123rc/medical_text huggingface dataset:
Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia. Because trimethoprim-sulfamethoxazole (TMP-SMX) causes neutropenia in children with leukemia, we investigated the possibility that pharmacokinetic interaction between methotrexate (MTX) and TMP-SMX causes accumulation of the antileukemia agent. We studied the pharmacokinetics of MTX given intravenously or orally to nine children with acute lymphoblastic leukemia, once with and once without TMP-SMX. There was an increase in free MTX fraction during TMP-SMX therapy in all patients, from (mean +/- SD) 37.4 +/- 11% without TMP-SMX to 52.2 +/- 6.4% with TMP-SMX (p less than 0.01). Plasma clearance of total MTX did not change significantly, whereas clearance of free MTX decreased significantly (from 12.5 +/- 4 to 7.6 +/- 1.5 ml/kg/min; p less than 0.05). There was a consistent decrease in the renal clearance of free MTX (from 12.1 +/- 6.8 to 5.6 +/- 2.4 ml/kg/min; p less than 0.05). Elimination half-life of MTX was not affected significantly by TMP-SMX. There was a significant correlation between serum concentrations of TMP-SMX and the percentage of decrease in the renal clearance of free MTX (r = 0.91; p less than 0.05). These changes in protein binding and tubular clearance of MTX, caused by competition with TMP-SMX, result in a mean 66% increase in systemic exposure to MTX and may explain the myelotoxicity often observed with the coadministration of the two drugs.
Clinical prediction rule for pulmonary infiltrates OBJECTIVE: To derive and validate a clinical rule for predicting pneumonic infiltrates in adult patients with acute respiratory illness. DESIGN: Prevalence studies in three settings. SETTING: Emergency departments of the University of Illinois Hospital at Chicago, the University of Nebraska Medical Center at Omaha, and the Medical College of Virginia at Richmond. PATIENTS: Symptoms, signs, comorbidity data, and chest roentgenogram results were recorded for 1134 patients from Illinois (the derivation set), 150 patients from Nebraska, and 152 patients from Virginia (the validation sets). All patients presented to the emergency department and had a chest roentgenogram to evaluate fever or respiratory complaints. MEASUREMENTS AND MAIN RESULTS: Within the training set, temperature greater than 37.8 degrees C, pulse greater than 100 beats/min, rales, decreased breath sounds, and the absence of asthma were identified as significant predictors of radiographically proved pneumonia in a stepwise logistic regression model (P = 0.001). The logistic rule discriminated patients with and without pneumonia in the training set with a receiver operating characteristic (ROC) area of 0.82. In the validation sets, the rule discriminated pneumonia and nonpneumonia with ROC areas of 0.82 and 0.76 after adjusting for differences in disease prevalence (P greater than 0.2 compared with the training set). The predicted probability of having pneumonia for patients with different clinical findings corresponded closely with the incidence of pneumonia among patients with such findings in the three settings. CONCLUSIONS: Among adults presenting with acute respiratory illness, a prediction rule based on clinical findings accurately discriminated patients with and without radiographic pneumonia, and was used in two other samples of patients without significant decrement in discriminatory ability. This rule can be used by physicians to develop more effective strategies for detecting pneumonia and for helping to determine the need for radiologic study among patients with acute respiratory disease.
Treatment of refractory oral candidiasis with fluconazole. A case report. We describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was demonstrated as well. The patient received temporary relief with intravenous amphotericin B therapy, but this was associated with serious adverse effects, including transfusion-requiring anemia, azotemia, and severe thrombophlebitis. Despite two courses of intravenous amphotericin B therapy, the patient's highly symptomatic, recurrent oral and esophageal candidiasis continued. The patient was then treated with fluconazole and obtained immediate relief without associated adverse effects.
Annulo-aortic ectasia with DeBakey type II dissecting aneurysm in Gaucher's disease. Annulo-aortic ectasia is an extremely rare complication of Gaucher's disease. We report successful surgery in a patient with Gaucher's disease complicated by annulo-aortic ectasia and aortic dissection. Cabrol's operation was accomplished without bleeding or sternal adaptation problems.
