shukoor65/lab-rag-model huggingface dataset:
Effects of treatment with nasal continuous positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnoea. 1. Patients with obstructive sleep apnoea have increased diuresis during sleep, which decreases with nasal continuous positive airway pressure treatment. These changes have been attributed to an increased release of atrial natriuretic peptide in obstructive sleep apnoea, and its decrease with continuous positive airway pressure treatment. 2. In order to clarify the change in plasma atrial natriuretic peptide level and to investigate the underlying mechanisms, blood samples were taken at 10 min intervals from nine patients with obstructive sleep apnoea during two nights when the patients were either untreated or treated with continuous positive airway pressure. Polysomnographic monitoring, including transcutaneous oximetry, and measurement of oesophageal pressure were performed simultaneously. Plasma arginine vasopressin was also measured. 3. The plasma level of arginine vasopressin did not change. The level of atrial natriuretic peptide was high and exhibited secretion bursts in six out of the nine patients; it drastically decreased with continuous positive airway pressure treatment. 4. Across the patients, the mean plasma levels of atrial natriuretic peptide was correlated with the degree of hypoxaemia and the degree of oesophageal pressure swings during the sleep apnoeas. 5. Within the patients, cross-correlation studies suggested that the atrial natriuretic peptide secretory bursts were related either to the oesophageal pressure swings or to the apnoea-related hypoxaemia. 6. We conclude that release of atrial natriuretic peptide decreases with continuous positive airway pressure treatment in those patients with obstructive sleep apnoea who have increased release of atrial natriuretic peptide before treatment.
Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis. To assess the possible beneficial effects of combined therapy (fluconazole and flucytosine) in the treatment of cryptococcal meningitis in the immunocompromised host, we compared therapy with fluconazole and flucytosine, individually and combined, in the experimental murine model. BALB/c athymic (nu/nu) mice were infected intracerebrally with 150 to 300 CFU of Cryptococcus neoformans. In mortality studies, treatment was initiated 24 h postinfection and continued for 10 to 14 days with either fluconazole (1 to 15 mg/kg of body weight per day), flucytosine (60 to 120 mg/kg/8 h), both drugs, or 0.3% Noble agar (control). Combined therapy delayed mortality significantly when compared with controls and single-drug regimens. This was observed over a broad range of doses. Quantitative determinations of CFU in brain tissue demonstrated a significantly lower burden of C. neoformans in mice receiving combined therapy. The results indicate that combined therapy with fluconazole and flucytosine is superior to single-drug therapy.
Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects. OBJECTIVE: To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study. Results: RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P less than 0.05) and increased from 48.1 +/- 10.2 to 49.5 +/- 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups. CONCLUSIONS: Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates.
Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.
Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. OBJECTIVE: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. DESIGN: Retrospective comparison of two cohorts of patients. SETTING: Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. PATIENTS: Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. MAIN RESULTS: Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% CI, 33% to 43%) with chemotherapy and 44% (CI, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; CI, -3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. CONCLUSIONS: These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.
Relation between malpractice claims and adverse events due to negligence. Results of the Harvard Medical Practice Study III. BACKGROUND AND METHODS. By matching the medical records of a random sample of 31,429 patients hospitalized in New York State in 1984 with statewide data on medical-malpractice claims, we identified patients who had filed claims against physicians and hospitals. These results were then compared with our findings, based on a review of the same medical records, regarding the incidence of injuries to patients caused by medical management (adverse events). RESULTS. We identified 47 malpractice claims among 30,195 patients' records located on our initial visits to the hospitals, and 4 claims among 580 additional records located during follow-up visits. The overall rate of claims per discharge (weighted) was 0.13 percent (95 percent confidence interval, 0.076 to 0.18 percent). Of the 280 patients who had adverse events caused by medical negligence as defined by the study protocol, 8 filed malpractice claims (weighted rate, 1.53 percent; 95 percent confidence interval, 0 to 3.2 percent). By contrast, our estimate of the statewide ratio of adverse events caused by negligence (27,179) to malpractice claims (3570) is 7.6 to 1. This relative frequency overstates the chances that a negligent adverse event will produce a claim, however, because most of the events for which claims were made in the sample did not meet our definition of adverse events due to negligence. CONCLUSIONS. Medical-malpractice litigation infrequently compensates patients injured by medical negligence and rarely identifies, and holds providers accountable for, substandard care.
