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Biomedical subjects

D A Sack

Publications and source records attributed to D A Sack.

At least 91 records · Page 5Linked to original sources

Melatonin administration in insomnia.

Ten patients with persistent insomnia were randomized in a double-blind design and the effects of 1-mg and 5-mg oral dosages of melatonin on the electroencephalogram-recorded sleep were examined. Subjects showed no changes in either the onset or duration of sleep, nor any effect on mood or alertness the following day. A significant increase in rapid-eye-movement (REM) latency was noted at the 1-mg dose, though no other parameter of REM sleep was affected. The patients reported less sleep on both melatonin conditions. Despite this perception of decrease, overall subjective quality was reported to be improved.

Adult↗

Oral rehydration formula containing alanine and glucose for treatment of diarrhoea: a controlled trial.

OBJECTIVE: To determine whether adding L-alanine to the glucose based oral rehydration solution recommended by the World Health Organisation would improve its efficacy in treating acute diarrhoea. DESIGN: Randomised double blind controlled trial of oral rehydration solution containing L-alanine and glucose. SETTING: Inpatient service of a hospital treating diarrhoea. PATIENTS: 97 Male patients aged 6-59 years admitted to the hospital with acute and severe dehydration due to diarrhoea associated with Vibrio cholerae or enterotoxigenic Escherichia coli. Forty nine received the standard glucose based oral rehydration solution (control group) and 48 this solution with alanine added (study group). INTERVENTIONS: All of the patients received rapid intravenous acetate solution for the initial four hours after admission, which fully corrected the signs of dehydration. They were then admitted to the study and randomised. Immediately after the intravenous treatment oral rehydration treatment was started. All of the patients received oral tetracycline for 48 hours, starting 24 hours after start of the study. If signs of dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until they were fully corrected and then continued to take the assigned oral rehydration solution. END POINT: Passage of the last watery stool. MEASUREMENTS AND MAIN RESULTS: The median stool output/kg body weight during the initial 24 hours of oral rehydration treatment and until diarrhoea stopped was reduced in the study group compared with the control group from 309 ml to 196 ml and from 393 ml to 236 ml respectively. Intake of oral rehydration solution and intravenous acetate solution was reduced from 455 ml to 308 ml and from 616 ml to 425 ml respectively. Two patients in the study group compared with 18 patients in the control group required unscheduled rapid intravenous acetate solution to correct signs of dehydration during oral rehydration treatment. CONCLUSION: Oral rehydration solution containing L-alanine was considerably better than standard oral rehydration solution at reducing the severity of symptoms and the need for fluid of male patients with diarrhoea associated with V cholerae and enterotoxigenic E coli.

Adolescent↗

Longitudinal sleep EEG, temperature, and activity measurements across the menstrual cycle in patients with premenstrual depression and in age-matched controls.

After a 2-month evaluation period, eight women with moderate to severe premenstrual depression and eight age- and sex-matched controls underwent sleep electroencephalographic (EEG) and temperature recordings 2 nights a week over the course of one menstrual cycle. Overall, patients had more Stage 2 (%) sleep and less rapid eye movement (REM) sleep (% and minutes) than normal controls. Stage 3 sleep and number of intermittent awakenings varied with phases of the menstrual cycle. Temperature minima were earlier in patients compared with controls, but this difference was not statistically significant, and there was no significant effect of menstrual cycle phase on the timing of temperature minima. Wrist motor activity did not change during the menstrual cycle in patients or controls. Thus, in this sample of women with premenstrual depression, we did not find sleep EEG alterations similar to those reported in some patients with major depressive disorder. In light of the small number of subjects and the large individual variability, the absence of marked changes with the menstrual cycle may be a function of a Type II error.

Adult↗

New cholera vaccines.

Development of improved cholera vaccines has progressed rapidly in recent years. An oral killed vaccine, designed to evoke antibacterial as well as antitoxic intestinal immunity, has proved to be completely safe and to protect against cholera for at least 3 years. This vaccine also confers substantial though more short-lasting immunity against diarrhoea caused by enterotoxigenic Escherichia coli. Significant progress has also been made towards developing a live attenuated cholera vaccine using recombinant DNA techniques. The advent of effective oral cholera vaccines gives hope for improved control of cholera in the Third World.

Administration, Oral↗

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↗

Development of oral vaccines against enterotoxinogenic Escherichia coli diarrhoea.

Even though enterotoxin-producing Escherichia coli (ETEC) is the most important cause of diarrhoea in developing countries and among travellers, no vaccine for use in humans is yet available. New knowledge about virulence factors and protective antigens of ETEC, however, suggests that development of a useful vaccine may soon become possible. Such a vaccine should be given orally and ideally evoke both anticolonization and antitoxic immune responses in the gut. An oral cholera vaccine, containing a component (B subunit) which crossreacts immunologically with the major, heat-labile enterotoxin (LT) of ETEC, has been shown to afford significant protection against diarrhoea caused by LT-producing ETEC. Promising prototype oral ETEC vaccines combining B subunit toxoid with inactivated ETEC bacteria expressing the most prevalent colonization factor antigens (CFAs) have been developed, and work is in progress to find means for adding to this CFA-toxoid vaccine a component that could also provide immunity against heat-stable enterotoxin.

Antigens, Bacterial↗

Acute lower respiratory infections: a major cause of death in children in Bangladesh.

