Kala azar in eastern Upper Nile Province, southern Sudan.
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Biomedical subjects
Publications and source records attributed to J Seaman.
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In a previous study we evaluated the mechanism of alveolar-arterial PO2 (AaPO2) reduction when nitrogen is replaced with helium in normoxia (FIO2 = 0.21). The reduction in AaPO2 was not due to changes in VA/Q inequality, pulmonary O2 diffusing capacity, or cardiac output, but to more complete diffusion equilibration as a consequence of the higher ventilation and thus PAO2 (which reduced the average slope of the hemoglobin O2 dissociation curve (ODC), and thus enhanced diffusive equilibration). We hypothesized that hypoxic He/O2 breathing in contrast would not reduce the AaPO2 because PAO2 and PaO2, although higher with He than N2, would remain constrained to the linear region of the ODC. Breathing hypoxic gas mixtures did constrain the PAO2 to the linear region of the ODC, even when PAO2 was increased by He/O2 breathing. Thus, the average slope of the ODC did not change when He replaced N2 and this explains the lack of change in AaPO2, as hypothesized.
An open trial of liposomal amphotericin B (AmBisome [L-AmB]; Vestar, San Dimas, CA) for treatment of complicated visceral leishmaniasis was performed in Sudan. Forty-nine patients were treated, and there were six deaths (12% mortality); these were not attributed to therapy. Thirty-seven patients were selected for the trial because of (1) relapse after treatment with a combination of pentavalent antimony (Sbv) and aminosidine, (2) incomplete parasitological response to Sbv and aminosidine, or (3) severe illness. Drug regimen 1 (3 doses of 3-5 mg/kg, on days 0, 3, and 10) cured 8 (50%) of 16 patients; regimen 2 (6 doses of 3-5 mg/kg, on days 0, 3, 6, 8, 10, and 13) cured 14 (88%) of 16. For four of 10 partial responders, "rescue" therapy with L-AmB alone (3 mg/kg daily for 10 days) resulted in cure. Twelve less-unwell patients received regimen 3 (4 doses of 4-5 mg/kg, on days 0, 2, 5, and 7); seven of 11 patients evaluated (64%) were cured. The optimal regimen of L-AmB in these circumstances is administration of 4 mg/kg on days 0, 3, 6, 8, 10, and 13.
A highly sensitive method was developed for the quantitative analysis of codeine and morphine in human hair. After addition of deuterated internal standards, hair samples were digested overnight in 1N NaOH at 37 degrees C. Hydrolysis was performed on certain digests by addition of 1 mL 6N HCl. Digest solutions were extracted using a solid-phase procedure with Bond Elut Certify extraction columns. Derivatized extracts were analyzed on a Finnigan ion trap mass spectrometer (Magnum) in the positive ion chemical ionization mode using acetone as the reagent gas, helium as the carrier gas, and a DB-5 MS (30 m x 0.25-mm i.d.) capillary column. The assay was linear to 75 ng/mg (r = 0.99) and was capable of detecting 10 pg of codeine and morphine on-column. Intra-assay precision ranged from 8 to 20%. The method was used to quantitate codeine in human hair obtained from two male volunteers with dark brown to black hair after a single oral dose of 120 mg codeine phosphate liquid. Hair samples were plucked from the scalp for 28 days and then cut at the scalp. Codeine was detectable in 1-cm long hair (containing the bulb) at 12 h following the dose and remained detectable in the hair shaft for at least 8 weeks. Codeine metabolites were not detected in the hair of these two subjects. The method is currently being used in dose-response disposition studies to quantitate codeine and its major metabolites in human subjects.
Exercise in normal human subjects causes deterioration of matching of ventilation to blood flow in the lungs, but only in about 50% of those examined. A previous study (Wagner et al. 1989) of 5 horses showed no significant worsening of ventilation/blood flow (VA/Q) relationships during heavy exercise as determined by multiple inert gas elimination technique (MIGET). Because of the small number of horses in that study and the 50% human incidence of exercise induced VA/Q mismatch, we studied an additional 6 Thoroughbreds, comparing VA/Q relationships at the walk (1.4 m/s, 0 degrees incline) and during galloping (9.6 +/- 0.3 m/s, 7% incline). Such data were collected under 4 different conditions wherein inspired gas was 1) air, 2) 21% O2 in helium, 3) 15% O2 in N2 and 4) 15% O2 in helium. Each horse exercised 4 times (morning and afternoon of 2 days, with inspired gas conditions randomised). There was a small but significant increase in VA/Q mismatch (similar under all 4 conditions). The second moment of the VA/Q distribution (determined by the MIGET) increased significantly (P < 0.01) from 0.31 +/- 0.01 at the walk to 0.38 +/- 0.02 during gallop. This increase however is small: 0.38 is well within the range of this parameter for normal human subjects (where the 95% upper confidence limit is 0.60). This study shows that a small amount of exercise induced VA/Q mismatch can occur in the horse as in man, but the mechanism remains to be elucidated and its clinical significance remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to increase the application potential of the direct agglutination test (DAT) for the detection of anti-Leishmania antibodies in human serum samples, we developed an antigen based on stained and freeze-dried Leishmania donovani promastigotes. We describe here the evaluation of the performance of the DAT based on this freeze-dried antigen. It was shown that the freeze-dried antigen remains fully active, even after storage at 56 degrees C for 18 months. With a cutoff value of 1:1,600, the sensitivity of the DAT was shown to be 92% and the specificity of the test was 99.7%, which were comparable with the results found for the DAT based on liquid antigen. The major advantages of the freeze-dried antigen are that the production of a large batch of this antigen allows reproducible results in the DAT over a long period of time and that the freeze-dried antigen can be stored at ambient temperature, which, as was shown, makes the test a valuable diagnostic tool for use in the field.
Four intravenous regimens of pamidronate (Aredia) were evaluated for palliative treatment of bone metastases in 2 randomized open-label trials in patients with breast cancer (n = 61) or prostate cancer (n = 58). In breast cancer patients, administration of pamidronate 60 mg every 4 weeks, 60 mg every 2 weeks, or 90 mg every 4 weeks for 3 months resulted in statistically and clinically significant reductions in bone pain, with accompanying decreases in biochemical markers of bone turnover; a regimen of 30 mg every 2 weeks was not effective. Healing of bone lesions was observed in 25% of breast cancer patients. In prostate cancer patients, the same regimens of pamidronate produced reductions in bone pain, but no dose-response relationship was apparent. Moreover, there were no consistent changes in biochemical indices in these patients, and no healing of bone lesions occurred. The different response to pamidronate in those 2 patient populations may reflect the different severity of metastatic disease at baseline. Side effects of pamidronate were mild and transient in both studies.
A combination of interview, serology and skin testing was used to investigate the status of apparently healthy villagers during a visceral leishmaniasis epidemic in southern Sudan. The number of people who had died equalled the number who were alive at the time of the survey. The direct agglutination test (DAT) identified 10% of the people as being serologically positive. Most young children (36/39) and 34% (22/64) of adults had neither positive serology nor skin test. About 64% (42/66) of adults had positive skin tests. In two villages, 54% and 76% of those over four years of age showed evidence of having been infected. The mortality associated with infection was estimated as at least 69%; 25% of those infected appeared to have cured spontaneously. The outcome for the remaining 6% was still doubtful. Even in this devastating epidemic there is, therefore, evidence of a considerable amount of infection without severe disease. Serological tests, while useful clinically, are apparently not useful for detecting early cases. Combined skin testing and serology produces a comprehensive though partially hypothetical picture.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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A 37-year-old man with a history of abdominal pain, diarrhea, and weight loss was found to have an 8-cm-diameter tumor in the head of the pancreas, a biopsy specimen of which revealed histologically and ultrastructurally typical pancreatoblastoma. The tumor was unresectable and demonstrated no response to chemotherapy; however, substantial tumor shrinkage resulted from intraoperative and external beam radiation therapy. This rare tumor, to our knowledge not previously reported in an adult, should be considered in the differential diagnosis of adults as well as children with pancreatic epithelial tumors.