.4% by 2 years. Pressure ulcers were associated with an increased rate of mortality, but not hospitalization. Longitudinal follow-up of residents with pressure ulcers demonstrated that a majority of their lesions were healed by 1 year. Most of the improvement occurred early in a person's nursing home stay. Although nursing home residents with pressure ulcers have a higher mortality, with good medical care pressure ulcers can be expected to heal. ",16 1252,"Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. This study of the safety and efficacy of cryotherapy in treating severe retinopathy of prematurity registered 9751 infants with birth weights less than 1251 g at 23 study centers. Two hundred ninety-one infants developed a defined threshold retinopathy of prematurity, and cryotherapy was performed in approximately half of the eyes through a randomization protocol. Twelve months after randomization, results of masked grading of fundus photographs of the posterior pole were similar to results obtained 3 months after randomization, and indicated an unfavorable outcome in 25.7% of the eyes that received cryotherapy compared with 47.4% of the control eyes (P less than .0001). For the first time, masked Teller Acuity Card assessment of grating acuity was performed in this study group and indicated an unfavorable functional outcome in 35.0% of the treated eyes compared with 56.3% of the control eyes (P less than .0001). These results indicate that cryotherapy reduces the risk of unfavorable retinal and functional outcome from threshold retinopathy of prematurity. ",10 3298,"Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery. Thirty-five patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) were allocated randomly in a prospective double-blind study to receive either nimodipine 0.5 micrograms kg-1 min-1 or placebo. Cerebral blood flow (CBF) was measured during and immediately after CPB. Neuropsychological tests were performed 6 months after surgery to determine any relationship between ischaemic damage and CBF and administration of nimodipine. There were no differences in CBF between the nimodipine (n = 18) and placebo groups (n = 17). Significant changes in neuropsychological tests were found in six patients tested 6 months after surgery but there were no conclusive signs of ischaemic damage. The nimodipine-treated group performed better in tests of verbal fluency and visual retention, suggesting that some memory functions were preserved better in this group. ",22 1957,"Repair of flail anterior leaflets of tricuspid and mitral valves by cusp remodeling. We present an alternative approach to extensive rupture of the chordae tendineae leading to flail anterior leaflets. Resection of the affected cusp segment, suture of the cut edges, and extensive plication of the segment of annulus devoid of leaflets abolished massive regurgitation while maintaining an adequate valve orifice. ",13 2460,"The renal concentrating defect associated with potassium depletion is independent of prostaglandin E2. Prostaglandin E2 (PGE2) impairs the hydrosmotic effect of vasopressin in toad bladder and mammalian kidney. Because some studies in animals have suggested that potassium depletion enhances renal PGE2 production, the present study examined whether the renal concentrating defect of potassium depletion in humans is mediated by PGE2. Five normal volunteers were studied before and after moderate potassium depletion achieved by 10 days of dietary potassium restriction and administration of a polystyrene sulfonate potassium exchange resin (Kayexalate). Maximal urinary osmolality (Umax) decreased from 1,094 +/- 58 (mean +/- SEM) to 820 +/- 26 mmol/kg (mOsm/kg) (P less than 0.01) following potassium depletion, but urinary PGE2 excretion did not change (496 +/- 145 and 435 +/- 186 ng/d, respectively). Indomethacin suppressed PGE2 excretion significantly, but failed to increase Umax in either the normal or the potassium-depleted state (1,094 +/- 34 and 825 +/- 56 mmol/kg, respectively). It is concluded that the renal concentrating defect produced by moderate potassium restriction in humans is not mediated by PGE2. ",17 3275,"Modeling human performance in running. This paper focuses on the characteristics of a model interpreting the effect of training on athletic performance. The model theory is presented both mathematically and graphically. In the model, a systematically quantified impulse of training produces dual responses: fitness and fatigue. In the absence of training, both decay exponentially with time. With repetitive training, these responses satisfy individual recurrence equations. Fitness and fatigue are combined in a simple linear difference equation to predict performance levels appropriate to the intensity of training being undertaken. Significant observed correlation of model-predicted performance with a measure of actual performance during both training and tapering provides validation of the model for athletes and nonathletes alike. This enables specific model parameters to be estimated and can be used to optimize future training regimens for any individual. ",22 1565,"Nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction in patients with mitral valvular disease Using the rapid-response thermistor pulmonary artery catheter and transoesophageal echocardiography, this study examined the effects of 100 per cent oxygen, 70 per cent nitrous oxide/30 per cent oxygen, and 70 per cent nitrogen/30 per cent oxygen on the pulmonary circulation and ventricular function in ten patients with pulmonary hypertension. In comparison with baseline measurements, nitrous oxide administration resulted in small but statistically significant (P less than 0.05) changes in mean arterial pressure (76 +/- 14 to 67 +/- 12), mean pulmonary arterial pressure (37 +/- 14 to 33 +/- 13 mmHg), and cardiac output (3.7 +/- 1.4 to 3.2 +/- 1.1 L.min-1). Seventy per cent nitrogen resulted in no significant changes from baseline. The repeat 100 per cent oxygen measurements were nearly identical to the nitrous oxide measurements. It is concluded that nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction during high-dose fentanyl anaesthesia in patients with mitral valvular disease. ",13 2941,"Comparison of support provided by a semirigid orthosis and adhesive ankle taping before, during, and after exercise. The purpose of this study was to compare the relative effectiveness of athletic taping and a semirigid orthosis in providing inversion-eversion range restriction before, during, and after a 3 hour volleyball practice. The effect of each support method on the subjects' vertical jumping ability was also assessed. Fourteen ankles were treated with both methods of support. Passive inversion-eversion range of motion was measured on an ankle stability test instrument during five testing sessions: 1) before support, 2) before exercise, 3) 20 minutes during exercise, 4) 60 minutes during exercise, and 5) after exercise. The two-way analysis of variance and posthoc comparisons revealed maximal losses in taping restriction for both inversion and eversion at 20 minutes into exercise. The orthosis demonstrated no mechanical restrictive failure until before and after exercise comparisons were made, and then only eversion range of motion was compromised. Neither support system affected subjects' vertical jumping ability. These results suggest that the semirigid orthosis may be more effective than taping in providing initial ankle protection and in guarding against ligamentous reinjury. ",20 1036,"ACTH therapy in infantile spasms: relationship between dose of ACTH and initial effect or long-term prognosis. The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage, provided the dose was greater than 0.015 mg (0.6 IU)/kg/day, and the outcome of seizures and electroencephalographic abnormalities; however, ACTH 0.04-0.06 mg (1.6-2.4 IU)/kg/day and a total ACTH dose of 1.1-1.5 mg (44-60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects. ",9 772,"Azathioprine in the treatment of children with inflammatory bowel disease. During a 6-year period, we treated 21 patients with azathioprine, 2 