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Biomedical subjects

R Blair

Publications and source records attributed to R Blair.

At least 73 records · Page 4Linked to original sources

Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.

PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Acquired Immunodeficiency Syndrome↗

Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.

Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty-four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic.

Acquired Immunodeficiency Syndrome↗

Tolerance of growing pigs for dietary vitamin A, with special reference to bone integrity.

Weanling crossbred pigs (144) of 8 kg initial weight were fed to 90 kg on diets containing graded levels of vitamin A representing 0, 1, 5, 10, 50 and 100 times the NRC (1988) estimated requirement. No clinical signs of deficiency or toxicity were recorded although plasma and liver retinol levels were affected by treatment. Histopathological examination indicated a high incidence of lesions in the cartilage of the distal femur and ulna, but they were not related to treatment. There was some evidence that excessive vitamin A levels in the diet significantly reduced the uronic acid concentration in joint cartilage, indicating a reduced concentration of proteoglycans. However no relationship was established between dietary vitamin A level and the incidence of clinical osteochondrosis. The results suggest that the allowable range of vitamin A set out in the Canadian feeds regulations is appropriate for practical pig production.

Animals↗

Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels.

OBJECTIVE: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study using stored specimens. SETTING: A referral center and several private hospitals. PATIENTS: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. MEASUREMENTS: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. MAIN OUTCOME MEASURE: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. MAIN RESULTS: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; CI, 0.03% to 6.6%) obtained on 56 occasions (1.8%; CI, 0.04% to 9.6%) from controls (specificity, 98.2%; CI, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; CI, 10.9% to 69.2%) but in 0 of 9 control patients (CI, 0% to 28.3%). CONCLUSION: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.

Acquired Immunodeficiency Syndrome↗

Correlation of Histoplasma capsulatum polysaccharide antigen with the severity of infection in murine histoplasmosis.

We sought to determine if Histoplasma capsulatum polysaccharide antigen (HPA) levels correlate with the extent of infection in murine of histoplasmosis. Separate groups of mice were inoculated intratracheally with varying numbers of H. capsulatum yeast cells. After 1 week, HPA levels and fungal burden (quantitative culture of lung and spleen and histopathologic stain of lung) were determined in lung and spleen, and HPA levels in serum. HPA levels, cultures and histopathological stain results of lung and spleen tissue showed a direct correlation with increasing inoculum size. HPA levels in serum also correlated with the size of inoculum. H. capsulatum antigen in lung correlated with silver stain scores of lung tissue, (R = 0.948, P less than 0.001) and with quantitative culture scores of lung, (R = 0.929, P less than 0.001). HPA levels in spleen tissue also correlated with spleen culture scores, (R = 0.724, P less than 0.001). These results indicate that determination of HPA level in serum and tissue may be a useful test in evaluating the severity of diseases as well as efficacy of antifungal therapy in histoplasmosis.

Animals↗

Redox modulation of N-methyl-D-aspartate-stimulated neurotransmitter release from rat brain slices.

Rat brain cortical slices released tritiated norepinephrine ([3H]NA) during a 2-min stimulation with N-methyl-D-aspartate (NMDA). Dithiothreitol (DTT; 0.1-5 mM), present for 6 min prior to stimulation, dose-dependently increased the release of [3H]NA from cortical slices stimulated with a maximally effective concentration of NMDA (500 microM). Similar results were observed for [3H]NA release from hippocampal slices and tritiated and endogenous dopamine release from striatal slices. DTT treatment also markedly shifted the dose-response curve of NMDA to the left. Cortical slices released approximately the same amount of [3H]NA with 10 microM NMDA following DTT treatment (about 5%) as non-DTT-treated control slices did with 500 microM NMDA. The effects of DTT were fully reversed by subsequent treatment with 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB; 0.5 mM). DTT treatment did not significantly alter the ability of magnesium (1.3 mM) or the polyamine antagonist arcaine to block the NMDA-stimulated release of [3H]NA. In contrast, DTT treatment significantly attenuated the antagonist effects of the competitive glycine antagonist, 7-chlorokynurenic acid, and the competitive NMDA antagonist, 2-aminophosphonopentanoic acid. These results suggest that oxidation and reduction of disulfide bonds located within the NMDA receptor complex might regulate the activation of the NMDA receptor. This could have important consequences in vivo if endogenous oxidizing/reducing systems are found to have similar effects on NMDA-stimulated responses.

Animals↗