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Does somatostatin analogue prevent experimental acute pancreatitis? Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201-995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis.
4
Management of childhood diarrhoea by pharmacists and parents: is Britain lagging behind the Third World? OBJECTIVE--To investigate the role of community pharmacists in providing advice and treatment for children with diarrhoea; to investigate mothers' responses to diarrhoea in their children. DESIGN--Cross sectional questionnaire study of a random selection of community pharmacists and of mothers attending child health clinics. Pharmacists were interviewed and given a questionnaire and a separate group was visited by a researcher posing as a parent; mothers were interviewed at the clinic. SETTING--Newcastle upon Tyne. SUBJECTS--20 pharmacists were interviewed and visits by a researcher posing as a parent were carried out to 10 different pharmacists; 58 mothers were interviewed. MAIN OUTCOME MEASURES--Advice given by pharmacists was contrasted with standard advice on management of diarrhoea in children. RESULTS--Half of the pharmacists interviewed and 70% of pharmacists visited by a researcher posing as a parent recommended inappropriate treatment of childhood diarrhoea (such as antidiarrhoeal drugs and withholding breast milk), and only 30% at interview stated that they would ask for the age of the child. Mothers' knowledge of home treatment was inadequate. All pharmacists in the posed visits recommended a purchased treatment. CONCLUSION--Pharmacists are widely used by parents for consultation for children's ailments but their advice is not always appropriate; hence they should be given more consistent training in recognising and managing clinical problems. Medical advice on management of diarrhoea is also inconsistent and should be modified to conform to the guidelines of the World Health Organisation.
1
Human immunodeficiency virus-induced immunosuppression: a risk factor for human papillomavirus infection. In a group of 92 women with genital condylomata, 15 (16.3%) human immunodeficiency virus-positive patients were found, whereas no case was detected in a control group of 100 women. The relative risk was greater than 19.28. Human immunodeficiency-positive status was associated with other parameters: lower age and parity, major frequency of induced abortions, and sexually transmitted diseases. Thus although human immunodeficiency-positive status seems to be a true risk factor in relation to the altered immunologic state, an indirect association cannot be discarded. Such patients should be screened closely for human papillomavirus infection and cervical cancer. Among human immunodeficiency-positive women, a more resistant behavior of human papillomavirus-associated lesions was detected (recurrence-persistence of 41.7% versus 12%), a fact that might also be in relation to the immunodepressed status.
0
Incidence of cocaine-associated rhabdomyolysis. STUDY HYPOTHESIS: Rhabdomyolysis is a common complication of cocaine use, and muscle symptoms fail to predict its development. STUDY POPULATION: A prospective, convenience sample of patients presenting to the emergency department of a large inner-city hospital with complaints related to cocaine use were eligible for inclusion. Patients were excluded if they had other potential causes of elevated creatine kinase (CK) levels or rhabdomyolysis. A control group comprised patients who were not cocaine users and satisfied the exclusion criteria. Sixty-eight patients were studied. METHODS: Initial evaluation included determination of the presence of muscle pain or swelling and total CK levels. Patients with a CK level of more than 800 U/L had additional tests, including a urine myoglobin, urine drug screen, and serum phosphorus. Rhabdomyolysis was defined by a serum CK level of more than 1,000 U/L (more than fivefold that of normal). CK levels were compared by two-tailed Student's t test. Muscle symptoms were compared with the development of rhabdomyolysis by Fisher's exact test. RESULTS: The CK level in the cocaine group was 931 +/- 1,785 U/L (mean +/- 1 SD). The CK level in the control group was 242 +/- 168 U/L (P = .028). Of the cocaine users, 24% (eight of 34) had rhabdomyolysis; one developed multiorgan failure and died. No patient in the control group had a CK level of more than 1,000 U/L. Only one cocaine user who developed rhabdomyolysis had muscle symptoms. Three cocaine users had muscle symptoms but did not develop rhabdomyolysis. No patient in the control group had muscle symptoms or developed rhabdomyolysis. Muscle symptoms did not predict the CK level (P = .55). CONCLUSION: This study revealed that 24% of the cocaine users had rhabdomyolysis. Many of the cases of rhabdomyolysis were not predictable from history or physical examination, making laboratory evaluation essential.
4
Antifungal therapy and its use in surgical treatment. Modern surgery continues to make significant therapeutic advances, and a major component in the adjunctive care allowing these improved procedures is the successful use of broad-spectrum antibacterials. However, the widespread administration of potent antibacterials and the frequent use of a variety of catheters, along with an increase in the number of immune compromised patients requiring invasive procedures, have allowed deep-seated mycoses to become more common. Nosocomial fungal infections are frequent, particularly in the urinary tract and in the blood. This rise in identified fungal infections, along with frequent empiric treatment of suspected infection, has significantly increased amphotericin B therapy in surgical services in the last five years. While amphotericin B remains the standard for treatment of nosocomial mycoses, other antifungal agents are available (flucytosine, miconazole, ketoconazole and fluconazole). Despite experience with the older agents and the development of new agents, many questions remain concerning the use of currently available antifungal treatments in postsurgical patients. The following discussion attempts to summarize the magnitude of the problem, the difficulties with diagnosis and laboratory evaluations, the characteristics of the antifungal agents and particular problems with antifungal treatment in surgery.
4
Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease. To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Women's Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis.
3
Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase. A brother and sister with long-standing symptoms of postural hypotension are described. They were considerably worse in the morning, after exercise and in warm weather. In the male, erection was unaffected but ejaculation was prolonged or absent. Both had nocturia, but there were no urinary bladder, bowel or sweating abnormalities. Autonomic function tests confirmed sympathetic adrenergic failure with spared sympathetic cholinergic and intact parasympathetic function. There were no other neurological abnormalities. Noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was elevated. Urinary levels of noradrenaline and adrenaline metabolites were below detection limits, but dopamine metabolites were normal or elevated. Dopamine beta-hydroxylase activity was undetectable in the plasma. Immunohistochemical studies of perivascular cutaneous tissue confirmed normal peptidergic and tyrosine hydroxylase immunoreactivity, with absent dopamine beta-hydroxylase immunoreactivity. The findings were consistent with an enzymatic deficit in the conversion of dopamine to noradrenaline. The parents were clinically and biochemically normal. Treatment of both patients with the synthetic amino acid, d-l-threo-dihydroxyphenylserine, which contains a hydroxyl group and is converted to noradrenaline by dopa-decarboxylase, reduced symptoms and signs of postural hypotension and increased levels of plasma noradrenaline and its urinary metabolites. In the male, ejaculation became possible. Behavioural changes included a feeling of confidence and optimism, with a tendency to be argumentative. The laevo isomer also raised blood pressure and plasma noradrenaline levels. The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa.
3
Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow. In nine cases of Shy-Drager syndrome, the changes in blood pressure and cerebral blood flow on sitting up from a supine position were studied. The influence of fludrocortisone, a synthetic mineralocorticoid, and L-threo-3,4-dihydroxyphenylserine (DOPS), a precursor of norepinephrine, on these changes was examined. On sitting up, the regional cerebral blood flow (rCBF) measured by Xe133 inhalation showed a tendency to decrease. Fludrocortisone reduced the fall of the mean blood pressure significantly. DOPS reduced the fall of both the diastolic blood pressure and rCBF significantly.
2
Pathologic fracture through a solitary enchondroma of the radial diaphysis: case report. Solitary enchondromata are rare but well recognised benign bone tumours. They are extremely rare in the radius. We report the case of a pathologic fracture through a solitary enchondroma in the radial diaphysis and its successful treatment.
0
Serum sialic acid concentration and cardiovascular mortality OBJECTIVE--To determine whether serum sialic acid concentration may be used to predict short and long term cardiovascular mortality. DESIGN--Prospective study on all men and women who had their serum sialic acid concentration measured as part of a general health survey in 1964 or in 1965. All were followed up for an average of 20.5 years. SETTING--Geographical part of the county of Varmland, Sweden. SUBJECTS--Residents in the area participating in a health check up in 1964-5 (27,065 men and 28,037 women), of whom 372 men (169 with incomplete data and 203 lost to follow up) and 345 women (143 and 202 respectively) were excluded; thus 26,693 men and 27,692 women entered the study. The study sample was restricted to subjects aged 40-74 during any of the 20 years' follow up. MAIN OUTCOME MEASURES--Serum sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, body mass index at the general health survey visit; cardiovascular and non-cardiovascular deaths during three periods of follow up (0-6 years, 7-13 years, and 14-20 years), according to the Swedish mortality register, in subjects aged 45-74. RESULTS--Mean serum sialic acid concentration (mg/100 ml) was 68.8 (SD 8.0) for men and 69.2 (8.0) for women; the average concentration increasing with age in both sexes. A total of 5639 (21%) men and 3307 (12%) women died during the follow up period, in whom death in 3052 (54%) men and 1368 (41%) women was from cardiovascular causes. During short (0-6 years), medium (7-13 years), and long (14-20 years) term follow up the relative risk of death from cardiovascular disease increased with increasing serum sialic acid concentration. The relative risk (95% confidence interval) associated with the highest quartile of sialic acid concentration compared with the lowest quartile was 2.38 (2.01 to 2.83) in men and 2.62 (1.93 to 3.57) in women. Similar results were found for deaths from non-cardiovascular disease with relative risks of 1.50 (1.34 to 2.68) in men and 1.89 (1.57 to 2.28) in women, but these relative risks were significantly lower than those for deaths from cardiovascular disease (p less than 0.001 and p less than 0.005 respectively). In multivariate analysis of total mortality and of cardiovascular mortality with sialic acid concentration, serum cholesterol concentration, diastolic blood pressure, and body mass index as independent variables the impact of sialic acid concentration was virtually the same as in univariate analysis. CONCLUSION--Serum sialic acid concentration is a strong predictor of cardiovascular mortality. A possible explanation of these findings is that the serum sialic acid concentration may reflect the existence or the activity of an atherosclerotic process, and this may warrant further investigation.