mg/kg/day, as an adjunct to their customary regimen. Nine patients had ulcerative colitis and 12 patients had Crohn disease; the patients' ages ranged from 3 to 17 years. The median duration of disease before the start of azathioprine therapy was 2 years, and median follow-up was 2 years. Sixteen patients seemed to respond to azathioprine therapy: six patients in each disease group had complete responses and four patients (one with ulcerative colitis and three with Crohn disease) had partial responses. Two patients with ulcerative colitis and three patients with Crohn disease did not respond. The median time until patients responded was less than 3 months for patients with ulcerative colitis and 4 months for those with Crohn disease. Reduction of corticosteroid dose was possible for all patients who responded to azathioprine therapy. Only minimal side effects were attributable to the drug. We conclude that azathioprine is an effective adjunctive agent for the treatment of inflammatory bowel disease in childhood, but because questions remain regarding its long-term safety, its use should be reserved for children with refractory disease or severe and unacceptable side effects of corticosteroids. ",5 1114,"Circulatory and thermal adjustments to prolonged exercise in paraplegic women. The circulatory and thermal responses to 90 min of wheelchair ergometer exercise were examined in five wheelchair dependent (WD) women with low level spinal dysfunction and five able-bodied (AB) women who served as a comparison group. Metabolic rate during exercise was 221 W for WD and 255 W for AB (P greater than 0.05). Oral temperature (Tor), mean skin temperature (Tsk), oxygen uptake (VO2), heart rate (HR), and cardiac output (Qc) were assessed periodically throughout the exercise period. Ambient conditions were 24-25 degrees C and 38-52% relative humidity. A significant group X time interaction was found for Tor (P less than 0.001) and Tsk (P less than 0.001). Tor of the WD group steadily increased during the exercise, whereas the AB group showed a stable Tor. Tsk of WD increased rapidly during the first 5-10 min of exercise and continued to rise at a slower rate throughout the exercise. In contrast, Tsk of AB rose to a peak during the first 10 min and then showed a decreasing trend. VO2 and HR remained stable in both groups throughout the exercise period. Following an initial increase in Qc from minute 10 to minute 20 in both groups, values for WD continually decreased until Qc at 80 min was 14% lower than at 10 min. The findings suggest that the WD women had greater thermoregulatory strain than the AB women as indicated by a higher Tor and Tsk and by an inability to maintain Qc due to paralysis of the lower limbs and perhaps an increase in cutaneous blood volume. ",9 602,"Long scoliosis fusion to the sacrum in adults with nonparalytic scoliosis. An improved method. The first 17 adults with nonparalytic scoliosis having long fusion to the sacrum treated with the Luque-Galveston technique were reviewed. There were 3 men and 14 women. Their average age at the time of surgery was 47 years and the mean follow-up period was 42 months. There were no neurologic complications and no patient developed significant loss of lumbar lordosis. Fusion occurred in 88% of patients. Two patients developed pseudarthrosis, neither of whom had anterior fusion at the level of pseudarthrosis. The best results occurred in patients who had two-stage procedures, with initial anterior lumbar fusion to the sacrum without instrumentation followed by posterior segmental instrumentation with the Galveston technique of fixation to the pelvis. ",4 129,"Measles update. The incidence of measles in the United States dramatically increased in the 1980s, from a low of 1,497 cases in 1983 to over 17,000 cases in 1989. Family physicians can help reverse this trend by following the revised immunization schedule, which includes a measles-mumps-rubella (MMR) booster for preschool-age children. New guidelines also recommend that either the two-dose MMR schedule or serologic evidence of immunity be required for all persons entering college or employed in the medical field. Immunization policies for physician's offices should ensure that all office staff have acquired measles immunity and that a triage policy separating patients with rash from those with other illnesses is utilized. Mild upper respiratory illness, a history of seizures, nonanaphylactic egg allergy and asymptomatic human immunodeficiency virus infection are not contraindications to measles vaccine. All cases of measles should be reported to the local health department. ",1 366,"Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study. A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted. ",3 418,"Demonstration of Lipiodol in paraffin sections using a modified silver impregnation technique. To demonstrate postangiographic Lipiodol (LIP) in hepatocellular carcinoma (HCC) in paraffin sections, direct impregnation of formalin-fixed tissue blocks with silver nitrate (AgNO3) was followed by routine processing. LIP appeared as black globules in the sinusoids. Ninety-four tissue blocks from 13 postangiographic LIP HCCs and 69 from 8 non-LIP HCCs and 4 fatty livers were studied. Seventy-two of 73 negative controls and all positive blocks as seen on soft tissue radiographs (STRs) were correctly coded (specificity 98.6%, sensitivity 100%). Twenty-six of the 44 LIP-negative areas on STRs from LIP cases contained scanty globules of less than 10 microns in diameter. Fatty change gave no positive readings. Thus, modified AgNO3 impregnation is a simple, accurate means of detecting LIP in high-quality paraffin sections suitable for tumor diagnosis and, if applied to postangiographic LIP, ultrasonographically guided liver biopsy, can verify that a biopsy has reached a suspected tumor focus. ",3 206,"Rectal carcinoma: CT staging with water as contrast medium. Computed tomography (CT) was used to study 42 patients with rectal carcinoma. Water was used as a contrast medium for studying the local extent of tumor in all patients. Scans were read prospectively without knowledge of the histologic staging and then compared with pathologic specimens. CT depicted the tumor in all patients. Comparison of CT and histologic results (following the Dukes classification) showed that disease was correctly staged as A in three of four patients, as B in eight of 12, as C in 15 of 17, and as D in nine of nine. Overall, carcinoma was correctly staged with CT in 35 of 42 patients (diagnostic accuracy, 83.3%). The accuracy in the assessment of local invasion was 97.6% (41 of 42). In the detection of lymph node involvement, the accuracy was 78.6% (sensitivity, 88%; specificity, 64.7%). CT is recommended in the preoperative staging of rectal carcinoma and as an aid in choosing the appropriate therapy. The use of water enema and complete distention of the rectum are reliable techniques for improving the accuracy of CT in the assessment of local invasion by cancer. ",3 2765,"Fatal big cat attacks. Two cases of fatal attacks by large cats are presented. In the first case, a 30-year-old female zoo worker was attacked by a jaguar that had escaped its cage. In the second case, a 2-year-old girl was fatally injured by her father's pet leopard. The pattern of injuries in these cases is nearly identical to those of these cats' prey in the wild. ",20 1203,"Disturbance in daily sleep/wake patterns in patients with cognitive impairment and decreased daily activity. The sleep/wake patterns of 121 chronically ill, mentally and physically handicapped patients were visually monitored hourly for 14 consecutive days. Four types of sleep/wake patterns were found. In order to investigate how cognitive and physical functions correlated with sleep disorders, patients were classified based on a scale of mental function and the grading of daily activity. The percent of total sleep hours and the sleep rating, showing disturbances in sleep/wake pattern, were evaluated. We found a high degree of individuality in sleep/wake patterns. Sleep disturbance was associated with daily activity as well as with