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Biomedical subjects

B A Kay

Publications and source records attributed to B A Kay.

At least 37 records · Page 2Linked to original sources

Enterotoxin and cytotoxin production by enteroinvasive Escherichia coli.

It has long been suspected that besides their ability to invade enterocytes, enteroinvasive Escherichia coli (EIEC) strains have the ability to elaborate an enterotoxin. We tested 35 EIEC strains for cytotoxins and 9 (1 per serogroup) for enterotoxins. All 35 strains exhibited low levels of Vero cell cytotoxins that are immunologically and genetically distinct from Shiga-like toxin I or II of enterohemorrhagic E. coli. Sterile supernatants and cell lysates of two EIEC strains were tested in rabbit ileal loops, and both stimulated moderate fluid accumulation (circa 0.5 ml/cm) without tissue damage; secretory activity was confirmed in Ussing chambers, where these two strains and the seven others tested significantly increased short circuit current without altering tissue conductance. Curing the 140-MDa invasiveness plasmid from an EIEC strain did not diminish enterotoxin production. Culture in minimal Fe2+ medium is necessary to detect expression of the enterotoxin which is circa 68 to 80 kDa in size and is distinct from the EIEC cytotoxin.

Animals↗

Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans.

In this study, 27 volunteers received one of three non-O group 1 Vibrio cholerae strains in doses as high as 10(9) CFU. Only one strain (strain C) caused diarrhea: this strain was able to colonize the gastrointestinal tract, and produced a heat-stable enterotoxin (NAG-ST). Diarrhea was not seen with a strain (strain A) that colonized the intestine but did not produce NAG-ST, nor with a strain (strain B) that produced NAG-ST but did not colonize. Persons receiving strain C had diarrhea and abdominal cramps. Diarrheal stool volumes ranged from 154 to 5,397 ml; stool samples from the patient having 5,397 ml of diarrhea were tested and found to contain NAG-ST. The median incubation period for illness was 10 h. There was a suggestion that occurrence of diarrhea was dependent on inoculum size. Immune responses to homologous outer membrane proteins, lipopolysaccharide, and whole-cell lysates were demonstrable with all three strains. Our data demonstrate that V. cholerae of O groups other than 1 are able to cause severe diarrheal disease. However, not all strains are pathogenic for humans: virulence of strain C may be dependent on its ability both to colonize the intestine and to produce a toxin such as NAG-ST.

Adolescent↗

Clostridium perfringens type C in bloody and watery diarrhea in Bangladesh.

A two-week age-matched case-control survey to detect Clostridium perfringens type C-associated illness was conducted among diarrheal patients hospitalized following the consumption of high protein meals on the occasion of an annual religious festival. From the stool of 33 patients screened, C. perfringens type C was isolated from one patient with bloody diarrhea and from two patients with watery diarrhea. In Bangladesh, C. perfringens type C has been isolated in both bloody and watery diarrhoeal illness and is not necessarily associated with necrotizing enteritis (pigbel).

Bangladesh↗

Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. I. Cross-reacting antigens of members of family Vibrionaceae and the vaccines.

Antigenic similarity between the oral cholera B subunit-whole cell (BS-WC) and whole-cell only (WC) vaccines and strains of the family Vibrionaceae was studied by crossed immunoelectrophoresis. A reference system consisting of Vibrio cholerae Inaba E1 Tor antigenic extract and homologous rabbit antiserum was applied in the study. The system was represented by 30 anodically migrating antigens forming distinct precipitation bands. Antigenic extracts of other members of the family Vibrionaceae showed the following numbers of cellular antigens shared in common with the reference system: Vibrio cholerae non-01-30, V. mimicus-23, V. fluvialis-15, V. parahaemolyticus-10, Aeromonas hydrophila-7, A. sobria-5, A. caviae-4 and Plesiomonas shigelloides-5 antigens. Homologous rabbit antiserum reacted with 11 antigens of BS-WC vaccine and 10 antigens of WC vaccine. The number of antigens which members of the family Vibrionaceae shared in common with those preserved in the WC component of the vaccines were as follows: Vibrio cholerae non-01, 7; V. mimicus, 5; V. fluvialis, 3; V. parahaemolyticus, 3; Aeromonas hydrophila, 2; A. sobria, 2; and A. caviae, 2; Plesiomonas shigelloides, 1. None of the strains produced an antigen reacting with anti-cholera toxin antibodies. The presence of common antigens in the vaccine and among members of family Vibrionaceae indicates that the oral cholera vaccine could stimulate immunity effectively against other members of the family.

