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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.
1
Femoral artery cannulation for monitoring in critically ill children: prospective study. Seventy-seven attempted percutaneous femoral artery cannulations were prospectively evaluated in 74 children. Artery cannulation was successfully accomplished in 73 (95%) cases and lasted for a mean of 6 days. Sixty percent of the catheters were inserted on the first attempt. Fifty-two (71%) patients weighed less than 10 kg and 55 (75%) patients were less than 12 months old. Fifty-one (70%) patients received inotropic support at the time of cannulation, and 27 (37%) eventually died from causes unrelated to catheter insertion. There was one episode each of line-associated infection and transient distal ischemia not resulting in tissue loss, and two episodes of catheter malfunction. In eight (11%) patients, signs of distal vascular insufficiency developed shortly catheter placement and resolved after catheter removal. The development of this complication correlated significantly (p less than .05) with younger age (5.5 vs. 22.3 months). We conclude that femoral artery cannulation has a high degree of success in very small, critically ill children. It should be considered an acceptable alternative to small-vessel cannulation when the latter is not technically achievable, or in the unstable patient where rapid establishment of reliable arterial access is necessary.
3
Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic. A filovirus, serologically related to Ebola virus, was detected by "post-embedment" immunoelectron microscopical examination of MA-104 cells. These had been infected by inoculation with serum samples obtained during the 1989 epizootic in cynomolgus monkeys (Macaca fascicularis), imported from the Philippines and maintained at Reston, Virginia, USA, a primate holding facility. The immunoelectron microscopy method, when used in conjunction with standard transmission electron microscopy (TEM) of infected cells, provided consistent results and was simple to perform in this epizootic. It is concluded that immunoelectron microscopy is potentially useful in the direct immunological diagnosis of Ebola and related filoviral infections (such as Marburg) in clinical samples obtained from those with acute infection.
4
A preliminary study of dye-enhanced laser photosclerosis. Laser ablation of veins after injection of wavelength-specific dyes to enhance and localize energy absorption could provide a useful adjunct to current treatment options. To enhance the absorption of diode laser energy at 808 nm, ear veins of 41 rabbits were infused with 2 to 3 ml of indocyanine green dye (maximum absorption, 805 nm) and exposed for 2 to 20 seconds. Animals were killed between 0 and 28 days after operation. Discrete time intervals of laser exposure exist during which various-sized vessels can be ablated without significant thermal injury to the overlying tissue. Small vessels (0.2 mm in diameter) blanch after 2 to 3 seconds of exposure, whereas medium-sized vessels (2 mm in diameter) require 8 to 10 seconds. Vessels can be ablated with a power density as low as 11.1 W/cm2. Specimens taken immediately after laser exposure show vessel wall thinning and a reirradiation effect, created as laser energy initially absorbed by dye is reemitted. By the seventh day after operation, a brisk inflammatory response and acanthosis of the overlying epidermal layer develop. The lumen is partially filled by thrombus with cellular invasion. By postoperative day 28, the epidermal thickening and inflammatory reaction have resolved; the vessel walls are fibrotic. The use of low-power, air-cooled diode lasers, in conjunction with wavelength-specific dyes, may provide a simple, viable, and cosmetically appealing alternative to the treatment of superficial varicosities of the extremities.
4
Pathologic features of sharp curettings in complete hydatidiform mole. Predictors of persistent gestational trophoblastic disease. The medical records and pathologic specimens were reviewed from 33 patients with complete molar pregnancy at Brigham and Women's Hospital between 1980 and 1989. Two pathologists (D.R.G. and R.W.R.) reviewed all slides from the original sharp curettage to identify pathologic features that may be associated with persistent gestational trophoblastic tumor (GTT). The pathologic features evaluated were implantation site, presence of myometrium, presence of villi, presence and degree of atypia in cytotrophoblast, syncytiotrophoblast and intermediate trophoblast, presence of fibrinoid, presence of implantation site inflammatory cells, volume of tissue and area of trophoblastic tissue. Only one pathologic feature, fibrinoid deposits, identified in sharp curettings was associated with the development of persistent GTT. While 12 (48%) of 25 patients who attained remission without chemotherapy had fibrinoid deposits, only 1 (12.5%) of 8 patients who developed persistent GTT had them (P less than .10).
0
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.
0
The association of hydrocephalus with intramedullary spinal cord tumors: a series of 25 patients. 171 patients with intramedullary spinal cord tumors were operated on, of which 25 patients (15%), mostly children, developed symptomatic hydrocephalus. Twenty patients (12%) had malignant tumors, with 13 of the 20 cases (63%) complicated by increased intracranial pressure and ventriculomegaly. Of the remaining 151 patients with benign tumors (89%), only 12 (8%) developed symptomatic hydrocephalus. In an effort to understand the relationship between hydrocephalus and intramedullary spinal cord tumor, the authors analyze the level and histology of the neoplasm, as well as its association with spinal cysts. A review of the neurosurgical literature reveals that 34 similar cases of hydrocephalus associated with intramedullary spinal cord tumors have been reported to date. The authors note that the presence of hydrocephalus in patients with malignant intramedullary astrocytomas is associated with a shorter rate of survival than in those patients with high-grade lesions but without hydrocephalus, apparently due to rapid tumor progression. The ventriculomegaly seen with benign spinal cord gliomas has no statistically significant effect upon long-term prognosis.
2
Phenytoin administration by constant intravenous infusion: selective rates of administration. STUDY OBJECTIVES: To determine the adequacy of seizure control and the adverse effects of administering an IV loading dose of phenytoin by constant infusion pump. DESIGN: A prospective study of patients presenting with acute onset of seizures. Patients were divided into two groups. Group 1 comprised all patients 50 years of age or younger without a history of atherosclerotic cardiovascular disease (ASCVD). Group 2 comprised all patients older than 50 years or with a history of ASCVD. SETTING: A rural community hospital emergency department. TYPE OF PARTICIPANTS: Forty-two adult patients. INTERVENTIONS: Both groups received an IV loading dose of phenytoin at 15 mg/kg. Infusion rates were 50 mg/min and 25 mg/min for groups 1 and 2, respectively. Cardiac rhythm and vital signs were monitored throughout and after infusion. MEASURES AND MAIN RESULTS: Group 2 demonstrated significantly more cardiovascular side effects (hypotension and bradycardia) than did group 1 (Fisher's exact test, P less than .05). CONCLUSION: Phenytoin provided adequate seizure control in both groups. For individuals with ASCVD, IV phenytoin administration rates should not exceed 25 mg/min. For individuals without ASCVD, phenytoin administration at 50 mg/min appears safe and without significant cardiovascular side effects.
2
Appendectomy in primary and secondary staging operations for ovarian malignancy. Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.
0
Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation. Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor.
0
Nebulized albuterol in acute bronchiolitis. In a double-blind, placebo-controlled trial, 40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg/dose) or placebo (saline solution) for two administrations 1 hour apart. The albuterol therapy resulted in a significantly greater improvement in the accessory muscle score (decreases 0.70 vs decreases 0.30; p = 0.03), oxygen saturation (increases 0.71% vs decreases 0.47%; p = 0.01) after one dose, and in the accessory muscle score (decreases 0.86 vs decreases 0.37; p = 0.02), respiratory rate (decreases 19.6% vs decreases 8.0%; p = 0.016), and oxygen saturation (increases 0.76% vs decreases 0.79%; p = 0.015) after two doses of the drug. The response to therapy was similar in infants younger and those older than 6 months of age. The heart rate rose slightly more in the albuterol group (increases 7.76 from baseline) versus the placebo group (decreases 6.79). There were no other side effects of the treatment. Of the 34 children from whom nasal specimens were obtained by swab for viral identification, 24 had positive test results (21 for respiratory syncytial virus, 1 for parainfluenza, 1 for paramyxovirus, and 1 for influenza A). We conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis.
4
Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity. Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3-diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air.
4
Intrapartum uterine rupture and inflammatory bowel disease. The incidence of uterine rupture in pregnant women ranges from 0% to 1.1% in large series. This case report describes a woman with a history of obstetric complications, uterine rupture, and active inflammatory bowel disease that was treated with high-dose prednisone.