The importance of acute lower respiratory infections (ALRI) as a cause of death in children was estimated using systematically collected demographic data on the population of the Teknaf area of southern Bangladesh. Of 1349 children aged 1-59 months who died between 1 January 1982 and 31 December 1985, ALRI was diagnosed by verbal autopsy in 390 (29%) and was the leading cause of death. ALRI mortality rates were highest in the youngest age groups (136/1000 for those less than or equal to 5 months) and decreased in older children (16/1000 for those 3-4 years old). Half of all fatal ALRI cases occurred in children less than 6 months old. In older children, ALRI-associated deaths tended to occur during the months October to January, while deaths in infants tended to follow the seasonal birth pattern. Significant predisposing factors for fatal ALRI were malnutrition and measles, detected, respectively, in 18% and 8% of children who died from ALRI. This study emphasizes the importance of ALRI as a major cause of death in developing countries and suggests that interventions to reduce childhood mortality are needed and should be targeted to specific age groups at risk.

Acute Disease↗

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↗

Rapid identification of Vibrio cholerae serotype O1 from primary isolation plates by a coagglutination test.

A coagglutination test was developed for identifying suspected colonies of Vibrio cholerae serotype O1 directly from primary isolation plates. Visible agglutination occurs when V. cholerae O1 antibody attached to cell-wall protein A of Staphylococcus aureus reacts with its homologous antigen. From 314 faecal samples from clinically suspected cases of cholera, 210 colonies from thiosulphate citrate bile salts sucrose (TCBS) agar and 222 colonies from taurocholate tellurite gelatin (TTG) agar were tested as suspect V. cholerae. In each case 204 isolates were identified as V. cholerae O1 by conventional methods and also gave positive results for V. cholerae O1 in the coagglutination test; with one partial exception, no other colonies tested gave positive results. The coagglutination test is simple and inexpensive and provides a result 24 h earlier than conventional methods.

Agglutination Tests↗

The use of phage-sensitivity patterns for tracing heat labile toxin-positive (LT+) Escherichia coli.

The heat-labile toxin (LT) positive Escherichia coli colonies from 785 stool specimens obtained during a cholera vaccine trial were examined for their phage-sensitivity pattern to 31 E. coli phages. These specimens originated from 105 index cases and their contacts. Isolates with common phage-sensitivity patterns were grouped and were studied further both serologically and for their plasmid profile. The largest group (42 isolates) belonged to serogroup O78 and the second largest group (19 isolates) belonged to serogroup O6. There were 23 index cases which had E. coli with the same phage-sensitivity pattern as some of their contact strains. The identity of isolates from 16 index cases with strains from their respective contacts could be verified serologically. For the remaining seven index cases and their contacts, the isolates did not agglutinate with available antisera. However, subsequent studies demonstrated that, when the phage-sensitivity pattern among the strains matched, the plasmid profiles of these strains also matched. This further indicates the ability of phage-sensitivity patterns to serve as markers in tracing strains.

Bacterial Toxins↗

Use of monoclonal antibodies to type Shigella flexneri in Bangladesh.

A panel of 10 mouse and rat monoclonal antibodies specific for different type- and group-specific O-antigenic determinants of Shigella flexneri lipopolysaccharide was used to serotype 240 isolates of S. flexneri from Bangladesh. Three immunoglobulin M antibodies were used in a direct slide agglutination test; seven immunoglobulin G antibodies were absorbed to Staphylococcus aureus and used in a coagglutination assay. All but 13 of the isolates could be serotyped by using the monclonal antibodies. The six most common serotypes were (in descending order) 2a, 2b, Y (E1037), 1a, 3a, and 1b and accounted for more than 80% of all isolates. Two of the nontypable strains were found to be of a new provisional serotype of S. flexneri (T. Wehler and N.I.A. Carlin, Eur. J. Biochem. 176:471-476, 1988). The 11 remaining strains were found to be rough and therefore nontypable. The serotyping scheme based on the panel of monoclonal antibodies is specific and holds the potential to be developed into a useful tool for epidemiological investigation. The study also demonstrates that the recently described E1037 antigen is commonly found among at least four serotypes (4a, 6, X, and Y) of S. flexneri.

Agglutination Tests↗

Risk factors for persistent diarrhoea.

With a systematically sampled population of children aged under 5 attending this centre for diarrhoeal disease research during 1983-5 a retrospective analysis of persistent diarrhoea (defined as greater than 14 days' duration) was performed to identify the possible risk factors for this syndrome. Of the 4155 children included in the analysis, 410 (10%) gave a history of persistent diarrhoea. A comparison with children with acute diarrhoea matched for age showed that 11 factors were correlated with persistent diarrhoea, and strongly associated factors were stools with blood or mucus, or both, lower respiratory tract infection, malnutrition, vitamin A deficiency, and antibiotic use before presentation. The peak age was 2 years, and there was no sex difference. Deaths occurred more often in the group with persistent diarrhoea. Although Shigella spp, Campylobacter jejuni, and Giardia lamblia were frequently identified, their rates of isolation were not significantly higher among patients with persistent diarrhoea. No seasonal variation was observed in the rates of persistent diarrhoea. Although the introduction of family food to the diet was associated with higher rates, this factor was difficult to separate from the age dependent risks.

Acute Disease↗

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↗

The diurnal variation in plasma homovanillic acid level persists but the variation in 3-methoxy-4-hydroxyphenylglycol level is abolished under constant conditions.

Plasma concentrations of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined every two hours for two consecutive days in seven depressed patients and seven matched normal controls. On the first day subjects followed their regular ward routine. On the second day they were placed on a regimen in which activity, posture, diet, and wakefulness were held constant. There were significant diurnal variations in both MHPG and HVA concentrations on the baseline day, whereas on the constant routine, a diurnal variation was present only in HVA. We conclude that diurnal variations in plasma MHPG are evoked by changes in physical activity, posture, or other factors controlled on the constant routine, and that a major component of the diurnal variation in plasma HVA concentrations is regulated by a circadian oscillator that is independent of sleep or activity.

Adult↗