3
Ionic channels, cholinergic mechanisms, and recovery of sensorimotor function after neocortical infarcts in rats. Unilateral photochemical infarcts were produced in the hind limb sensorimotor neocortex of 243 rats by intravenous injection of the fluorescein derivative Rose Bengal and focal illumination of the intact skull surface. Facial contact stimuli governed the degree and recovery rate of contralateral tactile/proprioceptive forelimb placing reactions. Contralateral forelimb placing recovered, whereas hind limb placing was resistant to recovery. Infarcted rats displayed marked recovery of spontaneous limb usage (beam traversing). However, deficits in isolated tactile/proprioceptive hind limb placing reactions endured. Posttreatment with the class IV calcium antagonist flunarizine after neocortical infarction protected sensorimotor function in a dose-dependent manner. This protective effect may be due to the peculiar ionic channel blocking profile of flunarizine. Scopolamine hydrobromide reinstated contralateral placing errors in infarcted rats at a dosage that did not affect neurologically intact rats. The cognitive enhancer sabeluzole, a novel benzothiazol derivative, dose-dependently blocked the anticholinergic-induced deterioration of a sensorimotor deficit in rats.
2
Operative and conservative treatment of moderate spondylolisthesis in young patients. We made a retrospective study of 149 children and adolescents with moderate spondylolisthesis (slip less than or equal to 30%), 77 treated by fusion and 72 conservatively at an average follow-up of 13.3 years. Both groups were fully comparable with regard to age at diagnosis, sex distribution (46% girls), and mean slip. The patients who were treated operatively had more pain before treatment and showed more initial progression of the slip. They had better clinical results and less pain at latest review, but the total progression of the slip over the whole follow-up showed no statistical differences between the two groups. Patients with a pseudarthrosis after attempted fusion had had a longer period of postoperative pain, but at the latest review had no more pain than those with sound fusion. None of those treated conservatively came to fusion later and the long-term results in 18 patients who had refused the advised operation were no worse than those for other conservatively treated patients. Our results suggest that a moderate grade of spondylolisthesis in adolescents usually has a benign course. It seems that spontaneous segmental stabilisation occurs as a result of degeneration of the disc at the level of the slip.
2
Renal carcinoma in a solitary kidney. We studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney, including 6 treated at this hospital. Four patients had a contracted kidney and 22 had previously undergone nephrectomy. Partial nephrectomy was performed in 16 patients, enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour. Ex vivo surgery was carried out in 4 patients. The duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery (149 to 365 min). Of the 21 patients who underwent partial nephrectomy or enucleation, the serum creatinine level increased (greater than or equal to 2.0 mg/dl) post-operatively in 16 patients, of whom 9 required temporary haemodialysis. No recurrence has been noted in those who underwent partial nephrectomy, but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy. Kidney-preserving surgical procedures are considered to improve the quality of life, but careful follow-up is necessary.
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Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals. Sacrifice of major growth plates during resection and fixed-length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb-length inequality as growth progresses. A limb-length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit. In the lower extremity, tumors about the knee, including the distal femur and proximal tibia, usually present the dilemma of whether limb salvage by arthrodesis, osteoarticular allograft, or endoprosthetic replacement would result in a significant limb-length inequality and whether amputation of the extremity is a preferable procedure. The techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur. With regard to survival and function, the results obtained with these innovative methods are favorable compared with those of a high above-knee amputation.
0
Detection and location of myocardial infarction using technetium-99m sestamibi imaging at rest. Technetium-99m (Tc-99m) sestamibi imaging at rest has been used to detect and localize myocardial infarction. The largest study to date is a cooperative study of 146 patients in 17 institutions. There were 24 normal subjects and 122 patients with documented myocardial infarction based on clinical, enzymatic or electrocardiographic criteria. The presence of segmental myocardial perfusion defects was compared to the presence of a Q wave on the electrocardiogram or wall motion abnormality on gated blood pool scans, performed within 48 hours of the Tc-99m sestamibi study. Of the 122 infarct patients, 118 (97%) showed perfusion abnormalities by Tc-99m sestamibi imaging. A perfusion defect was found in 110 (99%) of 111 patients with a Q wave and a wall motion abnormality, 113 (99%) of 114 patients with a wall motion abnormality and 113 (98%) of 115 patients with a Q wave. Of the 24 normal subjects, 22 (92%) had normal Tc-99m sestamibi images. In 75% of 1,986 segments, both a Tc-99m sestamibi defect and a regional wall motion abnormality on gated blood scans were present. In 11% of segments, wall motion was normal but Tc-99m sestamibi imaging was abnormal; in 14% of segments, wall motion was abnormal and Tc-99m sestamibi images were normal. In the 24 control subjects, 99% of the segments were normal. Thirty-eight patients had coronary angiography. A close relation existed between the coronary anatomy and myocardial Tc-99m sestamibi uptake. All 9 territories supplied by an occluded vessel and poor collaterals had grade 0 uptake (scale 0 to 2: 0 = markedly reduced; 2 = normal).
3
Surgical indication and significance of portal vein resection in biliary and pancreatic cancer. Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection.
0
Pseudopsammomatous meningioma with elevated serum carcinoembryonic antigen: a true secretory meningioma. Case report. A sphenoid-wing meningioma in a 60-year-old woman was accompanied by elevated serum carcinoembryonic antigen (CEA) levels, which returned to normal after removal of the tumor. Light microscopic examination revealed a secretory meningioma containing numerous pseudopsammoma bodies and a prominent vascular pattern. Immunohistochemical analysis showed the tumor cells and pseudopsammoma bodies to be CEA-positive. This case illustrates the possibility that secretory meningioma may be associated with clinically detectable secretion of CEA. The report also documents the rare occurrence of elevated serum CEA in a primary benign intracranial tumor.
2
Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep. In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury.
4
Problems and solutions of pedicle screw plate fixation of lumbar spine. Fifty-seven patients with low back pain and sciatica of various causes were reviewed with reference to problems associated with pedicle plate fixation of the lumbar spine. Eleven percent of patients had neurologic problems postoperatively and 3.5% (two patients) had severe sensory impairments. All patients had this complication in the early phases of the study. Of 297 screws, 17 broke, ie, 5.7%. These breakages occurred in 12 of 57 patients (21%). In patients with spondylolisthesis, the degree of slip correction averaged 53% postoperatively, which decreased to 35% at the 1-year follow-up. Slip angle was maintained after correction. Pedicle screw plate fixation is an effective form of immobilization of the lumbar spine used in achieving arthrodesis. The surgeon must be fully trained in methodology. It is recommended that screw and plate materials be improved to prevent screw breakage.
4
Further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma. A series of 30 patients who have been treated for advanced carcinoma of the parotid gland using radiotherapy followed by radical surgery is presented. Three patients deteriorated during preoperative radiotherapy and remained unfit for surgery; the remaining 27 underwent radical parotidectomy with block dissection of the neck. Twelve patients received additional radiotherapy after operation. Of those patients undergoing surgery, three have been lost to follow-up, 17 have died and seven remain alive; the period of follow-up ranges from 3 to 133 months. Fourteen patients remained free of recurrent disease at death or when last seen, and six patients developed a local recurrence at a medium period of 10.5 (range 3-36) months after surgery. For all 30 patients, the cumulative proportion surviving for 5 years was 30 per cent.
4
Isovolumic hemodilution with dextran 40 in the rat: effect on the development of peripheral edema and various physiologic parameters. Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats.
4
Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury. Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection.
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Emergency adenotonsillectomy for acute postoperative upper airway obstruction Peri-operative acute upper airway obstruction may be life-threatening. A case is reported of a child with severe adenotonsillar hypertrophy who developed acute upper airway obstruction after a routine surgical procedure and required emergency adenotonsillectomy. The importance of pre-operative assessment is stressed.
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Superiority of retrograde cardioplegia after acute coronary occlusion. Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion. In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus. After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours. Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining). Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion.
3
Comparison of outcomes of double and single lung transplantation for obstructive lung disease. The Toronto Lung Transplant Group. Single lung transplantation has recently been applied with success in patients with obstructive lung disease. Such patients were previously managed by bilateral pulmonary transplantation. Between November 1986 and January 1990, 18 patients underwent transplantation for obstructive lung disease in our center. Eleven double lung transplants and seven single lung transplants were performed in patients having a mean age of 43.4 and 44.1 years, respectively. Operative death occurred in two of 11 double lung transplantations and one of seven single lung transplantations. Each patient underwent preoperative and 3-month postoperative pulmonary function tests, arterial blood gas analyses, nuclear lung scans, and 6-minute walk tests. There was no difference in the preoperative values for any of these parameters. Double lung recipients had significantly higher forced expiratory volume in 1 second and forced vital capacity than single lung recipients. However, the ratios of forced expiratory volume in 1 second to vital capacity were not different. Arterial oxygen and carbon dioxide tension were not different between the two procedures. Whereas double lung transplantations caused a slight preponderance of perfusion to the right lung, the transplanted lung in single lung recipients received a mean of 79.5% +/- 12.3% of predicted flow and only 61.6% +/- 5.0% of predicted ventilation. Three-month 6-minute walk distances were markedly improved in both groups, with double lung recipients achieving 573.0 +/- 44.7 m in comparison with the 528.0 +/- 43.0 m achieved by the single lung recipients. Single lung transplantation is a satisfactory option in patients with obstructive lung disease and might offer significant advantages to the older patient population, in which risk of double lung transplantation is high.