Administration, Oral↗

Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. II. Field evaluation of cross-protection against other members of the Vibrionaceae family.

Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae (NCV), the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a randomized, double-blind field trial in Bangladesh. Children aged 2-15 years and women aged greater than 15 years (62,285 in number) received three doses of BS-WC vaccine, WC-only vaccine, or a placebo consisting of Escherichia coli K12 strain (K12). During 1 year of follow-up, the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens (non-01 Vibrio cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus) in the placebo group was low (1.9 cases per 10,000 recipients) and identical to that for the two vaccine groups combined. The incidence (per 10,000 recipients) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher, but nearly identical in the three groups (26.1 cases for BS-WC, 26.0 cases for WC; 25.9 cases for K12). Pleisiomonas shigelloides was not isolated from any participant. It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms.

Administration, Oral↗

Case report of Plesiomonas shigelloides-associated persistent dysentery and pseudomembranous colitis.

An adult Bangladeshi woman had persistent bloody diarrhea. Repeated stool cultures yielded Plesiomonas shigelloides in pure growth. Tissue specimens of the colon were consistent with pseudomembranous colitis. Treatment with tetracycline, to which the isolate was susceptible, brought prompt recovery; the stool cultures became negative and the serum antibody titer against P. shigelloides lipopolysaccharide, as measured by hemagglutination inhibition with P. shigelloides lipopolysaccharide-sensitized sheep erythrocytes, declined from 1:160 to 1:40.

Adult↗

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↗

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↗

Plasmid analysis of Shigella dysenteriae type 1 isolates obtained from widely scattered geographical locations.

Plasmid profiles and antimicrobial susceptibility patterns of 343 strains of Shigella dysenteriae type 1, obtained from 18 different geographical locations, were analyzed. Three plasmids, with molecular sizes of 140, 6, and 2 megadaltons (MDa), were present in 94, 98, and 96%, respectively, of the 343 strains isolated during either epidemic or nonepidemic periods from 1965 to 1987. In addition to these plasmids, 83% of the strains harbored a 4-MDa plasmid and 25% harbored a 20-MDa plasmid. Various plasmid profiles were observed in which the 140-, 6-, and 2-MDa plasmids occurred commonly, irrespective of the place of isolation and drug resistance pattern of the strains. Certain profiles showed significant association with drug resistance patterns. These findings suggest that three plasmids, of molecular sizes 140, 6, and 2 MDa, are unique to S. dysenteriae type 1 strains and may indicate the global spread of a pathogenic bacterial clone. Additionally, these core plasmids, plus plasmids of various other sizes, could be used to identify emerging subclones which are causing both epidemic and sporadic disease. Thus, plasmid profiles of S. dysenteriae type 1 strains can be used to monitor possible pandemic strains as well as individual epidemic strains.

Drug Resistance, Microbial↗

Enrichment for Plesiomonas shigelloides from stools.

Bile peptone broth and alkaline peptone water (pH 8.5) were examined as enrichment media for the isolation of Plesiomonas shigelloides from stools, with salmonella-shigella agar as the isolation medium. After 423 parallel examinations in two different experiments, bile peptone broth enrichment for 24 h was observed to be six times more effective (P less than 0.01) than direct plating alone on salmonella-shigella agar. Bile peptone broth was found to be twice as effective as alkaline peptone water for the recovery of P. shigelloides from stools.

Culture Media↗

Space-time behavior of single and bimanual rhythmical movements: data and limit cycle model.