1
The Greenfield filter as the primary means of therapy in venous thromboembolic disease. During a five year period at Akron City Hospital, 165 Greenfield filters were placed in 165 patients. Of this group, 78 patients were available for long term analysis, and of these, 42 did not receive anticoagulation treatment for venous thromboembolic diseases, either acutely or on an outpatient basis. An analysis of the outcome for these 42 patients who had the Greenfield filter only as the primary mode of therapy for the disease included chart review and asking each person a standard set of questions. Leg swelling was the most common complaint, occurring in 33 per cent of patients. Venous stasis ulceration occurred in two patients and recurrent deep venous thrombosis occurred in one patient. When compared with a historical control group with venous thromboembolic disease that was treated with anticoagulation alone, the incidence of these sequelae in Greenfield-treated patients was not significantly different. Finally, in this review, the Greenfield filter is better than 95 per cent effective in the prevention of pulmonary embolism. This is no less effective than anticoagulation alone, the efficacy of which is 95 to 98 per cent. The placement of a Greenfield filter is a safe procedure that can usually be done after a local anesthetic was administered to the patient with a complication rate of less than 10 per cent. Unfortunately, major complications of anticoagulation (usually hemorrhage) are relatively common at a rate of 2 to 15 per cent, and occur more frequently in the older population. It is for reasons of safety of therapy and of an equal or better efficacy that the Greenfield filter is recommended in a broader range of clinical circumstances. In particular, it is concluded that the Greenfield filter should be used as a primary means of therapy in venous thromboembolic disease, particularly in those patients who are more than 65 years of age, when the risks of anticoagulation are most threatening.
3
Infectious diarrhea. Managing a misery that is still worldwide. Infectious diarrhea is the largest single cause of morbidity and mortality in the world. Bacteria, viruses, and protozoan parasites are the most common causative agents. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Antimicrobial therapy is reserved for very ill patients only. With the exception of Cryptosporidium, for which no effective agent is yet available, all protozoan infections are treatable with metronidazole.
1
Combined epidural and general anesthesia in aortic surgery. The perioperative course of 144 consecutive patients undergoing aortic reconstructive surgery was studied to assess the potential benefit of employing a combined epidural and light general anesthesia technique. A group of 67 patients had general anesthesia alone (GA), while in the group of 77 remaining patients, a combined epidural and general anesthesia (Epi-GA) was employed. The two groups were similar in regards to age, medical risk factors, preoperative assessment of cardiac and pulmonary function, and type of surgical reconstruction. There was no significant difference in the anesthetic, operative time, or operative fluid requirements between the two groups. There was a lower rate pressure product in the Epi-GA group during aortic cross clamping (P less than 0.05). More patients in the GA group required a prolonged ventilatory support (P less than 0.05) and a high parenteral narcotic administration (P less than 0.025) during the first 48 hours. While the mortality rate was similar for the two groups (3.0% for GA group vs 5.2% for Epi-GA group), there was a higher percent of postoperative pulmonary complications observed in the GA group (7.6%) compared to the Epi-GA group (2.6%). By facilitating early extubation and a decreased need for systemic narcotics in the early postoperative period, Epi-GA may be beneficial in the high risk pulmonary patient undergoing aortic reconstruction.
2
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.
2
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.
4
The automatic implantable cardioverter-defibrillator in young patients. An international survey identified 40 patients less than 20 years old who underwent surgical implantation of an automatic implantable cardioverter-defibrillator (AICD). There was a history of aborted sudden cardiac death or sustained ventricular tachycardia in 92.5% of these patients. Twenty-two patients (55%) had structural heart disease; dilated and hypertrophic cardiomyopathy were the most common diagnoses. Eighteen patients (45%) had primary electrical abnormalities including seven with the congenital long QT syndrome. There were no perioperative deaths associated with device implantation. Concomitant drug therapy was administered to 75% of the patients. Defibrillator discharge occurred in 70% of the patients, with 17 patients (42.5%) receiving at least one appropriate shock. There were two sudden and two nonsudden deaths at 28.2 months' median follow-up. Sudden death-free survival rates by life table analysis at 12 and 33 months were 0.94 and 0.88, respectively. Total survival rates at 12 and 33 months were 0.94 and 0.82, respectively. The AICD represents an effective treatment approach for young patients with life-threatening ventricular tachyarrhythmias.
4
Chronic neutropenia during childhood. A 13-year experience in a single institution. To evaluate the clinical course and characteristics of children with chronic neutropenia, we reviewed the charts of all such patients seen at our center during a 13-year period. A total of 50 patients with chronic neutropenia were identified. Three patients had documented congenital neutropenia, and two siblings had cyclic neutropenia. The remaining 45 children had chronic neutropenia of unknown origin. All children except two had a remarkably benign course despite markedly reduced granulocyte counts. Of six girls in this group who had abscess or cellulitis of the labia majora, it was a presenting manifestation in three. Resolution of neutropenia was documented in 23 (62%) of 37 patients for whom follow-up information was available, with a median duration of neutropenia of 19 months. No differences were evident between patients with positive antineutrophil antibody test results and those in whom the test yielded negative results or was not performed. Chronic neutropenia in childhood is a relatively uncommon entity, characterized by a benign course and eventual resolution in the majority of patients.
4
Extended hepatectomy for hepatocellular carcinoma. The results of extended hepatectomy in 25 patients with hepatocellular carcinoma performed over a 16 year period have been reviewed, analysed and compared with those of 144 patients who underwent lesser liver resection. Five left and 20 right extended hepatectomies were performed for tumours ranging from 3 to 20 cm in diameter. Seventeen (68 per cent) of the patients had non-cirrhotic livers. The major postoperative complications were: haemorrhage in five cases, major bile duct injury in three, subphrenic abscess in two, liver failure in one and wound dehiscence in one. The 30-day (operative) mortality rate was 12 per cent and the median survival duration, including operative mortality, was 9.7 (range 0.2-32.1) months. The survival rate was 46 per cent at 1 year, 33 per cent at 2 years and 22 per cent at 3 years. The morbidity, mortality and survival data of extended hepatectomy were comparable with the results of lesser hepatic resections for hepatocellular carcinoma. We conclude that extended hepatectomy is a worthwhile operation for large hepatocellular carcinomas and a viable alternative to liver transplantation.
0
Anterior femoral cutaneous nerve injury following femoral artery reconstructive surgery. Two cases are presented exhibiting symptoms and signs of bilateral anterior femoral cutaneous nerve injury, clinically sparing femoral nerve branches to the saphenous nerve and quadriceps muscles. This occurred following surgical dissection in the femoral triangles associated with femoral artery reconstructive surgery. Anterior femoral cutaneous nerve injury should be considered when anterior medial thigh pain and numbness occur following aortofemoral bypass graft surgery and other types of femoral artery reconstructive surgery.
4
In vivo leukocyte migration in arthritis. We quantitated in vivo migration of neutrophils into the knees of patients with rheumatoid arthritis (RA) and osteoarthritis, using 99mtechnetium-hexamethyl-propylene-amineoxime-labeled leukocytes and gamma scintigraphy. Significant neutrophil migration occurred in patients with RA irrespective of disease duration, and it was reduced by 60% following intraarticular steroid injection. The reduction in neutrophil migration correlated with reduction in pain. Leukocyte migration into osteoarthritic joints was also demonstrated, although it was much less than that seen in rheumatoid joints. No significant leukocyte migration into the joints of patients without arthritis was demonstrated. This technique appears to provide a sensitive method for quantitatively assessing the neutrophil component of inflammation in individual joints of patients with arthritis.
2
Symptoms of achalasia in young women mistaken as indicating primary anorexia nervosa. The case of a young women with dysphagia, regurgitation, and weight loss, who was diagnosed as having anorexia nervosa but in whom reevaluation showed that achalasia was causing the symptoms, is presented together with related observations. Misinterpretation of esophageal symptoms may occur not only as a consequence of inadequate history taking and of being biased by a patient's emaciation, age, and gender, which leads to view certain aspects of the patient's history and behavior as suggesting a pathologic attitude towards eating and body weight, but also as a consequence of a misinterpretation of the symptoms as indicative of an eating disorder by the patients themselves. In some cases a disordered attitude toward eating and body weight may develop together or coexist with achalasia. The clinical evaluation of patients with symptoms suggestive of anorexia nervosa but also of bulimia nervosa should include the taking of a thorough history regarding swallowing and vomiting in order to recognize a possible esophageal motor disorder.
1
Calcium ionophore, A23187, induces commitment to differentiation but inhibits the subsequent expression of erythroid genes in murine erythroleukemia cells. Murine erythroleukemia (MEL) cells are a useful model for studying the processes that regulate erythroid differentiation because exposure of these cells to a variety of chemical inducing agents results in expression of erythroid-specific genes and the resultant loss of cellular immortality. Previously it has been suggested that the calcium ionophore, A23187, has effects on the early cellular events that lead to the commitment of these cells to differentiation, but was not in itself sufficient to induce differentiation. We demonstrate here that A23187, as well as another calcium ionophore, ionomycin, are capable of inducing commitment to differentiation. Unlike other inducing agents, continual exposure to A23187 inhibits transcription of the erythroid-specific genes, beta-globin and Band 3. This effect is not attributable to an increase in cytosolic calcium concentration, because cells induced by ionomycin produce normal amounts of hemoglobin. These effects of A23187 on MEL cells confirm that commitment to differentiation is a distinct event from the subsequent transcriptional activation of erythroid genes. The ability of both ionophores to induce commitment to differentiation suggests that an increase in cytosolic calcium can trigger commitment to differentiation. These agents should prove useful in investigating the cellular processes that are responsible for commitment to differentiation.