4
Laser angioplasty in peripheral vascular disease: symptomatic versus hemodynamic results. Most early reports on the efficacy of laser angioplasty have used subjective symptoms rather than objective hemodynamic parameters to evaluate clinical results. We reviewed our experience with hot tip laser-assisted balloon angioplasty in 99 occluded or stenotic arterial segments during 80 procedures in 71 patients, ranging from the aortic bifurcation to the tibial-peroneal trunk. Initial failure to successfully recanalize occluded or stenotic segments occurred in 13 instances (16%). Forty-one procedure-related complications occurred in 31 patients (39%). Functional results were evaluated by use of life-table methods on the basis of symptomatic versus hemodynamic improvement. Cumulative patency rates for symptomatic and hemodynamic improvement were 91% and 64% at 1 month, 71% and 48% at 6 months, and 57% and 34% at 1 year, respectively. These data suggest that symptomatic improvement alone gives a misleadingly high estimate of the efficacy of laser angioplasty when compared with more objective hemodynamic criteria (p less than 0.005). Hemodynamic success was more likely in aortoiliac lesions than femoropopliteal lesions (58% vs 18% at 1 year, p less than 0.01). Hemodynamic parameters should be used to evaluate the success of laser angioplasty, which in its present form, is associated with frequent complications and poor long-term success.
3
A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in two protein S-deficient families. Genomic DNA samples from 12 protein S-deficient families with hereditary thrombophilia were analyzed by Southern hybridization using protein S cDNA probes. Protein S-deficient members of families A and B possessed identical restriction fragment length polymorphisms, which suggest the absence of 5.3 kb from one of their protein S alpha alleles. The abnormal alleles from individuals A7 and B1 were amplified by the polymerase chain reaction using a forward primer in intron K and a reverse primer in exon XIV. The amplified DNA was cloned and sequenced. Sequence comparison with the normal protein S alpha gene showed that most of intron L (roughly 4.7 kb), the entire exon XIII (151 bp), and about a quarter of intron M (407 bp) were missing from both the A7 and B1 clones. Exon XIII contains all three potential N-glycosylation sites in human protein S. This deletion may result in RNA transcripts in which exon XII is spliced to exon XIV. Such an arrangement would generate a stop codon at position 463 and consequently produce a nonglycosylated protein S molecule truncated by 173 amino acids.
3
Unilateral asterixis. We describe three patients with unilateral asterixis. One diabetic patient with a moderately-sized haematoma in the left putamen initially developed bilateral and symmetrical asterixis, which became confined to the right side as his diabetes mellitus was controlled. Two patients showed unilateral asterixis due to haematomas in the contralateral basal ganglia and thalamus, respectively. The present findings indicate that not only lesions of the thalamus but also those of the basal ganglia can cause unilateral asterixis, and bilateral and symmetrical asterixis does not necessarily exclude the presence of a focal mass lesion in the cerebrum.
2
Surgical complications with the cochlear multiple-channel intracochlear implant: experience at Hannover and Melbourne. The surgical complications for the first 153 multiple-channel cochlear implant operations carried out at the Medizinische Hochschule in Hannover and the first 100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and Ear Hospital, are presented. In the Hannover experience the major complications were wound breakdown, wound infection, electrode tie erosion through the external auditory canal, electrode slippage, a persistent increase in tinnitus, and facial nerve stimulation. The incidence of wound breakdown requiring removal of the package was 0.6% in Hannover and 1.0% in Melbourne. The complications for the operation at both clinics were at acceptable levels. It was considered that wound breakdown requiring implant removal could be kept to a minimum by making a generous incision and suturing the flap without tension.
4
Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy. Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.
4
Reperfusion adjunctive therapy. The beneficial effects of coronary thrombolytic therapy may be enhanced by certain adjunctive therapies. Some of these are of proven value, some appear to offer no benefit in spite of theoretical advantages, and some remain to be evaluated in clinical trials. Acetylsalicylic acid markedly enhances the mortality reduction of thrombolytic therapy and should be used routinely. There is a strong theoretical rationale for the use of heparin, but evidence for its benefit exists primarily in small angiographic trials, and convincing clinical benefit has not yet been demonstrated. Early intravenous beta-blockers were shown in the prethrombolysis era to confer modest benefit, but extensive data on their adjuvant use with thrombolysis are available from only one trial. Intravenous nitrates were demonstrated to reduce mortality in the prethrombolysis era, and are soon to be evaluated in trials employing thrombolytic therapy. The calcium channel blockers, in spite of a variety of theoretical benefits, have proved to be of no value acutely, and in the subacute setting, only diltiazem appears to confer benefit in the subgroup of patients with non-O-wave infarction. Angiotensin-converting enzyme inhibitors are likely to be of value in survivors of acute myocardial infarction with left ventricular dysfunction, and benefits observed with acute use in experimental infarction are now being evaluated in clinical trials.
3
Delayed detection of coarctation in infancy: implications for timing of newborn follow-up. During a recent 5-year period, 74 patients younger than 6 months of age were diagnosed with coarctation of the aorta. Coarctation was correctly diagnosed in only 22% of patients prior to referral despite readily apparent femoral pulse abnormalities in 86%. Infants whose symptoms were detected between 5 and 14 days of age were significantly more ill than infants outside this age range and had a high mortality rate (25%). The number of associated cardiac defects was not related to the severity of clinical illness in this group, suggesting that closure of the ductus arteriosus is the primary determinate of disease severity. Observations in two patients suggested that a detectable pulse discrepancy occurs between 3 and 5 days postnatally. Upper extremity hypertension was found commonly in infants after 5 days of age despite the presence of congestive heart failure. Earlier detection of coarctation in the newborn requires a diligent cardiovascular and peripheral pulse examination between 3 and 7 days of life, upper extremity and lower extremity blood pressure measurement, and a high index of suspicion.
3
Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences. This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms.
4
Grading white matter lesions on CT and MRI: a simple scale. We developed and tested a simple three-point scale for grading white matter lesions in anterior and posterior regions of the brain. Twenty four CT scans and 24 MRI scans were separately judged by 11 and five observers, respectively, on the presence and severity of white matter lesions. The observers were radiologists and neurologists. For CT scans, these periventricular changes were graded according to their extent as absent, or partly involving the white matter, or extending up to the subcortical region. The MRI lesions were graded as no lesion or only a single one, multiple focal lesions, and multiple confluent lesions. The pairwise agreements of all possible combinations of observers for each scan were corrected for chance (kappa statistics; maximal agreement 1.0). The weighted kappa value, for anterior and posterior regions combined, was 0.63 for CT scans, and 0.78 for MRI scans. This three-point scale for two separate regions seems suitable as a basis for cross-sectional or longitudinal studies of large series of patients.
2
Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic progressive multiple sclerosis: expected lack of clinical utility. We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-alpha and IL-1 beta, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients.
2
Immunopathology of olfactory mucosa following injury to the olfactory bulb. Removal of the olfactory bulb was performed on rats in an attempt to elucidate the processes of olfactory dysfunction following head injury. Degeneration and regeneration of the olfactory mucosa were examined, histopathologically and immunohistochemically. We used antisera to olfactory marker protein (OMP) and neuron specific enolase (NSE) as a marker of the mature olfactory receptor neurons. Following rapid degeneration after bulbectomy, the olfactory receptor neurons regenerated. OMP and NSE containing cells re-appeared 49 days later. However, the cell population of the neuroepithelium did not revert to the numbers observed in the non-operated neuroepithelium, even three months later. The lack of a connection between regenerated axons and the olfactory bulb may result in immature neuronal replacement and reduce the number of olfactory receptor neurons.
4
Effects of preoperative radiotherapy on rectal cancer. Preliminary report on combining radiation with intratumor injections of peplomycin and bromodeoxyuridine. Between 1976 and 1983, 61 patients with advanced rectal cancer underwent Miles' operation at the authors' institution. All lesions were located 10 cm or less from the anal verge. Of these patients, 25 were treated by surgery alone and 36 were given preoperative radiotherapy. The total dose was 42.6 Gy, (30.6 Gy [1.8 Gy/fr x 5/week]) delivered to the entire pelvis plus an additional 12 Gy (3.0 Gy/fr x 4/week) delivered to the primary tumor. Of 36 patients, 21 were administered intratumor injections of peplomycin and bromodeoxyuridine at the time of boost radiation and 15 were treated without intratumor injections. During the follow-up period (3 to 9 years), in the groups of patients who underwent radiation, there was only one local failure (2.8 percent). In contrast, in the group of patients treated by surgery alone, eight local failures occurred (32 percent). The intratumor injection significantly enhanced the effect of radiation on tumor regression. The incidence of positive lymph nodes was higher in patients in the surgery alone group than it was in the groups treated with radiation. There was no difference in the rate of distant metastasis among the three treatment groups. The five-year survival rate for the radiation with intratumor injection group, radiation alone group, and surgery alone group, was 77.8, 69.2, and 56.0 percent, respectively. No severe complication was experienced.
0
Antigen-induced cross-linking of the IgE receptor leads to an association with the detergent-insoluble membrane skeleton of rat basophilic leukemia (RBL-2H3) cells. Cross-linking of the IgE receptor on the surface of rat basophilic leukemia cells by multivalent Ag (DNP-BSA) causes a rapid conversion to a detergent-insoluble form. There is a concurrent increase in the amount of filamentous actin associated with the plasma membrane. Both the degree of receptor detergent insolubility and the rise in F-actin content are rapid with a half-maximal response of less than 1 min and can be rapidly reversed by the addition of monovalent Ag (DNP-lysine). These two early steps in the triggering of rat basophilic leukemia cells can be dissociated from each other by pretreatment of the cells with either cytochalasin or sodium azide. These reagents block the increase in F-actin but have no effect on receptor detergent insolubility. This indicates that microfilaments are not responsible for detergent insolubility of the receptor and that it may be the membrane skeleton that is interacting with the complex. This was further confirmed by the finding that cross-linking of the IgE receptors on the surface of purified plasma membranes also leads to detergent insolubility of the receptor. Therefore, all of the components necessary for detergent insolubility of the receptor are present in the plasma membrane, and cytoplasmic components are not needed. These results suggest that detergent insolubility and immobility of the cross-linked receptors are caused by multivalent interaction with the membrane skeleton. Actin filaments may then interact with these receptor-membrane skeletal complexes in order to produce large scale clustering and capping. The membrane skeleton may therefore be acting as an intermediate structure between the cell-surface receptors and microfilaments.
