Technology assessment in teaching hospitals.
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Biomedical subjects
Publications and source records attributed to D Marshall.
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In vivo nuclear magnetic resonance (NMR) spectroscopy was used to define several intracellular high energy phosphate variables of the gastrocnemius muscle of normal subjects during rest, graded plantar flexion exercise to exhaustion, and recovery. There were nine males and eight females with an average age of 34 +/- 8 years. At rest, pH averaged 7.09 +/- 0.03 and the energy cost index (ECI)--the ratio of inorganic phosphate to phosphocreatine--averaged 0.13 +/- 0.03. At peak exercise, the ECI increased markedly to 2.71 +/- 2.0 (P less than 0.001) and pH fell precipitately to 6.76 +/- 0.17 (P less than 0.001), indicating the high intensity of the exercise. Exercise endurance averaged 12 +/- 5 mins; it was not highly correlated with sex, age (r = 0.35), rest pH (r = 0.26), rest ECI (r = 0.38), peak exercise pH (r = 0.23) or peak exercise ECI (r = 0.38), nor exercise changes in pH (r = 0.17) and ECI (r = 0.28). At 23 mins post exercise all variables were similar to rest. Rest pH was the only variable different between males (7.10 +/- 0.03) and females (7.07 +/- 0.03) (P less than 0.05). Thus, dynamic exercise of large skeletal muscles in normal subjects was characterized by marked temporal changes in high energy phosphate profiles and very low pH at exhaustion. No single metabolic variable correlated highly with exercise endurance, suggesting that the intracellular pathophysiology of exhaustive muscle exercise and clinical fatigue may be multifactorial.
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STUDY OBJECTIVE: To determine the appropriate role for vancomycin in neutropenic patients with cancer. To review the incidence, types, and outcome of gram-positive infections in a series of neutropenic patients with cancer. DESIGN: Retrospective review. SETTING: Inpatient units of the Medical and Pediatric Oncology Branches of the National Cancer Institute. PATIENTS: Five hundred and fifty consecutive episodes of fever and neutropenia in patients with cancer randomized prospectively on another study to receive either ceftazidime alone or combination antibiotics for initial empirical therapy. INTERVENTION: Intravenous vancomycin (dosage adjusted by serum levels). MEASUREMENTS AND MAIN RESULTS: Gram-positive organisms were the commonest of the bacterial pathogens isolated (63%). Of the 53 gram-positive organisms accounting for primary infections (isolated at initial presentation), there were 36 staphylococcal isolates (19 coagulase-negative and 17 coagulase-positive), 13 streptococcal isolates (8 non-group D and 5 group D), and 4 polymicrobial isolates. Of the 22 secondary gram-positive infections (occurring after institution of initial antibiotics), there were 10 streptococcal isolates (9 group D and 1 non-group D), 7 staphylococcal isolates (6 coagulase-negative and 1 coagulase-positive), and 5 polymicrobial isolates. Vancomycin was used to treat 26 of the 53 primary infections, but was begun only after knowledge of the isolate in 25. Vancomycin was used to treat 17 of the 22 secondary infections, and begun only after knowledge of the isolate in 14. This approach resulted in no treatment failures for the primary infections, and a single microbiological failure for the secondary infections. There was a tendency towards a greater proportion of secondary gram-positive infections in the monotherapy group compared to the combination therapy group (16 of 282 compared with 6 of 268 respectively, P2 = 0.04 by the chi-squared test); but all were treated successfully. CONCLUSION: Vancomycin need not be included in routine empirical therapy for febrile neutropenic patients, but should be added when clinical or microbiological data suggest the need.