0
Effects of exercise on myocardial catecholamine content and ischemic injury in dogs with gradual coronary occlusion. The effects of exercise on catecholamine content and the extent of myocardial damage in dogs with Ameroid constrictor occlusion of the left circumflex coronary artery were determined. Tissue samples from both the anterior and posterior walls of the left ventricle were obtained for determination of catecholamine content, and the rest of the ventricles were processed for histologic examination. When subjected to treadmill exercise for 40 days after surgery, obstructed animals performed significantly less exercise than sham-operated animals and showed significantly higher percentages of ischemia and necrosis in the left ventricle than sedentary, obstructed, sham-operated, or control dogs. Levels of norepinephrine and epinephrine in the posterior wall of the left ventricle were significantly lower than in the other groups. Our data show that exercise in this well-known model of chronic coronary artery stenosis produced deleterious effects on the myocardium and suggest a marked heterogeneity of catecholamine stores in the myocardium that may have important functional and electrophysiologic consequences.
4
Bleeding ectatic vascular lesion involving the sigmoid colon, endoscopically indistinguishable from angiodysplasia, in an 8-yr-old boy. An 8-yr-old Japanese boy was hospitalized, complaining of active hematochezia. He was shown to have a cherry-red, blood-oozing area of vascular dilation with mucosal prominence in the sigmoid colon by endoscopy, but had no other mucocutaneous vascular abnormalities. A family history was noncontributory. Under the clinical diagnosis of angiodysplasia of the sigmoid colon, he underwent an elliptical resection of the part, based on the intraoperative endoscopic findings. However, histological examination of the surgical specimen revealed a totally different picture from that seen in angiodysplasia: the thin-walled, markedly ectatic, nontortuous veins with hemorrhage were seen only just below the muscularis mucosae, around which the normal ones were shown to coexist. He has had no rebleeding for the past 3 yr. This lesion is considered to be an isolated congenital visceral telangiectasia involving veins.
1
Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.
0
Parkinsonian tremor loses its alternating aspect during non-REM sleep and is inhibited by REM sleep. Non-REM sleep transforms the waking alternating Parkinsonian tremor into subclinical repetitive muscle contractions whose amplitude and duration decrease as non-REM sleep progresses from stages I to IV. During REM sleep Parkinsonian tremor disappears while the isolated muscle events increase significantly.
2
Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial. In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.
4
Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.
3
AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea OBJECTIVE: To investigate occult enteric infections and morphologic changes in the small intestine in patients with advanced human immunodeficiency virus (HIV) infection and chronic diarrhea of undefined cause. DESIGN: Case-control study. SETTING: Referral-based clinic and hospital in tertiary care center. PATIENTS: Twenty-two patients with advanced HIV infection (19 with the acquired immunodeficiency syndrome [AIDS], 3 with AIDS-related complex) with chronic diarrhea, selected because of previously negative stool evaluations for bacterial or parasitic pathogens, were compared with 13 patients with advanced HIV infection (9 with AIDS, 4 with AIDS-related complex) without diarrhea by analysis of endoscopic biopsies using light and electron microscopy, viral culture, and morphometric studies. Both groups were convenience samples and had at least 7 months follow-up. MEASUREMENTS AND MAIN RESULTS: Eleven of twenty-two patients with HIV infection and chronic diarrhea but only 1 of 13 patients without diarrhea showed occult enteric pathogens (that is, undetected by routine studies) after extensive evaluation of duodenal and colorectal biopsies. Mycobacterium avium-intracellulare and microsporidia were the most common occult agents in study patients with diarrhea (5 each). Patients with diarrhea and occult enteric infections had greater weight loss (mean, 14.3 kg compared with 6.2 kg; P less than 0.05) and shorter survival (1 of 11 compared with 8 of 11 still alive; P less than 0.004) than those with diarrhea but no identified pathogens (defined as "AIDS enteropathy"). Duodenal morphometry showed decreased villus-to-crypt ratios because of villus atrophy and crypt elongation in HIV-infected patients both with and without diarrhea compared with normal controls (P less than 0.001 for each). All three groups showed comparable frequencies of epithelial mitoses. CONCLUSIONS: Further endoscopic biopsy evaluation of patients with AIDS who had unexplained chronic diarrhea showed an occult infectious cause in half of the cases. However, altered villus and crypt architecture in advanced HIV infection was independent of the presence of diarrhea or enteric infection and therefore did not correlate with AIDS enteropathy. Subnormal epithelial proliferation in response to injury could be a factor, but the underlying cause of the architectural changes remains obscure. We suggest that T-cell dysfunction may play a role.
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Maternal and fetal complications in pregnant women with systemic lupus erythematosus. Recent studies provide important insights into maternal complications in patients with systemic lupus erythematosus (SLE) established before onset of pregnancy. Exacerbations or relapse occur during the course of pregnancy and immediately postpartum in 25% to 60% of pregnancies. However, the likelihood of increased clinical activity of SLE during pregnancy is influenced by signs of activity present at onset of pregnancy. In the absence of signs of clinical activity for at least 6 months before conception, relapses occur in about one third, whereas in patients with clinical activity at onset of pregnancy, persistent activity or exacerbations occur in approximately two thirds. Fetal survival in these patients parallels the incidence of SLE activity: 85% to 95% in the group with inactive disease at conception and 50% to 80% in subjects with active disease at onset of pregnancy. The introduction of an assay for anticardiolipids has led to a new concept for the pathogenesis of autoimmune disease, namely immune-related thrombosis. Recent studies suggest that this mechanism may play an important role in clinical episodes in SLE, involving late fetal death and maternal arterial and venous thrombosis.
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Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula Serous detachment of the macula is a well-known complication in patients with an optic nerve pit. Despite the many descriptions of this condition and possible treatment options, the long-term natural history is not well known. The authors identified 15 eyes of 15 consecutive patients seen over 21 years who were diagnosed with a serous detachment of the macula arising from an optic nerve pit. Average length of follow-up was 9 years. Twelve eyes lost three or more lines of vision, two eyes remained unchanged, and only one eye improved. All of the 12 eyes losing three or more lines of vision experienced this decrease within the first 6 months of follow-up. Although only two patients had a visual acuity of 20/200 or less initially, 12 of 15 patients had a visual acuity of 20/200 or less at the time of their last examination. The appearance of the macula at last examination included cystic changes of the neurosensory retina, full-thickness hole formation, retinal pigment epithelial mottling, and lamellar hole formation in the outer retinal layer. The long-term visual prognosis in patients with optic nerve pit and untreated serous retinal detachment of the macula is poor, and visual loss occurs within 6 months of the serous detachment.
2
1990 Volvo Award in clinical sciences. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation, and physical loading. The occurrence of symmetric disc degeneration, anular ruptures, end-plate defects, vertebral body osteophytosis, and facet joint osteoarthrosis was examined radiographically and osteologically in 86 male cadavers for whom occupational, physical loading, and back pain histories were obtained from the men's families. History of back pain and the parameters of spinal pathology were related to the highest and lowest degrees of physical loading. In multivariate analyses, history of back injury was related to the occurrence of symmetric disc degeneration, anular ruptures, and vertebral osteophytosis. Symmetric disc degeneration was associated with sedentary work, and vertebral osteophytosis was related to heavy work. History of back pain was related to occupational physical loading after control for the effects of the other covariates. The results indicate that the least pathology stemmed from moderate or mixed physical loading, but the least back pain was associated with sedentary work.
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The acute and insidious onset of pulmonary metastatic transitional cell carcinoma. Transitional cell carcinoma is a common urologic neoplasm. Although pulmonary metastases from this tumor are often not appreciated clinically, they are frequently documented in autopsy studies. Therefore, the clinical recognition of this condition can be problematic. To illustrate this point, we present three patients with progressive unexplained dyspnea and histories of transitional cell carcinoma. Since ineffective and possibly detrimental therapeutic approaches may be initiated, a high index of suspicion for pulmonary metastatic embolization must be maintained. Early histologic identification of these metastatic emboli and initiation of effective chemotherapy may prove beneficial for improved quality of life.
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Anoxic injury of mammalian central white matter: decreased susceptibility in myelin-deficient optic nerve. The rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia-induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin-deficient (md) strain of rat. Acutely isolated optic nerves from 19- to 21-day-old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37 degrees C, and exposed to a standard 60-minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action potential, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 +/- 25%) than did control optic nerves (33 +/- 21%; p less than 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter.
4
Human papillomavirus in oesophageal squamous cell carcinoma. Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma.
