Showing papers in "The New England Journal of Medicine in 1992"
Harvard University1, University of Texas Health Science Center at Houston2, Stony Brook University3, University of Manitoba4, Washington University in St. Louis5, University of Arizona6, University of Missouri7, Université de Montréal8, Icahn School of Medicine at Mount Sinai9, Laval University10, Yeshiva University11
TL;DR: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events.
Abstract: Background. Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with the angiotensin-converting—enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. Methods. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive double-blind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. Results. Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent conf...
5,503 citations
TL;DR: The two hypotheses to explain the pathogenesis of atherosclerosis, the "incrustation" hypothesis and the "lipid" hypothesis, are now known.
Abstract: IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .
3,779 citations
TL;DR: The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction.
Abstract: Background It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. Methods Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. Results There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). Conclusions The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.
3,554 citations
TL;DR: A randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects.
Abstract: Background. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known. Methods. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. Results. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetu...
2,951 citations
TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Abstract: Background. In atopic asthma, activated T helper lymphocytes are present in bronchial-biopsy specimens and bronchoalveolar-lavage (BAL) fluid, and their production of cytokines may be important in the pathogenesis of this disorder. Different patterns of cytokine release are characteristic of certain subgroups of T helper cells, termed TH1 and TH2, the former mediating delayed-type hypersensitivity and the latter mediating IgE synthesis and eosinophilia. The pattern of cytokine production in atopic asthma is unknown. Methods. We assessed cells obtained by BAL in subjects with mild atopic asthma and in normal control subjects for the expression of messenger RNA (mRNA) for interleukin-2, 3, 4, and 5, granulocytemacrophage colony-stimulating factor (GM-CSF), and interferon gamma by in situ hybridization with 32P-labeled complementary RNA. Localization of mRNA to BAL T cells was assessed by simultaneous in situ hybridization and immunofluorescence and by in situ hybridization after immunomagnetic enrichment or...
2,898 citations
TL;DR: The effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women are studied.
Abstract: Background. Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. Methods. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [±SD] age, 84±6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 μg (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Results. Among the women who completed the 18-month study, the number of hip fra...
2,714 citations
TL;DR: A 15-fold increase in rates of mortality due to cardiovascular disease and coronary heart disease among subjects with large-vessel peripheral arterial disease that was both severe and symptomatic was revealed.
Abstract: Background. Previous investigators have observed a doubling of the mortality rate among patients with intermittent claudication, and we have reported a fourfold increase in the overall mortality rate among subjects with large-vessel peripheral arterial disease, as diagnosed by noninvasive testing. In this study, we investigated the association of large-vessel peripheral arterial disease with rates of mortality from all cardiovascular diseases and from coronary heart disease. Methods. We examined 565 men and women (average age, 66 years) for the presence of large-vessel peripheral arterial disease by means of two noninvasive techniques — measurement of segmental blood pressure and determination of flow velocity by Doppler ultrasound. We identified 67 subjects with the disease (11.9 percent), whom we followed prospectively for 10 years. Results. Twenty-one of the 34 men (61.8 percent) and 11 of the 33 women (33.3 percent) with large-vessel peripheral arterial disease died during follow-up, as compa...
2,409 citations
TL;DR: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up and was a more powerful predictor of these risks than overweight in adulthood.
Abstract: Background. Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. Methods. We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. Results. Overweight in adolescent subjects was associated with an increase...
2,260 citations
Journal Article•
1,956 citations
TL;DR: In this article, a phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg persquare meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGyof radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus.
Abstract: Background. The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited. The median survival is less than 10 months, and less than 10 percent of patients survive for 5 years. Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival. Methods. This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy. Results. The median survival was 8.9 months i...
1,873 citations
TL;DR: Screening by sigmoidoscopy can reduce mortality from cancer of the rectum and distal colon and a screening once every 10 years may be nearly as efficacious as more frequent screening.
Abstract: Background The efficacy of sigmoidoscopic screening in reducing mortality from colorectal cancer remains uncertain. A randomized trial would be ideal for clarifying this issue but is very difficult to conduct. Case–control studies provide an alternative method of estimating the efficacy of screening sigmoidoscopy. Methods Using data on the 261 members of the Kaiser Permanente Medical Care Program who died of cancer of the rectum or distal colon from 1971 to 1988, we examined the use of screening by rigid sigmoidoscopy during the 10 years before the diagnosis and compared it with the use of screening in 868 control subjects matched with the case subjects for age and sex. Results Only 8.8 percent of the case subjects had undergone screening by sigmoidoscopy, as compared with 24.2 percent of the controls (matched odds ratio, 0.30; 95 percent confidence interval, 0.19 to 0.48). Adjustment for potential confounding factors increased the odds ratio to 0.41 (95 percent confidence interval, 0.25 to 0.69)...