Intermittent pneumatic compression therapy in posttraumatic lower limb edema: computed tomography and clinical measurements. The purpose of our study was to assess the amount of posttraumatic lower limb edema and its distribution between subcutaneous and subfascial compartments before and after intermittent pneumatic compression (IPC) therapy in patients with fractures of the lower leg immobilized with a cast for six to 12 weeks. Computed tomography (CT) was used as an objective method of measuring the compartmental distribution of edema. Sixteen patients with a mean age of 37 years (range 19 to 64 years) were investigated by clinical measurement of the leg circumference and by CT at the ankle joint and at three equidistant (10cm) levels above it. The unaffected leg served as a control for the evaluation of the amount of edema and density of the tissues. Edema was found primarily in subcutaneous tissue. The IPC treatment decreased relative edema from 23% to 15.9% (p less than 0.01) as measured by CT, and from 23.5% to 13.2% as measured clinically. The density of muscle tissue increased 9% (p less than 0.01) and that of subcutaneous tissue decreased 5.6% (p less than 0.05). The IPC treatment influenced both the amount of edema and the density of tissue compartments.
High-dose chemotherapy with reinfusion of purged autologous bone marrow following dose-intense induction as initial therapy for metastatic breast cancer. We assessed the toxicity and efficacy of high-dose chemotherapy consolidation with reinfusion of purged autologous bone marrow in women with metastatic breast cancer responding to a dose-intense outpatient regimen. Thirty women with hormone-unresponsive metastatic breast cancer, previously untreated with adjuvant doxorubicin or with any chemotherapy for metastatic disease, were treated with cyclophosphamide, methotrexate, doxorubicin, fluorouracil, vincristine, and leucovorin for 16 weeks. Twenty-four patients responded to therapy; 8 showed a complete response, and 16 showed a partial response. These patients proceeded to the next phase of the protocol, ie, marrow harvest and treatment with 6000 mg/m2 cyclophosphamide and 800 mg/m2 thiotepa given over 4 days. Harvested marrow was purged with 100 micrograms/mL 4-hydroperoxycyclophosphamide, and all patients engrafted satisfactorily. The predominant side effects were myelosuppressive and gastrointestinal, and there were no deaths from toxic effects. Three of the 16 patients who showed a partial response after the outpatient phase of treatment achieved a complete response after high-dose therapy. The partial response seen in two more patients converted to a complete response at all sites except bone. The median time to disease progression for all patients in this study was 13 months, and the median survival was 22 months. Four of the original 30 patients remained without disease progression a median of 27 months from entry into the study. This study indicates that this dose-intense regimen can be safely administered, even with the use of purged marrow, with an acceptable toxicity profile. This approach results in a high response rate in women with metastatic breast cancer and could form the basis for a regimen to be tested in the high-risk adjuvant setting.