Sequential esophageal motility studies after endoscopic injection sclerotherapy: a prospective investigation. To assess prospectively the effects of endoscopic intravariceal sclerosis (EIS) on esophageal function, we performed esophageal manometry on 13 cirrhotic patients before EIS, 24 h after the second session and 4 wk after the fourth session. EIS had no impact on lower esophageal sphincter pressure. However, a significant decrease in the amplitude of peristaltic waves was observed immediately post-EIS in the lower two-thirds of the esophagus. There was no modification of duration or velocity of progression of peristaltic waves. A four-fold increase in simultaneous contractions was observed early after EIS. These changes were reversible, as assessed by late esophageal testing after EIS. No correlations were demonstrated between esophageal motor parameters and doses of sclerosant. We conclude that sclerosant injection into the esophageal wall acutely impairs esophageal motility, but motor function is partially restored 4 wk after completion of EIS, suggesting that dysmotility is reversible.
Survey of adolescents with severe intellectual handicap. A diagnostic survey was undertaken of children aged 11 to 19 years in Tameside with severe learning difficulties (intelligence quotient less than or equal to 50). Eighty-two children were identified and their medical records reviewed. A specific diagnosis for the retardation was documented in 25 (30%) of the children, 18 of whom had Down's syndrome. A probable aetiology or a disorder of unknown aetiology had been identified in a further 21 (26%) children. To confirm the existing diagnosis, identify new diagnoses, and offer genetic counselling, the parents of 63 children were offered detailed reassessment of their child. Fifty three children were reviewed, and a specific disorder identified in 25 out of 31 previously undiagnosed children. The most frequent diagnoses made were fragile X syndrome and Rett's syndrome. On completion of the survey, 61 of the 82 children (74%) had a specific diagnosis or probable aetiology identified, 12 (15%) had associated disorders such as cerebral palsy, and in only nine of the 82 children (11%) were there no clues at all to the cause of their retardation.
Repair of cartilage lesions using biological implants. A comparative histological and biomechanical study in goats. We report the experimental use of three different biological implants to restore articular surface defects: glutaraldehyde-fixed bovine meniscal xenograft, glutaraldehyde-fixed bovine costal cartilage xenograft, and viable osteochondral allografts. The grafts were implanted in the knees of 19 goats who were allowed free-field activity and were studied for up to one year. The natural articular surfaces of meniscal fibrocartilage provided excellent articular surfaces at all times. Equally good articular surfaces were restored by host tissue growth covering costal cartilage grafts at six months, but by 12 months this surface had degenerated. The majority of the allografts survived and integrated with the host at six months, but many showed signs of failure at 12 months. Only three out of seven ungrafted defects healed completely at six months and the healed surfaces were degenerating at 12 months.
Sudden unexpected nocturnal death syndrome in the Mariana Islands. Sudden unexpected nocturnal death syndrome (SUNDS) is a distinct clinical entity in previously healthy, young, Southeast Asian males. It is well known in the Philippines and more recently recognized in the U.S. by nonspecific autopsy findings, with no evidence of underlying disease and absence of toxic drug or alcohol levels. In 1973-89, 14 cases of apparent SUNDS came to coroner's autopsy in the Commonwealth of the Northern Marianas (CNMI) and Guam. All 14 cases, with the exception of one Yapese, were previously healthy, male Filipinos, aged 23 to 55, who were either found dead in bed, or described by their colleagues as having nocturnal seizure activity consisting of gurgling, frothing, and tongue biting immediately prior to death. Autopsy findings showed no anatomic findings to account for death. Comprehensive serum and urine drug analyses were negative. All decedents showed absence of significant atherosclerosis or grossly detectable structural cardiac anomaly, while four showed cardiomegaly. Migrants from Southeast Asia carry with them a pre-disposition to this syndrome, which appears to decline with longer residence in the new country. The mechanism of death in SUNDS is believed to be ventricular fibrillation, possibly precipitated by sudden sympathetic discharge. Studies suggest at least some deaths may be associated with an abnormal cardiac conduction system. Acute pancreatitis has been a finding in some series, but not our cases. Why the condition is virtually limited to males and seemingly sleep-triggered, has not been adequately explained. Stress and depression are believed to be predisposing factors.
Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records. The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma. Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records. Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur.