0
Vascular hypertrophy, renin and blood pressure in the young spontaneously hypertensive rat. 1. Cardiovascular reactivity, blood vessel morphology, blood pressure and the activity of the renin-angiotensin system were determined in the 3-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and outbred Wistar (WIS) rat. 2. In an isolated perfused mesenteric artery preparation the SHR had a significantly increased maximum response to KCl and noradrenaline (P less than 0.02) compared with the WKY. Using a myograph, vascular structure was measured over a range of resistance arteries and showed a significant correlation between lumen diameter and both media cross-sectional area and thickness, with the regression line for the SHR shifted upwards indicating both increased media area and thickness. This was associated with a slight, but significant, narrowing of the lumen (P less than 0.01) and an increased media/lumen ratio (0.049 +/- 0.01, 0.034 +/- 0.007, 0.036 +/- 0.008 for SHR, WKY and WIS, respectively, means +/- SD P less than 0.001). The SHR had a greater heart/body weight ratio than either the WKY or the WIS (P less than 0.001). 3. Both mesenteric artery and membrane protein content were higher in the SHR, indicating an increase in cell size or number. 4. Plasma renin activity (means +/- SD) was lower in the SHR (1.0 +/- 0.7 pmol of angiotensin I h-1 ml-1) than in the WKY (2.2 +/- 1.2 pmol of angiotensin I h-1 ml-1, P less than 0.001) but not different from that in the WIS (1.2 +/- 0.8 pmol of angiotensin I h-1 ml-1). Mesenteric artery vascular renin concentration was also lower in the SHR (P = 0.06).
4
Dominant negative regulation of the mouse alpha-fetoprotein gene in adult liver. Transcription of the mouse alpha-fetoprotein gene is activated in the developing fetal liver and gut and repressed in both tissues shortly after birth. With germline transformation in mice, a cis-acting element was identified upstream of the transcription initiation site of the alpha-fetoprotein gene that was responsible for repression of the gene in adult liver. This negative element acts as a repressor in a position-dependent manner.
4
Vitamin E in gastric mucosal injury induced by ischemia-reperfusion. To clarify the relationship among vitamin E, oxygen radicals, and lipid peroxidation in ischemia-reperfusion, we produced an experimental model of gastric mucosal injury in rats by ischemia-reperfusion with clamping of the celiac artery and measurements of the area of gastric erosion, thiobarbituric acid (TBA)-reactive substances, and alpha-tocopherol in serum and gastric mucosa during ischemia-reperfusion. The area of gastric erosions and TBA-reactive substances in gastric mucosa were significantly increased after 30 and 60 min of reperfusion. The serum alpha-tocopherol-cholesterol ratio and gastric mucosal alpha-tocopherol were significantly decreased after 30 and 60 min of reperfusion. On the other hand, in vitamin E-deficient rats, gastric mucosal injury induced by ischemia-reperfusion was more severe than that in vitamin E-nondeficient rats. These results indicate that vitamin E is consumed in the process of lipid peroxidation induced by oxygen radicals in ischemia-reperfusion to prevent the development of tissue damage.
3
Incidence and prevalence of ulcerative colitis in the upper Galilee, Northern Israel, 1967-1986. An epidemiological study of ulcerative colitis was performed in the Upper Galilee, Israel, over a 20-yr period (1967-1986). The average annual incidence of ulcerative colitis was 2.23 per 100,000 population, and the prevalence on December 31, 1986, was 44.58 per 100,000. Considering the fact that strict steps were taken to include only definite cases, these figures are probably an underestimation. An increase of the average annual incidence from 0.88 in the period 1967-1976 to 3.79 in 1977-1986 was found. When the data were stratified according to ethnic groups, the highest average annual incidence and the highest point prevalence was found in Israeli-born Jews (6.9 and 138.2 per 100,000 population, respectively). When Jewish residence patterns were compared, the highest average annual incidence and point prevalence were found among Kibbutz members (5.52 and 110.39, respectively), and the lowest (1.94 and 38.76) among Moshav inhabitants. There were 10 Arab patients with an average annual incidence of 0.96 and a point prevalence of 19.27. There were 25 women and 28 men (female:male ratio of 0.89). Among the Jews, the female:male ratio was 1.04. Peak incidence was found in the 25- to 34-yr-old range. No second peak was noticed. Anemia was demonstrated in 66.6% of the women and 27.5% of the men in our study. We suggest that the increase in UC incidence and prevalence in Israeli and Asia/africa-born Jew and in Arabs in the Upper Galilee points toward environmental factors in the etiology of this disease.
1
Successful treatment of neonatal Citrobacter freundii meningitis with ceftriaxone. Citrobacter meningitis is an uncommon enteric gram-negative infection that afflicts neonates and young children. Approximately 30 percent of children treated or untreated die from the infection. We report a case of C. freundii meningitis that was resistant to ampicillin and was successfully treated with ceftriaxone, a third-generation cephalosporin. A 13-day-old, full-term baby was admitted to the hospital with a one-day history of fever up to 38.8 degrees C. On admission the infant had a temperature of 39.2 degrees C, pulse of 140 beats/min, and a respiratory rate of 32 breaths/min. Except for a slightly bulging fontanelle, the rest of the physical examination was within normal limits. Complete blood count revealed a white blood cell (WBC) count of 12.5 x 10(9)/L, with 0.66 polymorphonuclear cells, 0.10 bands, 0.18 lymphocytes, and 0.06 monocytes. A stat lumbar puncture showed 10 WBCs per high-power field with gram-negative rods. Empiric therapy with ampicillin 225 mg q12h and gentamicin 11 mg q8h was started. Both antibiotics were discontinued after culture and sensitivity results were positive for C. freundii in the blood and spinal fluid. The patient was successfully treated with nine days of ceftriaxone 250 mg q12h.
2
Trochanteric fractures. Mobility, complications, and mortality in 607 cases treated with the sliding-screw technique. Six hundred seven trochanteric fractures (563 patients) were treated with a sliding-screw technique and followed clinically and roentgenographically for at least one year. Of 351 patients admitted from their homes, 209 (60%) were discharged to their homes after an average of 18 days in the hospital. During the first year another 61 (17%) patients returned home after rehabilitation in a geriatric ward. Of 446 patients walking without support or with one cane before surgery, 360 (80%) had regained the same mobility after one year. The one-year mortality rate was 18%, while the ten-year rate was 74%. Compared with a control cohort, the mortality rate was increased during the first two years after fracture. The increase in mortality was influenced by advanced age, admission from long-term care institutions, male gender, and ambulatory or nonambulatory status before surgery. Forty-five (7.4%) were reoperated, 17 because of technical complications, three because of infection, and three because of nonunion. No further nonunions occurred. The deep infection rate was nine of 339 (2.7%) before and two of 268 (0.8%) after the introduction of antibiotic prophylaxis. Thromboembolic complications decreased from 4.1% to 1.2% after the introduction of dextran 70 as thromboembolic prophylaxis.
3
New angiotensin converting enzyme inhibitors. Their role in the management of hypertension. The introduction of orally active angiotensin converting enzyme (ACE) inhibitors has revolutionized the treatment of hypertensive disorders and provided an effective alternative for the management of congestive heart failure (CHF). By interfering with the formation of angiotensin II, the active agent of the renin system, ACE inhibitors block the system's vasoconstrictive and sodium-retaining effects, with a consequent reduction in systemic blood pressure. The net effect is improved blood flow and reduced cardiac work. Thus, ACE inhibitors are likely to improve cardiac work capacity and quality of life. Their mechanism of action differs markedly from that of traditional antihypertensive agents which lower blood pressure while reducing cardiac output and blood flow. Since the primary action of ACE inhibitors is to block the renin system, a dramatic response to monotherapy suggests a large renin factor while the lack of a response suggests a low-renin state more amenable to treatment with a diuretic or calcium antagonist. Because of their many attributes, ACE inhibitors are increasingly used as first-line therapy for the treatment of hypertension or CHF. The prototype orally active ACE inhibitor, captopril, is a sulfhydryl compound with a good safety profile at the recommended dosages but reported toxicity at higher dosages. Second-generation ACE inhibitors (eg, enalapril and quinapril) are more potent sulfhydryl-free esters with a greater affinity for the converting enzyme. These newer agents are pro-drugs requiring ester hydrolysis to form the active free acid compound.
2
Initial failure of surgical exploration in patients with primary hyperparathyroidism. To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration.
0
Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the oropharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended.
0
Modification of pain on injection of propofol--a comparison between lignocaine and procaine. Pain on injection of propofol was assessed in a controlled, randomised study of 273 patients. They received either lignocaine 10 mg, procaine 10 mg or isotonic saline 0.5 ml, 15 seconds before the injection of propofol into a vein on the back of the hand. The incidence of pain on injection in the control group (51%) was comparable with other studies. Lignocaine and procaine both significantly reduced the pain (35% and 34% respectively, p less than 0.05) but there was no statistical difference between these two groups.
2
Delayed central nervous system myelination in the sudden infant death syndrome. This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.
