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Biomedical subjects

J Seaman

Publications and source records attributed to J Seaman.

At least 37 records · Page 2Linked to original sources
PubMed1996

The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994.

BACKGROUND: Although endemic in parts of southern Sudan, visceral leishmaniasis (VL) had not been reported in Western Upper Nile (WUN) until an epidemic was confirmed in 1989. A combination of circumstances created conditions for transmission among a population of mainly Nuer and Dinka people who had no immunity. The civil war which restarted in 1983 has been a major contributing cause and continues to hinder provision of treatment, data collection and control measures. METHODS: Since the first of three clinics to treat VL was established in WUN in 1989, data on the epidemic and mortality have been collected in seven retrospective surveys of villages and among patients. Adults were interviewed about surviving family members and those who had died since the epidemic came. Survey death rates are used here to estimate mortality from VL and 'excess mortality' above expected levels. RESULTS: The surveys found high mortality at all ages and suggest an overall death rate of 38-57% since the epidemic started in 1984, and up to 70% in the most affected areas. Both methods of estimation suggest that around 100,000 deaths, among about 280,000 people in the epidemic area, might be attributable to VL. CONCLUSIONS: This continuing epidemic has shown that VL can cause high mortality in an outbreak with astonishingly high infection rates. Population movement has been a major factor in transmission and poor nutritional status has probably contributed to the risk of clinical infection. Although over 17,000 people have been successfully treated for VL at the clinics in WUN, the disease is likely to become endemic there.

Adolescent↗
PubMed1995

Hypoxic helium breathing does not reduce alveolar-arterial PO2 difference in the horse.

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.

Animals↗
PubMed1995

Liposomal amphotericin B (AmBisome) in the treatment of complicated kala-azar under field conditions.

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.

Adolescent↗
PubMed1995

Quantitative determination of codeine and its major metabolites in human hair by gas chromatography-positive ion chemical ionization mass spectrometry: a clinical application.

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.

Administration, Oral↗
PubMed1995

Exercise induced ventilation/perfusion inequality in the horse.

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)

Analysis of Variance↗
PubMed1995

Leish-KIT, a stable direct agglutination test based on freeze-dried antigen for serodiagnosis of visceral leishmaniasis.

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.

Agglutination Tests↗
PubMed1994

Mechanism of reduction in alveolar-arterial PO2 difference by helium breathing in the exercising horse.

Previous work has shown that replacing N2 in air with He at the same inspired O2 fraction reduces the exercise-induced alveolar-arterial PO2 difference (AaPO2) in horses but has provided no mechanism explaining this effect. We sought to distinguish among possible causes by using the multiple inert gas elimination technique. Six horses were studied on a high-speed treadmill while they breathed either ambient air or normoxic He-O2. O2 uptake reached 138.0 ml.min-1.kg-1 and was not affected by He-O2. Temperature-corrected arterial PO2 was 76.7 Torr (air) and 86.9 Torr (He-O2) (P < 0.01). Corresponding AaPO2 was 22.3 and 15.9 Torr, respectively (P < 0.01). Mean AaPO2 predicted from ventilation-perfusion inequality did not change with He-O2 (12.7 Torr with air and 11.9 Torr with He-O2). Mean arterial PCO2 was 50.1 Torr with air and 44.1 Torr with He-O2 (P < 0.01); minute ventilation and tidal volume were correspondingly higher by 140 l/min and 1.0 liter, respectively, with He-O2. Pulmonary O2 diffusing capacity, cardiac output, and all ventilation-perfusion dispersion indexes did not change with He-O2. Intrapulmonary shunt was insignificant. Higher ventilation with He-O2 explained only approximately 4 Torr of the 10-Torr rise observed in arterial PO2. The remainder (and the corresponding fall in AaPO2) was due to more complete diffusion equilibration as a consequence of the higher minute ventilation and thus alveolar PO2, which reduced the average slope of the O2 dissociation curve, thereby increasing the ratio of diffusive to perfusive conductance.

Animals↗
PubMed1994

Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer.

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.

Adult↗
PubMed1993

Hypoglycemic and insulin response to a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF-I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states.

Adult↗
PubMed1993

Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions.

The effect of the rate of infusion of disodium aminohydroxypropylidene bisphosphonate (APD; CGP 23339A), an inhibitor of bone resorption, on urinary excretion of this agent was studied in a randomized open-label study in 20 cancer patients. Ten patients received 60 mg of APD over 4 h, and the remaining 10 patients received the same dose over 24 h. Urine collected during specified intervals for 72 h after the start of the infusion was analyzed by high-performance liquid chromatography for unchanged APD. Mild and transient adverse experiences were observed in 12 (60%) patients; the most common were headache, fever, and phlebitis at the infusion site. No clinically significant laboratory abnormalities were observed, and none of the experiences were serious enough to require discontinuation of treatment. Cumulative urinary excretion of APD was a linear function of time, increasing rapidly after both the 4- and 24-h infusions were started. The mean (+/- standard deviation) cumulative urinary excretion of APD was 51.1 +/- 13.0% of the dose in the 20 patients, 55.0 +/- 15.0% in the 10 patients given the 4-h infusion, and 47.2 +/- 9.9% in the 10 patients receiving the 24-h infusion. Thus, the rate of infusion of the 60-mg dose did not influence retention of APD at 72 h after the start of therapy. Similarly, the presence or absence of bone metastases did not influence cumulative urinary excretion or the retention of APD.

Adult↗
PubMed1993

Epidemic visceral leishmaniasis in Sudan: a randomized trial of aminosidine plus sodium stibogluconate versus sodium stibogluconate alone.

In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600. Patients (200) were randomized to receive sodium stibogluconate (Sbv) at 20 mg/kg/day for 30 days (groups S, n = 99) or Sbv at 20 mg/kg/day plus aminosidine at 15 mg/kg/day for 17 days (group AS, n = 101). Of 192 patients who had spleens or lymph nodes aspirated at entry, 134 (70%) were positive for parasites. During treatment, 7% in group S and 4% in group AS died. All 184 patients who completed treatment were clinically cured. At days 15-17, microscopy of aspirates showed that 57 (95%) of 60 in group AS were negative for parasites compared with 47 (81%) of 58 in group S (P = .018). At day 30, 57 (93.4%) of 61 group S aspirates were negative.

Adolescent↗
PubMed1993

Increased urinary excretion of pyridinium cross-links in cancer patients.

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients.

Adult↗