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Biomedical subjects

R B Sack

Publications and source records attributed to R B Sack.

At least 91 records · Page 5Linked to original sources

Acute toxicity of vitamin A given with vaccines in infancy.

A double-blind, randomised, placebo-controlled trial was conducted to evaluate the safety and toxicity of vitamin A supplementation within the Expanded Programme on Immunisation (EPI) in rural Bangladesh. 191 infants received 3 doses of either 50,000 IU of vitamin A or placebo at about 1.5, 2.5, and 3.5 months and were examined on days 1, 2, 3, and 8 after supplementation. 11 infants (11.5%) supplemented with vitamin A had episodes of bulging of the fontanelle as opposed to 1 (1%) in the placebo group. 16 of the 17 events occurred in the vitamin A supplemented group. No other side effects were noted. There was a tendency towards a cumulative effect of toxicity with increasing doses.

Bangladesh↗

A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease.

BACKGROUND: Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. METHODS: We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. RESULTS: Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. CONCLUSIONS: Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.

Acute Disease↗

Malnutrition, cell-mediated immune deficiency, and diarrhea: a community-based longitudinal study in rural Bangladeshi children.

A community-based longitudinal study was conducted in Matlab, a rural area of Bangladesh, from May 1988 to April 1989 to examine the associations among malnutrition, cell-mediated immune deficiency, and the incidence of diarrhea in children under age 5 years. A cohort of 705 children was followed for a year; illnesses were ascertained every fourth day by home visits, anthropometric status was evaluated monthly, and cell-mediated immune status was assessed by a multiple antigen skin test at baseline and every 3 months. The diarrhea incidence rate was 4.6 episodes per year. Approximately three quarters of the children were below -2 z score weight for age and height for age, and about a third were below -2 z score weight for height. There was a modest association between undernutrition and the incidence of diarrhea. About 10-20% of the study children were anergic, and these children experienced a 50% increased incidence of diarrhea compared with their immunocompetent counterparts. This association persisted after controlling for the effects of age, nutritional status, socioeconomic status, and history of diarrhea in the previous 3 months. Malnutrition and cell-mediated immune deficiency were important independent risk factors for the occurrence of diarrhea and must both be considered in the design of interventions for the control of this condition.

Bangladesh↗

Cell-mediated immune deficiency and malnutrition are independent risk factors for persistent diarrhea in Bangladeshi children.

A community-based longitudinal study was carried out at Matlab, Bangladesh, to investigate the magnitude of the problem of persistent diarrhea; 705 children aged < 5 y were followed, yielding 7300 child-months of observation in 1 y. Morbidity data were collected every fourth day by home visit, anthropometric status was determined monthly, and cell-mediated immune status was assessed every 3 mo. The incidence of persistent diarrhea was 34 episodes per 100 child-years; rates were highest in infancy and declined through the remainder of childhood. In a logistic-regression model, weight-for-height status and immune status were significant predictors of persistent diarrhea. Compared with those at zero Z score, children with weight-for-height at -2 would have a 3.5 times increased risk of persistent diarrhea. Compared with immunocompetent children, immunodeficient children had about twice the risk of developing persistent diarrhea. Thus, nutritional status and cell-mediated immune status were important independent risk factors for persistent diarrhea.

Bangladesh↗

Use of the polymerase chain reaction and fluorescent-antibody methods for detecting viable but nonculturable Shigella dysenteriae type 1 in laboratory microcosms.

Epidemiological studies of shigellosis in Bangladesh have demonstrated that surface-water sources can act as foci of infection. Studies of laboratory microcosms have shown that shigellae become nonculturable but remain viable when exposed to environmental samples of water. The present study was carried out to detect viable but nonculturable Shigella dysenteriae 1 from laboratory microcosms by the polymerase chain reaction and the fluorescent-antibody techniques. S. dysenteriae 1 was inoculated into laboratory microcosms consisting of water samples collected from ponds, lakes, rivers, and drains in Bangladesh. The survival of S. dysenteriae in microcosms was assessed by viable counting on MacConkey agar. After 2 to 3 weeks, S. dysenteriae 1 became nonculturable but remained viable. After 6 weeks, this nonculturable but viable S. dysenteriae 1 was detected by both the polymerase chain reaction and the fluorescent-antibody methods. The viable but nonculturable state of S. dysenteriae 1 demonstrated in this study may be important for understanding the epidemiology of shigellosis.

Base Sequence↗

Clonal relationships among classical Vibrio cholerae O1 strains isolated between 1961 and 1992 in Bangladesh.