4
Long term effects of gastrocystoplasty in rats. Twenty prepubescent rats underwent microsurgical gastrocystoplasty by a technique which is described. An equal number of control rats had their bladders opened and closed. Rats were sacrificed at 16 to 18 months postoperatively. There were no differences in final weight, serum electrolytes, or renal function between the two groups. Prominent histopathologic changes of the bladder occurred in the gastrocystoplasty group. These changes included papillomas present in five of the 15 rats surviving long term. No significant changes occurred in the bladders of the control group of rats. Possible etiologies and the significance of the rats. Possible etiologies and the significance of the gastrocystoplasty related lesions are discussed.
0
Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts. As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.
0
Median nerve somatosensory evoked potentials and the Glasgow Coma Scale as predictors of outcome in comatose patients with head injuries. Median nerve somatosensory evoked potential (SSEP) grades and Glasgow Coma Scale (GSC) scores were obtained from 51 patients with head injuries within 1 week after the injury to determine the relationship of these scores, both individually and combined, to outcome scores obtained more than 6 months after the injury. SSEP grading was based on the presence or absence of the cortical evoked potential, the amplitude of the early cortically generated P22 wave form, and the conduction time through the brain (P/N13-N20 interpeak latency). SSEP responses from both sides of the brain were combined and graded from 1 to 6. The GCS was graded without the verbal component (maximum score, 10), because all patients were intubated. All patients were unresponsive to commands. Median SSEP grades correlated better with Glasgow Outcome Scale and Barthel Index scores (R = 0.57 and 0.64, respectively; P less than 0.00001) than GCS scores did (R = 0.35 and 0.37, respectively, P less than 0.00001), and combining SSEP grades and GCS scores did not improve the predictive power of the model (R = 0.57 and 0.64, respectively; P less than 0.00001). All SSEP Grade 1 patients (n = 13) either died or remained in a vegetative state. In contrast, all SSEP Grade 6 patients (n = 7) had a moderate disability or good recovery. This study demonstrates the prognostic value of early quantitative median nerve SSEP grading for patients with head injuries who are unresponsive to commands within 1 week after the injury.
4
Impairment of esophageal emptying with hiatal hernia. Concurrent videofluoroscopy and manometry were used to analyze esophageal emptying during barium swallows in 22 patients with axial hiatal hernias and in 14 volunteers. Subjects were divided into three groups: (a) volunteers with maximal phrenic ampullary length less than 2 cm (controls); (b) patients or volunteers with maximal ampullary/hiatal hernia length greater than or equal to 2 cm that reduced between swallows (reducing-hernia group); and (c) patients with hernias that did not reduce between swallows. Complete esophageal emptying without retrograde flow was achieved in 86% of test swallows in the controls, 66% in the reducing-hernia group, and 32% in the nonreducing-hernia group (P less than 0.05). Impaired emptying in the reducing-hernia group was attributable to "late retrograde flow," whereby barium squirted retrograde from the hernia during emptying. Impaired emptying in the nonreducing-hernia group was attributable to "early retrograde flow" that occurred immediately after LES relaxation. The nonreducing-hernia group also had longer acid clearance times than the controls (P less than 0.05). We conclude that gastroesophageal junction competence is severely impaired in patients with nonreducing hiatal hernias, suggesting a mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis of reflux disease.
1
Treatment of solitary arteriovenous fistulas. Four patients with a solitary arteriovenous fistula were treated by transvascular balloon embolization technique, which resulted in complete fistula closure in three patients and partial closure in one. There were two vertebral arteriovenous fistulas, one peroneal arteriovenous fistula, and one radial arteriovenous fistula. The first two fistulas were spontaneous, the other two were traumatic. The only partial occlusion of the peroneal fistula was, in our opinion, due to a technical failure, the balloon was inflated slightly proximal to the fistular orificium instead of in the orificium itself. There were no complications, and there was no morbidity. In our opinion transvascular balloon embolization technique is the treatment of choice for solitary arteriovenous fistulas.
4
Lung function and pulmonary regurgitation limit exercise capacity in postoperative tetralogy of Fallot. Fifty-five patients with repair of tetralogy of Fallot were evaluated with treadmill exercise, pulmonary function testing and rest two-dimensional and Doppler echocardiography to determine the relation among cardiopulmonary function, exercise capacity and ventricular arrhythmias. The mean age at repair was 8.1 +/- 2.1 years; age at the time of study ranged from 15 to 37 years (mean follow-up time after repair 18 +/- 5 years). Exercise duration was 92 +/- 17% of predicted. Maximal heart rate was 94 +/- 7% of predicted. No exercise test was stopped because of an arrhythmia. Thirty patients had oxygen consumption and ventilation measured during their final minute of exercise. Peak oxygen consumption was 31 +/- 8 ml/kg per min (86 +/- 18% of predicted). Twenty-five patients (45%) had low vital capacity at rest (less than 80% of predicted). Pulmonary regurgitation was identified in 42 (75%) of the patients and judged to be moderate in 10 (18%). Mild tricuspid valve regurgitation was identified in 64%. Doppler estimated right ventricular outflow gradient was greater than 15 mm Hg in 15% of the patients (mean gradient 24 mm Hg [range 16 to 56]). Age at repair, duration of follow-up and type of repair did not correlate with echocardiographic variables, ventilatory data, exercise performance or arrhythmias. Moderate pulmonary regurgitation was associated with increased right ventricular diastolic area and both were inversely related to exercise duration and vital capacity. Decreased breathing reserve during maximal exercise was associated with moderate pulmonary regurgitation and decreased vital capacity. The results indicate that exercise capacity in these patients is in general good; however, right ventricular volume loading and ventilatory dysfunction may produce exercise limitation.
3
Tumors of the shoulder girdle. Technique of resection and description of a surgical classification. Limb-sparing surgery is safe and reliable for most bone and soft-tissue tumors of the shoulder girdle. Eighty to ninety percent of patients with high-grade sarcomas of the shoulder can be safely treated by the various surgical techniques described. Attention must be paid to appropriate patient selection, preoperative staging, and planning. In addition, careful skeletal and muscular reconstruction of the surgical defect is necessary for a successful outcome. A new, universal, classification schemata (types I-VI) of shoulder girdle resections has been developed. This classification system is based on the bones resected, the status of the abductor mechanism, and the relationship to the glenohumeral joint. This system permits easy description and comparison of the various limb-sparing procedures performed.
0
Cutaneous manifestations of multiple myeloma. We report the cutaneous manifestations of multiple myeloma, using a retrospective review of 115 patients' records obtained from tumor registry files. Five patients were found to have biopsy-proved extramedullary plasmacytomas without extension from an underlying bony focus. Twelve patients had ecchymoses without thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma. The last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis, and, in the course of a standard workup, he was diagnosed with multiple myeloma. These findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma.
0
Tumefactive fibroinflammatory lesions of the head and neck. The term 'tumefactive fibroinflammatory lesion' has been used to describe a fibrosclerosing disorder which has a locally destructive nature but is characterized by a benign histological appearance. We report five patients, over a five year period, with such a lesion. The clinical behaviour and surgical findings suggest the lesion to be an invasive malignancy. However, the histological appearance of an admixture of chronic inflammatory cells and fibrosis is consistent with a benign condition. We recommend surgical excision of the lesion as the mainstay of treatment; other studies report the use of steroids and radiotherapy.
4
Polyglucosan body disease. Adult polyglucosan disease has been described in 15 cases. All had signs of peripheral neuropathy, upper motor neuron signs, and 12 of the 15 had sphincter problems. Dementia was prominent in 8 of 15 cases. We reported 2 cases that contained these clinical features. Electrophysiological studies showed axonal neuropathy. Somatosensory evoked potentials on the second patient were abnormal. Sural nerve biopsy showed clusters of polyglucosan bodies. Although the presence of polyglucosan bodies in biopsy is nonspecific, the number as well as the clinical features are necessary to make the diagnosis. Branching enzyme activity in muscle extracts of the muscles were normal. Hence, a specific enzyme abnormality is not yet known.
1
Tyrosine kinase and control of cell proliferation. The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated tyrosine kinases is discussed in this report. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of Class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only after the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral Class 1 oncogenes, which are endowed with deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of exogenous ligands. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at the molecular level, and the mechanisms responsible for its enzymatic activation have been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other situations such as Class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors, or deregulated activity of c-abl-encoded proteins in chronic myelogenous leukemia and acute lymphoblastic leukemia. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology.
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Transfection of C6 glioma cells with connexin 43 cDNA: analysis of expression, intercellular coupling, and cell proliferation. C6 glioma cells express low levels of the gap junction protein connexin 43 and its mRNA and display very weak dye coupling. When implanted into the rat cerebrum, these cells quickly give rise to a large glioma. To investigate the role of gap junctions in the tumor characteristics of these cells, we have used Lipofectin-mediated transfection to introduce a full-length cDNA encoding connexin 43. Several transfected clones were obtained that exhibited various amounts of connexin 43 mRNA transcribed from the inserted cDNA. Immunocytochemical analysis revealed an increase in the amount of connexin 43 immunoreactivity in the transfected cells, being localized at areas of intercellular contact as well as in the cytoplasm. The level of dye coupling was also assessed and found to correlate with the amount of connexin 43 mRNA. When cell proliferation was followed over several days, cells expressing the transfected cDNA grew more slowly than non-transfected cells. These transfected cells will be useful in examining the role of gap junctions in tumorigenesis.
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Status epilepticus in infancy and childhood. Status epilepticus implies a prolonged seizure or recurrent seizures with persistent decreased consciousness, lasting at least 30 minutes. Both convulsive and nonconvulsive forms exist, either of which may lead to death or additional neurologic deficit. Therapy involves careful supportive care plus some combination of benzodiazepines, phenytoin, or phenobarbital. The outcome depends first on the etiology and second on the rapidity with which seizures are controlled.