cognitive impairment. This monitoring system provides medical personnel with valuable information for clinical management. ",9 2668,"Response patterns of hairy cell leukemia to B-cell mitogens and growth factors. The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL-2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL-6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL-5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL. ",19 439,"Hepatic vein reconstruction for preserving remnant liver function. Hepatic malignancies often infiltrate to the major hepatic vein. Recently, we performed hepatic resection combined with hepatic vein reconstruction for preserving remnant liver function in three such patients. One patient had a saphenous vein graft. Postoperative liver function of the patients who underwent hepatic vein reconstruction was compared with those of eight patients who underwent hepatic resection of segments VII and VIII. The right hepatic vein in four of them was resected and in the remaining four was preserved by skeletalization using an ultrasonic aspirator. Although four patients with right hepatic vein resection showed severe lowering of liver function after surgery, the postoperative course of patients with preservation or reconstruction of the right hepatic vein maintained good liver function. Liver regeneration of three patients with hepatic vein reconstruction was good on computed tomography. Besides this report, to our knowledge, there is no other report of hepatic vein reconstruction for preserving the remnant liver function. Problems with hepatic resection combined with hepatic vein reconstruction are discussed. We conclude that hepatic vein reconstruction is one of the means for extending indication of the malignant tumor resection of the liver. ",3 980,"The effect of rifampicin on rhinoscleroma: an electron microscopic study. Twenty-five cases suffering from rhinoscleroma were divided into two groups. The first group consisted of 15 patients treated with rifampicin systemically. The other group consisted of 10 patients treated locally with rifampicin in the form of ointment. Electron microscopic study of the pathological changes in the lesions showed that rifampicin is highly effective both systemically and locally in the treatment of rhinoscleroma. ",7 42,"Protective effects of polyclonal sera and of monoclonal antibodies active to Salmonella minnesota Re595 lipopolysaccharide during experimental endotoxemia. Mice were passively immunized with sera from blood donors active for rough lipopolysaccharides (LPS), the J5 (Rc chemotype) mutant of Escherichia coli O111:B4, and the Re595 (Re chemotype) mutant of Salmonella minnesota. All protected the mice against lethal challenge with smooth E. coli WF96 LPS, E. coli and Salmonella rough mutant LPS, or free lipid A. Epitopes recognized by monoclonal antibodies (MAbs) reacting with the LPS of S. minnesota Re595 or lipid A were localized in the 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) region and on lipid A. Core-reactive MAbs reacted with their homologous Re LPS and with free lipid A. One, GL11, cross-reacted with the KDO alone. MAbs GL6, GL11, L.4, L.6, and L.8 protected the actinomycin D-sensitized mice against the lethal effects of LPS from E. coli WF96, Salmonella enteritidis, E. coli J5, S. minnesota Re595, and free lipid A. The GL11 antibody was also protective when injected after LPS challenge. These results indicate that antibodies directed against the core glycolipid of S. minnesota Re595 LPS may be useful as an additive form of therapy that may enable decreased mortality during gram-negative bacterial sepsis. ",0 744,"Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease. ",5 442,"Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia. We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using 18F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity. ",3 2965,"Assessing nutritional needs for the burned patient. Assessment of nutritional needs following thermal injury remains an important adjunct to providing dietary therapy designed to minimize the detrimental effects of hypermetabolism and subsequent catabolism. Most anthropometric measurements, frequently utilized in nonburned patients, have relatively little usefulness in assessing burned individuals. Energy expenditure can be adequately estimated for most patients by direct calorimetry, indirect calorimetry, or formulae. Direct calorimetry is the most expensive and complicated method, while use of a formula is the most inexpensive and least complicated. All yield good results in the clinical setting. Differences in estimated energy expenditure by the multiple formulae may be statistically significant, but rarely are clinically significant. Therefore selection of a formula should be based on simplicity. Estimations by formula require readjustment at intervals of 1 to 2 weeks. In general, enteral feedings remain superior to parenteral delivery of nutrients. Finally, current animal research suggests significant differences in metabolic and immunologic effects of the diet depending on qualitative make-up of dietary fat sources. ",20 2523,"Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy. To assess whether subclinical hypothyroidism is associated with changes in lipoprotein fractions, 13 patients maintained in a stable state of subclinical hypothyroidism for at least 3 months were studied prior to and 2 and 4 months following restoration of a euthyroid state with incremental levothyroxine sodium therapy. Thyrotropin levels ( +/- SEM) had decreased from 16.6 +/- 3.2 mU/L to 3.1 +/- 0.7 mU/L and 3.2 +/- 0.7 mU/L at 2 months and 4 months. At 2 months, levothyroxine treatment led to a decrease in levels of total cholesterol from 5.5 +/- 0.3 mmol/L (213 +/- 12 mg/dL) to 4.8 +/- 0.3 mmol/L (186 +/- 12 mg/dL), in low-density lipoprotein cholesterol (LDL-C) from 3.7 +/- 0.3 mmol/L (143 +/- 12 mg/dL) to 2.9 +/- 0.3 mmol/L (112 +/- 12 mg/dL), and in apolipoprotein B from 91 +/- 8 mg/dL to 74 +/- 7 mg/dL. At 4 months, levels of LDL-C and apolipoprotein B remained significantly lower than pretreatment values (2.9 +/- 0.2 mmol/L [112 +/- 8 mg/dL] and 75 +/- 6 mg/dL, respectively). While high-density lipoprotein cholesterol (HDL-C), HDL3-C, and apolipoprotein A-I were not significantly affected by levothyroxine therapy, there was a slight trend of increase in HDL2-C during levothyroxine substitution. There was also a tendency for a decrease in triglyceride levels from 1.3 +/- 0.2 mmol/L (115 +/- 18 mg/dL) to 0.9 +/- 0.1 mmol/L (80 +/- 9 mg/dL) at 4 months of levothyroxine therapy. Levels of HDL-C tended to decrease from 4.8 +/- 0.4 mmol/L (186 +/- 15 mg/dL) to 4.5 +/- 0.5 mmol/L (174 +/- 19 mg/dL) at 2 months and to 3.9 +/- 0.4 mmol/L (151 +/- 15 mg/dL) at 4 months. The LDL-C/HDL-C ratio also decreased from 3.3 +/- 0.3 mmol/L (128 +/- 12 mg/dL) to 2.9 +/- 0.5 mmol/L (112 +/- 19 mg/dL) and 2.5 +/- 0.3 mmol/L (97 +/- 12 mg/dL) at 2 months and 4 months, respectively. These results suggest that long-term levothyroxine therapy in patients with subclinical hypothyroidism is associated with a decrease in LDL-C and apolipoprotein B levels that are reflected in a trend of decreases in cholesterol/HDL-C and LDL-C/HDL-C ratios known to have a relationship with coronary artery disease. ",18 2939,"Pathologic synovial plica of the knee. Results of conservative treatment. Observations of 136 cases of pathologic synovial plica of the knee were analyzed with regard to etiology, symptoms, and the results of conservative treatment. The results obtained with conservative treatment were good in 40% of cases, average in 20%, and poor in 40%. In our opinion, these results justify the treatment of this condition with physical therapy before proceeding with surgical correction. The objective of physical therapy was to decrease the compressive forces in the anterior compartment of the knee by increasing the structural flexibility of the flexor and extensor muscles. This increase in flexibility was obtained by instituting stretching exercises for the hamstrings, gastrocnemius, and quadriceps. ",20 3244,"Gadolinium-enhanced