In Bangladesh, the replacement of classical Vibrio cholerae by the E1 Tor biotype in 1968 and the reappearance of the classical biotype and its coexistence with the E1 Tor biotype after 1982 were never adequately explained. We have analyzed 23 classical V. cholerae isolates collected between 1961 and 1968, 14 classical isolates collected between 1982 and 1992 from the capital city, Dhaka, and 6 classical V. cholerae isolates collected from two southern districts of Bangladesh and studied restriction endonuclease cleavage patterns of rRNA genes (ribotypes) to investigate the clonal relationships among the isolates. Southern blots of total DNA digested with restriction enzyme BamHI, BglI, EcoRI, HindIII, or PstI were probed, using a cloned Escherichia coli rRNA operon. While restriction enzymes BamHI, EcoRI, and PstI failed to differentiate the isolates on the basis of ribotyping, BglI and HindIII produced digestion patterns that allowed differentiation. Ribotyping the isolates with BglI and HindIII revealed five different clones (ribotypes IA, IB, IIA, IC, and IIC) of classical vibrios in Bangladesh. Strains belonging to ribotypes IA and IB were isolated in Dhaka before 1968, and one ribotype (IA) was again isolated between 1982 and 1992. Ribotype IIA was isolated in 1988 and 1989, when both clones (IA and IIA) of classical vibrios coexisted with the EI Tor vibrios. Isolates belonging to ribotypes IC and IIC were collected in the southern districts of Bangladesh and were clearly different from those collected in Dhaka between 1968 and 1992 by ribotyping analysis with BglI. These results support the previous assumption that classical vibrios were never completely replaced in Bangladesh and also demonstrate the existence of more than one genetically different clone of classical V. cholerae.

Bangladesh↗

Comparison of three methods to obtain upper small bowel contents for culture.

In this study of 27 patients with dyspepsia, we compared three methods for obtaining upper small bowel contents for culture: 1) the Enterotest or string capsule method, 2) duodenal intubation using a closed polyethylene tube filled with water that had been boiled for sterilization and removal of dissolved oxygen, and 3) brushing of duodenal mucosa with a cytology brush protected by a sheath (the last two done during endoscopy). In 12 of the 27 patients, duplicate intubations and brushings were performed. The samples obtained were cultured aerobically. Parameters used to compare the three methods were: the contribution of each method to the diagnosis of upper small bowel bacterial overgrowth (USBBO), agreement between the methods in diagnosis of USBBO and in detailed microbiological findings, and the reproducibility of diagnosis of USBBO and of microbiological findings in duplicate intubation and brushing. Intubation and brushing were highly reproducible and superior to the Enterotest in all of the tested parameters. Intubation and brushing are equally efficacious, but intubation is preferred because of the slight cost advantage, ease of specimen processing, and the ability to obtain anaerobic specimens.

Adult↗

Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age.

A longitudinal study of diarrhea was carried out from May 1988 to April 1989 by household surveillance of 705 children less than 5 years old in rural Bangladesh. Stool samples were examined for enteric pathogens at the beginning of each diarrheal episode. For persistent episodes, stool examination was repeated on days 15-17 of the illness. For each case of persistent diarrhea, stool samples from age-matched acute diarrheal and healthy controls were examined. Compared with healthy controls, cases of diarrhea were associated with Shigella species (P = .07) and rotavirus (P less than .05). Diffusely adherent Escherichia coli (P less than .05) and cryptosporidia (P = .07) were the only enteropathogens associated with persistent diarrhea in comparison with acute diarrhea. No more than 15% of children had the same class of pathogen identified from stool on both days 1-3 and days 15-17, indicating that persistent infection was uncommon. However, a different enteropathogen was frequently found on days 15-17, suggesting that sequential infection may be a cause of persistent diarrhea.

Bangladesh↗

Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children.

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.

Acute Disease↗

Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú.

In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Perú, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re-infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries.

Acute Disease↗

Human colonic epithelial cells, HT29/C1, treated with crude Bacteroides fragilis enterotoxin dramatically alter their morphology.

Bacteroides fragilis has been associated with causation of diarrheal disease in livestock and humans. To date, conventional tissue culture and animal assays used to detect the biologic activity of bacterial enterotoxins have failed with enterotoxigenic B. fragilis. Although enterotoxigenic B. fragilis stimulates intestinal secretion in lamb and calf ligated intestinal loops, infant rabbits, and adult rabbits with ligated ceca, these animal systems are costly and complicated, which limits their usefulness for identification of enterotoxigenic B. fragilis strains. Using the cloned human colonic-epithelial-cell line HT29/C1, we have developed an in vitro assay that is 89% sensitive and 100% specific in detecting enterotoxigenic B. fragilis strains as defined by the lamb ligated-intestinal-loop assay. Subconfluent HT29/C1 cells treated with concentrated bacterium-free culture supernatants of enterotoxigenic B. fragilis strains develop specific and striking morphologic changes including loss of cell-to-cell attachments, rounding, swelling, and, in some cases, pyknosis. These morphologic changes are initially visible at 1 h after treatment and progress over at least the first 24 h. This tissue culture assay should prove useful in epidemiologic studies of enterotoxigenic B. fragilis and may facilitate basic studies to identify the B. fragilis toxin(s) and its mechanism of action.