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A case of lisinopril-induced lithium toxicity We describe a patient who developed lithium toxicity when lisinopril was substituted for clonidine. Possible mechanisms of angiotensin-converting enzyme (ACE) inhibitor-induced lithium toxicity are discussed. Aggressive serum lithium concentration monitoring and a reduction in the dose of lithium is advised when using ACE inhibitors because of disturbances and shifts in fluid and electrolyte balance.
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Retrovirus-induced spongiform myeloencephalopathy in mice: regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons. The Cas-Br-E murine leukemia virus (MuLV) induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis. We have used in situ hybridization with a Cas-Br-E MuLV-specific probe to study viral expression in the central nervous system. Infected cells were concentrated in regions where spongiform lesions and gliosis are detected (lumbosacral spinal cord, brainstem, deep cerebellar regions), suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease. However, viral expression was not in itself sufficient to cause disease, since significant viral expression was observed in regions that did not exhibit pathological changes (cerebellar cortex, hippocampus, corpus callosum, peripheral nervous system). In both diseased and nondiseased regions, endothelial and glial cells were identified as the main target cells. Neurons in diseased regions did not show viral expression. The regional distribution of the spongiform changes appears to be laid down very early following infection, since expression could be detected at 10 days postinfection in regions that become diseased. These results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells.
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131I treatment of thyroid papillary carcinoma in a patient with renal failure. Procedures for 131I ablation in renal failure are not known. In one patient receiving dialysis, detailed dosimetry and health safety aspects were obtained. The results showed insignificant contamination of equipment, but a surprisingly significant reduction in biologic half-life of 131I due to efficient dialysis extraction. The data indicate that 131I ablation can be done safely and easily during dialysis but that much higher 131I doses must be used to achieve equivalent results to those obtained in patients with normal renal function.
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Transcranial stab wounds: morbidity and medicolegal awareness. In this series of eight patients with transcranial stab wounds, the importance of classifications of such wounds as a separate traumatic entity is stressed. The mechanisms of neuronal and vascular damage in these wounds are discussed and are found to be specific from other head injuries. Cerebral injury by stabbing is largely restricted to the wound tract. Frontal stabs (two cases) are accompanied by the least morbidity and mortality, while temporal stabs (four cases) are more commonly fatal. In transorbital stabs (two cases) carotid-cavernous fistulae resulted. Early recognition, administration of antitetanus serum and antibiotics, and debridement may minimize complications.
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New insights into the causes of cancer. Recent advances in molecular biologic analysis have led to major new insights concerning the genetic mechanisms underlying the development of cancer. This article examines the current state of our understanding of the genetic basis underlying the possible mechanisms of carcinogenesis and metastasis. The nature of the genetic lesions found in some cancer-causing genes, cancer-inhibiting genes, growth factor genes, and metastasis genes is discussed, as is the impact that these may have on clinical oncology.
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Remodeling of the rat right and left ventricles in experimental hypertension. Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.
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Safety of same-day sequential extracorporeal shock wave lithotripsy and dissolution of gallstones by methyl tert-butyl ether in dogs. Passage of stone fragments after extracorporeal shock wave lithotripsy (ESWL) of gallstones has resulted in biliary colic, duct obstruction, and pancreatitis in some patients. Rapid dissolution of these fragments with methyl tert-butyl ether (MTBE) may prevent such side effects and achieve complete clearance of gallstones within hours rather than several months to a year or longer. This study examines the safety of same-day ESWL fragmentation and MTBE dissolution of surgically implanted human gallstones in 15 dogs. The animals were randomly assigned to one of four treatment groups to assess MTBE absorption from the gallbladder and to observe hematology and chemistry profiles after 0, 400, and 1,200 shock waves from a lithotriptor followed by MTBE dissolution therapy. They were sacrificed either immediately after treatment (12 dogs) or 2 weeks later (3 dogs). The results demonstrated that although ESWL causes moderate trauma to the gallbladder, this did not result in increased MTBE absorption or histologic evidence of mucosal disruption. Blood profiles demonstrated an increase in only the level of aspartate aminotransferase. The three dogs that were sacrificed 2 weeks after the combined treatment had no residual evidence of gallbladder injury or remaining stone material. In all animals, severe injury occurred where shock waves passed through lung or air-filled colon. This study suggests that same-day sequential fragmentation of gallstones by ESWL followed by dissolution of stone fragments with use of MTBE may be associated with only mild to moderate and reversible gallbladder trauma and can rapidly achieve clearance of gallstones.
1
Paraileostomy hernia: a clinical and radiological study. Forty-six patients who underwent colectomy with end ileostomy for ulcerative colitis (n = 33) or Crohn's disease (n = 13) have been reviewed for paraileostomy hernia (PIH) formation 1-16 years after surgery. PIH developed in 13 of these patients (28 per cent) and was not related to the original disease or excessive weight gain. Twenty-eight patients underwent limited computed tomography (CT) scanning of the stomal region. Eight of these had a clinically detectable PIH, which was demonstrated on CT. A further two patients had PIH demonstrated on CT which was not detected by clinical examination. The rate of PIH was similar where the stoma emerged lateral to the rectus abdominis muscle (six out of 16 patients, 37 per cent) to where the stoma emerged through the rectus (four out of 12 patients, 33 per cent). Recurrence following operative repair of PIH was common. PIH occurs more frequently than previously supposed. CT can detect PIH and may be useful in evaluating a patient with stoma-related symptoms for occult PIH formation.
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Management of acute uncomplicated urinary tract infection in adults. Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity and health care costs. Acute cystitis is a superficial infection of the bladder mucosa, whereas pyelonephritis involves tissue invasion of the upper urinary tract. Localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials. Because of the superficial nature of cystitis, single-dose and 3-day regimens have gained wide acceptance as the preferred methods of treatment. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to be more effective than those with beta-lactams, regardless of the duration. Acute pyelonephritis does not necessarily imply a complicated infection. Upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, and 14-day regimens are often used. We prefer to use antimicrobials that attain high renal tissue levels, such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women with frequently recurring infections can be successfully managed by continuous prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in compliant patients, by early self-administration of single-dose or 3-day therapy as soon as typical symptoms are noted. Our drug of choice for all these regimens is trimethoprim-sulfamethoxazole. Acute uncomplicated cystitis in adult men is very uncommon, but it is occasionally noted in homosexual men who practice insertive and intercourse or in heterosexual men whose partners have vaginal colonization with E. coli.
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Mallory-Weiss syndrome after cardiopulmonary resuscitation. We report hematemesis from Mallory-Weiss tears after successful cardiopulmonary resuscitation (CPR). A computer search of the English language literature disclosed only 3 similar cases, and we review them. This complication of CPR may occur more frequently than recognized and should be prevented by careful technique.
1
ACE inhibition improves vagal reactivity in patients with heart failure. The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement.
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[Ca2+]i transients in the cardiomyopathic hamster heart. Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.
3
Clinical observation on the association of gallstones and colorectal cancer. A possible association between gallstones, colorectal cancer, and gastric cancer was investigated. The age distribution and mean age of the two cancer groups were identical. The incidence of gallstones in 378 colorectal cancer cases and 869 gastric cancer cases was 7.1% and 5.5%, respectively. Of colorectal cancer cases, 33 cases with multiple carcinomas had a significantly higher gallstone incidence than cases with a solitary carcinoma--24.2% and 5.5%, respectively. The mean age was 5 years older in gallstone cases than in those without gallstones in both cancer groups, and it was 4 years older in multiple-carcinoma cases than in solitary-carcinoma cases in the colorectal cancer group. These results suggest that the higher levels of same causative factors (i.e., dietary fat) are associated with a longer duration of gallstone formation and colorectal cancer development as demonstrated by multiple colorectal-carcinoma cases.
1
Carbamazepine overdose: a prospective study of serum levels and toxicity. A cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age, chronic exposure, or previous disorder or cardiovascular disease could be used as prognostic indicators. Seventy-three consecutive cases were collected from two regional certified poison control centers from January 1989 to August 1989. There were 25 exposures in children less than 6 yrs., 11 exposures in adolescents, and 37 exposures in adults. Ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information. Peak measured serum levels ranged from 0.3 to 56 mcg/ml. Using the presence of coma, seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity, we found poor correlation between rising serum levels of carbamazepine and toxicity. Increased serum levels of carbamazepine did appear to correlate with increased hospital stay, but not with ICU stay. History of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose. In this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect. Serum levels below 40 mcg/ml do not appear to accurately predict the severity of toxicity. Cardiac conduction defects were rare (one child). Anticholinergic findings, as evidence by decreased bowel motility and sinus tachycardia were common. Previous cardiovascular disease and age did not appear to be important prognostic indicators.
2
Emery-Dreifuss muscular dystrophy. Emery-Dreifuss syndrome is a rare form of muscular dystrophy associated with cardiac complications that lead to sudden death. The disorder and its potential anaesthetic implications in the management of a patient who presented for orthopaedic surgery is described.
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Squamous cell carcinoma of the anus and HIV infection. We retrospectively reviewed six patients with squamous cell carcinoma of the anus (SCCA) and human immunodeficiency virus (HIV) infection treated between 1985 and 1988. All six patients were homosexual men. Five patients had AIDS and one was HIV-positive. The most common symptoms and signs were pain (n = 5), mass (n = 5), and bleeding (n = 5). The average tumor size was 3.2 cm with a range of 1-10 cm. Five tumors were located in the anal canal and one at the anodermal junction. One patient was treated with biopsy alone, one with local excision, one with wide local excision and radiation therapy, and two with diverting colostomy. The average follow-up was 8 months. Of the five AIDS patients, two died, one was transferred to a hospice facility, one was lost to follow-up, and one remains alive 1 year following treatment. The HIV-positive patient died secondary to metastatic SCCA. This group of patients raises the question of a possible association between HIV and SCCA.