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Biliary calcium and gallstone formation. The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones.
1
Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells. The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta-positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients.
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Gene mapping and other tools for discovery. Genetic mapping provides a means of understanding the molecular basis of inherited diseases whose biochemistry is unknown. Adequate pedigrees, informative genetic markers, and accurate identification of the disease phenotype are necessary. For dominant inheritance, mapping studies can be done in a single large pedigree; the larger the number of affected individuals sampled the better the estimate of recombination between the gene causing the disease and one or more nearby genetic markers. For recessive inheritance, nuclear families with more than one affected sibling provide the best information. The development of many polymorphic DNA markers on the human genome has contributed to the success of mapping unknown genes because, as the genome is now densely covered with markers, the probability is good that at least one marker will be linked to the disease locus in a family that is segregating a disease allele. Most genetic markers now in use depend upon restriction fragment length polymorphisms (RFLPs), which are either the result of single-base-pair substitution or the presence of a variable number of tandemly repeated oligonucleotide units at a locus (VNTRs). RFLPs can be recognized by digesting DNA with restriction enzymes and separating the fragments by size on an electrophoretic gel. VNTRs can vary widely among individuals, and they provide more linkage information than single-site polymorphic markers because family members are more likely to be heterozygous. Genetic maps of each chromosome, constructed from linkage data relating marker loci to one another in normal reference families, permit rational choices of markers for disease-mapping studies.
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The Los Angeles experience with laparoscopic cholecystectomy. Surgeons should be competent in diagnostic laparoscopy before performing laparoscopic cholecystectomy (LC). Well-structured and endorsed courses with experienced faculty are important. Within 12 months, 418 LCs were performed in our hospital. The number of open cholecystectomies decreased to one third of all cholecystectomies performed. Cholangiography was attempted routinely and the duct was successfully cannulated in 90%. Inquiries were made at 6 other hospitals within a 5-mile radius where a total of 220 LCs were performed. The following gray areas need to be addressed: patients with slightly increased liver function tests but no jaundice, and unsuspected stones discovered by cholangiography. New projects are in progress to explore the common bile duct via the cystic duct or directly through the common bile duct with insertion of a T tube. The authors recommend proper training as well as caution and sound judgment before commencing with LC.
1
Acute autonomic neuropathy. Two cases and a clinical review. Acute autonomic neuropathy is an uncommon syndrome, usually affecting healthy young people. Presentation is often dramatic and initial misdiagnosis is common. We describe two young women with acute autonomic neuropathy who presented with gastrointestinal involvement heralding widespread dysautonomia and review 26 additional cases of acute autonomic neuropathy from the English language literature. Acute autonomic neuropathy can be primarily cholinergic without orthostatic hypotension (26%) or pandysautonomic (74%) involving sympathetic adrenergic functions. Onset has been temporally related to viral syndromes in 20% of cases, with autonomic deficits usually evolving over 1 to 3 weeks. Gastroparesis (69%) and syncope (12%) are frequent presenting complaints. Spinal fluid protein levels are often (75%) elevated in pandysautonomic subtypes. Prolonged and incomplete recovery is the rule (60%), with persistent gastroparesis and orthostatic hypotension. Other specific diseases that occasionally mimic acute autonomic neuropathy include botulism, porphyria, amyloidosis, and paracarcinomatous neuropathies. Acute autonomic neuropathy shares several clinical features with acute idiopathic polyneuropathy (Guillain-Barre syndrome), suggesting an immune-mediated pathogenesis.
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Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography. Regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography (CT) in 12 noncirrhotic and five cirrhotic patients. Liver volumes were measured by abdominal CT 3 days, 10 days, 3 months, 6 months, 1 year, and 1.5 years after resection. Of the 17 patients, liver remnant volume was increased in 21.2% +/- 6.7% and 30.6% +/- 12.7% at 3 months and 6 months after resection, respectively. Noncirrhotic livers were 28.4% +/- 9.5% and 48.4% +/- 17.8% larger at 3 and 6 months. For cirrhotic livers, the increase was 8.5% +/- 3.6% and 12.9% +/- 4.5%. In five patients with right hepatectomy (65% resection), the liver remnant volumes were increased 38.4% +/- 11.7%, 48.0% +/- 16.2% and 95.1% +/- 4.5% at 3 months, 6 months, and 1 year after resection, respectively. In seven patients with right partial hepatectomy (30% to 35% resection), the percentages were 7.4% +/- 3.2%, 21.8% +/- 8.4%, and 63.9% +/- 18.3% and in five patients with left lateral segmentectomy (15% resection), they were 15.6% +/- 8.2%, 27.8% +/- 12.2%, and 33.0% +/- 14.5% 3 months, 6 months, and 1 year after resections, respectively. Noncirrhotic livers showed better regeneration than cirrhotic livers. Complete regeneration took about 1 year. The noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume.
1
Retrospective application of prognostic indices to pancreatitis discovered at necropsy. Six prognostic indices, which were developed to assess inpatients with acute pancreatitis, were evaluated for possible retrospective application. When applied to a series of 14 cases in whom pancreatitis was first diagnosed at necropsy, the index devised by Jacobs et al was found to be the most useful, because in nine of these cases eight or more of the variables required were available for assessment from the case records. In the other indices evaluated fewer than eight of the required variables were available for retrospective assessment in most cases. Although undiagnosed pancreatitis is probably uncommon as a sole cause of death, the retrospective use of one or more of these indices may help assess the severity of the patient's condition on admission to hospital.
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Complete spontaneous regression of multiple basal cell carcinomas in the basal cell nevus syndrome: the possible role of transepithelial elimination. A 36-year-old Latin American man with the basal cell nevus syndrome had multiple, soft, hairless, depressed scars of the face, scalp, neck, and back, ranging in size from 0.3 x 0.5 cm to 3.5 x 3.9 cm. These areas had never been treated and previously were sites of basal cell carcinomas that underwent complete spontaneous regression 4-5 years from the date of onset. Pathology of these spontaneously regressed sites was consistent with the criteria established by Curson and Weedon (1979). Type III transepithelial elimination was demonstrated for a basal cell carcinoma. Type III transepithelial elimination may play a role in the spontaneous regression of basal cell carcinomas.
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MR imaging of blood-borne liver metastases in mice: contrast enhancement with Fe-EHPG. To determine whether iron(III)ethylenebis-(2-hydrophenylglycine) (Fe-EHPG), a prototype hepatobiliary magnetic resonance imaging agent, can enhance the liver-to-tumor contrast-to-noise ratio (C/N) in models of liver tumors in mice, two types of cell inoculation were used: intrahepatic implantation of M5076 sarcoma and intrasplenic injection of colon tumor (C-26) or M5076 sarcoma. Significant enhancement of the liver-to-tumor C/N and/or improved visualization of small lesions was consistently observed on T1-weighted images obtained after injection of the contrast material. For intrahepatic implants, the C/N on postinjection T1-weighted images was superior to that on T1- and T2-weighted preinjection images. For the C-26 metastatic liver lesions of larger diameter (greater than 5 mm), the C/N on postinjection T1-weighted studies was superior to that on preinjection T1-weighted images but was comparable to that on preinjection T2-weighted images. However, higher C/N after administration of Fe-EHPG improved visualization of medium-sized (3-5 mm) and small (1-3-mm) metastatic lesions in both M5076 and C-26 models. These results demonstrate that MR imaging with appropriate hepatobiliary agents appears promising for early detection of liver metastases.
0
Benign missense variations in the cystic fibrosis gene. The common mutation causing cystic fibrosis is a deletion of phenylalanine 508 (delta F508), which occurs in a putative nucleotide-binding fold of the gene product. We report two additional mutations, substitution of cysteine for phenylalanine 508 (F508C) and substitution of valine for isoleucine 506 (I506V). Three compound heterozygous persons, two delta F508/F508C and one delta F508/I506V, had normal clinical and epithelial physiological studies indicating that the F508C and I506V mutations are benign. This opportunity to study the in vivo function of these mutations suggests that amino acid substitutions are more benign than changes in the length of this portion of the putative nucleotide-binding fold. These mutations must be taken into account when performing molecular diagnosis and carrier detection for cystic fibrosis.
4
Myocarditis simulating acute transmural myocardial infarction. A patient with cardiogenic shock had typical electrocardiographic findings of acute anterior transmural myocardial infarction. Cardiac catheterization revealed normal coronary arteries and severe biventricular failure. Postmortem examination confirmed normal coronary arteries; acute myocarditis, but no evidence for infarction, was found. Electrocardiographic changes of myocarditis may be indistinguishable from acute transmural infarction. In suspected cases, cardiac catheterization should be considered prior to thrombolytic therapy.