magnetic resonance imaging in Bell's palsy. Inflammation of the facial nerve in Bell's palsy can be demonstrated on gadolinium-enhanced magnetic resonance imaging. We have studied a series of 17 Bell's palsy patients with gadolinium-enhanced magnetic resonance imaging, and the purpose of this paper is to report our findings and discuss their significance. Most acute Bell's palsy cases demonstrate facial nerve enhancement, usually in the distal internal auditory canal and labyrinthine/geniculate segments. Other segments demonstrate enhancement less often. Gadolinium enhancement occurs regardless of the severity of the paralysis and can persist after clinical improvement of the paralysis. The findings of this study corroborate other evidence that the segments of the facial nerve most often involved in Bell's palsy are the only segments that are most often enhanced with gadolinium-enhanced magnetic resonance imaging. The role of gadolinium-enhanced magnetic resonance imaging in the management of Bell's palsy patients is discussed. ",22 929,"Measurement of histamine in nasal lavage fluid: comparison of a glass fiber-based fluorometric method with two radioimmunoassays. The determination of histamine in nasal secretions and nasal lavage fluid may be of importance to monitor activation of histamine containing cells in the nasal cavity. However, such studies have been besieged by controversy, specifically to findings of changes in histamine levels in relation to allergenic stimulation. This controversy may be due to the specificity and accuracy of the various methods used to determine histamine in the nasal fluid. We have therefore applied and compared three new methods to determine histamine in nasal lavage fluids obtained before and after allergen challenge in normal subjects and patients with allergic rhinitis. We used a fluorometric glass fiber-based histamine method (FHR) and two RIAs, I and II. The FHR (detection limit, 7.0 nmol) and the RIA II (detection limit, 0.2 nmol) are specific for histamine itself, whereas the RIA I (detection limit, 18.0 nmol) measures mainly methylhistamine and cross-reacts to some extent with histamine. The histamine levels in the nasal lavage fluids from the nasal challenges demonstrated histamine values between 100 and 2000 nmol/L of histamine with significantly higher levels in the postallergen challenges for the allergic subjects as compared to the normal control subjects. The FHR correlated well with the RIA I and RIA II methods with correlation coefficients of 0.77 to 0.88 (p less than 0.001), respectively. However, the RIA I (methylhistamine antibody) always demonstrated absolute histamine values 5% to 20% of values measured by the RIA II (at the level of cross-reactivity to histamine). ",7 3211,"Lidocaine local anesthesia for arthroscopic knee surgery. Forty-five patients were evaluated during knee arthroscopy performed using local anesthesia produced by lidocaine with epinephrine to determine the dose-response relationship for operative analgesia. Serum lidocaine concentrations were also measured. Patients were randomized prospectively to receive 20 mL of 0.5%, 1.0%, or 1.5% lidocaine with epinephrine intraarticularly. Intraoperative discomfort was measured by verbal response on an 11-point linear pain scale. Pain scores were significantly higher in patients receiving 0.5% lidocaine during the first 45 min of surgery (P = 0.03). After 45 min, pain scores continued to be higher in the 0.5% lidocaine group than in the 1.0% or 1.5% groups, but the differences were not statistically significant. Ninety-four percent of patients in the 1.5% lidocaine group were willing to repeat this anesthetic technique for surgery compared with 83% of those in the 1.0% lidocaine group and 75% of those in the 0.5% lidocaine group (P greater than 0.05). The duration of postoperative analgesia was similar in all groups. Serum lidocaine concentrations before and 15, 30, 60, and 120 min after instillation of lidocaine were highest in the 1.5% lidocaine group with a peak concentration of 278 ng/mL. No patient had symptoms of lidocaine toxicity. We recommend that lidocaine concentrations of 1.0% or 1.5% be used when 20 mL is instilled intraarticularly for knee arthroscopy based on patient comfort and absence of lidocaine toxicity. ",22 2468,"Quantitative histologic study of the sural nerve in Lesch-Nyhan syndrome. The sural nerve of a 31-year-old man with Lesch-Nyhan syndrome obtained at autopsy was studied histologically. Large, myelinated nerve fibers were reduced in number and no myelinated nerve fibers larger than 5 microns were seen. Diameter distribution of myelinated nerve fibers did not demonstrate a bimodal pattern. The density of myelinated nerve fibers was 5,530/mm2 and was decreased as compared to the controls. On electron microscopic examination, lipid-like inclusions were observed in the cytoplasm of some Schwann cells. The role of these inclusions could not be elucidated, but reduction of larger myelinated nerve fibers suggests a peripheral nervous disorder in patients with this syndrome; therefore, patients with Lesch-Nyhan syndrome must be reappraised for disorders of the peripheral nervous system. ",17 2882,"Pediatrician's knowledge and practices regarding parental use of alcohol. Problems with alcohol are common in the United States but are too frequently ignored by physicians, particularly those working with children. We explored pediatricians' knowledge and practices regarding parental use of alcohol and compared these attributes with those of family practitioners. Child health care providers attending three continuing medical education courses in general pediatrics were surveyed using a closed-item questionnaire. One hundred ninety (69%) of the participants responded, including 90 pediatricians and 39 family practitioners. Forty-six percent of responding pediatricians, compared with 90% of family practitioners, stated that they ask about problems with alcohol in taking a routine family history. Thirty-eight percent of pediatricians who knew the frequency of alcoholism, compared with 47% of those who did not, indicated that they include it in taking a routine family history. Forty-six percent of pediatricians who have experienced a problem with alcohol in their own family, compared with 20% of pediatricians without such personal experience, routinely address the issue of alcohol use with parents and children. Similar analyses among the family practitioners revealed no significant differences. We conclude that fewer than half of pediatricians ask about problems with alcohol in taking a family history. The likelihood of asking about such problems was not influenced by the health care provider's knowledge of alcoholism, but it was influenced by the provider's personal family history of problems with alcohol. Because of the important morbidity associated with alcohol use in families, and because intervention can improve functioning and adaptation of the child, training and Continuing Medical Education courses should address this issue. ",20 2590,"Functional assessment scales: a study of persons with multiple sclerosis. The purpose of this study was to investigate disability in persons with multiple sclerosis (MS) by using combinations of functional assessment scales and subscales to predict (1) the burden of care measured in minutes of assistance provided per day by another person in the home, and (2) the subject's level of satisfaction with life in general. The Functional Independence Measure (FIM), Incapacity Status Scale, Environmental Status Scale, and the Barthel Index had high intercorrelations with each other. Although each was predictive of the MS subject's physical care needs, the FIM was the most useful. A change in total FIM score of one point was equivalent to an average of 3.38 minutes of help from another person per day. With the Brief Symptom Inventory and the Environmental Status Scale, the FIM contributed to predicting the patient's general satisfaction as well. We propose that burden of care and subjective satisfaction with life be the standards by which functional assessment instruments are compared to