Prostacyclin-to-thromboxane A2 ratio in arteriogenic impotence. It has been suggested that penile hypercoagulability predisposes to aging penile vascular changes and impotence, and that elevated thromboxane A2 during erection may contribute to hypercoagulability and atherosclerosis. Since the ratio of the prostacyclin concentration to the thromboxane A2 concentration is constantly maintained in normal hemostatic responses, an imbalance between thromboxane A2 and prostacyclin may be a factor to initiate vascular diseases and decrease blood flow. We assess the usefulness of the prostacyclin-to-thromboxane A2 ratio in penile blood during erection for diagnosis of arteriogenic impotence. The ratio in the arteriogenic impotence group was significantly lower (p less than 0.01) than in the psychogenic and venogenic impotence groups. Therefore, the prostacyclin-to-thromboxane A2 ratio seems to be useful to diagnose arteriogenic impotence.
Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension. Patients with untreated hypertension have been shown to be resistant to insulin-stimulated glucose uptake and are more hyperinsulinemic and hypertriglyceridemic than matched groups of patients with normal blood pressure. In addition, insulin resistance, hyperinsulinemia, and hypertriglyceridemia have been demonstrated in spontaneous hypertensive rats and in Sprague-Dawley rats fed a fructose-enriched diet. The defect in insulin-stimulated glucose uptake in these experimental models can also be shown at the cellular level. Experimental interventions that prevent insulin resistance or hyperinsulinemia from developing in fructose-fed rats also greatly attenuate the increase in blood pressure. Since endogenous hyperinsulinemia and hypertriglyceridemia have been identified as factors that increase the risk of coronary artery disease (CAD), it is likely that they contribute to the increased prevalence of CAD in hypertensive patients. Antihypertensive treatment may have exacerbated these metabolic abnormalities, which could help explain why it has been difficult to show that lowering blood pressure decreases the risk of CAD. These observations raise the possibility that abnormalities of carbohydrate and lipoprotein metabolism may play a role in both the etiology and clinical course of hypertension.
Premature menopause because of an inherited deletion in the long arm of the X-chromosome. A family is described in which both a mother and an infertile daughter had premature menopause at the ages of 31 and 28 years, respectively. Initially, an extensive investigation revealed no apparent cause for their conditions. However, when cytogenetic analysis in the daughter was performed, a terminal deletion in the long arm of one of the X-chromosomes was found. The karyotype was: 46,Xdel(X),(q25-qter). Chromosomal investigation in the mother showed an identical deletion. The karyotype of the patient's 35-year-old sister is normal. She has a normal menstrual cycle and two normal children. The presence of such familial cases suggests that chromosomal investigation should be considered in young women with oligomenorrhea, especially those whose mothers have experienced a premature menopause.
Superior hypophyseal artery aneurysm. Report of two cases. Two cases of saccular intracranial aneurysms arising from the superior hypophyseal artery take-off from the internal carotid artery are presented. The angiographic findings and technical details of the operative approach are discussed. Particular attention is focused on the use of fenestrated angled clips.
Effects of exercise on myocardial catecholamine content and ischemic injury in dogs with gradual coronary occlusion. The effects of exercise on catecholamine content and the extent of myocardial damage in dogs with Ameroid constrictor occlusion of the left circumflex coronary artery were determined. Tissue samples from both the anterior and posterior walls of the left ventricle were obtained for determination of catecholamine content, and the rest of the ventricles were processed for histologic examination. When subjected to treadmill exercise for 40 days after surgery, obstructed animals performed significantly less exercise than sham-operated animals and showed significantly higher percentages of ischemia and necrosis in the left ventricle than sedentary, obstructed, sham-operated, or control dogs. Levels of norepinephrine and epinephrine in the posterior wall of the left ventricle were significantly lower than in the other groups. Our data show that exercise in this well-known model of chronic coronary artery stenosis produced deleterious effects on the myocardium and suggest a marked heterogeneity of catecholamine stores in the myocardium that may have important functional and electrophysiologic consequences.