3
Open depressed skull fracture missed on computed tomography: a case report. A case of an open depressed skull fracture that was missed on standard computed tomographic (CT) scan is presented. The fracture was seen on a CT generated lateral scout film, and after repositioning the gantry, further CT images clearly showed the fracture and underlying brain injury. The authors recommend that all patients with head trauma undergoing head CT have either a CT generated lateral scout film or a lateral skull radiograph to assess the vertex of the skull, an area poorly visualized on standard axial images.
2
Pancreatic transplantation: radiologic evaluation of vascular complications. Transplantation of the pancreas is an increasingly common therapeutic option for preventing or delaying complications of type I diabetes mellitus. The authors studied the relative roles of various radiologic examinations in diagnosing vascular complications in these grafts including arterial and venous thrombosis, stenosis, and anastomotic leak (the most common vascular factors that necessitate pancreatectomy of the transplant), as defined with pathologic or arteriographic data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies were evaluated in 52 patients who received a total of 27 cadaveric and 26 living-donor grafts over a 12-year period. These results were correlated with the data from 45 gross and microscopic pathologic studies and 37 arteriograms to determine their relative value in enabling detection of graft thrombosis and other vascular complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive in detection of generalized graft abnormalities but lacked specificity in defining the underlying etiologic factors.
3
Lateral temporal bone resections. Eighteen consecutive patients underwent a lateral temporal bone resection for the treatment of tumors originating in the auricle, the external auditory canal, the periauricular skin, or the parotid and were retrospectively analyzed. The different lateral temporal bone resections performed have been categorized into four types. The type I resection consists of the removal of the tympanic bone and the external auditory canal lateral to the tympanic membrane. The type II resection consists of the removal of the entire tympanic bone, the tympanic membrane, the incus, and the malleus, preserving the facial nerve and the inner ear. Type III resections remove, in addition to the those structures removed in type II resections, the distal facial nerve and fallopian canal, the mastoid tip, the styloid process, and the stylomastoid foramen. The type IV resection consists of the removal of only the mastoid tip and the inferior portion of the tympanic bone. When the techniques of lateral temporal bone resection are used appropriately, adequate surgical treatment of patients with selected advanced and recurrent malignant tumors of the external ear, the periauricular skin, and the parotid is possible with low morbidity and a high probability of local regional control.
4
Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials. Because the safety of withholding standard therapy and enrolling patients with stable angina in placebo-controlled trials is not known, we identified all events leading to dropout from trials of 12 antianginal drugs submitted in support of new drug applications to the US Food and Drug Administration. Persons who dropped out of the trials were classified as cause due to adverse cardiovascular events or other causes without knowledge of drug assignment. There were 3161 subjects who entered any randomized, double-blind phase of placebo-controlled protocols; 197 (6.2%) withdrew because of cardiovascular events. There was no difference in risk of adverse events between drug and placebo groups. A prospectively defined subgroup analysis showed that groups who received calcium antagonists were at an increased risk of dropout compared with placebo groups (P = .04), primarily because of a disproportionate number of adverse events in studies of one drug. In conclusion, there were few adverse experiences associated with short-term placebo use. Withholding active treatment does not increase the risk of serious cardiac events.
3
Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their distinction with the use of immunohistochemical methods. Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically. To develop criteria useful in resolving problem cases, the authors compared the reactivities of these conditions (nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme, antimacrophage M, and leukocyte common antigen (LCA). In granulomatous prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin; however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods.
0
Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature. Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature.
0
Concurrent intradural and extradural meningiomas of the cervical spine. A case of an extradural spinal meningioma presenting with a separate intradural meningioma at the same cord level is reported. Review of the English literature on spinal epidural meningiomas reveals a high incidence of concurrent intradural tumors in patients with epidural meningiomas. This leads to the conclusion that the intradural space should be evaluated carefully when an epidural meningioma is encountered.
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Ulnar nerve decompression with medial epicondylectomy for neuropathy at the elbow. Ulnar nerve decompression with medial epicondylectomy was performed in 66 elbows between 1966 and 1986 for compressive ulnar neuropathy at the elbow. This study is an updated review that adds 36 cases to a previously published report on 30 cases. These elbows were graded preoperatively and postoperatively using McGowan's grading system. Eighty-three percent improved one or two grades, and 11% improved subjectively although they showed no objective improvement, 3% noted no change, and 3% were subjectively worse. One early case sustained damage to the ulnar collateral ligament with resultant instability. No other complications occurred. The best results were seen in the Grade I and II lesions, whereas those with Grade III lesions were the least predictable. The procedure is technically uncomplicated with minimal morbidity and reliable results.
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Atenolol in essential hypertension during pregnancy OBJECTIVE--To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN--Prospective, randomised, double blind, placebo controlled study. SETTING--Hospital clinic. PATIENTS--33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES--Blood pressure and birth weight. INTERVENTION--14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS--The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION--Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.
3
Gastric antral vascular ectasia ("watermelon stomach"): radiologic findings. Radiologic findings in a patient with gastric antral vascular ectasia are described on computed tomographic scans, upper gastrointestinal series, and specimen radiographs. Findings include prominent, scalloped antral folds radiating to the pylorus and thickening of the gastric antrum. Pathognomonic red vascular folds, likened to stripes on a watermelon, can be seen endoscopically.
3
Transcranial electrical motor evoked potentials as a prognostic indicator for motor recovery in stroke patients. Transcranial electrical motor evoked potentials (MEP) were examined in 33 patients within three days after stroke. Normal values for MEP and motor central conduction time (CCT) were obtained in 46 healthy controls whose MEPs were evaluated during slight voluntary muscle contraction and at rest. Two months later 23 patients were re-examined clinically and electrophysiologically. Motor function change was correlated with MEP results. Two months after stroke the patients with normal or prolonged CCT had an improved motor function compared with those with absent CCT. MEP may be a valuable prognostic indicator in the acute stage of paralytic stroke for recovery of motor function.
4
Posterolateral rotatory instability of the elbow. Recurrent posterolateral rotatory instability of the elbow is an apparently undescribed clinical condition that is difficult to diagnose. We treated five patients, ranging in age from five to forty years, who had such a lesion and in whom the instability could be demonstrated only by what we call the posterolateral rotatory-instability test. This test involves supination of the forearm and application of a valgus moment and an axial compression force to the elbow while it is flexed from full extension. The elbow is reduced in full extension and must be subluxated as it is flexed in order to obtain a positive test result (a sudden reduction of the subluxation). Flexion of more than about 40 degrees produces a sudden palpable and visible reduction of the radiohumeral joint. The elbow does not subluxate without provocation. The cause for this condition, we think, is laxity of the ulnar part of the lateral collateral ligament, which allows a transient rotatory subluxation of the ulnohumeral joint and a secondary dislocation of the radiohumeral joint. The annular ligament remains intact, so the radio-ulnar joint does not dislocate. Operative repair of the lax ulnar part of the lateral collateral ligament eliminated the posterolateral rotatory instability, as revealed intraoperatively in our five patients.
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Infection with HIV as a risk factor for adverse obstetrical outcome. We carried out a case-control study to investigate the role of sexually transmitted diseases (STDs), including infection with HIV, as risk factors for adverse outcome of pregnancy. Overall, 1507 women were enrolled within 24 h of delivery. Cases (n = 796) were mothers of low-birthweight infants (less than 2500 g) or of stillborns. Low-birthweight infants were divided into preterms (n = 373) and neonates small for gestational age (n = 234). Stillborns were separated into intrauterine fetal deaths (n = 120), and intrapartum fetal deaths (n = 69). Controls were selected from mothers delivering a live baby of greater than or equal to 2500 g (n = 711). The maternal HIV seroprevalence in the control group was 3.1%. Prematurity was associated with maternal HIV antibody [8.6% seropositive; adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1-4.0], as was being born small for gestational age (7.7% seropositive; adjusted OR 2.3; 95% CI 1.2-4.2). In mothers who delivered a stillborn baby, both intrauterine fetal death (11.7% seropositive; adjusted OR 2.7; 95% CI 1.3-5.5) and intrapartum fetal death (11.6% seropositive; adjusted OR 2.9; 95% CI 1.3-6.5) were independently associated with HIV seropositivity in the mother. Maternal syphilis was confirmed as an important risk factor for intrauterine fetal death (14.3% positive; adjusted OR 4.8; 95% CI 2.4-9.5). No significant association was found between other STDs, including gonococcal and chlamydial infection, and adverse obstetrical outcome. These results suggest an association between maternal HIV infection and adverse obstetrical outcome, defined as low birthweight and stillbirth.
4
Cerebral air embolism treated by pressure and hyperbaric oxygen. We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI. This outcome contrasts with reports of infarct and disability among untreated victims of air embolism.
