Melricflash/CW_MedAbstractsAlt 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. 

Category: neoplasms
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. 

Category: general pathological conditions
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. 

Category: digestive system diseases
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. 

Category: cardiovascular diseases
Prognostic factors in alcoholic liver disease. VA Cooperative Study Group. Two hundred eighty-one alcoholic patients were prospectively evaluated by clinical, biochemical, and histologic parameters during a 4-yr period to assess their prognosis. They were stratified into four categories of injury: 1) fatty liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and 4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival and variables correlating with survival varied according to the group. At 48 months, 70% of the patients with fatty liver were alive, 58% in the alcoholic hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed upon cirrhosis. Within group one, deaths were due to causes unrelated to liver disease. In the alcoholic hepatitis group, factors significantly correlating with survival were ascites, alanine amino-transferase levels, grams of alcohol consumed, continuation of alcohol intake, and clinical severity of disease. Survival in patients of group three correlated significantly with prothrombin time and histologic severity score. Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis, with the most significant predictors of survival being age, grams of alcohol consumed, the ratio of serum aminotransferases (AST:ALT) and the histologic and clinical severity of the disease. Although a different pattern of correlates was observed for each pathologic level of injury, knowledge of the various correlates aids in prognostic assessment. 

Category: general pathological conditions
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. 

Category: digestive system diseases
Diltiazem therapy for symptoms associated with nutcracker esophagus. A randomized double-blind, cross-over prospective trial in 22 patients was designed to evaluate possible effect of an oral calcium channel blocker, diltiazem, on symptoms of chest pain and/or dysphagia in patients with nutcracker esophagus. We studied 22 consecutive patients referred to an esophageal diagnostic center for evaluation of noncardiac chest pain or dysphagia having high amplitude esophageal contractions, 14 of whom completed the study. Diltiazem (60-90 mg qid) was compared with placebo, each being administered for 8 wk. Patients were evaluated with esophageal motility pre- and posttreatment periods and with regular symptom assessment throughout each 8-wk treatment. Active diltiazem therapy resulted in significantly lower (p less than 0.05) mean distal esophageal peristaltic pressure (128 +/- 20 mm Hg; +/- SE) than placebo (158 +/- 16 mm Hg). Mean chest pains scores were significantly (p less than 0.05) lower with diltiazem therapy than with placebo. Only nine of the 14 patients fulfilled presently acceptable criteria for diagnosing nutcracker esophagus, and the diltiazem effect was similar, although not significant, because of the smaller sample. Conclusions: In this preliminary study involving 14 patients, the oral calcium channel blocker, diltiazem, appeared to improve noncardiac chest pain associated with strong esophageal contraction, the nutcracker esophagus. These improved symptoms were associated with significant decreases in contraction pressure. 

Category: digestive system diseases
Infantile systemic hyalinosis: newly recognized disorder of collagen? Four infants with stiff skin and painful joint contractures in the first few months of life are described. Other features included small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia, persistent diarrhea, and failure to thrive. Two of these infants died before the age of 18 months. In each case hyaline material was found in the papillary dermis. Ultrastructurally, there was a distinctive fibrillogranular appearance in which a banding pattern could be observed. This material was also found within membrane-bound vacuoles in macrophages and fibroblasts. It had an appearance and localization identical with that of collagen type VI. These features are similar to those reported in juvenile hyaline fibromatosis. It is believed that these infants have a closely related, but nonetheless distinctive, inherited disorder of collagen. 

Category: nervous system diseases
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. 

Category: nervous system diseases
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. 

Category: general pathological conditions
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. 

Category: general pathological conditions
Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina. Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression. 

Category: cardiovascular diseases
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. 

Category: neoplasms
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. 

Category: cardiovascular diseases
Direct measurement of skeletal muscle fatigue in patients with chronic heart failure. Skeletal muscle function was measured as force production and fatigue in both the quadriceps (a large locomotive muscle) and adductor pollicis (a small intrinsic hand muscle) in five healthy volunteers, five patients with mild chronic heart failure, and five patients with severe chronic heart failure. The quadriceps of patients with chronic heart failure had a reduced muscle cross sectional area, a reduced maximum isometric force production, and an increased tendency to fatigue. Isometric force production and fatigue of the adductor pollicis, however, were not significantly different between the three groups under control conditions. But during circulatory occlusion fatigue in the adductor pollicis increased more in the patients with severe chronic heart failure. These differing findings in quadriceps and adductor pollicis suggest that skeletal muscle atrophy and reduced isometric force production are not a necessary consequence of chronic heart failure per se, because they were only present in the large locomotive muscle. The normal values for muscle fatigue observed in adductor pollicis in patients with chronic heart failure imply that skeletal muscle blood flow must increase normally during muscle activation when only a small muscle mass is used. These results are not compatible with the concept of a generalised impairment of normal vasodilatation within active skeletal muscle. In contrast, activation of a large muscle, such as quadriceps, results in the rapid onset of fatigue in patients with severe chronic heart failure. This fatigue may be related to the inability of the cardiovascular system to provide the required blood flow for the activation of a large muscle mass. 

Category: cardiovascular diseases
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. 

Category: cardiovascular diseases
Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. To investigate the incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection, a prospective follow-up study was conducted in two consecutive groups of patients. Group I consisted of 984 patients (859 men and 125 women) with biopsy-proven chronic type B hepatitis, whereas group II consisted of 1,598 asymptomatic chronic carriers (998 men and 600 women) with normal serum aminotransferase activity. During a mean follow-up period of 4.0 +/- 2.3 yr, 19 patients (1.9%) of group I cleared HBsAg from their serum, whereas 35 patients (2.2%) in group II did so in a mean follow-up period of 2.7 +/- 1.4 yr. The annual incidence of delayed serum HBsAg clearance was 0.5% in group I and 0.8% in group II (p less than 0.02). The cumulative probability of HBsAg clearance was also higher in group II than in group I (p less than 0.007). Antibodies to HBsAg developed in 9 patients (47.4%) with chronic hepatitis and in 11 (31.4%) asymptomatic carriers who cleared serum HBsAg. Those who were HBeAg negative and those older than 40 at entry and those who exhibited cirrhosis during follow-up had a higher incidence of delayed HBsAg clearance. Gender, initial histological changes and hepatitis delta virus infection did not influence the occurrence of HBsAg clearance. Serum HBV DNA was not detectable by slot-blot hybridization but was still detectable by polymerase chain reaction in serum specimens collected within 1 yr of HBsAg clearance. Liver biopsy performed later in 10 patients showed no significant hepatitis activity or tissue HBV DNA, HBsAg or HBcAg. 

Category: digestive system diseases
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. 

Category: general pathological conditions