Tuberculosis drugs--old and new.
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Biomedical subjects
Publications and source records attributed to R J O'Brien.
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We have examined the specificity and the mechanism of acetylcholine receptor (AChR) accumulation at embryonic chick nerve-muscle contacts that form in culture. Spinal cord motoneurons were identified in vitro after labeling them in vivo with Lucifer Yellow-wheat germ agglutinin conjugates. All of their processes induced receptor clusters on contacted myotubes; after 24 to 48 hr of co-culture, the incidence of neurite-associated receptor patches (NARPs) was approximately 1.2/100 microns of contact. In contrast, NARPs were rarely associated with spinal cord interneurons (approximately 0.1/100 microns of contact). Neurons dissociated from ciliary ganglia induce NARPS to the same extent as motoneurons. The relative contribution to NARPs of AChRs present in the membrane prior to plating ciliary ganglion neurons and of "new" AChRs inserted 8, 11, or 17 hr after addition of neurons was assessed with two fluorescent receptor probes. Rhodamine-conjugated alpha-bungarotoxin was used to label either old or new receptors; a monoclonal, anti-receptor antibody visualized with fluorescein-second antibody was used to label all (new and old) receptors. Analysis of digitized fluorescence images showed that NARPs contained both new and old receptors but that within the first 24 hr of co-culture the majority (60 to 80%) were new. We estimate that cholinergic neurites increase the rate of receptor insertion 4- to 5-fold during the first 8 hr of NARP formation. The contribution of new receptors to NARPs declines with time. After 3 days of co-culture, receptors inserted over an 8-hr interval comprised only 20% of the total NARP complement.(ABSTRACT TRUNCATED AT 250 WORDS)
Planimetric measurements of total lung capacity (TLC) were made from posteroanterior and lateral chest roentgenograms obtained during a nationwide survey of the civilian, noninstitutionalized United States population. Regression equations for TLC, residual volume (RV), and the ratio of RV to TLC for healthy, nonsmoking participants are presented. The equations predict values that agree closely with previously published normal values obtained by other methods.
To estimate rates of hepatotoxicity in the United States among children treated for tuberculosis, we conducted a retrospective survey of health departments and individual practitioners. We received 874 reports suitable for analysis of children treated during 1977 to 1979. A total of 16 hepatotoxic reactions were reported; 14/430 (3.3%) children receiving isoniazid and rifampin had a hepatotoxic reaction, which approximates the rate seen in adults taking these drugs. Half of the reactions occurred during the first month of therapy, and all of the well-documented reactions were noted during the first 10 weeks. Because the likelihood of hepatotoxicity may be increased with higher drug doses, limiting the dose of isoniazid to 10 mg/kg and that of rifampin to 15 mg/kg may help minimize hepatotoxic reactions. Because more serious disease, especially disseminated tuberculosis, may further increase the risk of hepatotoxicity, close monitoring of such children receiving isoniazid and rifampin should help minimize serious hepatotoxicity. Routine biochemical monitoring may not be necessary for all children, eg, those with mild forms of disease and those with normal pretreatment liver function who are treated with lower drug doses.
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Forty-four fatal cases of Rocky Mountain spotted fever (RMSF) occurring in 1974 were compared with 50 nonfatal cases of similar age, sex, date of onset, and place of occurrence. Diagnosis and initiation of treatment in fatal cases were substantially delayed compared with nonfatal cases. Several reasons for this delay were identified: (1) the rash appeared later in the course of illness in the fatal cases, often not until the patient was terminal, (2) a history of tick bite was less often obtained during life or obtained late in the clinical course in fatal cases, and (3) initial nonspecific symptoms or unexpected symptoms led to an initial diagnosis of more common diseases. Only two fatal cases were treated with either tetracycline or chloramphenicol before the sixth day of illness. Presumptive diagnosis of RMSF and initiation of tetracycline therapy before onset of rash may be necessary to reduce mortality.
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Reported cases of Rocky Mountain spotted fever in the United States have been increasing since 1960 and reached an all-time high of 754 cases in 1974. Detailed clinical and epidemiologic information was obtained on 1522 (55%) of the 2757 cases reported in the 5-year period 1970 through 1974. Fifty-one percent of cases were confirmed by one or more laboratory test. The increase has occurred predominantly in the southeastern part of the United States. A comparison of laboratory-confirmed and unconfirmed cases suggests that a variety of febrile exanthems may be confused with Rocky Mountain spotted fever. Neither a history of tick bite nor rash was universally present, and both were significantly less frequent in fatal cases. The overall death-to-case ratio during this period was 6.8%. Death-to-case ratios were significantly higher for nonwhites (13.9) than whites (5.8), for male patients (8.2) than female patients (4.5), and for person older than 30 (13.9) than persons younger than 30 (5.4).
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Labeled lecithin (32P, 2-3H-glycerol, 1-14C-palmitate) was prepared for studying absorption of lecithin by rat intestine and its incorporation into microsomal and prechylomicron-chylomicron lecithin. Bile fistula rats were perfused intraduodenally with bile salts and lecithin plus a liquid diet. Intestinal samples were obtained after sacrifice and specific activities (DPM/mumol) of isotopes in lecithin were determined. Ratios of specific activities of isotopes were calculated and compared to respective ratios in the original perfusate lecithin. Radioactivity rapidly appeared in jejunal lecithin following perfusion. When specific activities of isotopes in prechylomicron-chylomicron lecithin were compared to those in microsomal lecithin, specific activities were always greater in prechylomicron-chylomicron lecithin. Analysis of ratios of specific activities of isotopes in jejunal lecithin showed that the ratios were nearly identical to those in perfusate phospholipid, indicating that the lysolecithin portion of luminal lecithin can be absorbed intact and can then be utilized for jejunal lecithin synthesis.
The acute effects of intraduodenal administration of ethanol, 5 g/kg body weight, on intestinal activities of lipid-reesterifying and disaccharidase enzymes of the small bowel were studied. Results were compared to those produced in controls receiving isocaloric amounts of glucose by the same route. Acyl-CoA:monoglyceride acyltransferase, acyl-CoA synthetase (acid:CoA ligase (AMP) EC 6.2.1.3), sucrase, and lactase assays were performed on jejunal samples; acyl-CoA synthetase assay was performed on ileal samples. Ethanol produced greater activities of the lipid-reesterifying enzymes in the jejunum than did glucose. Ileal specific activity of acyl-CoA synthetase was also increased in the experimental group. No effect of ethanol on jejunal disaccharidase enzyme activities was noted. It is concluded that ethanol given acutely has a specific stimulating effect on intestinal enzymes involved in lipid absorption.
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