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Biomedical subjects

D A Sack

Publications and source records attributed to D A Sack.

At least 109 records · Page 6Linked to original sources

Nocturnal TSH and prolactin secretion during sleep deprivation and prediction of antidepressant response in patients with major depression.

In order to test the hypothesis that changes in the hypothalamic-pituitary axis during sleep deprivation are related to the antidepressant effects of this procedure, we measured thyroid-stimulating hormone (TSH) and prolactin levels in 32 depressed patients at 2:00 AM during a night before, during, and after total sleep deprivation (TSD). TSH levels increased significantly (p less than 0.05) during TSD, and prolactin levels decreased significantly (p less than 0.0001). When we divided the patients into responder and nonresponder groups based on a 30% reduction in the Hamilton Rating Scale, there was no difference between the two groups in their hormone levels on the baseline, TSD, or recovery nights. Changes in prolactin or TSH were not correlated with clinical improvement when the two groups were considered together or in the responder/nonresponder groups separately. Baseline values of both hormones were significantly (p less than 0.01) correlated with their respective levels during TSD and recovery sleep. These findings indicate that the relative levels of nocturnal TSH and prolactin are stable even within acutely depressed individuals and that changes in their levels are not related to the clinical response to sleep deprivation.

Adult↗

Discontinuation of breast-feeding during episodes of diarrhoea in rural Bangladeshi children.

Discontinuation of breast-feeding during an episode of childhood diarrhoea is widely regarded as a common, high-risk practice in the developing world. We studied cessation of breast-feeding in a rural Bangladeshi population under comprehensive surveillance for medically treated diarrhoeal episodes. Among 2129 episodes in children aged under 36 months and breast-fed before the onset of diarrhoea, there were only 33 (2%) in whom breast-feeding had stopped before presentation for care. Children in whom breast-feeding had stopped (cases) differed little from those in whom it had not (controls) in respect to exclusive vs partial breast-feeding, age, gender, or several maternal characteristics (maternal age, education, and recent maternal diarrhoeal illness). In contrast, cases were more likely to have presented with clinically severe illness or to have died within 30 d of presentation (odds ratio = 2.20, P less than 0.05). We conclude that discontinuation of breast-feeding during diarrhoea is an infrequent phenomenon in this population. However, the association of cessation of breast-feeding with severe clinical outcomes may be of considerable importance, particularly in countries where discontinuation of breast-feeding is more common.

Bangladesh↗

Deficient nocturnal surge of TSH secretion during sleep and sleep deprivation in rapid-cycling bipolar illness.

Rapid-cycling bipolar patients have a high prevalence of hypothyroidism, and this disturbance in their hypothalamic-pituitary-thyroid (HPT) function may provide a model for understanding the less severe thyroid dysfunction present in other forms of affective disorder. For these reasons, we investigated HPT function in eight rapid-cycling bipolar patients and eight normal controls by measuring plasma levels of thyroid-stimulating hormone (TSH) and cortisol every 30 min during a baseline 24-h period and during an additional night of sleep deprivation. Thyrotropin-releasing hormone (TRH) (500 micrograms) challenge tests were also performed in the patients. Controls exhibited a significant circadian variation in TSH with a nocturnal rise that was augmented by sleep deprivation. In the rapid cyclers, the nocturnal rise in TSH was absent, and sleep deprivation failed to raise their TSH levels significantly compared with baseline. Low nocturnal TSH levels were associated with blunted TSH responses to TRH infusions; due to the relatively brief sampling interval used in the TRH challenge tests, however, these results do not reliably discriminate between hypothalamic and pituitary dysfunction as an etiology for low nocturnal TSH levels. Additional studies are needed to determine the precise nature of the HPT disturbance in rapid-cycling patients.

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↗

The timing and duration of sleep in partial sleep deprivation therapy of depression.

The antidepressant response to partial sleep deprivation early in the night (PSD-E) was compared with the response to partial sleep deprivation late in the night (PSD-L) in 16 drug-free depressed inpatients using a balanced order crossover design. PSD-L had a significantly greater antidepressant effect that PSD-E. The response to PSD-L was sustained and enhanced by a second night of treatment. Patients had significantly shorter sleep durations and reduced REM sleep on PSD-L that did not occur in the PSD-E situation. There was a significant negative correlation between response to PSD and sleep duration, and in particular, REM sleep duration, in the late sleep deprivation situation. Thus, the amount and timing of sleep appear to be factors in the response to PSD, but additional studies are needed to evaluate the relative importance of these parameters.

Adult↗

Environmental and behavioral influences on affective illness.

A behavioral factor, sleep, and a physical environmental factor, light, can trigger or terminate episodes of affective illness. The authors review the experimental evidence for these effects and discuss recent research on their biological mechanisms. In light of these findings the authors speculate that affective illness could partly be a disorder of systems that mediate the organism's adaptations to changes in the physical environment.