TL;DR: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.
Abstract: Background. Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. Methods. In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody—blocking assay. Results. Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who h...
TL;DR: Monitoring the timing of antibiotic prophylaxis and the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or "clean—contaminated" surgical procedures at a large community hospital found that 10 patients who received the proPHylactic antibiotics preoperatively subsequently had surgical-Wound infections.
Abstract: Background. Randomized, controlled trials have shown that prophylactic antibiotics are effective in preventing surgical-wound infections. However, it is uncertain how the timing of antibiotic administration affects the risk of surgical-wound infection in actual clinical practice. Methods. We prospectively monitored the timing of antibiotic prophylaxis and studied the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or "clean—contaminated" surgical procedures at a large community hospital. The administration of antibiotics 2 to 24 hours before the surgical incision was defined as early; that during the 2 hours before the incision, as preoperative; that during the 3 hours after the incision, as perioperative; and that more than 3 but less than 24 hours after the incision, as postoperative. Results. Of the 1708 patients who received the prophylactic antibiotics preoperatively, 10 (0.6 percent) subsequently had surgical-wound infections. Of the 282 patients who recei...
TL;DR: Six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation were identified and the failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome.
Abstract: Background and Methods. Reports of fatal or near-fatal anaphylactic reactions to foods in children and adolescents are rare. We identified six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation. All the cases but one occurred in one of three metropolitan areas over a period of 14 months. Our investigations included a review of emergency medical care reports, medical records, and depositions by witnesses to the events, as well as interviews with parents (and some patients). Results. Of the 13 children and adolescents (age range, 2 to 17 years), 12 had asthma that was well controlled. All had known food allergies, but had unknowingly ingested the foods responsible for the reactions. The reactions were to peanuts (four patients), nuts (six patients), eggs (one patient), and milk (two patients), all of which were contained in foods such as candy, cookies, and pastry. The six patients who died had symptoms within 3 to 30 minute...
TL;DR: This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period.
Abstract: Background. Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Vasodilator drugs have been used as a treatment, but their efficacy is uncertain. Methods. We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers. Patients who responded to treatment (defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge) were treated for up to five years. Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health (NIH) Registry on Primary Pulmonary Hypertension. Warfarin was given to 55 percent of the patients as concurrent therapy, on the basis of a lung scan showing nonuniformity of pulmonary blood flow (47 percent of patients who responded and 57 percent of those who did not respond). Results. Seventeen patients (26 percent) responded to treatment, as indicated by a 39 percen...
TL;DR: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage, and this benefit extended to patients over 70 years of age.
Abstract: Background. Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. Methods. We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. Results. Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (...
TL;DR: Type II cryoglobulinemia is strongly associated with concomitant HCV infection and a high rate of false negative serologic tests, suggesting a role for HCV in the pathogenesis of mixed cryoglOBulinemi.
Abstract: Background. Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors, the cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected. Methods. We studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV infection. Quantitative HCV antibody and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Results. Eight patients (42 percent) had HCV antibodies, and 16 (84 percent) had HCV RNA. Of the 19 patients, 5 (26 percent) had HBV markers, but only 1 had evidence of active HBV infection. Control serum samples from nine patients with Type I cryoglobulinemia were negative for HCV antibody and HCV RNA. There was a close, although not exclusive, association of one type of rheumatoid factor (WA) with HCV RNA. HCV antibody and HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in the T...
TL;DR: The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis.
Abstract: Background and Methods. Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet — low total energy expenditure and underreporting of caloric intake — in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. Results. Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic...
TL;DR: Cisplatin, given daily in combination with the radiotherapy described here to patients with nonmetastatic but inoperable non-small-cell lung cancer, improved rates of survival and control of local disease at the price of substantial side effects.
Abstract: Background and Methods. Cisplatin (cis-diamminedichloroplatinum) has been reported to enhance the cell-killing effect of radiation, an effect whose intensity varies with the schedule of administration. We randomly assigned 331 patients with nonmetastatic inoperable non—small-cell lung cancer to one of three treatments: radiotherapy for two weeks (3 Gy given 10 times, in five fractions a week), followed by a three-week rest period and then radiotherapy for two more weeks (2.5 Gy given 10 times, five fractions a week); radiotherapy on the same schedule, combined with 30 mg of cisplatin per square meter of body-surface area, given on the first day of each treatment week; or radiotherapy on the same schedule, combined with 6 mg of cisplatin per square meter, given daily before radiotherapy. Results. Survival was significantly improved in the radiotherapy—daily-cisplatin group as compared with the radiotherapy group (P = 0.009): survival in the radiotherapy—daily-cisplatin group was 54 percent at one ...