reflect, in pragmatic terms, the impact of disability on the lives of individuals and on the human and economic resources of the community. ",19 3114,"Effect of antiplatelet and anticoagulant therapy on patency of femorotibial bypass grafts. In a retrospective study, 210 autogenous femorotibial saphenous vein grafts inserted during the 15 years from 1967 to 1982 were followed-up for a mean period of 62.3 +/- 5.7 months. Seven patients, who had had eight grafts died in hospital. The remaining 202 grafts fell into three groups: (1) Sixty grafts in patients who received 325 mg of dipyridamole and 1.0 g of acetylsalicylic acid daily, starting on the second postoperative day and continuing for six months. (2) One hundred and two grafts in patients on no antithrombotic therapy. (3) Forty grafts in patients on warfarin therapy to maintain the prothrombin time (prothrombin-proconvertin method) within the therapeutic range (0.10 to 0.20). Medication was continued for six months. This group included more high-risk patients than the other two groups. The mean ages and the incidence of risk factors did not vary significantly between the groups. The patency rates in three groups at five years were 62.5%, 44.0% and 26.0% and at ten years 48.5%, 25.0% and 21.5% for the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups, respectively. The limb salvage rates were 100%, 96% and 85% in the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups respectively. Thus, the best results were seen in the aspirin/dipyridamole group. ",22 1085,"Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring. Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep. ",9 2606,"Anaphylactic shock associated with chymopapain skin test. A case report and review of the literature. The allergic response to chymopapain intradiscal therapy has been well documented. The most serious of these reactions is anaphylactic shock, which may result in death. Various screening methods, including skin tests, have been proposed to identify susceptible patients. Anaphylactic shock occurred in a 40-year-old woman from application of the screening skin test. Appropriate therapeutic intervention should be readily accessible when this test is performed. ",19 802,"Extracorporeal cholecystolithotripsy without oral chemolitholysis. One hundred thirty-six patients completed extracorporeal biliary lithotripsy (EBL) for symptomatic cholecystolithiasis. Sonographic evidence of complete clearance of all stone fragments was the only criterion for treatment success, which occurred in 32 of the 71 patients (45%) followed up for 24 weeks and in 36 of the 59 patients (61%) followed up for 52 weeks. The authors' protocol varied from protocols of other researchers primarily in that no adjuvant chemolitholysis was used. However, the number of treatment sessions and total number of shock waves (a maximum of 4,000 shock waves per treatment session, 12,000 shock waves in a patient demonstrating no significant fragmentation, and 20,000 shock waves in a patient whose stones responded well to fragmentation) was higher than those in other reports. The results of treatment and complication rates in this study are comparable with those at centers using both shock-wave lithotripsy and chemotherapy. The authors conclude that EBL is developing into an important alternative to surgery, which was obviated in all patients with complete clearance of fragments from the gallbladder. ",5 1876,"Long-term outcome after surgical repair of isolated atrial septal defect. Follow-up at 27 to 32 years BACKGROUND. Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients. METHODS. To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred. RESULTS. The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality was 3.3 percent (four deaths). Actuarial 27-year survival rates among patients in the younger two quartiles according to age at operation (less than or equal to 11 years and 12 to 24 years) were no different from rates among controls--97 percent and 93 percent, respectively. In the two older quartiles (25 to 41 years and greater than 41 years), 27-year survival rates were significantly less (P less than 0.001)--84 percent and 40 percent, respectively--than in controls (91 and 59 percent). Independent predictors of long-term survival according to multivariate analysis were age at operation (P less than 0.0001) and systolic pressure in the main pulmonary artery before operation (P less than 0.0027). When repair was performed in older patients, late cardiac failure, stroke, and atrial fibrillation were significantly more frequent. CONCLUSIONS. Among patients with surgically repaired atrial septal defects, those operated on before the age of 25 have an excellent prognosis, but older patients require careful, regular supervision. ",13 6,"Possible role of bacterial siderophores in inflammation. Iron bound to the Pseudomonas siderophore pyochelin can function as a hydroxyl radical catalyst. Tissue injury has been linked to neutrophil associated hydroxyl radical (.OH) generation, a process that requires an exogenous transition metal catalyst such as iron. In vivo most iron is bound in a noncatalytic form. To obtain iron required for growth, many bacteria secrete iron chelators (siderophores). Since Pseudomonas aeruginosa infections are associated with considerable tissue destruction, we examined whether iron bound to the Pseudomonas siderophores pyochelin (PCH) and pyoverdin (PVD) could act as .OH catalysts. Purified PCH and PVD were iron loaded (Fe-PCH, Fe-PVD) and added to a hypoxanthine/xanthine oxidase superoxide- (.O2-) and hydrogen peroxide (H2O2)-generating system. Evidence for .OH generation was then sought using two different spin-trapping agents (5.5 dimethyl-pyrroline-1-oxide or N-t-butyl-alpha-phenylnitrone), as well as the deoxyribose oxidation assay. Regardless of methodology, .OH generation was detected in the presence of Fe-PCH but not Fe-PVD. Inhibition of the process by catalase and/or SOD suggested .OH formation with Fe-PCH occurred via the Haber-Weiss reaction. Similar results were obtained when stimulated neutrophils were used as the source of .O2- and H2O2. Addition of Fe-PCH but not Fe-PVD to stimulated neutrophils yielded .OH as detected by the above assay systems. Since PCH and PVD bind ferric (Fe3+) but not ferrous (Fe2+) iron, .OH catalysis with Fe-PCH would likely involve .O2(-)-mediated reduction of Fe3+ to Fe2+ with subsequent release of ""free"" Fe2+. This was confirmed by measuring formation of the Fe2(+)-ferrozine complex after exposure of Fe-PCH, but not Fe-PVD, to enzymatically generated .O2-. These data show that Fe-PCH, but not Fe-PVD, is capable of catalyzing generation of .OH. Such a process could represent as yet another mechanism of tissue injury at sites of infection with P. aeruginosa. ",0 1305,"Development of hypertension from unilateral renal artery stenosis in conscious dogs. The renal and systemic changes after stenosis of the left renal artery (n = 5) or sham stenosis (n = 6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component. Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance. ",11 18,"Ceftazidime/clindamycin versus tobramycin/clindamycin in the treatment of intra-abdominal infections. In order to assess the efficacy and toxicity of ceftazidime as a substitute for aminoglycosides in the treatment of intra-abdominal sepsis, a prospective randomized trial was conducted. Ninety-four patients (49% trauma) were randomized to receive ceftazidime/clindamycin (CAZ/C) (n = 47) or tobramycin/clindamycin (T/C) (n = 47). CAZ (2.0 gm) and C (0.9 gm) were administered intravenously every 8 hours while T dosage was adjusted to maintain peak (5-8 mg/L) and trough (less than 2 mg/L) concentrations. Age, sex, baseline serum creatinine, and etiology of infection were comparable in the two groups. Clinical cure was similar in culture-positive and culture-negative patients who received CAZ/C (94% vs 88%). The clinical cure rate however was significantly lower in the T/C culture positive (73%) than in the culture negative patients (100%) (P = 0.016). Pathogenic organisms were eradicated in 100% (30/30) and 76% (13/17) of CAZ/C and T/C patients, respectively (P = 0.0006). Nephrotoxicity Nephrotoxicity or ototoxicity was observed in none of the CAZ/C patients and in one and two T/C patients, respectively. CAZ/C more effectively eradicated the bacteria isolated from these patients and no significant difference in clinical response was observed in culture-positive patients. These findings plus the lack of toxicity suggest that CAZ/C is an effective alternative for treatment of IAI. ",0 2389,"The changing epidemiology of diabetes mellitus among Navajo Indians. Although early descriptions of diabetes mellitus among Navajo Indians characterized the disease as an infrequent and ""benign chemical abnormality,"" the prevalence of diabetes and its complications among Navajos appears to have increased substantially in this century. We reviewed recent Indian Health Service inpatient and ambulatory care data and compared these data with previous reports. Of the estimated Navajo population aged 45 years or older, 4,331 (16.9%) had an ambulatory care visit for diabetes between October 1, 1986, and September 30, 1987. Diabetes was coded for 1,041 (7.0%) of hospital admissions of persons aged 20 and older. Of 377 lower-extremity amputations done from 1978 to 1987, diabetes was involved in 245 (66%). The 1986 age-adjusted mortality rate from diabetes was 30.3 per 100,000, approximately twice that for the general US population. The explanation for the increased prevalence of diabetes mellitus among Navajos probably relates to an increasing prevalence of obesity. ",17 2724,"Immunology of HIV infection, I: Biology of the interferons. Interferons (IFN) are the prototypic biologic response modifiers. They comprise a multigene family of regulatory proteins and glycoproteins that affect a variety of cellular functions, including normal and neoplastic cell growth, immune reactivity, and host-parasite interactions. Their importance to basic cell biology and cellular immune defense, and their interactions with human immunodeficiency viruses (HIV) on the molecular and cellular levels, form the basis for this review. ",19 1646,"Effects of enalapril and neuroendocrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. This study enrolled 253 patients with severe heart failure (New York Heart Association functional class IV) from 35 centers in Scandinavia, randomly assigned to treatment with placebo or enalapril, in addition to their usual treatment for heart failure. After an initial titration period, the daily doses of enalapril ranged from 2.5 to 40 mg. At the end of the trial, 46% of the placebo-treated patients and 61% of the enalapril-treated patients were alive (p = 0.003); the survival figures at 8 months after completion of the trial were 32 and 48%, respectively (p = 0.001); and 21 and 30%, respectively (p = 0.006) at the 2-year follow-up. In the placebo group, there was a significant positive association between mortality and baseline levels of norepinephrine, epinephrine, angiotensin II, aldosterone and atrial natriuretic peptide; no such association was found in the enalapril-treated patients. The results suggest that the effects of enalapril on mortality are related to a counteraction of the neuroendocrine activation in general and to the renin-angiotensin system in particular. ",13 1968,"Beta-adrenergic receptors in lymphocyte subsets after exercise. Alterations in normal individuals and patients with congestive heart failure. Dynamic exercise increases the number of beta-adrenergic receptors in mixed lymphocytes by a mechanism that is incompletely understood. In a set of in vivo studies, we have investigated the effects of dynamic exercise on the subset distribution of circulating lymphocytes and on the number of beta-adrenergic receptors in each of these subsets in two groups of patients. In healthy subjects, exercise increased plasma norepinephrine and epinephrine and caused lymphocytosis. Whereas the number of Thelper cells increased only modestly, the number of Tsuppressor/cytotoxic and natural killer cells more than tripled. The number of beta-adrenergic receptors varied among subsets but was not significantly altered by dynamic exercise in any subset except natural killer cells (35% increase, p = 0.0302). In a group of patients with congestive heart failure, dynamic exercise increased plasma norepinephrine but did not alter plasma epinephrine and did not cause significant lymphocytosis. We did not detect any significant alterations of circulating leukocyte subsets or beta-adrenergic receptors in any of these subsets after exercise. A combined analysis of healthy patients and heart failure patients revealed a significant correlation between increases in plasma epinephrine and increases in circulating lymphocytes. We conclude that the exercise-induced increase in beta-adrenergic receptors of mixed lymphocytes is predominantly caused by a redistribution of circulating cell subsets that differ in their beta-adrenergic receptor number. This appears to be mediated by epinephrine rather than norepinephrine. ",13 2855,"Salvage posterior urethroplasty after failed initial repair of pelvic fracture membranous urethral defects. Experience with 20 salvage urethroplasties in patients with pelvic fracture membranous urethral defects who failed previous delayed urethroplasty is presented. A total of 15 patients was successfully managed by 1-stage procedures, 14 by bulboprostatic reanastomosis and 1 by a tubed pedicled island of skin. Substitution urethroplasty with a staged perineoscrotal skin tube inlay was performed in 5 patients in whom an anastomosis could not be achieved either due to an excessively long urethral defect or inelasticity of the anterior urethra precluding its elongation for an anastomosis free of tension. A successful result was achieved in 19 of the 20 patients (95%). The rationale for procedure selection is discussed. ",20 3218,"An objective appraisal of the role of computed tomographic (CT) guided drainage of intra-abdominal abscesses. Computed tomographic (CT) guided drainage is an important tool in the treatment of intra-abdominal abscess. Its most important role is in the treatment of small, unilocular, well-placed abscesses. Success rates in our experience diminish considerably in abscesses involving necrotic tumors or those infected with yeast. As is frequently characteristic of new technologic procedures, the initial evaluation of the success rate of the procedure is overly optimistic. The procedure carries a considerable complication rate (13%) and mortality rate (15%). Most importantly, success is usually evident early; within the first 24 to 48 hours. After this length of time, careful evaluation to consider further treatment should be contemplated. ",22 2450,"Approaching the protein-sparing modified fast. The protein-sparing modified fast is a safe and effective method for losing a large amount of weight relatively quickly. This diet should be used in combination with an exercise program, behavior modification and patient education. Caloric intake is in the range of 400 to 800 per day. Candidates for the diet should be generally healthy; they should have at least 40 lb to lose or be at more than 120 percent of their ideal body weight. ",17 739,"Computed tomography in patients with esophageal perforation. Contrast esophagram is the diagnostic procedure of choice in patients with clinically suspected perforation of the esophagus. In patients in whom the usual clinical signs or symptoms are unrecognized and in whom the diagnosis is obscure, the diagnosis of a perforated esophagus may be suggested by the finding of mediastinal fluid and air on CT. Three patients are reviewed. The perforations included one spontaneous, one from erosion of an esophageal carcinoma, and one iatrogenic. In two of the three patients, the diagnosis of perforated esophagus had not been made initially and in one patient the initial esophagram was interpreted as normal. Computed tomography of the chest in each patient led to the suspected diagnosis of perforated esophagus. Prompt appropriate surgical intervention followed. The findings of mediastinal fluid and more