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Enteroclysis and small bowel series: comparison of radiation dose and examination time. Respective radiation doses and total examination and fluoroscopy times were compared for 50 patients; 25 underwent enteroclysis and 25 underwent small bowel series with (n = 17) and without (n = 8) an examination of the upper gastrointestinal (GI) tract. For enteroclysis, the mean skin entry radiation dose (12.3 rad [123 mGy]) and mean fluoroscopy time (18.4 minutes) were almost 1 1/2 times greater than those for the small bowel series with examination of the upper GI tract (8.4 rad [84 mGy]; 11.4 minutes) and almost three times greater than those for the small bowel series without upper GI examination (4.6 rad [46 mGy]; 6.3 minutes). However, the mean total examination completion time for enteroclysis (31.2 minutes) was almost half that of the small bowel series without upper GI examination (57.5 minutes) and almost four times shorter than that of the small bowel series with upper GI examination (114 minutes). The higher radiation dose of enteroclysis should be considered along with the short examination time, the age and clinical condition of the patient, and the reported higher accuracy when deciding on the appropriate radiographic examination of the small bowel.
1
Flexible sigmoidoscopy as a screening procedure in rural patients. In this study of flexible sigmoidoscopy as a screening procedure for rural, impoverished patients, 16% of asymptomatic patients who were screened by sigmoidoscopy and 23% of patients with a positive test for fecal occult blood were found to have a polyp or carcinoma. Flexible sigmoidoscopy appears to be an important part of the physical examination of patients older than 50. It is a test that can readily be done by primary care physicians in a rural setting.
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Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity for the potassium analogue rubidium-82 for assessing infarct size in man by PET Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is extracted after i.v. injection and retained in viable myocardium but is not trapped or washed out of necrotic regions. To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software. Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.
3
Treatment of intractable arterial hemorrhage during stereotactic brain biopsy with thrombin. Report of three patients. Of 165 consecutive patients undergoing computerized tomography- or magnetic resonance imaging-guided stereotactic brain biopsies at the Cleveland Clinic between June, 1987, and November, 1989, four patients (2.4%) developed arterial hemorrhage refractory to conventional efforts to secure hemostasis. Craniotomy was performed in one of these patients to control the hemorrhage; in the other three, 0.5 to 2 cc of thrombin (5000 U/cc) was slowly injected via the biopsy cannula, resulting in immediate control of bleeding in all three cases. Postoperatively, the first two patients treated with 1 to 2 cc of thrombin were slow to awaken; one had evidence of vasospasm by transcranial Doppler ultrasound studies and multiple infarcts on cranial computerized tomography, while the other had a moderate-sized frontal hematoma with intracranial hypertension. After prolonged recovery periods, only mild neurological deficits persisted in both patients. The third patient, treated with 0.5 cc of thrombin, had an uneventful postoperative course. Thrombin is highly effective for stopping intractable arterial hemorrhage during stereotactic brain biopsy; however, it is a vasospastic agent and may have been responsible for the cerebral infarctions in one patient. Therefore, thrombin should be used only as a last resort, short of craniotomy, to control intractable arterial hemorrhage during stereotactic brain biopsy.
4
Training, credentialling, and granting of clinical privileges for laparoscopic general surgery. Despite the lack of scientific data comparing it with traditional open operations, laparoscopic surgery has gained rapid acceptance and implementation by general surgeons. Individual hospitals, which have the responsibility for developing their own privileging criteria, are searching for guidance as to the amount and type of additional training required to grant clinical privileges in laparoscopic general surgery. Laparoscopic surgery involves techniques different from those learned during general surgery residency training. Therefore, until such techniques are regularly included in general surgery residency programs, additional training for and granting of separate privileges in laparoscopic surgery are appropriate. Adequate training for surgeons already experienced in abdominal and biliary tract surgery can be acquired through a preceptorship in diagnostic laparoscopy, attending a course in laparoscopic surgery that includes both didactic instruction and live animal experience, assisting with the procedures in humans, and being proctored and certified as competent by an experienced general surgeon.
1
Strain differences in baroreflex inhibition by centrally infused enalapril in old rats. To determine whether inhibition of the brain renin-angiotensin system would affect baroreflexes similarly in old rats of different strains, we compared 24-month-old male Fischer 344 and Sprague-Dawley rats. Baroreflex sensitivity was tested while the rats were awake by recording reflex heart rate responses elicited as blood pressure was elevated with phenylephrine or lowered with sodium nitroprusside. Sprague-Dawley rats had higher blood pressures and lower heart rates initially. Chronic infusion of enalapril, a converting enzyme inhibitor, into a lateral cerebral ventricle (ICV) for two weeks lowered blood pressure in Sprague-Dawley but not in Fischer 344 rats. Furthermore, reflex bradycardia was unaffected in either rat strain, but reflex tachycardia was selectively suppressed in Fischer 344 rats. Thus, although time controls were not done to rule out spontaneous changes during the 14-day infusion period, these results suggest that central cardiovascular regulation does not change similarly with age in these two rat strains. As removal of the brain renin-angiotensin system lowered blood pressure in one strain and inhibited reflex tachycardia in the other, the divergence could mean that the brain renin-angiotensin system acts differently to keep blood pressure elevated in Sprague-Dawley rats and modulate reflex tachycardia in Fischer 344 rats.
3
Coronary morphology after percutaneous directional coronary atherectomy in humans: autopsy analysis of three patients. The morphologic basis of angiographically successful percutaneous directional atherectomy and subsequent restenosis in human coronary arteries is unknown. The clinical and pathologic features of three patients who died after coronary atherectomy are described. Tissue fragments obtained with atherectomy demonstrated atheromatous and fibroproliferative intima, media and adventitia. At autopsy, treated vascular segments (from the left anterior descending artery in two patients and a vein graft in one patient) demonstrated discrete defects in the vascular wall. Defects extending into atheroma, media or adventitia corresponded with the presence of these tissues in the atherectomy specimens. Tissues were otherwise not disrupted in the manner associated with balloon angioplasty. Acute mural thrombus deposition was evident in the resection zone in one patient. Late findings included fibroproliferative intimal tissue extending from the resected areas into the vascular lumen. In one patient intimal hyperplasia was sufficient to narrow the vascular lumen by 82% and was implicated in subsequent myocardial ischemia and infarction. The study indicates that 1) the vascular injury associated with atherectomy is distinct from that associated with balloon angioplasty, 2) acute mural thrombus deposition may occur even with resection limited to the intima, and 3) intimal hyperplasia may develop in regions treated with atherectomy and may be associated with late myocardial ischemia and infarction.
3
Endoscopic palliative intubation of the esophagus invaded by lung cancer. Thirty-two patients with esophageal involvement by lung cancer were managed by endoscopic intubation. In 22 patients with extrinsic esophageal strictures, the success rate of intubation was 91%, and 82% were discharged with their dysphagia relieved and esophageal patency restored. The mean survival rate was 4.4 months. In 10 patients with esophago-bronchial fistulas, 3 had the fistulous tract obliterated and lived a mean of 5 months. This low success rate of closing fistulas is due to failure to seal off the space between the stent and the fistula because of absence of tumor-associated stenosis. The overall morbidity rate was 28.1% (18.8% perforation, 6.3% hemorrhage, and 3.1% tracheal obstruction). The overall mortality rate was 18.8%. Although complications were more frequent than in primary esophageal tumors, endoscopic intubation was the only way to palliate this desperate condition and provided 66.6% of patients with relief of symptoms, nutritional improvement, and a mean survival time of 4.5 months.
1
Limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy. An analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring. Seventy patients (15%) had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed. Ischemic encephalographic changes occurred in 26% of patients with an occluded contralateral carotid artery, 21% of patients with a prior stroke history, and 12% of patients with no stroke history and a patent contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this experience. Ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia. Five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure. Two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure, and thus deficits not manifest by operative electroencephalographic changes developed. Our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy.
3
Aortic dissection with the entrance tear in transverse aorta: analysis of 12 autopsy patients. Clinical and autopsy findings are described in 12 patients who had fatal aortic dissection with the entrance tear in the transverse aorta. The 12 patients represent 7% of 182 autopsies of spontaneous aortic dissection studied by us. The ages of the 12 patients at death ranged from 37 to 87 years (mean, 67 years). Eight were men; 8 had a history of systemic hypertension, and 10 had hearts of increased weight. Diagnosis of aortic dissection was made during life in only 4 of the 12 patients. All 12 patients died of rupture of the false channel within 2 weeks of onset of signs or symptoms compatible with dissection. The direction of aortic dissection from the entrance tear was entirely retrograde in 4 patients, entirely anterograde in 4 patients, and in both directions in 4 patients. Hemopericardium occurred in the first group, left hemothorax in the second group, and either in the last group. Of the 8 patients in whom the ascending aorta was involved, the retrograde dissection in each extended to the aortic root, 6 had pulmonary adventitial hemorrhage, and 4 had involvement of the arch arteries by dissection. In the 4 patients with strictly anterograde dissection, none had dissection in the arch arteries. Thus, tear in the transverse aorta causes a dissection that is usually fata, that often dissects retrogradely, and that may mimic dissection from a tear in ascending aorta. Aortic dissection from a tear in transverse aorta requires early operative intervention.