Technetium-99m sestamibi myocardial imaging: same-day rest-stress studies and dipyridamole. Unlike thallium-201, technetium-99m (Tc-99m) sestamibi does not redistribute in the myocardium after injection. Thus, 2 separate injections, 1 at rest and the other at stress (or after dipyridamole), are required to differentiate ischemia from scar. From a physical viewpoint, a 24-hour interval between the 2 injections is preferable for detection of coronary artery disease (CAD) with Tc-99m sestamibi imaging. However, same-day studies are more convenient in clinical practice. Results of studies using different Tc-99m sestamibi injection protocols are presented with emphasis on the advantages of a rest-stress injection sequence with a low dose at rest (7 mCi) followed 2 hours later by a higher dose at stress (25 mCi). A prospective study was conducted in a patient population with proven CAD using same-day studies to compare a rest-stress (7 and 25 mCi, respectively) to a stress-rest (7 and 25 mCi) Tc-99m sestamibi injection sequence. There was an agreement in 87.3% of the analyzed segments between the 2 protocols. However, the largest discordance for type of defect applied to 7.4% of the segments judged ischemic in the rest-stress protocol, which were called scars on stress-rest. This study showed that a rest-stress sequence is preferable when using a same-day protocol with a short time interval (less than 2 hours) between the 2 Tc-99m sestamibi injections because the rest image performed initially represents a "true" rest study, which is not necessarily the case with the stress-rest sequence. Preliminary studies were performed to evaluate dipyridamole with Tc-99m sestamibi imaging in normal subjects and in patients with CAD. These studies showed that treadmill and dipyridamole Tc-99m sestamibi imaging are comparable and the results are similar to those obtained with thallium-201.
Primary undifferentiated small cell carcinoma of the esophagus: clinicopathological and flow cytometric evaluation of eight cases. We present a clinicopathological and flow cytometric evaluation of eight primary small cell carcinomas of the esophagus representing 1.5% of all esophageal malignancies diagnosed during a 22-year period (1965-1987) in the Tampere University Central Hospital. The mean age of the patients (four male and four female) was 67 years (range 55-75 years). Five cases had distant metastases at the time of diagnosis. Three patients were treated by esophageal resection, one by laser vaporisation, and four by chemotherapy. The median survival time was 4 months (range 9 days to 8 months). A complete local response to chemotherapy in serial esophagogramms was detected in one patient. All four patients given chemotherapy survived longer than those treated with esophageal resection only. Four (67%) of the six carcinomas analyzed by DNA flow cytometry contained DNA-aneuploid stemlines. The median S-phase fraction of these small cell carcinomas was high (16.3%), reflecting rapid cell proliferation rate, which may be related to their responsiveness to chemotherapy.
Stress and sodium intake in neural control of renal function in hypertension. The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process.
Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue lesions. Both DNA index and Ki-67 score were independently reported to be associated with grade and prognosis in sarcomas, but no direct comparison of these two variables was made. It was attempted to measure proliferative activity in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen, p105. Lesions were given a grade according to lesion category (reactive, 1; benign, 2; low-grade malignant, 3; and high-grade malignant, 4). Ki-67 reactivity correlated relatively well with this grading system (r = 0.59); benign lesions usually exhibited a low Ki-67 score and malignant lesions usually but not always exhibited a high score. For example, some malignant fibrous histiocytomas contained only rare positive cells. Some disparity between Ki-67 score and grade and within histologic types indicates some independence from these features, a fact that may be important when correlation with prognosis is performed. However Ki-67 did not correlate well with flow data such as percentage S phase (r = 0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39). This probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas these are excluded in flow data analyses. Anti-p105 highlighted almost all nuclei in all cases tested, including fibromatosis, and did not correlate with Ki-67 score, histologic grade or DNA flow cytometric data. Results with p105 could not be favorably affected by titration experiments. It is reasonable to conclude that the Ki-67 score is a variable related to but independent of histologic grade, histologic type, and DNA flow values. Whether it is prognostically important in human sarcomas, as has been suggested, awaits further clinicopathologic study.
Systemic pattern of free radical generation during coronary bypass surgery. Diffuse impairment of ventricular function after cardiac surgery may be related to the generation during reperfusion of the myocardium of free radicals derived from oxygen. Fifteen patients undergoing elective coronary bypass surgery were studied by previously described assays for peroxidised lipids and for isomerised lipids which were used as indices of free radical activity. Serial blood samples were obtained from systemic arterial, mixed venous, and coronary sinus catheters before, during, and after the ischaemic period. The patients underwent coronary artery surgery on cardiopulmonary bypass with a membrane oxygenator, relative hypothermia 30-34 degrees C, and intermittent cross-clamping of the aorta. During the ischaemic periods there were no significant changes in the indices of free radical activity. During the reperfusion phase there was a significant increase in free radical indices in arterial and mixed venous blood. A small rise in free radical indices in coronary venous blood was not statistically significant. These data indicate that free radical activity is increased in patients shortly after the cessation of cardiopulmonary bypass. The pattern of distribution between the different sampling sites suggests that much of the observed increase in isomerised and peroxidised lipids originates from tissues other than the myocardium.