importantly mediastinal air on CT of the chest are strongly suggestive of esophageal perforation. ",5 1599,"A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/- 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site. ",13 3185,"Constipation: pathophysiology and treatment. Although many physicians consider constipation a trivial problem, it is one of the most frequent and chronic digestive disorders in the United States, affecting 4.53 million people and causing considerable morbidity. More than $200 million are spent for over-the-counter laxatives and untold millions of dollars are spent for prescription drugs and other medical services to manage this disorder. Successful management requires an appreciation of the magnitude of the problem, an understanding of colorectal function and a clear assessment of the causes. Careful examination of the patient's anorectal anatomy and improvement in the patient's dietary habits are the first steps in management. Therapeutic options include behavioral modification strategies, diet and lifestyle changes, pharmacologic therapy and, rarely, surgical intervention. ",22 2795,"Serum and urinary beta-hexosaminidase as markers of heavy drinking. Serum and urinary beta-hexosaminidase (SHEX and UHEX) were determined in 32 alcoholic men admitted to inpatient detoxification treatment for seven days, and in 27 teetotallers. On the admission SHEX was increased in 68.8% and UHEX in 81.3% and after seven days of abstinence the corresponding percentages were 37.5 (SHEX) and 71.9 (UHEX). During the treatment SHEX decreased significantly while UHEX did not. On the admission to the treatment UHEX correlated positively with SHEX (r = 0.54; P less than 0.01). The results suggest that UHEX may be a more sensitive marker of heavy drinking than SHEX. Furthermore UHEX stays longer elevated than SHEX. ",20 3262,"Longitudinal study of diagnoses in children of women with unipolar and bipolar affective disorder. School-age children of unipolar depressed, bipolar, chronically medically ill, or normal women were diagnosed every 6 months for up to 3 years. Offspring of unipolar women had the highest rates of disorder at all evaluations, but children of bipolar and medically ill mothers also experienced significant rates of disorder. Observing diagnoses from both past lifetime and prospective follow-up assessments, it appeared that most children who had diagnoses had onsets in preadolescence and continued a chronic or intermittent course of disorder. Thus, risk to offspring of ill mothers is not transitory and indicates a pernicious course that commonly includes effective disorders alone or in combination with behavior and anxiety disorders. ",22 1652,"Early postoperative balloon coronary angioplasty for failed coronary artery bypass grafting. In a small number of patients, coronary artery bypass grafting (CABG) fails to relieve anginal symptoms. The usefulness of coronary angioplasty for the treatment of early (less than or equal to 90 days) recurrent ischemia after CABG was examined. Forty-five patients were treated from 2 to 90 days after CABG, including 8 patients studied emergently for prolonged ischemic symptoms. One-, 2- and 3-vessel native disease was found in 4, 10 and 31 patients, respectively. At the time of postoperative angiography, the major anatomic mechanism of recurrent ischemia was complete vein graft occlusion in 12 patients (27%), internal mammary artery occlusion in 3 (7%), vein graft stenoses in 13 (29%), internal mammary artery stenoses in 10 (22%), unbypassed disease in 4 (8%) and disease distal to the graft insertion site in 3 (7%). Angioplasty was successful at 91 of 98 sites (93%), including 95% of 41 lesions in native arteries, 89% of 46 lesions in vein grafts and 100% of 11 internal mammary artery lesions attempted. Complete revascularization was achieved in 84% of patients. There were 2 in-hospital deaths and 2 myocardial infarctions. Two additional patients underwent repeat CABG before discharge after uncomplicated but unsuccessful angioplasty. At late follow-up of the 43 survivors (mean 44 months), there were 4 deaths, 2 of which were noncardiac. Repeat CABG was required in only 3 patients and repeat angioplasty was performed in 10. Angina was absent or minimal in 35 patients; 17 patients were employed full time. Thus, percutaneous transluminal coronary angioplasty can relieve myocardial ischemia after unsuccessful CABG in the majority of patients. ",13 1370,"Triamterene nephrolithiasis: renewed attention is warranted. Although triamterene has been known to contribute to urinary calculus formation, it has been presumed to be a rare phenomenon. Our review of stone analyses performed during the last decade by a single laboratory reveals an increasing incidence of triamterene stones. Awareness of the calculogenic potential of triamterene-containing medications should be re-emphasized. ",11 1537,"Transplantable rat choriocarcinoma cells express placental lactogen: identification of placental lactogen-I immunoreactive protein and messenger ribonucleic acid. The purpose of this investigation was to evaluate the abilities of a transplantable rat choriocarcinoma (Rcho) to produce placental PRLs. The Rcho tumor was analyzed biochemically and histologically for the expression of placental PRLs. Expression of placental PRL mRNAs was determined by Northern blot and in situ hybridization analyses. Expression of placental PRL proteins was determined by Western blot and immunocytochemical analyses. Histologically, Rcho tumors were characterized by the appearance of giant cell surrounding hemorrhagic regions. Female rats bearing the Rcho tumor beneath their kidney capsule showed extensive mammary gland development. The Rcho tumors expressed placental lactogen-I (PL-I) mRNA and protein, but there was no evidence of placental lactogen-II (PL-II), PRL-like protein-A (PLP-A), or PRL-like protein-B (PLP-B). Rcho PL-I mRNA and proteins migrated as a 1-kilobase species and a 36- to 40-kDa species similar to those expressed by normal rat trophoblast tissues. The cell type responsible for Rcho PL-I production was the giant cell, similar to that observed in normal rat trophoblast tissues. In summary, we have demonstrated the production of PL-I by a transplantable rat choriocarcinoma (Rcho). The Rcho tumor resembles rat trophoblast tissue at early postimplantation stages (days 6-10 of gestation) and may be a useful tool for studying placental PRL expression during trophoblast differentiation. ",12 918,"High-frequency oscillation during simulated altitude exposure. Ventilatory requirements using high-frequency oscillation (HFO) during simulated altitude exposure were investigated in control dogs and animals with oleic acid-induced lung injury. FIO2 values of 0.21 and 1.0 were supplied by bias flow to the normal and injured dogs, respectively. After a control period, animals were exposed to a simulated altitude of 8,000 ft (barometric pressure 564 torr), followed by a second control period at ground level. Both experimental groups had similar values of PaCO2 at ground level and during exposure to reduced barometric pressure. The tidal volume necessary to maintain eucapnia was higher in oleic acid-injured animals compared with the control group; cardiac output and functional residual capacity were lower. The alveolar-arterial oxygen difference was substantially larger in the oleic acid group. Adequate gas exchange can be maintained with HFO during exposure to altitude provided that ventilation and inspired PO2 are not reduced below normobaric levels. ",7 2746,"Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon. We reviewed 21 patients with 22 ruptures of the extensor pollicis longus at a mean of 5.3 years after transfer of the extensor indicis proprius tendon. Of these, 19 with 21 transfers described the result as good, and two as fair. The mean deficit of extension between the operated and unoperated thumbs was 1.4 cm, and the mean flexion deficit 0.6 cm. Pressure gauge measurements showed that the strength of the transfer was 51% of that of the uninjured extensor. The two fair results had an extensor lag of over 1.5 cm. Independent extension of the index was maintained in all patients, none having a discernible lag, but the strength of index extension was reduced to 49% of that of the normal finger. There was no evidence of functional loss. Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon is a simple and reliable procedure with few complications. It gives satisfactory long-term extension of the thumb. ",20 2973,"Effects of a 2.15-micron laser on human atherosclerotic xenografts in vivo. The thulium-holmium-chromium:yttrium-aluminum-garnet (THC:YAG) laser has a tissue effect similar to that of the CO2 laser, with the advantage of transmissibility through flexible fibers. The authors used a human-rabbit xenograft model to evaluate the thrombotic and healing responses of atherosclerotic vessels subjected to laser energy. Occluded atherosclerotic human coronary artery segments were recanalized in vitro by use of the THC:YAG laser. Destruction of plaque by the laser was achieved with minimal collateral thermal damage. These vascular segments were then transplanted into the rabbit abdominal aorta. The authors observed that the luminal surface of the lased vessels was more thrombogenic than that of the nonlased control vessels. However, occlusion of the lased vessels did not occur. Repair of laser-treated tissue progressed until a mature, nonthrombogenic fibrin-platelet aggregate was adherent to the luminal wall. Overall, the lased vessels behaved in a fashion similar to the nonlased control vessels. On the basis of these results, the authors believe that the THC:YAG laser may have use in human angioplasty. ",21 2872,"Leakage of fluid administered epidurally to rats into subcutaneous tissue Epidural catheters were implanted in rats under halothane/nitrous oxide anaesthesia. Contrast medium (Iopamidol) was injected via the catheter under fluoroscopic control 24-48 h after implantation. In 15 of 20 rats contrast could be seen leaking out of the epidural space, usually after only 25 microliters was administered. Leakage was associated with diminished antinociceptive response to morphine administered via the catheter. Both leakage and decreased response to morphine could be largely prevented by applying a drop of Supa-Glue over the site of entry of the catheter to the epidural space at the time of catheter implantation. Investigators using epidurally cannulated rats should document that leakage does not occur or discard results from rats showing evidence of leakage. ",20 102,"Chancroid: results from an outbreak in Houston, Texas. A recent (and continuing) epidemic of chancroid in Houston has included morphologic variation in the disease, including so-called dwarf, classic, giant, transient, follicular, phagedenic, and pseudogranuloma inguinale types. Most cases were clearly acquired by unprotected sexual encounters with local prostitutes. The strain of Haemophilus ducreyi responsible for this outbreak was relatively easily cultured on routine media; unexpected sensitivity of this strain to vancomycin rendered the recommended ""selective"" growth medium much less optimal for isolation. Therapeutic success uniformly followed the use of intramuscular ceftriaxone sodium; one case responded to oral ciprofloxacin hydrochloride. ",0 1103,"Fatal or severely disabling cerebral infarction during hospitalization for stroke or transient ischemic attack. Six (1%) of 578 patients admitted for cerebral infarction or transient ischemic attack (TIA) suffered a fatal or severely disabling in-hospital cerebral infarction following a period of stabilization or improvement lasting more than 1 day. These infarctions were characterized by the sudden onset of stupor or coma and subsequent development of transtentorial herniation due to carotid or middle cerebral artery territory infarction, or widespread brain-stem infarction due to basilar occlusion. Only one patient survived. Four patients had large-vessel disease documented by Doppler, angiography, or at autopsy. Each of these six infarcts occurred during the morning hours, 4-9 days after the initial event, 3-8 days after initiation of intravenous heparin, and within 4-8 h after intravenous heparin had been discontinued. No coagulation abnormalities were documented. We believe that these cases indicate that among patients admitted for cerebral infarction or TIA, fatal or severely disabling in-hospital cerebral infarction after a period of stabilization or improvement may occur in patients having an initially mild to moderate clinical deficit, that those suffering large artery disease may be at greater risk, and that there may be a relationship between heparin withdrawal and cerebral infarction in some patients. ",9 2610,"Multiple alterations in insulin responses to glucose in islets from 48-h glucose-infused nondiabetic rats. To examine the biochemical mechanisms by which hyperglycemia produces insulin secretory abnormalities, we studied isolated islets from control rats and rats infused for 48 h with a 50% glucose solution. To preserve the effects of in vivo hyperglycemia during in vitro handling for islet isolation, our standard isolation procedure utilized buffers containing 16.8 mM glucose. Islets from infused rats released similar amounts of insulin in low or high glucose during first incubations at 37 degrees C (92.4 +/- 7.0 ng.10 islets-1.45 min-1 at 2.8 mM, 84.4 +/- 4.1 ng.10 islets-1.45 min-1 at 16.8 mM) in contrast with control (uninfused) islets (18.6 +/- 2.8 ng.10 islets-1.45 min-1 at 2.8 mM and 109.8 +/- 8.0 ng.10 islets-1.45 min-1 at 16.8 mM glucose) (P less than 0.01). Secretion by islets of glucose-infused rats was lower during 60-min second incubations at 28 mM glucose than in first incubations of the same islets in low glucose (P less than 0.01). This phenomenon is comparable to the paradoxical hypersecretion observed during the first 10-15 min of exposure of glucose-infused pancreas to low-glucose perfusions. Paradoxical secretion in low glucose waned rapidly, so that during second incubations at 37 degrees C, little immunoreactive insulin release occurred at 2.8 mM glucose, despite the persistence of two additional lesions. The glucose-insulin dose-response curves in second incubations showed a leftward shift for glucose-infused islets, with two- to threefold higher secretion at 5.6-8.4 mM glucose than control islets. This is termed sensitization to glucose. ",19 2161,"Histiocytosis X. S-100 protein, peanut agglutinin, and transmission electron microscopy study. Twenty-seven cases of histiocytosis X (HX) for which paraffin blocks were available were studied with the use of S-100 protein immunohistochemistry, peanut agglutinin affinity histochemistry, and transmission electron microscopy. The results show that these techniques did enable identification of Langerhans'-type histiocytes in 88.5%, 75%, and 47.4% of cases, respectively. All techniques were proved to be of some diagnostic value for HX, but none was able to confirm the diagnosis in all instances and none could foretell the prognosis of the patients. This study shows that besides the Langerhans' cells, the indeterminate cells of the skin and the interdigitating dendritic reticulum cells of the lymph node may also be involved in this process. Moreover, some multinucleate giant cells and foamy cells may be derived from Langerhans' and related cells. ",14 592,"Pediatric spondyloarthropathies. Seronegative spondyloarthropathies in childhood are often misdiagnosed as juvenile rheumatoid arthritis, but recognition of their distinct clinical manifestations and unique underlying pathophysiologies can aid in making a proper diagnosis. Ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease are arthritides most often found in young adults, but they may also be present in children. Extraarticular manifestations include inflammation of the eyes, skin, gastrointestinal tract, and genitourinary tract associated with inflammation of the entheses. The proper diagnosis will allow for treatment regimens that differ from those usually used for juvenile rheumatoid arthritis. Early diagnosis and treatment often lead to an early recovery and a return to normal daily activities. ",4