TL;DR: Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy, and identification of the optimal combination of chemotherapy and radiotherapy will require further trials.
Abstract: Background. In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. Methods. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. Results. The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up peri...
TL;DR: An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension.
Abstract: Background. Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium. Methods. We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls. Results. The...
TL;DR: ALS is associated with a defect in high-affinity glutamate transport that has disease, region, and chemical specificity and could lead to neurotoxic levels of extracellular glutamate and thus be pathogenic in ALS.
Abstract: Background. Amyotrophic lateral sclerosis (ALS) is a chronic degenerative neurologic disorder characterized by the death of motor neurons in the cerebral cortex and spinal cord. Recent studies have suggested that the metabolism of glutamate, a potentially neurotoxic amino acid, is abnormal in patients with ALS. We hypothesized that the high-affinity glutamate transporter is the site of the defect. Methods. We measured high-affinity, sodium-dependent glutamate transport in synaptosomes from neural tissue obtained from 13 patients with ALS, 17 patients with no neurologic disease, and 27 patients with other neurodegenerative diseases (Alzheimer's disease in 15 patients and Huntington's disease in 12 patients). The groups were comparable with respect to age and the interval between death and autopsy. Synaptosomes were prepared from spinal cord, motor cortex, sensory cortex, visual cortex, striatum, and hippocampus. We also measured sodium-dependent transport of γ-aminobutyric acid and phenylalanine i...
TL;DR: New MRI neuroimaging techniques are used to derive volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls to discover the degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.
Abstract: Background. Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. Methods. We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. Results. As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus—amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]...
TL;DR: The use ofβ-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma and the regular use of β2-agonist bronchodilators.
Abstract: Background. Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of β2-agonist bronchodilators. Methods. Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case–control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. Results. The use of β-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence...
TL;DR: Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.
Abstract: Background. Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. Methods. We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. Results. The mean (±SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58±3 v...
TL;DR: Catheter ablation of the atrial end of the slow pathway using radiofrequency current, guided by ASP potentials, can eliminate AVNRT with very little risk of atrioventricular block.
Abstract: Background. Atrioventricular nodal reentrant tachycardia (AVNRT), the most common form of supraventricular tachycardia, results from conduction through a reentrant circuit comprising fast and slow atrioventricular nodal pathways. Antiarrhythmic-drug therapy is not consistently successful in controlling this rhythm disturbance. Catheter ablation of the fast pathway with radiofrequency current eliminates AVNRT, but it can produce heart block. We hypothesized that catheter ablation of the site of insertion of the slow pathway into the atrium would eliminate AVNRT while leaving normal (fast-pathway) atrioventricular nodal conduction intact. Methods and Results. Eighty patients with symptomatic AVNRT were studied. Retrograde slow-pathway conduction (in which the earliest retrograde atrial potential was recorded at the posterior septum, close to the coronary sinus) was present in 33 patients. The retrograde atrial potential was preceded by a potential consistent with activation of the atrial end of the...
TL;DR: In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine, and whether this favorable effect on bone mineraldensity is accompanied by a decrease in the risk of fractures remains to be determined.
Abstract: Background and Methods. Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node—negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. Results. In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P<0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteoc...
University of Minnesota1, University of California, Los Angeles2, University of Oklahoma3, Ohio State University4, Rush University Medical Center5, University of Pittsburgh6, University of California, San Diego7, Loyola University Chicago8, University of Texas Health Science Center at San Antonio9, University of Washington10, University of Pennsylvania11, New York Medical College12, Cleveland Clinic13, Vanderbilt University14, Temple University15, University of Michigan16, Pfizer17
TL;DR: Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.
Abstract: Background and Methods. Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved. Results. By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P<0.001). Systemic fungal in...
TL;DR: The phylogenetic relations of this bacterium, its distinct morphologic characteristics, and the unusual features of the disease are sufficient grounds for naming this bacillus Tropheryma whippelii gen. sp.
Abstract: Background. Whipple's disease is a systemic disorder known for 85 years to be associated with an uncultured, and therefore unidentified, bacillus. Methods. We used a molecular genetic approach to identify this organism. The bacterial 16S ribosomal RNA (rRNA) sequence was amplified directly from tissues of five unrelated patients with Whipple's disease by means of the polymerase chain reaction, first with broad-range primers and then with specific primers. We determined and analyzed the nucleotide sequence of the amplification products. Results. A unique 1321-base bacterial 16S rRNA sequence was amplified from duodenal tissue of one patient. This sequence indicated the presence of a previously uncharacterized organism. We then detected this sequence in tissues from all 5 patients with Whipple's disease, but in none of those from 10 patients without the disorder. According to phylogenetic analysis, this bacterium is a gram-positive actinomycete that is not closely related to any known genus. Conclu...