Warm heart surgery and results of operation for recent myocardial infarction. Revascularization procedures after recent myocardial infarction are associated with higher mortality and morbidity compared with elective coronary artery bypass grafting. Traditional methods of myocardial protection impose a further ischemic insult on already compromised myocardium. Continuous cold blood cardioplegia may eliminate ischemia but may still leave the heart anaerobic. Theoretically, warm aerobic arrest addresses both of these issues and may become an attractive alternative to standard hypothermic ischemic arrest in this setting. In 115 nonrandomized patients undergoing coronary artery bypass grafting within 6 hours to 7 days of an acute myocardial infarction, myocardial protection was provided with continuous cold (4 degrees C) or continuous warm (37 degrees C) blood cardioplegia. Fifty-one patients (after 1988) protected with warm blood cardioplegia were compared with a historical cohort of 64 patients (before 1988) protected with cold blood cardioplegia. Results indicate that the warm cardioplegia group had no mortality versus 10.9% for the cold group (p less than 0.05), a myocardial infarction rate of 2.0% in the warm versus 9.3% in the cold group, and use of intraaortic balloon pump of 0% versus 12.5%, respectively (p less than 0.05). It is concluded that continuous warm aerobic arrest may minimize ischemia and anaerobic metabolism during the operative procedure, and may be of benefit to patients who have a limited tolerance to ischemic insult.
Normal pressure hydrocephalus in a patient with systemic lupus erythematosus. We describe a patient who had concomitant systemic lupus erythematosus (SLE) and a normal pressure hydrocephalus. She improved only after appropriate therapy for each. Although 6 patients with arthritis and normal pressure hydrocephalus have been described, this is the first report of it occurring in a patient with SLE. It has been emphasized that normal pressure hydrocephalus can easily be overlooked in elderly patients with arthritic conditions. Since neuropsychiatric symptoms are likelier to occur in patients with SLE than in other rheumatologic conditions, the diagnosis of normal pressure hydrocephalus may be delayed or overlooked. Because normal pressure hydrocephalus is a potentially reversible cause of neurologic dysfunction, it should be considered in appropriate populations.
"Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson's disease. We reviewed the histories of patients seen in a large Parkinson's disease clinic from 1983 to 1989 to determine if there is a relationship between the timing of initiation of levodopa therapy and the development of motor response fluctuations, dyskinesias, and dementia. There were no factors predisposing to the development of response fluctuations or dementia. Younger age at disease onset predisposed to the development of dyskinesia. Dyskinesias occurred in a greater proportion of patients in whom the initiation of levodopa therapy was delayed by more than 2 years from disease diagnosis than among those in whom treatment was started earlier. We thus failed to identify any adverse consequences of early levodopa treatment in our patient population.
A multicenter comparison of the safety and efficacy of isradipine and enalapril in the treatment of hypertension. This multicenter trial compared the efficacy and safety of isradipine and enalapril in 160 patients with essential hypertension. Patients received isradipine or enalapril for 10 weeks after a placebo wash-out period of three to five weeks. Dosage was titrated for six weeks on the basis of blood pressure (BP) response and was then maintained for the remainder of the study. Isradipine reduced systolic and diastolic BP by 12 and 9 mm Hg, respectively, and enalapril by 10 and 7 mm Hg, respectively (between-treatment difference P less than .05 for diastolic BP). Overall, isradipine resulted in a higher responder rate, particularly among patients who had higher entry BPs. Fifteen enalapril-treated patients and four isradipine-treated patients discontinued treatment (four taking enalapril and none taking isradipine withdrew because of lack of efficacy). The most frequently reported adverse reactions were headache, dizziness, and edema in the isradipine group, and cough, headache, and chest pain in the enalapril group. Both drugs produced significant reductions in BP, but, in this study isradipine was more effective. The drugs were similarly well tolerated.
Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene Genetic factors contribute to heart disease. In this study, linkage analyses have been performed in a family that is predisposed to sudden death from cardiac arrhythmias, the long QT syndrome (LQT). A DNA marker at the Harvey ras-1 locus (H-ras-1) was linked to LQT with a logarithm of the likelihood ratio for linkage (lod score) of 16.44 at theta = 0, which confirms the genetic basis of this trait and localizes this gene to the short arm of chromosome 11. As no recombination was observed between LQT and H-ras-1, and there is a physiological rationale for its involvement in this disease, ras becomes a candidate for the disease locus.