3
Recombinant human erythropoietin does not increase clotting in vascular accesses. The incidence of vascular access clotting was evaluated over 5.25 years. The first 32 months served as a control period. During the second period of 31 months, recombinant human erythropoietin (epoetin) was used for an average duration of 13 months (range, 2-32 months) in 79 patients. The overall incidence of vascular access clotting decreased from a monthly rate of 0.06 to 0.03 events per patient-month over the 5 year period. Distribution of the number of events per patient did not differ between the two periods, with 55% to 60% of patients having no clotting episode. Patients with recurrent clotting (two or more events) accounted for 68% of episodes. During the second period, there were no differences in the incidence of vascular access clotting in epoetin treated patients vs untreated patients (0.38 events per patient-year vs. 0.46 events per patient-year, both slightly lower than in period 1 [0.52 events per patient-year]). It is concluded that epoetin does not increase vascular access clotting.
3
Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides. Monoclonal (MAbs) and polyclonal antibodies were produced against the major capsid protein of detergent-disrupted, purified bovine papillomavirus type 1 (BPV-1). The precise locations of the corresponding epitopes were identified by the reactivity of MAbs and selected polyclonal antibodies with synthetic, overlapping, hexameric peptides corresponding with 95% of the BPV-1 major capsid protein. The topography of these epitopes was determined by reactivity of antibodies with intact (conformational and nonconformational surface epitopes) and disrupted (external or internal nonconformational epitopes) BPV-1 virions. The distribution of epitopes in various papillomaviruses of 13 different species was determined by reactivity of the MAbs and polyclonal sera with productively infected, formalin-fixed papillomas, fibropapillomas, and fibromas. Epitope scanning, using MAbs and polyclonal antisera, resulted in the precise location of BPV-1 hexameric epitopes that could be correlated with their topography on the capsid and distribution in papillomatous lesions of various species.
0
Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: a new marker of triple-vessel disease. To investigate the significance and mechanism of dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging, we performed both dipyridamole thallium-201 imaging and dipyridamole radionuclide angiography on 83 patients with known angiograms. The dipyridamole/delayed ratio of the left ventricular dimension from the thallium-201 image was defined as the left ventricular dilatation ratio (LVDR). An LVDR greater than the mean + two standard deviations in patients without coronary artery disease was defined as abnormal. Twenty-two of 83 patients showed an abnormal LVDR, and 18 of the 22 patients (82%) had triple-vessel disease. By defect and washout analysis, the sensitivity and specificity for correctly identifying the patients as having triple-vessel disease was 72% and 76%, respectively, whereas LVDR had a sensitivity of 72% and a specificity of 93%. When LVDR was used in combination with the defect and washout criteria, sensitivity increased to 84% without a loss of specificity. In those 22 patients with abnormal LVDRs, end-diastolic volume measured by radionuclide angiography did not change after dipyridamole infusion. Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging reflected relative subendocardial hypoperfusion induced by dipyridamole rather than actual chamber enlargement. The LVDR was moderately sensitive and highly specific for triple-vessel disease and provided complementary information to dipyridamole thallium-201 imaging.
3
Advanced assessment of the abdomen and gastrointestinal problems. There are many unique physical assessment findings that are associated with specific gastrointestinal disorders. The detection of these findings enables the nurse to manage gastrointestinal emergencies on the patient unit in a timely fashion, preventing deterioration and maintaining the safety of the patient. These skills build well on the traditional, detailed, and comprehensive assessments the nurse makes when using the nursing process. Specific abdominal assessments include detection of signs associated with appendicitis such as rebound tenderness and McBurney's, Rosvig's, and Aaron's signs. The nurse must always be alert to the possibility of peritonitis and the urgency of early detection and treatment. The patient with cirrhosis of the liver presents a distinct clinical picture. There is a need for subtle evaluation of mental status to detect early signs of hepatic coma. Another extra-abdominal assessment of this complication is asterixis. Finally, the assessment of the patient is enhanced when the nurse is able to help identify the location of bleeding. Improving abdominal and gastrointestinal system assessment leads to early detection of nursing problems and appropriate interventions.
1
Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions. Myocardial areas distal to complete coronary artery occlusions are poorly protected by antegrade cardioplegia. We assessed the effects of coronary sinus cardioplegia in 30 patients undergoing bypass operations and at high risk of cardioplegic maldistribution because of the following anatomical patterns of coronary artery disease: critical (greater than or equal to 50%) stenosis of the left main trunk with total occlusion of the right coronary artery (16 patients) or critical (greater than or equal to 70%) stenosis of the right coronary artery with total occlusion of the left anterior descending (11 patients) or circumflex artery (3 patients). After induction of arrest through the aorta, coronary sinus cardioplegia was given intermittently during the cross-clamp period at a flow rate of 100 mL/min. Intraoperatively, occluded arteries were consistently found to be filled with the retrogradely infused solution. One patient died early postoperatively of low cardiac output and a second patient died later during his hospital stay, presumably of an arrhythmia. At autopsy, none of them had pathological evidence of inadequate myocardial protection. One patient sustained a myocardial infarction and 3 others required inotropes for more than 24 hours postoperatively. Postoperative values for right and left stroke volume indices were not significantly different from prebypass levels. Overall, these results are consistent with the occurrence of limited intraoperative ischemic damage and, by inference, suggest the efficacy of the coronary sinus route in preserving myocardial areas supplied by completely occluded coronary arteries and, hence, in jeopardy of inadequate cardioplegia delivery.
3
Clinical and instrumental evaluation of sensory function before and after percutaneous anterolateral cordotomy at cervical level in man. Sensory perception thresholds were assessed by clinical testing and by quantitative instrumental testing before and after operation in 16 subjects for whom unilateral percutaneous cervical cordotomy was performed for the relief of pain due to malignant disease, and compared with clinical assessments of sensory function. We were able to confirm the association between deficit in pin-prick sensation and pain relief in the majority of instances, though the completeness or otherwise of pain relief does not correspond to absence of pin-prick sensation. There is no objective interference with low threshold mechanical sensation as measured instrumentally, although cordotomised subjects do not experience startle, tickle, or cutaneous erotic sensation when subjected to appropriate low intensity tactile sensation. Quantitative instrumental testing shows that the greatest deficits produced by cordotomy are in the sensations of skinfold pinch (? = tissue-damage pain) and skin cooling. The latter is transduced in the periphery by A delta fibres; sensations of warmth and hot pain, transduced by primary afferent C fibres, are much less significantly affected. Our findings thus fail to resolve the question as to whether chronic clinical pain is mainly an A delta- or a C fibre-mediated phenomenon.
0
Wide cavum septum pellucidum: a marker of disturbed brain development. A wide cavum septum pellucidum defined as a separation of greater than 1 cm of the leaves occurs uncommonly. Nine children with wide cavum septum pellucidum were studied; 8 were abnormal. Observed abnormalities included cognitive impairment (8), seizures (4), hypoplasia of the corpus callosum (4), optic nerve hypoplasia (2), and growth failure (4). The incidence of intellectual dysfunction, the association with midline anomalies of the brain, and growth failure all suggest that wide cavum septum pellucidum may represent part of a spectrum of midline brain anomalies.
2
Chylous ascites due to sarcoidosis. A 33-yr-old black female with systemic sarcoidosis developed chylous ascites. A CT scan showed extensive mesenteric lymphadenopathy. At laparotomy, the mesenteric and para-aortic lymph nodes were enlarged and diffusely matted. Histologically, normal lymph node morphology was virtually replaced with noncaseating granulomas. Corticosteroids and dietary manipulations were unsuccessful in managing the ascites, and repeated large-volume paracentesis was necessary to provide symptomatic treatment. This is the first reported case of chylous ascites caused by sarcoidosis.
1
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.
1
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.
0
A controlled clinical comparison of 6 and 8 months of antituberculosis chemotherapy in the treatment of patients with silicotuberculosis in Hong Kong. Hong Kong Chest Service/tuberculosis Research Centre, Madras/British Medical Research Council. Patients with silicotuberculosis have been reported to respond poorly to antituberculosis chemotherapy. Therefore, in a study in Hong Kong, 240 Chinese male patients with both silicosis and pulmonary tuberculosis were all prescribed treatment three times weekly with streptomycin, isoniazid, rifampin, and pyrazinamide, allocated at random to be given for a total duration of either 6 (M6 regimen) or 8 months (M8 regimen) in a concurrent comparison. Those with a history of previous antituberculosis chemotherapy received ethambutol as well for the first 3 months. The intake in the M6 regimen was terminated when preliminary results showed that it was inadequate, and a further 53 patients were assigned to the M8 series. Of 91 assessable patients in the concurrent comparison with susceptible strains pretreatment, 44% were culture negative at 1 month, 80% at 2 months, and 98% at 3 months, and 1 had an unfavorable bacteriologic response during chemotherapy. During 3 yr of assessment, bacteriologic relapse after chemotherapy occurred in 22% of the M6 compared with 7% of the M8 patients (p less than 0.025, log-rank test). Inadequate chemotherapy was received by 12% of the 240 patients in the concurrent comparison because of default and by 22% because of adverse effects, but by 3 yr 92% of patients with susceptible strains pretreatment in each series had a favorable status following retreatment for relapse or for initially inadequate chemotherapy when required. The results show that patients with silicosis require at least 8 months of treatment.