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Two types of benzodiazepine receptors have been identified in the central nervous system. The aim of these experiments was to determine if ligands for these receptors alter basal water absorption by rat ileum in vivo after central administration. Specifically, the effects on net water flux of the systemic and central administration of diazepam and the central administration of RO 5-4864, a "peripheral" receptor agonist, and of the "central" receptor agonists clonazepam and lorazepam were determined. Diazepam increased absorption at 4.3 mg/250 g body wt i.p. but not at 430 micrograms/250 g body wt. Intracerebroventricular diazepam (28 micrograms) increased water absorption. Larger doses had a greater effect. Intracerebroventricular RO 5-4864 (100 micrograms) increased net water absorption; intracerebroventricular lorazepam (50 or 100 micrograms) or clonazepam (100 micrograms) reduced basal water absorption. Systemic atropine (2 mg/kg i.v.) abolished the effect of lorazepam (100 micrograms i.c.v.). To evaluate the possibility that diazepam and RO 5-4864 have effects similar to those of calcium channel antagonists, nifedipine, nitrendipine, and diltiazem were administered intracerebroventricularly. The dihydropyridine calcium channel antagonists nifedipine and nitrendipine increased basal water absorption. Diltiazem, a benzothiazepine compound, did not alter basal water absorption. We conclude that the binding of benzodiazepine agonists to receptors located in the central nervous system alters net water absorption by the rat ileum. Agonists of the central benzodiazepine receptor reduce basal water absorption via a cholinergic neural pathway. Peripheral agonists increase net water absorption. In this model, diazepam behaves as a peripheral receptor agonist. This study provides further evidence of a role for the central nervous system in the regulation of intestinal absorption of water and ions.
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To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, we conducted a randomized trial comparing ceftazidime alone with a combination of cephalothin, gentamicin, and carbenicillin. Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination. All episodes were evaluated for responses at 72 hours after the start of treatment and at resolution of the neutropenia. Of the patients with unexplained fever who were given ceftazidime alone, 99 percent were alive at 72 hours and 98 percent were alive when the neutropenia resolved, as compared with 100 percent and 98 percent, respectively, of those given combination therapy. Of the patients with documented infection who were given ceftazidime alone, 98 percent were alive at 72 hours and 89 percent when the neutropenia resolved, as compared with 98 percent and 91 percent, respectively, of those given combination therapy. The majority of episodes of documented infection in both treatment groups necessitated additional antimicrobial treatment or other modifications of the initial regimen, as compared with only 22 percent of the episodes of unexplained fever. We conclude that initial single-agent therapy with certain beta-lactam antibiotics is a safe alternative to standard combination antibiotic therapy, although patients with documented infection or protracted neutropenia are likely to require additional or modified treatment.
Betamethasone (50 micrograms/kg body weight/day) given to young pigs reduced calcium absorption, growth and plasma vitamin D dependent calcium binding protein (CaBP) concentration. No changes occurred in plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and intestinal CaBP concentrations. 1,25(OH)2D3 (0.1 microgram/kg body weight/day) given with betamethasone increased calcium absorption although growth and plasma CaBP concentrations remained low. Intestinal CaBP levels remained unchanged. Plasma CaBP concentrations were not consistently related to intestinal CaBP or calcium absorption in the presence of betamethasone. We conclude that betamethasone-induced depression of calcium absorption was not mediated by alterations in intestinal CaBP, but the mechanism remains obscure.
The outcome and complications which developed in 8 hemodialysis patients who received 12 DiaTAP bioCarbon button vascular-access devices were reviewed. All patients had a poor vascular access history. Three of twelve devices have been replaced because of thrombosis and two because of infection. Four patients have had 10 episodes of reduced blood flow. Streptokinase infusion into the DiaTAP button led to improved blood flow in 8 of 10 episodes. The 6-month survival rate of the DiaTAP access device was 67% and the average functioning life was 9.4 months. It was a valuable form of access when others had failed.
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Transfusion-acquired cytomegalovirus (CMV) infections should be prevented in seronegative immunocompromised patients by providing blood products from donors who are also seronegative. Latex agglutination was investigated as a simple and rapid method for detecting antibody against CMV. Latex beads were coated with CMV antigen, incubated for 8 min at room temperature with 25 microliter of sera, and examined for agglutination. The sensitivity and specificity of latex agglutination was compared with that of indirect hemagglutination (IHA, Cetus Corp., Emeryville, Calif.) and enzyme immunoassay (EIA) with sera from 604 random blood donors or patients. Of 327 serum samples shown to be seronegative by EIA and IHA, 327 had a latex agglutination titer of less than 1:4 (specificity, 100%). Of 236 serum samples with detectable antibody by EIA and IHA, 228 had a latex agglutination titer of 1:4 or greater (sensitivity, 97%). Plasma collected with EDTA, heparin, or citrate was satisfactory for latex agglutination. Latex agglutination results correlated quantitatively with those of EIA, and the test also detected fourfold or greater rises in antibody with paired sera from six patients with posttransfusion CMV infections. Latex agglutination is a sensitive and specific assay that is rapid and simple to perform and should be effective in selecting seronegative blood donors to prevent posttransfusion CMV infections in seronegative recipients.