An objective method to identify inhomogeneity in washout curves.
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Biomedical subjects
Publications and source records attributed to E J Smith.
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The role of endogenous carotid body dopamine in the afferent chemoreceptor circuit was studied by means of haloperidol-induced dopamine antagonism. In 19 cats that were anesthetized with pentobarbital sodium and paralyzed, single carotid body nerve fibers were dissected free and placed on unipolar platinum wire electrodes. In 10 of these cats, the neural response to room air and the last 2 min of 6-min inhalations of 3, 6, and 9% CO2 were recorded, and blood samples were drawn for gas tension measurements. Haloperidol was administered at a dose (250 micrograms/kg) shown to block the inhibitory effect of injected dopamine. Following a 15-min equilibration, the CO2 response was again tested. In four other cats the CO2 response was tested with a hyperoxic background. In the remaining five cats the response to isocapnic hypoxia was recorded during administration of 15, 12, and 8% O2 before and following haloperidol. There was a significant increase in room air discharge activity and in hypoxic sensitivity following haloperidol. However, there was no significant change in hypercapnic sensitivity. These results suggest that there is a modulatory role for endogenous dopamine only in the hypoxic response.
A total of 2544 comparisons were used to study the relative efficiency of various test procedures currently used to detect lymphoid leukosis virus infection in chickens. Meconium, blood, cloacal swabs, and egg albumen were collected from day-old chicks and adult hens from four breeder flocks. The phenotypic mixing was used as the biological assay for infectious virus. The complement fixation test and enzyme-linked immunosorbent assays were used as direct assays for the group-specific antigen of the avian leukosis-sarcoma viruses. Analysis of test results of biological assays has shown that blood from virus-infected chicks was more frequently positive than meconium. Also, direct assay for group-specific antigen was as efficient as the biological assays for detection of positive albumen samples from freshly laid eggs. The rate of false-positive reactors recognized by direct assays was lower in albumen samples than in cloacal swabs collected from hens that produce endogenous virus or group-specific antigen. Data also showed a relatively high concordance, ranging from 71 to 100%, between various assays with test materials from adult hens. Progress in reducing rates of exogenous lymphoid leukosis virus infection can be significant if dams are selected on the basis of any one of the test procedures examined. For complete eradication however, day-old chicks should be selected on the basis of the biological assay of blood of individual chicks reared in small groups.
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A randomized and controlled study was conducted to evaluate the efficacy of adjunctive antithymocyte globulin (ATG) therapy for the treatment of the initial rejection episode in first transplants of Haplo-LRD and cadaveric kidneys. When compared to the control group, which received only standard antirejection treatment (SAT) of steroid pulsing and local irradiation, the adjunctive ATG treatment group demonstrated significantly faster recovery rates from rejection as well as better graft survival rates (67% versus 91%, respectively, p = .01) after the first rejection. ATG treatment did not result in fewer subsequent rejection episodes than SAT but long-term allograft survival rates remained significantly superior to controls for the entire 3-year study period. By avoiding ATG treatment in those patients who never experienced clinical rejection on maintenance immunosuppressive therapy, i.e. nonresponders (32/130--25%), complications associated with excessive immunosuppression were minimized, i.e., graft and patient survival were 100%. The combined results in a 1-year patient survival of 97% and graft survival of 84%. These results suggest that use of ATG therapeutically for the treatment of rejection is efficacious and may be superior to the prophylactic method of ATG treatment in renal transplant patients.
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The pharmacodynamics of thiabendazole (TBZ) and its metabolite, 5OH-thiabendazole (5OH-TBZ), were studied in an anephric patient with Strongyloides stercoralis pneumonitis. No toxic manifestations were noted in the patient, and serum TBZ and 5OH-TBZ levels were comparable to those in eunephric patients. We conclude that thiabendazole, in the usual recommended dose of 25 mg/kg twice daily, given to patients with compromised renal function is reasonable and safe.
The fungal metabolite, cyclosporin A, is a potent immunosuppressive compound. Experiments were performed in vitro with both human and nonhuman primate peripheral blood lymphocytes to study the effect of this agent on suppressor cell activity. Cyclosporin A did not affect the generation or function of concanavalin A-induced suppressor lymphocytes as measured by their ability to suppress thymidine uptake of lymphocytes in secondary cultures. No evidence of suppressor cell induction was noted by incubation of lymphocytes with only cyclosporin A. We conclude that, although cyclosporin A does not generate or induce suppressor cell lymphocytes, it does spare them, while inhibiting other subpopulations. This effect may create an imbalance in the immune system which results in profound suppression.