4
Antemortem diagnosis of diffuse Lewy body disease. Using the presence of widespread cortical Lewy bodies (LB) as the pathologic criteria of diffuse Lewy body disease (DLBD), we describe serial neurologic and mental status examinations in 6 patients with DLBD, 3 patients with Alzheimer's disease (AD), and 1 patient with Parkinson's disease (PD). The 6 patients with DLBD included 3 with neocortical neurofibrillary tangles (NFT) consistent with coincident AD. Most patients with DLBD had gait impairment concurrent with mild to moderate dementia. Abnormalities of tone or resting tremor were also prominent early symptoms in the subjects with DLBD, but not AD. Patients with DLBD frequently had abnormal EEGs with background posterior slowing and a frontally dominant burst pattern at the time of mild to moderate dementia. Agitation, hallucinations, and delusions were frequent early symptoms in DLBD patients. Patients with DLBD without concomitant AD had numerous Alz-50 negative cortical plaques. Patients with DLBD have a distinct clinical syndrome that can be differentiated from AD. Pathologic features, including the absence of Alz-50 immunoreactivity, also differentiate DLBD from AD.
2
Depressive symptoms following stroke. OBJECTIVE: The primary purpose of this study was to assess the relation of lesion location to mood and vegetative disturbance following stroke. METHOD: Fifty-two inpatients and outpatients who had had single, unilateral strokes were included. Patients with past CNS or psychiatric disorders were excluded. A modified Visual Analogue Dysphoria Scale was used to allow the inclusion of all but the most impaired aphasic patients. Sleep and eating disturbances were measured by using both self-report and nursing assessments. Location of lesions was determined by CT scan and classified according to three dimensions: right-left, dorsal-ventral, and frontal-nonfrontal. RESULTS: On measures of dysphoric mood and sleep disturbance, results indicated significant three-way interactions among the three lesion dimensions. No differences were found with regard to eating disturbance. Greater dysphoria and sleep disturbance were found in subjects with left parietal/occipital, left inferior frontal, right superior frontal, and right temporal lesions than in subjects with lesions in other locations. Depressive symptoms were not associated with functional impairment as measured by activities of daily living, motor strength, or severity of aphasia. CONCLUSIONS: These results support the hypothesis that lesion location is a valid and significant factor in the mixture of influences which may result in a dysphoric mood state following stroke. The relation between the site of the lesion and subsequent depressive symptoms, however, may be more complex than has been reported previously.
2
Oncogene rearrangements in chronic B-cell leukemia. Forty-four B-chronic lymphocytic leukemias (CLL) were studied by Southern blot analysis using probes for the Ig genes and bcl-1, bcl-2 (major, minor and 5' breakpoint region), bcl-3, c-myc, and retinoblastoma (Rb) loci. Eight cases had three or more rearranged JH bands, indicating oligoclonality, clonal evolution, or chromosomal translocation. One case had a rearrangement of the bcl-1 locus and three of the bcl-2 locus. In the first case, comigration of the rearranged bcl-1 and JH sequences indicated a t(11;14)(q13;q32) translocation, which, in contrast to previously described cases, seems to be completely reciprocal. One case with a bcl-2 rearrangement showed comigration of the bcl-2 major breakpoint region and a rearranged JH band. This indicates a t(14;18) (q32;q21). The two other cases showed rearrangements of the bcl-2 5' breakpoint region without apparent comigration. No rearrangements were detected of c-myc and bcl-3, located at chromosome 19, nor was a deletion of Rb found. All but three cases had CD5 expression. The exceptions included the t(11;14) and the t(14;18) cases. Our results confirm recent data on rearrangements at the 5' site of bcl-2 in CLL. Additionally, they corroborate the presumption that CD5-negative chronic B-cell leukemias should be considered apart from classical CLL.
0
Effect of weight reduction on hepatic abnormalities in overweight patients. The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of greater than or equal to 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a greater than or equal to 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken.
1
Chronic rupture of the Achilles tendon: a new technique of repair. A new operative technique is described for the treatment of patients who have a rupture of the Achilles tendon. The large gap between the proximal and distal stumps of the Achilles tendon in seven patients was bridged by use of the tendon of the flexor digitorum longus as the graft. At the most recent follow-up examination (average follow-up, thirty-nine months; range, two to six years), the result was excellent or good in six patients and fair in one. Postoperatively, two patients needed an adjuvant procedure: one, a local rotation flap and the other, a split-thickness skin graft. Both patients had excellent restoration of function. The patient who had a fair result had a persistent limp and residual discomfort. There were no re-ruptures.
4
Adenocarcinoma arising in a foregut cyst of the mediastinum. A case of malignant transformation in a mediastinal cyst of the esophageal reduplication type is presented. The cyst had been recognized 39 years previously, but remained asymptomatic until sudden growth occurred. It was resected totally from the esophagus and the patient recovered well. A review of the literature showed that malignancy in mediastinal foregut cysts is extremely rare.
4
Immediate breast reconstruction following mastectomy is as safe as mastectomy alone. We evaluated wound complications and potential risk factors after mastectomy with immediate breast reconstruction and compared them with similar data after modified radical mastectomy. The incidences of infection, seroma, hematoma, and epidermolysis were compared among 395 patients (305 with modified radical mastectomies and 90 with mastectomy with immediate breast reconstruction) from Virginia Mason Medical Center, Seattle, Wash, between 1983 and 1989. Obesity, age (60 years or older), smoking, antibiotics, and wound drainage were examined as possible risk factors. There were more wound complications in the modified radical mastectomy group (48% vs 31%), and specifically, more seromas (30% vs 13%). In the modified radical mastectomy group, age of 60 years or older was associated with seroma and infection, drainage greater than 30 mL per day (at time of drain removal) with seroma, and smoking with epidermolysis. In the mastectomy with immediate breast reconstruction group, obesity was associated with seroma and epidermolysis. We conclude that mastectomy with immediate breast reconstruction appears to be as safe as modified radical mastectomy alone with respect to wound complications.
0
Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important.
4
Surgery for acute and chronic cholecystitis. Cholecystostomy and cholecystectomy remain appropriate and effective therapy for acute and chronic cholecystitis. Cholecystectomy is the gold standard against which all alternative methods of treatment of inflammatory biliary stone disease should be judged. The pathogenesis, diagnosis, and surgical treatment of acute and chronic cholecystitis have been described. Techniques of cholecystostomy, cholecystectomy, and intraoperative cholangiography used by the author have been given. Our results and those generally described in the literature indicate that the overall mortality rate for cholecystectomy, in all age groups, is approximately 0.5%. This rate increases slightly in patients with acute cholecystitis and in those over the age of 65 years. Cholecystectomy remains the most effective and the definitive treatment for acute and chronic cholecystitis.
1
Neurotologic findings in basilar migraine. Treatment of a patient with otologic symptoms and associated migraine-like headache presents the otolaryngologist with formidable problems. Although clinical practice and scientific publications recognize their frequent association, relationships have yet to be well defined. This study seeks to add order to disarray by delineating symptoms and signs of a clearly identified group of migraine patients. Fifty patients with well-defined basilar migraine underwent a thorough neurotologic examination, as well as comprehensive auditory and vestibular testing. Patients were selected from 5880 patients seen over a 2-year period and were prospectively entered into the study after detailed questionnaires and testing were completed for each patient. The most common symptoms found were dysequilibrium, phonophobia, and head pressure. The most common signs were positional nystagmus, low-frequency hearing loss, abnormal loudness discomfort level, and an abnormality on caloric examination. Advanced vestibular testing showed abnormal amplitude scaling, abnormal toes-down pertubation, and an abnormal sway (condition 6) on dynamic posturography. There was frequently an asymmetry on computerized rotation. The author concludes that the majority of patients have subtle findings on testing, but a few have severe peripheral injury due to the basilar migraine. Findings are consistent with the theory that basilar migraine is a central nervous system maladaptation syndrome which creates otoneurologic symptoms and, in a small percentage of cases, may injure the peripheral end-organ.
2
Postoperative ectopic craniopharyngioma. Case report. The case of an ectopic craniopharyngioma arising from a seed of tissue deposited along the operative track is reported. The uniqueness of this lesion is addressed. Ideal therapy and controversies regarding radiation therapy of craniopharyngiomas are discussed in light of this new variation in recurrence.