How do space and time relate in rhythmical tasks that require the limbs to move singly or together in various modes of coordination? And what kind of minimal theoretical model could account for the observed data? Earlier findings for human cyclical movements were consistent with a nonlinear, limit cycle oscillator model (Kelso, Holt, Rubin, & Kugler, 1981) although no detailed modeling was performed at that time. In the present study, kinematic data were sampled at 200 samples/second, and a detailed analysis of movement amplitude, frequency, peak velocity, and relative phase (for the bimanual modes, in phase and antiphase) was performed. As frequency was scaled from 1 to 6 Hz (in steps of 1 Hz) using a pacing metronome, amplitude dropped inversely and peak velocity increased. Within a frequency condition, the movement's amplitude scaled directly with its peak velocity. These diverse kinematic behaviors were modeled explicitly in terms of low-dimensional (nonlinear) dissipative dynamics, with linear stiffness as the only control parameter. Data and model are shown to compare favorably. The abstract, dynamical model offers a unified treatment of a number of fundamental aspects of movement coordination and control.

Functional Laterality↗

Toxin production by Vibrio mimicus strains isolated from human and environmental sources in Bangladesh.

Vibrio mimicus has recently been isolated from aquatic environments of Bangladesh. A total of 125 of 300 environmental isolates, representing various biotypes, and 19 human isolates were tested for enteropathogenicity by using several models. Less than 1% of the environmental isolates and slightly more than 10% of the clinical isolates produced cholera toxin-like toxin. A significant percentage of the environmental isolates (25%) and of the human isolates (74%) induced fluid accumulation in ligated rabbit ileal loops. One environmental strain produced heat-stable toxin-like enterotoxin, whereas all of the human isolates did not. V. mimicus strains were divided into the following three groups on the basis of their activity in various toxin assays: (i) organisms which produce a heat-labile enterotoxin immunobiologically similar to cholera toxin, (ii) organisms which produce a heat-stable enterotoxin-like toxin, and (iii) organisms whose whole-cell cultures have some activity characteristic of heat-labile toxin (e.g., fluid accumulation in ligated rabbit ileal loops and positive permeability factor) but are not positive by the GM1 enzyme-linked immunosorbent assay. One isolate from this group was able to elicit these results with cell-free culture filtrates. There was no correlation of biotype with toxic activity of V. mimicus isolates.

Animals↗

Field trial of oral cholera vaccines in Bangladesh.

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

Administration, Oral↗

Early treatment with erythromycin of Campylobacter jejuni-associated dysentery in children.

To evaluate the efficacy of early treatment with erythromycin on the duration of fecal excretion and of diarrhea associated with Campylobacter jejuni, 170 patients, age 3 to 60 months, were randomly assigned in a double-blind fashion to receive either erythromycin ethyl succinate or placebo immediately after being seen at Cayetano Heredia Hospital because of acute dysentery. The groups' pretreatment characteristics were comparable. Of the 30 patients with stools positive for C. jejuni, 12 were in the placebo group and 16 in the treatment group. After 2 days of treatment, none of the patients in the placebo group and 36% of those in the erythromycin group had normal stools (P less than 0.05). After 5 days of treatment, 50% of the patients in the placebo group and 93% of those in the erythromycin group had normal stools (P less than 0.02). Fecal excretion of the organism continued significantly longer in the placebo group (P less than 0.01). There were no treatment failures in the treatment group compared with five (42%) in the placebo group (P less than 0.01). Thus, early administration of erythromycin significantly reduced the duration of both diarrhea and fecal excretion of the organism in infants and children with acute dysentery associated with C. jejuni.

Campylobacter Infections↗

Bicarbonate versus citrate in oral rehydration therapy in infants with watery diarrhea: a controlled clinical trial.

In a double-blind, randomized trial, we compared the efficacy of bicarbonate-containing oral rehydration solution vs citrate-containing solution in the treatment of infantile diarrheal dehydration and acidosis. Ninety-seven infants 3 to 24 months of age were entered in the study; 49 received bicarbonate-containing solution and 48 citrate-containing solution. The two groups were similar in all respects at the beginning of the study. Oral rehydration was successful (i.e., no intravenously administered fluids were required) in 85% of study patients; the success rate was similar in both treatment groups. Serum total CO2 concentration increased in a similar fashion in both groups, reaching near normal values at 48 hours after admission. We conclude that sodium citrate can be substituted for sodium bicarbonate in the formulation of the orally administered rehydration solution recommended by the World Health Organization for treatment of diarrheal dehydration in infants.

Bicarbonates↗