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Outcome of prophylactic therapy for idiopathic anaphylaxis. OBJECTIVE: To determine the efficacy of a prophylactic regimen (prednisone, H1 blockade, and sympathomimetic amine therapy) in patients with idiopathic anaphylaxis. DESIGN: Clinical trial before and after treatment. SETTING: Referral-based allergy clinic at a major medical center. PATIENTS: Fifty-three patients with a history compatible with idiopathic anaphylaxis for at least 6 months before presentation to the allergy service and with subsequent management by the service for at least 6 months. INTERVENTIONS: Patients with frequent life-threatening symptoms were treated with a prophylactic regimen. Patients with infrequent episodes of idiopathic anaphylaxis were only treated acutely for each episode of anaphylaxis. MEASUREMENTS AND MAIN RESULTS: The results favored prophylactic treatment with prednisone for patients who were classified as generalized-frequent in the clinical outcome measures of frequency (per patient per year) of episodes (mean before treatment, 7.31 +/- 6.46; after treatment, 3.61 +/- 4.73; P less than 0.02) and emergency room visits (mean before treatment, 1.94 +/- 3.42; after treatment, 0.21 +/- 0.44; P less than 0.005) and for patients classified as angioedema-frequent in the frequency of episodes (mean before treatment, 14.93 +/- 15.89; after treatment, 2.58 +/- 2.18; P less than 0.003) and emergency room visits (mean before treatment, 0.76 +/- 1.01; after treatment, 0.07 +/- 0.11; P less than 0.025). No statistically significant difference was found for patients classified as generalized-infrequent in the frequency of episodes (mean before treatment, 2.01 +/- 1.30; after treatment, 1.36 +/- 1.79) or of the emergency room visits (mean before treatment, 0.56 +/- 0.71; after treatment, 0.32 +/- 0.75) or for patients classified as angioedema-infrequent in the frequency of episodes (mean before treatment, 1.94 +/- 1.55; after treatment, 2.03 +/- 2.16) or of emergency room visits (mean before treatment, 0.27 +/- 0.44; after treatment, 0.37 +/- 0.59). CONCLUSIONS: Prophylactic treatment with prednisone and H1 antihistamines with or without sympathomimetic amines improves clinical outcome in patients who are classified as idiopathic anaphylaxis-angioedema frequent and idiopathic anaphylaxis-generalized frequent.
3
Cholesterol and coronary heart disease. Future directions. The importance of high serum cholesterol levels as a risk factor for coronary heart disease and the benefit of lowering cholesterol levels for reducing risk are being increasingly accepted. A broad consensus to this effect has led to the establishment of the National Cholesterol Education Program. Although the available evidence fully justifies this program, its practical application to the American public has generated a series of new questions that must be explored. For example, it can be questioned whether reduction in coronary risk through lowering cholesterol levels extends to both sexes and all age groups. For people with high cholesterol levels, dietary modification is undoubtedly the first step of management, but the fraction of people responding adequately to dietary change remains to be determined. Finally, indications for drug therapy and choice of drugs need further exploration, particularly in the area of cost vs benefit. Thus, continuing research must be carried out in parallel with clinical and public health application of cholesterol education.
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A deletion in the gene for glycoprotein IIb associated with Glanzmann's thrombasthenia. The platelet fibrinogen receptor is composed of a complex of glycoproteins (GP) IIb and IIIa on the surface of platelets. Deficient function of this receptor prevents normal platelet aggregation, resulting in Glanzmann's thrombasthenia (GT). In this paper, we describe a black thrombasthenic patient who is either homozygous or hemizygous for a deletion within the GPIIb gene. Initial Western blot analysis of platelet proteins from this patient did not detect any GPIIb, but did detect small amounts of GPIIIa of normal mobility. Quantitation of vitronectin receptor (VNR) demonstrated that this thrombasthenic patient had approximately 1.5-2 times the number of these receptors per platelet compared with controls, a finding that has previously been noted in other thrombasthenic patients with defects in GPIIb. Genomic Southern blot studies demonstrated a deletion in the GPIIb gene of approximately 4.5 kilobasepairs (kb). Analysis of the isolated GPIIb gene demonstrated that the deletion begins between two Alu repeats within intron 1 and ends in intron 9. Polymerase chain reaction (PCR) studies using platelet RNA and oligonucleotides directed to both the 5' and 3' ends of the GPIIb cDNA sequence easily detected GPIIb transcript, suggesting that the genomic deletion of exons 2-9 does not significantly decrease the level of the GPIIb mRNA. Sequence analysis of PCR-generated GPIIb cDNA showed that a cryptic AG splice acceptor sequence was being utilized, resulting in a transcript that contained a portion of introns 1 and 9, as well as having a deletion of exons 2-9. Unlike the GPIIb gene, the GPIIIa gene appears to be intact by Southern blot analysis. PCR studies using platelet RNA and oligonucleotides directed to the GPIIIa cDNA sequence demonstrated the presence of GPIIIa mRNA. In summary, the thrombasthenic state in this patient appears to be due to a GPIIb gene deletion resulting in an abnormal transcript and no detectable platelet GPIIb. Platelet GPIIIa levels were secondarily low presumably due to the known instability of GPIIIa in the absence of GPIIb.
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Time course of improvement in ventricular function after ablation of incessant automatic atrial tachycardia. A patient with dilated cardiomyopathy and supraventricular tachycardia presumed to be of sinus origin was referred for cardiac transplantation. The extreme rate of the tachycardia during exercise, profound fluctuations in heart rate, and the presence of an abnormal P wave axis suggested the diagnosis of incessant ectopic atrial tachycardia rather than compensatory sinus tachycardia. Electrophysiologic study with endocardial activation sequence mapping confirmed the diagnosis of an ectopic left atrial automatic tachycardia, after which surgical cryoablation of the left atrial focus was carried out successfully and sinus rhythm was restored. Serial radionuclide angiocardiograms obtained before and after surgery demonstrated a very rapid recovery of left ventricular function to nearly normal within the first month after surgery, followed by further improvement to normal over the next several months. The diagnosis of tachycardia-related cardiomyopathy should be seriously considered in any patient with apparently end-stage dilated cardiomyopathy and persistent resting tachycardia.
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Childhood blindness in Peru. A survey of childhood blindness in Peruvian children was done. Although most causes of blindness were due to congenital and hereditary conditions, measles accounted for almost 10% of blindness. With widespread measles immunization, this preventable cause of blindness in children can be eliminated or dramatically reduced.
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Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation. The case of a 35-year-old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented. Histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level. Focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron-microscopic studies. It is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone-producing cell types. The factors accounting for differentiating to various cell populations have yet to be elucidated.
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Primary lymphoma of the liver: clinical and pathological features of 10 patients. Nine out of 10 patients with primary lymphoma of the liver presented in a manner that did not suggest a tumour. The initial diagnoses were chronic active hepatitis in three cases and "granulomatous cholangitis", inflammatory pseudotumour, and anaplastic carcinoma in one case each. Moreover, extensive haemorrhagic necrosis in three cases initially suggested the Budd-Chiari syndrome. All the tumours were diffuse non-Hodgkin's lymphomas like the 50 cases reported previously, but they differed from most of these in that nine were of T cell phenotype. Five were pleomorphic small T cell, two T zone, and two T lymphoblastic lymphomas: only one was centrocytic and of B cell lineage. This report extends the range of clinical manifestations (diffuse hepatomegaly without a tumour), histological appearances (resemblance to chronic inflammatory or vascular liver diseases) and phenotype (of T cell lineage) of primary lymphoma of the liver: these features seemed to be related in this series. Recognition is important as prognosis remains favourable in appropriately treated cases. Although the appearances of the liver biopsy specimens may be difficult to interpret, the destructiveness of the infiltrate is an important clue to the diagnosis.
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Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on the roles of endotoxin and tumor necrosis factor alpha (TNF alpha). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 +/- 0.50 U/mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 +/- 3.11 U/mL, p greater than 0.05 and 10.41 +/- 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury.
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Suprasellar pituitary adenoma arising from the pars tuberalis: case report. A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted.
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Tumorigenic 3T3 cells maintain an alkaline intracellular pH under physiological conditions. One of the earliest events in the response of mammalian cells to mitogens is activation of Na+/H+ exchange, which increases intracellular pH (pHin) in the absence of HCO3- or at external pH values below 7.2. The proliferative response can be blocked by preventing the pHin increase; yet, the proliferative response cannot be stimulated by artificially raising pHin with weak bases or high medium pH. These observations support the hypothesis that optimal pHin is a necessary, but not sufficient, component of the proliferative-response sequence. This hypothesis has recently been challenged by the observation that transfection of NIH 3T3 cells with yeast H(+)-ATPase renders them tumorigenic. Although previous measurements indicated that these transfected cells maintain a higher pHin in the absence of HCO3-, whether H(+)-ATPase transfection raised the pHin under physiologically relevant conditions was not known. The current report shows that these transfected cells do maintain a higher pHin than control cells in the presence of HCO3-, supporting the possibility that elevated pHin is a proliferative trigger in situ. We also show that these cells are serum-independent for growth and that they glycolyze much more rapidly than phenotypically normal cells.
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Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer. Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer. Since intestinal motility of the Roux limb has never been evaluated after this operation, pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction. Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal. During fasting only two patients had activity fronts and these were abnormal. All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions. The fed state was characterized by a severely reduced motor activity pattern and other abnormalities. Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity.
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Pediatric HIV disease. The newest chronic illness of childhood. HIV disease has emerged as a major chronic illness of childhood. Children with HIV infection and children with other chronic health impairments have much in common, including the need for comprehensive, multidisciplinary, coordinated care that includes special attention to the psychosocial effects on the child and family. However, because the mother and often the father and siblings share this lethal viral infection, the impact of HIV disease upon the family surpasses that of virtually all other chronic conditions. This is compounded by the association of the disease with drug use, its preponderance among the most disenfranchised populations in the United States, and the persistent public fear and discrimination surrounding AIDS. We have made substantial progress already in the medical management of this infection, and while we await the development of more effective therapies, we already have the tools and knowledge in hand to help these families.
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