Bacterial Toxins↗

Differentiation of Shigella flexneri strains by rRNA gene restriction patterns.

We studied the restriction endonuclease cleavage patterns of rRNA genes (ribotypes) of 72 clinical isolates of Shigella flexneri representing eight serotypes to determine whether ribotyping could be used to distinguish S. flexneri strains and to compare the discriminating ability of the method with that of serotyping. By using a cloned Escherichia coli rRNA operon as the probe, Southern blot hybridization of restriction endonuclease-digested total DNA was carried out. Ribotyping of the isolates with each of the five restriction endonucleases BamHI, EcoRI, HindIII, PstI, and SalI generated reproducible restriction patterns. However, HindIII produced the optimum digestion pattern of the rRNA genes and was more useful than the other enzymes used in differentiating strains. Analysis of the 72 isolates showed 11 different HindIII cleavage patterns of their rRNA genes. Four of these HindIII-generated ribotypes could be further differentiated into two to four subribotypes by using PstI. The results indicate that ribotyping has an application for differentiation of S. flexneri strains and can complement serotyping. Definition of strains in terms of both serotype and ribotype may be of greater use in epidemiological studies.

Bacterial Typing Techniques↗

Rotavirus diarrhea in Bangladeshi children: correlation of disease severity with serotypes.

To improve the understanding of the relative importance of serotypes of rotavirus in dehydrating diarrhea, we examined the correlation of clinical characteristics and disease severity with serotype in 2,441 diarrheal episodes among children younger than 2 years of age in rural Bangladesh. Of 764 rotavirus-associated episodes, a single G type (serotype 1, 2, 3, or 4) was determined by oligonucleotide probe in 485 (63%), while 233 episodes were nontypeable. Episodes with G types 2 and 3 were associated with more-severe dehydration than episodes associated with G type 1 or 4 or with nontypeable rotavirus. Episodes did not differ by G type in prevalence of vomiting, copious diarrhea, fever, abdominal pain, or length of treatment center stay. Rotavirus reinfections were detected in seven children, with homologous reinfection (G type 2) in one. Twelve children with diarrhea who died had rotavirus detected in stool specimens within 30 days of death. Children who died were more likely to be malnourished than were surviving children with rotavirus diarrhea. Of 40 specimens tested by polymerase chain reaction, 29 (72.5%) were P type 1, 9 (22.5%) were P type 2, 1 (2.5%) was P type 3, and 1 (2.5%) was nontypeable. One severely symptomatic diarrheal episode was associated with P type 3 rotavirus, a serotype usually found in asymptomatic nursery infections. Although G types 2 and 3 were associated with more-severe dehydration than other serotypes, the differences do not appear to be of major clinical importance. Effective vaccines should protect against all four major G types.

Bangladesh↗

Cholera epidemics in Bangladesh: 1985-1991.

In 1991, a major epidemic of diarrhoea broke out in Bangladesh. To estimate the extent of cholera during diarrhoea epidemics and to focus on the public health issues related to cholera in Bangladesh, we have used the government figures of the 1991 epidemic and data from our own experience of epidemic interventions in nearly 400 rural upazilas (sub-district) between 1985 and 1989 and in 1991. Our data showed that V. cholerae 01 was the most frequently (40%) isolated enteropathogen during the epidemics. The disease is widely distributed in the country. Only 24% of the total 1,648 laboratory confirmed cholera patients were below 5 years of age, and children below 2 years of age accounted for only 10% of the total. Access difficulty to medical care and absence of a reliable surveillance were thought to be the constraints to early detection and appropriate intervention, thus, there were more deaths during the epidemics. We have shown that a high proportion (59%) of cholera patients during their illness in the rural areas were not visited by the government surveillance staff and that most (80%) were treated at home. Access to treatment by qualified physicians was limited to 23% of the patients, whereas a large proportion of the patients were treated by the unqualified rural practitioners (68%), and the others (9%) had no access to any health care providers. Our experience also indicated a higher case fatality ratio (14%) prior to intervention by qualified physicians during epidemics and an overall fatality ratio of 4%, despite the significant reduction (less than 1%) achieved by the intervention. Cholera is highly epidemic in Bangladesh.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