Adult↗

Nutritional requirements of shigellae for growth in a minimal medium.

Most (about 81%) of the clinical isolates of shigellae that were tested failed to grow in a minimal medium. Of the auxotrophic isolates belonging to the four Shigella species, 98% grew in a minimal medium containing methionine, nicotinic acid, and tryptophan. The combination of methionine and tryptophan appears to be an obligatory requirement for Shigella dysenteriae serotype 1 strains, while the combination of nicotinic acid and tryptophan appears to be obligatory for serotype 2. Requirements which varied in other isolates were, however, genetically stable, indicating that the auxotypes may be useful as epidemiological markers. Cultures of shigellae in liquid minimal medium containing the above three supplements showed rapid growth and gave reasonably high cell yields.

Agar↗

Congo red binding and salt aggregation as indicators of virulence in Shigella species.

Smooth strains of Shigella dysenteriae type 1, Shigella flexneri, Shigella boydii, and Shigella sonnei which form pigmented colonies (Pcr+) on Congo red agar were virulent in the Sereny test. Smooth variants unable to bind Congo red (Pcr-) were avirulent. Measurements of dye uptake from solution showed that S. dysenteriae type 1 bound the most dye, followed in order of uptake by S. flexneri, S. boydii, and S. sonnei. Using the salt aggregation test (SAT) to determine cell surface hydrophobicity, we found the same order of species. The SAT could not, however, detect differences in surface properties between Pcr+ and Pcr- pairs of isogenic smooth strains. Enteroinvasive Escherichia coli strains used in the study showed SAT and Congo red-binding properties which were similar to those of the S. flexneri strains. A direct correlation was found between pigment-binding ability and the presence of the large 140-megadalton plasmid in S. flexneri, enteroinvasive E. coli, and S. boydii but not in S. dysenteriae type 1 or S. sonnei strains. Congo red interacted with outer membranes and outer membrane proteins of S. dysenteriae type 1 but not with lipopolysaccharides. However, rough mutants of Shigella species deficient in lipopolysaccharides bound Congo red and formed pigmented colonies, showing that dye binding as a virulence assay may be misinterpreted in such cases. There was complete correlation of the Pcr+ phenotype with virulence in the smooth strains in this study, suggesting that Congo red binding can be utilized as a quick and reliable alternative to the Sereny test.

Bacterial Adhesion↗

Atenolol in seasonal affective disorder: a test of the melatonin hypothesis.

To test the hypothesis that the antidepressant effects of bright light in seasonal affective disorder are mediated by the suppression of melatonin, 19 patients with this disorder were given atenolol, which suppresses melatonin secretion, and placebo in a double-blind crossover study. No difference in antidepressant efficacy was found between drug and placebo in the sample as a whole, which argues against the melatonin hypothesis of phototherapy. However, in three of the patients atenolol provided repeated, marked, and sustained relief of symptoms, suggesting that it may be useful in treating the winter depressive symptoms of some patients with seasonal affective disorder.

Adult↗

Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients.

For 51 patients with rapid cycling affective disorder, clinical and family history data indicated that the illness was phenotypically and genetically related to more typical forms of affective disorder, was characterized by a bipolar course (100%), and was more common in women (92%). Manic-depressive cycles were separate from menstrual cycles. At the time of onset of rapid cycling, 73% of the patients were taking antidepressant drugs; the continuation of rapid cycling was associated with antidepressant drug therapy in 51% of the patients. Although most patients had been referred to a research ward because they were considered to be refractory to treatment, 37% attained essentially complete remissions, usually during treatment with lithium and/or monoamine oxidase inhibitors.

Adult↗

Twenty-four-hour profiles of body temperature and plasma TSH in bipolar patients during depression and during remission and in normal control subjects.

The 24-hour patterns of body temperature and plasma thyrotropin (TSH) were measured in eight bipolar patients in both depressed and recovered (after 3 weeks of treatment) states and in eight normal control subjects. Clear circadian patterns were detected for both temperature and TSH. Nocturnal body temperature was increased and the nocturnal surge of TSH was blunted during depression; these abnormalities were corrected after recovery. The inverse relationship between changes in body temperature and TSH levels at night suggests that changes in thermoregulation may be responsible for the neuroendocrine disturbance and may play a role in the pathophysiology of depression.

Bipolar Disorder↗

Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1.

In an epidemic of shigellosis in southern Bangladesh the causal organism, Shigella dysenteriae type 1, was resistant to nalidixic acid as well as to co-trimoxazole (trimethoprimsulphamethoxazole) and ampicillin. The genes coding for resistance to nalidixic acid, but not those coding for resistance to co-trimoxazole or ampicillin, are located on a conjugative 20 megadalton plasmid. This epidemic is of particular importance because of the resistance to nalidixic acid, an antibiotic to which shigellae are seldom resistant, and because plasmids were previously thought not to mediate resistance to nalidixic acid.

Ampicillin↗