0
Computerized neuropsychological assessment of cognitive functioning in children with epilepsy. The value of a range of computer-aided tests in the neuropsychological assessment was investigated in 94-177 children with epilepsy, aged 8-18 years, compared with 68-161 controls in the same age group. Children from the age of 8 years could cope with rather complex tests in a wide range of functions: reaction time measurements, motor speed, information processing, and memory. The speed of performance tended to increase with age in both groups, with differences in information processing becoming apparent from the age of 12 years. The precise control of stimulus and response required to define the mainly minor differences between the epilepsy and control groups can only be fulfilled by computerized testing, which should undergo further refinement including voice and language recognition, followed by artificial intelligence.
2
Skeletal muscle metabolism in heart failure: a 31P nuclear magnetic resonance spectroscopy study of leg muscle. 1. The gastrocnemius muscle of seven patients with mild to moderate chronic heart failure and of five healthy control subjects was studied using 31P nuclear magnetic resonance spectroscopy. Spectra were collected at rest and during an incremental, symptom-limited, exercise protocol. Blood flow was measured in the same study during brief interruptions to exercise. 2. The phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio was lower in patients with heart failure than in control subjects at an exercise rate of 1.5 W, although intracellular pH and blood flow were similar. 3. The cytosolic free adenosine 5'-diphosphate concentration was markedly increased in patients with heart failure exercising at 1.5 W compared with control subjects exercising at the same workload. 4. Although the maximum workload achieved by patients with heart failure was less than half of that reached by control subjects, the pH and the phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio were lower in patients with heart failure at maximal load. Blood flow was less at maximal exercise in patients with heart failure than in control subjects in keeping with the reduced work load. 5. The phosphocreatine depletion induced in the gastrocnemius muscle by exercise was more severe than previously described in the forearm of patients with heart failure. 6. Metabolic abnormalities in skeletal muscle may contribute to exercise intolerance in heart failure, particularly during submaximal exercise.
3
Use of gadolinium-enhanced MR imaging for differentiating mucoceles from neoplasms in the paranasal sinuses. The purpose of this study was to determine whether additional clinically useful information could be obtained from gadolinium-enhanced magnetic resonance (MR) imaging compared with the information obtained from nonenhanced MR imaging and computed tomography (CT). Therefore, the authors selected 41 patients, whose results at CT examinations demonstrated a variety of pathologic conditions of the paranasal sinuses, to undergo MR imaging both with and without the use of gadopentetate dimeglumine for contrast enhancement. In 22 of 35 cases of neoplasms and mucoceles occurring separately, the lesions were correctly differentiated by established MR signal criteria alone. However, 32 of these 35 cases were accurately differentiated when gadolinium-enhanced MR images were obtained. Six cases demonstrated co-existing neoplasm and mucocele: Gadolinium-enhanced MR enabled correct differentiation of five of these lesions, while unenhanced MR enabled correct differentiation of three. On the basis of these results, the authors conclude that the use of gadopentetate dimeglumine for contrast enhancement at MR imaging is useful for differentiating mucoceles from neoplasms in the sinonasal tract.
0
Application of 1 nm gold probes on paraffin wax sections for in situ hybridisation histochemistry. An in situ hybridisation technique that uses 1 nm immunogold reagents and silver enhancement was devised to detect biotinylated DNA viral probes in formalin fixed, paraffin wax sections of human cervix. DNA probes labelled with biotin-11-deoxyuridine triphosphate were detected after hybridisation to nucleic acid sequences by an antibiotin antibody, followed by a gold labelled secondary antibody. Silver enhancement then permitted visualisation of the signal at the light microscopic level. The method was reliable and produced less background staining than previously described methods. The signal could be enhanced by epi polarisation microscopy. Furthermore, biotinylated DNA probes may be detected directly by a 1 nm gold labelled goat antibiotin antibody without loss of labelling intensity, and this may be preferable to the longer two layer technique, previously described.
0
Gastric contents retained in rat stomach following mild irritant exposure contribute to adaptive cytoprotection. Fluid retained in the gastric lumen immediately preceding the administration of a damaging product will dilute that product and decrease its injurious capacity. In an attempt to explain the phenomenon of adaptive cytoprotection, we studied the effect of mild irritant exposure on the volume of fluid retained in the gastric lumen. Rats treated with 0.2 N-0.4 N HCl had a larger volume of gastric fluid retained as compared to animals treated with 0.4 N NaCl. Additionally, a mixture of gastric juice derived from rats exposed to 0.4 N HCl with 2 ml ethanol was significantly less damaging to the gastric mucosa than a similar mixture containing an equal volume of gastric juice derived from 0.4 N NaCl-exposed rats. We conclude from our observations that in mild irritant-exposed stomachs, the gastric juice is a main contributor to the protection against ethanol injury.
4
A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome. Sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp & Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg daily. Usual side effects were mild sedation and dry mouth, but three patients found it impossible to sustain treatment due to nausea and vomiting. Most patients had significant relief of diarrhea, frequently associated with weight gain. Relief of flushing was uncommon. The therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5-hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced. Although there have been case reports of objective tumor regression with cyproheptadine therapy, this was not observed in any of these 16 patients. Cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome. An appropriate initial total daily dose is 0.4 mg/kg divided in three fractions with prompt modification to produce minimal and tolerable side effects.
2
Ulcerative colitis and giant cell arteritis associated with sensorineural deafness Sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis. A patient is described in whom acute sensorineural deafness occurred in association with episcleritis, ulcerative colitis and clinical features suggesting giant cell arteritis.
1
No confirmation of visual evoked potential diagnostic test for migraine. We have attempted to replicate the results of studies on a diagnostic test reported to have 90% sensitivity and 89-96% specificity for migraine. The technique is based on peak-to-peak measurements of fast background electroencephalographic activity during a visual evoked potential (VEP) study. VEP latencies and amplitudes did not differ significantly, and showed substantial overlap, between a group of eight migraine patients and ten age-matched healthy controls. We could not recognise previously described fast activity or measure it objectively by peak-to-peak measurements. We cannot confirm that measurement of fast wave activity in the VEP background is useful in diagnosis of migraine.
2
Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein. We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.
4
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.
0
Unusual cause of 'piriformis muscle syndrome'. The piriformis muscle syndrome is a controversial "clinical" syndrome primarily characterized by signs and symptoms of sciatic nerve compression at the region of the piriformis muscle as it passes through the greater sciatic notch. The syndrome is often referred to; however, cases are rarely reported, and it is generally an uncommon diagnosis. Of those cases reported, the incidence is six times more frequent in females than in males, and is typically temporally related to minor pelvic or buttock trauma. We describe a case of a 40-year-old woman presenting with signs and symptoms suggestive of piriformis muscle syndrome following a gynecologic procedure performed in the dorsal lithotomy position. Electromyographic findings were consistent with this clinical entity. Operative exploration, however, revealed the source of neural compression to be a pseudoaneurysm of the inferior gluteal artery adjacent to the piriformis muscle. The diagnostic features of this clinical syndrome are discussed.
2
A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta. This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006).
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Ischaemic heart disease among men in Norway during the period 1966-1985: two counties with different mortality time trends. We have examined regional differences in mortality from ischaemic heart disease, including sudden, unexpected death (IHD/SUD), among Norwegian men aged 30-69 years, during the period 1966-1985. Mortality time trends were considered. The two counties with the most widely differing IHD/SUD mortality time trends were Rogaland and Oppland. Rogaland, located in south-western Norway, experienced a 24.1% IHD/SUD mortality rate decrease between 1966-1970 and 1981-1985, while Oppland, in central south-eastern Norway, experienced a mortality rate increase of 12.4%. Marked regional differences within these counties were found. The highest IHD/SUD mortality rate increase occurred in rural areas of Oppland. Urban areas of Rogaland had sharply decreasing rates. Knowledge of such regional mortality differences could provide useful information regarding aetiological factors and serve as a basis for preventive measures and health-care planning.
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Distribution of cholesterol between vesicles and micelles in human gallbladder bile: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid. The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone-free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 A. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% +/- 4%) compared with the gallstone-free (28% +/- 3%), ursodeoxycholic acid (28% +/- 3%) and chenodeoxycholic acid (18% +/- 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% +/- 12%, 51% +/- 9% and 65% +/- 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone-free and chenodeoxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The nucleation time of bile from the gallstone group was short (2 +/- 1 days) compared with the gallstone-free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 +/- 3, 24 +/- 6 and 14 +/- 3 days, respectively.
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Spontaneous rupture of a normal bladder. We have reported a case of spontaneous rupture of a normal urinary bladder. Patients with this rare condition characteristically have a recent history of heavy alcohol intake, sudden onset of abdominal pain coincidental with bloody urine, generalized peritonitis, and abnormal renal chemistry. A high index of suspicion will lead to early diagnosis and treatment, minimizing the mortality attributed to this condition.
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