A randomized and controlled study was conducted to evaluate the efficacy of adjunctive antithymocyte globulin (ATG) therapy for the treatment of the initial rejection episode in first cadaveric transplants. When compared to the control group (29), which received only standard antirejection treatment (SAT) of steroid pulsing and local irradiation, the adjunctive ATG treatment group (23) demonstrated significantly faster recovery rates (8.9 +/- 4.1 versus 6.9 +/- 3.7 days, P = 0.05, respectively) and better graft survival rates (62 +/- 9% versus 91 +/- 7%, respectively) after the first rejection. ATG treatment did not result in fewer subsequent rejection episodes than SAT but long-term allograft survival rates remained superior to controls for the entire 3-year study period. By avoiding ATG treatment in those patients who never experienced clinical rejection on maintenance immunosuppressive therapy, i.e., nonresponders (23 of 90), complications associated with excessive immunosuppression were minimized. The combined results of the non-responder group of patients and ATG-treated patients resulted in a 1-year patient survival of 97% and graft survival of 86%. These results suggest that the most efficacious use of ATG is therapeutic and not prophylactic in renal transplant patients.
Fatty acid compositions of lipids from six bacteria and four yeasts were determined. Fatty acid de novo synthetases were investigated with respect to chain length specificity towards acyl-CoA primers of various chain lengths. Four species of bacteria (Bacillus subtilis, Corynebacterium cyclohexanicum, Micrococcus luteus, and Pseudomonas maltophilia) possess branched-chain fatty acids of the iso and anteiso series as the major acids. De novo synthetases from these organisms exhibited specificity towards the chain length of the primer in the order butyl-CoA > priopionyl-CoA > acetyl-CoA. The remainder, two bacteria and all four yeasts, have the straight-chain type of fatty acids only and fall into two groups: (1) Eschericia coli B, Pseudomonas fluorescens, and Saccharomyces cerevisiae, which utilize the primers in the order acetyl-CoA > priopionyl-CoA > butyryl-CoA; and (2) Candida sake, Candida tropicalis, and Rhodotorula glutinis, which show the order propionyl-CoA > acetyl-CoA > butyryl-CoA. L-alpha-Keto-beta-methylvalerate, a precursor of the branched-chain primers, can be used as a source of primer for fatty acid synthesis by the organisms with branched-chain acids but not by those with the straight-chain type. The results indicate that organisms having straight-chain fatty acids lack the branched-chain equivalents for two reasons: first, their enzymes are not active toward primers with more than three carbons, and second, they lack a system of supply suitable branched-chain primers. It appears that activities of de novo synthetases from the organisms having straight-chain fatty acids generally have much higher activities than those from the organisms possessing branched-chain fatty acids
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The effect of infection with low-virulence, tissue culture-propagated strains of reticuloendotheliosis virus (REV) on protective vaccinal immunity against Marek's disease (MD) lymphomas was investigated. Vaccinated chickens inoculated at hatching with greater than 10(4) focus-forming units of REV and challenged with MD virus were poorly protected against MD lesion development as indicated by protective indices of 53 to 79% for strain CS (P less than 0.05) and 42 to 49% for strain T (P less than 0.01) compared to 78 to 100% for REV-free controls. Furthermore, the response of blood lymphocytes to mitogen stimulation and the antibody response to sheep erythrocytes and Brucella abortus were less in REV-inoculated chickens than in controls. The REV-induced depression of immune responses was more severe in chickens infected with mildly pathogenic strain T than in chickens infected with the apathogenic strain CS and was generally transient with both virus strains. Little or no depression of immune responses was observed in chickens inoculated with less than 10(3) focus-forming units of REV. These studies extend knowledge on the immunodepressive ability of low-virulence REV strains and establish that infection with these viruses depresses certain parameters of MD vaccinal immunity, an important model for cellular immunity against virus-induced neoplasia in the chicken.
Seven patients presented with a large perineal abscess eight months to seven years after complete healing of the perineal wound following proctocolectomy. Six patients had had total proctocolectomies for ulcerative colitis and a seventh had undergone abdominoperineal resection for cancer. A typical clinical picture of perineal pain, fever, urinary tract complaints (including retention), and minimal local perineal findings was present. Prostatitis or a urinary tract infection was considered in five patients, but none of them responded to antibiotics. Ultrasound examination of the perineum may confirm the diagnosis; however, diagnostic and therapeutic surgical exploration of the healed perineum is recommended when this diagnosis is unclear.
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During a 4-week period, Aspergillus fumigatus caused disease in 2 patients and colonized a third patient in a renal transplant ward. Our investigation indicated that increased exposure of these patients to spores probably occurred during renovation of the ward one floor above it. Cases were significantly clustered (P = 0.014) during the period when work overhead caused dust to filter down through pores in the acoustical tiles of the false ceiling of the renal transplant ward. Swab cultures demonstrated A. fumigatus in the dust, and air samples showed heavy contamination with A. fumigatus and other fungi at and below a renovation site, but not on 2 distant wards. We concluded that dust can be an important source of aspergilli and that release of dust and spores during activities such as renovation may increase the risk of nosocomial Aspergillus infection in exposed, immunosuppressed patients.
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