Evidence for hypoxic depression of CO2-ventilation response in carotid body-resected humans. Steady-state CO2-ventilation response curves with hyperoxia (end-tidal PO2 greater than 200 Torr) and mild hypoxia (end-tidal PO2 approximately equal to 60 Torr) were compared in five carotid body-resected (BR) patients and five control patients. The data were analyzed by fitting a linear equation, V = S(PETCO2-B), where V is minute ventilation S is the response curve slope. PETCO2 is end-tidal PCO2, and B is the response curve threshold. S slightly increased from hyperoxia to hypoxia in both BR and control groups. On the other hand, B moderately increased with hypoxia in BR patients, whereas it slightly decreased in controls. These changes were all not significant. However, in accordance with the change in B, the response curve to hypoxia at V of 10 1/min was significantly shifted in opposite directions in the two groups, i.e., rightward and leftward shift in BR and control groups, respectively. Thus the average magnitude of V calculated at PETCO2 of 40 Torr in hypoxia was significantly lower in BR patients than in controls (P less than 0.01). We conclude that this hypoxic depression of the CO2-ventilation response found in BR patients may have resulted, at least in part, from modulation of the brain stem neural mechanisms that were elicited by loss of afferent discharges from the carotid body.
Spinal cord stimulation in 60 cases of intractable pain. Sixty patients with spinal cord stimulators implanted for intractable pain lasting up to 50 years were followed for up to nine years. Forty seven per cent derived significant benefit, 23% modest benefit, 20% experienced no effect and 6.7% were made worse. Two were made worse after initial benefit. Complications, indications and factors relevant to the mode of action are discussed.
Influence of physical exercise on serum digoxin concentration and heart rate in patients with atrial fibrillation. Heart rate and serum digoxin concentration in eight patients with atrial fibrillation were studied at rest and during exercise when initial serum digoxin concentrations were zero and at low and high therapeutic values. Eight patients with ischemic heart disease and in sinus rhythm were studied for comparison. Though the serum digoxin concentration decreased significantly during exercise, the absolute reduction in heart rate was the same at rest and during exercise in patients with atrial fibrillation. Compared with the control patients in sinus rhythm, the heart rate in patients with atrial fibrillation was not adequately controlled during exercise by any serum digoxin concentration tested despite a reduction in heart rate with increasing digoxin concentration. The effects of digoxin on heart rate regulation in atrial fibrillation are complex and include direct effects on the myocardium as well as indirect effects mediated by modulation of the autonomic nervous system; the present results indicate that the drug is not displaced from the target organs by decreasing serum concentrations during exercise. In atrial fibrillation, because the demands on the filter function of the atrioventricular node are highly unphysiological, the effect of digoxin on heart rate during exercise is not adequate.
The role of immunoglobulin in bone marrow transplantation. Bone marrow transplantation has proven its value as a therapeutic approach to a variety of human diseases, primarily the hematopoietic malignancies. The major clinical problems preventing successful outcome of marrow transplant have been defined and therapeutic approaches to preventing or treating these complications have led to increased long-term disease survival. Passively administered antibody given as intravenous immunoglobulin has been studied as a therapeutic modality following bone marrow transplantation. Studies have demonstrated the efficacy of immunoglobulin in reducing bacterial infections in the posttransplant period; reducing severe CMV infections in allogeneic marrow transplant recipients who are seronegative for the virus and susceptible to primary infection; reducing mortality from CMV pneumonia in combination with ganciclovir; and reducing acute graft-versus-host disease following allogeneic BMT. In many cases alternate therapeutic strategies offer comparable or greater efficacy (eg, selective CMV-negative blood products for CMV seronegative allogeneic BMT recipients receiving bone marrow from a seronegative donor). However, it is clear that intravenous immunoglobulin has a place in the therapeutic armamentarium of bone marrow transplantation. Future controlled clinical trials are necessary to establish its exact role and to define which preparations and dose schedules provide the greatest therapeutic benefits.
Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers. The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens.