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Biomedical subjects

J Chakraborty

Publications and source records attributed to J Chakraborty.

At least 91 records · Page 5Linked to original sources

Epidemiology and cause of deaths among women in rural Bangladesh.

A total of 542 women aged 15 to 44 years died during the 10-year period 1976 to 1985 in the control area of Matlab, an area with a population of 90,000, representative of many other rural areas of southern Bangladesh. The corresponding age-specific mortality rate was 290 per 100,000 women 15-44 years. These deaths have been analysed retrospectively, using information collected through the Demographic Surveillance System set up by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and verbal autopsies conducted in the homes. Of these deaths, 175 (32%) were due to infectious diseases, 163 (30%) to direct obstetric complications, 67 (12%) to injuries, and the remaining 26% to other causes. Cause-specific and proportionate mortality rates showed a positive association with age for deaths due to infectious diseases, non-infectious diseases and unspecified causes, and an inverse association with age for deaths due to injuries. These rates showed a peak in the intermediate age group 25 to 34 years for deaths due to direct obstetric causes. No consistent trends were visible when annual rates were studied over time. Prior to death, 42% of the women were attended by traditional practitioners, and 33% were not attended at all. Demographic impact is discussed, emphasizing the contribution of obstetric causes to overall mortality. Priorities for health policy implications are proposed, focusing upon a strong maternity care programme, and improved availability of female health personnel, in the context of the socio-cultural constraints imposed on women in poor rural areas.

Adolescent↗

Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines.

We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62,285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P less than 0.0001 for BS-WC; PE = 54%, P less than 0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P less than 0.0001 for BS-WC; PE = 52%, P less than 0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.

Administration, Oral↗

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

1. Serum and salivary concentrations of caffeine (1,3,7-trimethylxanthine) and its dimethylxanthine metabolites were measured in 10 healthy control subjects and in 19 patients with cirrhosis, for up to 96 h following a 400 mg oral caffeine load. 2. Serum and salivary caffeine concentrations correlated significantly (r = 0.954; P less than 0.001) and no significant differences were observed in the pharmacokinetic data derived from the respective concentration-time curves. 3. In the control subjects, basal salivary caffeine concentrations did not exceed 0.4 mg l-1. The median (range) basal salivary caffeine concentrations in patients with compensated cirrhosis (n = 10), 0.2 (0-0.7) mg l-1 and decompensated cirrhosis (n = 9), 0.7 (0-5.8) mg l-1, were not significantly different from control values, although three patients with decompensated cirrhosis had basal salivary caffeine values above 2.0 mg l-1. 4. In the patients with compensated cirrhosis, the median peak salivary caffeine concentration, 10.9 (8.2-16.5) mg l-1 was significantly greater than in controls, 7.1 (4.7-11.8) mg l-1 (P less than 0.01) and the median apparent volume of distribution was significantly reduced, 0.38 (0.19-0.49) vs 0.41 (0.23-0.63) l kg-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of di-isopropyl 1,3 dithiol-2-ylidenemalonate (malotilate) on the hepatic changes induced by ethanol administration in the rat.

The sulphur-containing drug, di-isopropyl-1,3-dithiol-2-ylidenemalonate (Malotilate) protects against the increase in hepatic triglyceride concentration after acute ethanol administration (either 6 g/kg p.o. or 2 g/kg i.p.) in rats. The compound had no influence on the increased hepatic NADH:NAD ratio (measured as the lactate:pyruvate and 3-hydroxybutyrate:acetoacetate ratios) after acute ethanol dosing (2 g/kg i.p.), but was found to lower hepatic acetaldehyde concentrations and prevent some of the disturbances in lipid metabolism observed in liver slices from ethanol-treated animals (e.g. decreased oxidation of [1-14C]palmitate to 14CO2) after this ethanol dose. The drug did not inhibit ethanol metabolism in this acute experiment. Administration of Malotilate to Wistar rats (100 mg/kg/day orally) during chronic feeding of ethanol as 36% of the total calorie intake in a liquid diet, resulted in a lower intake of the alcohol-containing diet by ethanol-fed animals and reduced body weight gain in rats which received the drug, without blood ethanol levels or the ethanol intake (expressed in g/kg body weight/day) being affected. In ethanol-fed animals, Malotilate prevented the production of fatty liver and the adaptive increase in the ethanol elimination rate (EER) normally seen in ethanol-fed animals, although the drug actually caused a slight increase in EER in glucose pair-fed controls. Malotilate did not significantly decrease the degree of induction of microsomal cytochrome P-450 by ethanol, but the increase in aniline hydroxylation was much less marked in animals receiving ethanol and Malotilate, suggesting that the activity of the inducible microsomal ethanol oxidising system (MEOS) may be reduced by the compound. Determination of hepatic acetaldehyde concentrations during ethanol feeding, and during an acute ethanol challenge test following long-term ethanol treatment showed that the compound significantly lowered the level of this ethanol metabolite in the liver under both circumstances. This reduction of hepatic acetaldehyde concentrations, probably resulting in part from the reduced EER as well as increased low-Km aldehyde dehydrogenase activities and glutathione contents seen in the livers of Malotilate-treated rats, are possible mechanisms by which the drug protects against triglyceride accumulation after ethanol administration.

Aldehyde Dehydrogenase↗

Impact of B subunit killed whole-cell and killed whole-cell-only oral vaccines against cholera upon treated diarrhoeal illness and mortality in an area endemic for cholera.

The impact of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind trial in rural Bangladesh. 62,285 children aged 2-15 years and women aged over 15 ingested three doses of one of the vaccines or placebo. During the first year of follow-up there was a 26% reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22% reduction in the WC group. The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48% in the BS-WC group and 33% in the WC group. Overall mortality rates were 26% lower in the BS-WC group and 23% lower in the WC group during the first year, and reductions of mortality were observed only in women vaccinated at ages over 15 years. However, no differences in cumulative mortality were evident at the end of the second year of surveillance.

Administration, Oral↗

Caffeine clearance and biotransformation in patients with chronic liver disease.

1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load. 2. In the control group, the mean (+/- SD) serum caffeine clearance was 1.3 +/- 0.4 ml min-1 kg-1 and a mean of 56.4 +/- 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 +/- 1.4% of the administered caffeine was excreted unchanged. 3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 +/- 1.2 ml min-1 kg-1 and a mean of 57.2 +/- 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 +/- 0.9% of the administered caffeine was excreted unchanged. 4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 +/- 0.2 ml min-1 kg-1) was significantly impaired compared with controls (P less than 0.01) and a significant delay was observed in metabolite excretion in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Field trial of oral cholera vaccines in Bangladesh: results of one year of follow-up.

We assessed the protective efficacy (PE) of three doses of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines in a randomized, double-blind trial among 62,285 children and women residing in rural Bangladesh. After one complete year of surveillance, 110 cases of cholera were detected in the placebo group, 52 in the WC group (PE, 53%; P less than .0001), and 41 in the BS-WC group (PE, 62%; P less than .0001). Protection was greater for BS-WC recipients than for WC recipients only during the initial eight months of observation. Both vaccines conferred equivalent protection against cholera associated with life-threatening dehydration and against less severe cholera. High-grade, sustained protection was observed in persons vaccinated when older than five years; in younger persons protection was transient. We conclude that BS-WC and WC vaccines confer significant protection against cholera, particularly in persons vaccinated when older than five years.

Administration, Oral↗

Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial.

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).

Adolescent↗

Measles vaccination and childhood mortality in rural Bangladesh.

To ascertain whether measles vaccination was associated with reduced mortality rates in rural Bangladeshi children, the authors conducted a case-control study in four contiguous areas, two of which had participated in an intensive measles vaccination program which began in the spring of 1982. Cases were 536 children who had died in the four-area region at the age of 10-60 months between April 1982 and December 1984. Two age- and sex-matched controls were selected from the four-area region for each case; each control had survived at least through the date of death of the matched case. Measles vaccination was associated with a 36% (95% confidence interval 21%-48%) proportionate reduction in the overall rate of death and a 57% (95% confidence interval 43%-67%) reduction in the rate of deaths directly attributed to measles or ascribed to diarrhea, respiratory illness, or malnutrition. The association of measles vaccination and reduced mortality remained unchanged after the authors restricted controls to children who had survived at least one year after the deaths of their matched cases. Moreover, children vaccinated in 1982 exhibited a sustained reduction in the rate of death in 1983 and 1984. The authors concluded that measles vaccination was associated with a pronounced and sustained reduction in the rate of death among children in this study.

Bangladesh↗

Causes of maternal mortality in rural Bangladesh, 1976-85.

Of a total of 1037 women of reproductive age who died during the period 1976-85 in the Matlab area that was under demographic surveillance, 387 (37%) were maternal deaths. The mean maternal mortality over the 10-year period was 5.5 per 1000 live births (101 per 100 000 women of reproductive age). Major causes of maternal death, which were assessed using a combination of record review and field interviews, included postpartum haemorrhage (20%), complications of abortion (18%), eclampsia (12%), violence and injuries (9%), concomitant medical causes (9%), postpartum sepsis (7%), and obstructed labour (6.5%). Deaths caused by postpartum haemorrhage were positively associated with both maternal age and parity, whereas those caused by eclampsia and injuries were more common among young and low-parity women. If maternal deaths arising from complications of abortion are disregarded, 20% of all maternal deaths occurred during pregnancy, 44% during labour and the two days following delivery, and 36% during the remaining postpartum period.These findings support the need to develop a service strategy to address the risks of childbearing and childbirth in areas such as rural Bangladesh, where almost all deliveries take place at home. This strategy must be based not only on preventive and educational interventions, including family planning and antenatal care, but also on systematic attendance at home deliveries by trained professional midwives, backed up by an effective chain of referral.

Abortion, Spontaneous↗

Antibodies to 4-hydroxyandrostenedione--a new anti-breast cancer agent suitable for use in a radioimmunoassay.

A specific antiserum suitable for radioimmunoassay (RIA) of 4-hydroxy-4-androstene-3,17 dione (4-OHA) has been developed. Sheep antiserum was raised by injecting two different conjugates prepared by coupling 4-OHA to ovalbumin. Antisera obtained from a sheep immunised with 4-hydroxy-testosterone-17-hemisuccinate ovalbumin conjugate were of higher titre and more specific than antisera obtained from sheep immunised with 4-hydroxyandrostenedione-7 alpha-carboxyethylthioether. The antiserum bound 50% of 20 picograms of [6,7-3H]-4-OHA at an initial dilution of 1:270. The most relevant steroids, androstenedione (AD) and testosterone (T) were tested and showed cross reactivity of 2.7% and 5.1% respectively. The lower limit of detection was 4.5 pg/tube. Antisera from this animal will prove useful as the basis of a sensitive and specific RIA for clinical pharmacokinetic studies of 4-OHA.

Androstenedione↗

The use effectiveness of the Copper T-200 in Matlab, Bangladesh.

Using a unique record keeping system, the use effectiveness of the Copper T-200 is examined in rural Bangladesh. In Matlab the Copper T-200 is a highly effective contraceptive modality. The adopters are typically low to medium parity women under 30 years of age. The most important cause of termination among women in the study was voluntary removal of the device. The complaint most often reported was bleeding followed by pain and weakness. The Matlab experience suggests that sustained motivation and regular resupply are the two key components of this highly successful family planning program.

Adult↗

Unilateral torsion of spermatic cord in men: effect on Leydig cell.

In our previous studies, we reported that short-term unilateral spermatic cord torsion had no adverse effect on the germ cells and the Sertoli cell in the contralateral testis of men. As an extension of our earlier investigations on the testicular pathophysiology in humans after unilateral spermatic cord torsion, the present study was undertaken to assess the Leydig cell function employing both fine structural and morphometric analysis in patients with short-term spermatic cord torsion. Bilateral testicular biopsy samples obtained from 4 men (15-19 years) with short-term unilateral torsion of the spermatic cord and from a control group of 6 men (15-40 years) were used in the present investigation. No appreciable difference in the Leydig morphology was noted between the biopsy samples from control and the contralateral testes. This was substantiated by morphometric analysis. The present study clearly indicates that patients with unilateral torsion of the spermatic cord may not essentially have bilateral testicular abnormalities, as suggested by the previous investigators. This report, thus lends further support to our earlier contention that alteration in microcirculation is quite likely the earliest and possibly the most significant contributor to the contralateral testicular damage in man after ipsilateral spermatic cord torsion.

Adolescent↗

Monoclonal antibodies to human parathyroid hormone (1-34) and their use in the immunocytochemical detection of parathyroid tumours.

Monoclonal antibodies against the biologically active N-terminal fragment of human parathyroid hormone, hPTH (1-34), were produced. The procedure included the use of novel secondary immunization in vitro of mouse spleen cell cultures. Dissociated spleen cells from primary immunized Balb/c mice, were cultured for five days in the presence of thymocyte conditioned media (TCM) and synthetic hPTH (1-34). Contrary to previous findings by other workers, in our hands Balb/c mice responded well. Following immunization the spleen cells were fused with NSl myeloma cells and cultured for eleven days before screening for antibody. Using an enzyme linked immunosorbent assay (ELISA) a number of positive clones were detected. Positive cells were cloned by limiting dilution and fifteen specific monoclonal hybridomas were produced. The immunoglobulin class of the different monoclonal antibodies was found to be IgGl. The immunocytochemical reaction was tested with chief cell carcinoma tissue and found to be clearly positive.

Animals↗

Cellular immune competence and diarrheal morbidity in malnourished Bangladeshi children: a prospective field study.

A year-long prospective study of 152 Bangladeshi children with mild to moderate protein-calorie malnutrition related nutritional status and cellular immune defects to morbidity due to diarrheal, respiratory, and febrile diseases. In children older than 36 mo, wasting correlated with skin test anergy to three recall antigens and with inability to initiate hypersensitivity to dinitrochlorobenzene. In this older age group, anergy was associated with a 58% increased attack rate and an 83% increased duration of diarrheal diseases but not with febrile or respiratory infections. In stepwise regression analysis, this anergy effect was independent of the small negative impact of poorer nutritional status on morbidity. Ninety-three percent of diarrheal illnesses lasting at least 14 d were among anergic children. Cellular immune incompetence, indicated by anergy of unknown etiology, is associated with increased diarrheal morbidity and may promote the vicious cycle of repeated infections and deteriorating nutritional status.

Bangladesh↗

B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity.

We conducted a randomized trial among persons in rural Bangladesh to evaluate the side effects and immunogenicity of orally administered B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) cholera vaccines and a killed Escherichia coli strain K12 placebo proposed for field testing. Three doses of BS-WC, WC, E. coli, or a control agent were given with antacid to 1,257 women (aged greater than 15 years) and children (aged to to 15 years). The four groups exhibited no statistically significant differences in occurrence of symptoms after each dose, and rises in titers of vibriocidal (VC) antibodies to Inaba and Ogawa were twofold higher for vaccinees than for controls (P less than .001). Half of the persons with fourfold or greater VC responses to WC responded after the first dose; many additional patients, particularly young children, responded after subsequent doses. In contrast, 89% of persons who responded to BS-WC with twofold or greater rises in titer of IgG antibodies to cholera toxin did so after the first dose. After the third dose, vaccinees exhibited a fivefold higher rise in titer than did controls (P less than .001); a dose-to-dose booster effect was most evident in young children.

Administration, Oral↗