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Biomedical subjects

A Winokur

Publications and source records attributed to A Winokur.

At least 109 records · Page 6Linked to original sources

Withdrawal and pseudowithdrawal from diazepam therapy.

We present two cases from a double-blind placebo-controlled study of diazepam in treatment of anxiety that illustrate the importance of attitudes of patients and physicians towards use of diazepam. Patient 1 exhibited symptoms of nausea, depression and increased anxiety, which both he and the research psychiatrist interpreted as a withdrawal reaction. Examination of the treatment code, however, revealed that the patient had been kept on the same dose of diazepam throughout this period and that he had maintained therapeutic plasma diazepam levels. This case illustrated a "pseudowithdrawal reaction" in a patient being maintained on active drug treatment. Patient 2 benefited remarkably from maintenance diazepam therapy and had manifested considerable anxiety during double-blind placebo substitution but his private physician expressed great reluctance to continue this treatment regimen because he had been influenced by unfavorable publicity. Further information on maintenance diazepam therapy and problems with withdrawal must be obtained under carefully controlled conditions.

Adult↗

Acute metabolic response to cold exposure in unipolar and bipolar II patients.

The thermoregulatory response to cold exposure was examined in 11 unipolar and 5 bipolar II drug-free outpatients and 12 healthy controls. Subjects were studied in an environmental chamber at 10 C for 60 min. The heat production response was derived from the rate of oxygen consumption measured at 15-min intervals. Rectal and mean skin temperatures were continuously recorded from thermistor probes. Responses of the controls were used to establish a standard range against which the responses of the patients were compared. Six unipolar patients (54.5%) fell outside the standard range (chi 2 = 8.86, df = 1, p less than 0.005). Four of these patients showed a paradoxical decrease in heat production. Responses of the bipolar II patients fell within a narrow segment of the standard range, such that 10 of 12 controls (83.3%) responded outside the segment (chi 2 = 10.12, df = 1, p less than 0.005). These findings indicate that unipolar patients show greater variability and bipolar II patients less variability than controls in thermoregulatory response to cold. These observations extend previous suggestions of hypothalamic-limbic system dysfunction in patients with depression.

Adult↗

Withdrawal reaction from long-term, low-dosage administration of diazepam. A double-blind, placebo-controlled case study.

Symptoms of diazepam withdrawal developed in a young man who had been taking diazepam in dosages of 15 to 25 mg/day during a six-year period. This was verified in a study conducted under placebo-controlled, double blind conditions, with plasma levels of diazepam and its major metabolite, desmethyldiazepam, monitored throughout the course of the study. Severe symptoms of physiological withdrawal were observed within two days of replacement of diazepam with placebo capsules. The patient recovered promptly on reinstitution of diazepam administration, and relapsed during a second withdrawal phase. During an additional two week-period of placebo administration, the patient's condition first worsened, then gradually improved. Examination of plasma levels of diazepam and desmethyldiazepam indicated no obvious pharmacokinetic abnormalities. Thus, with long-term administration of diszepam, even in therapeutically accepted doses, withdrawal reactions can be encountered on abrupt termination.

Adult↗

Primary affective disorder in relatives of patients with anorexia nervosa.

The authors examined the incidence of primary affective disorder (PAD) in relatives of 25 patients with anorexia nervosa and of 25 normal control subjects. Among the relatives of patients with anorexia nervosa, 22% (N = 43) had histories of PAD, while only 10% (N = 17) of the relatives of controls had such histories. Among the PAD relatives of anorectic probands, 34 had histories of unipolar depression and 9 of bipolar affective disorder. These findings provide further evidence of a possible relationship between anorexia nervosa and affective illness.

Anorexia Nervosa↗

Subcellular distribution of thyrotropin-releasing hormone (TRH) in rat brain and hypothalamus.

TRH localization in rat brain and hypothalamic tissue was studied by determination of immunoassayable TRH in subcellular fractions prepared from homogenates of these tissues. In both hypothalamus and brain, most of the TRH was found in a crude mitochondrial fraction and its concentration was higher in the synaptosomal fraction isolated by density gradient centrifugation. Electron microscopy was used to verify the composition of the fractions. Exposure of the brain crude mitochondrial fraction to osmotic shock resulted in solubilization of TRH which then was sedimented by centrifugation at 96,000 X g. TRH added to brain homogenates in vitro was rapidly destroyed by incubation at 37 degrees C, but no endogenouse TRH was lost by such incubation. The localization of TRH of hypothalamic and brain tissue to subcellular fractions consisting largely of synaptosomes and synaptic vesicles is compatible with a neurotransmitter function for this substance.

Animals↗

Thyrotropin-releasing hormone content of rat brain and hypothalamus: results of endocrine and pharmacologic treatments.

Studies of hypothalamic and regional brain TRH content in the rat after administration of various hormonal and pharmacologic agents were performed. No consistent changes in TRH content in the hypothalamus or brain followed thyroidectomy, hypophysectomy or administration of thyroxine or dexamethasone. There was a significant fall in hypothalamic forebrain and brain stem TRH content 60 min after insulin administration and in brain stem TRH at 30 and 120 min as well. Administration of alpha-methyl-paratyrosine, parachlorophenylalanine or reserpine, in varying doses and for varying periods, did not alter hypothalamic or regional brain TRH content. Thus, little evidence that hypothalamic or brain TRH content is dependent on hormonal milieu or neurotransmitter content was found.

Animals↗

Thyrotropin-releasing hormone: regional distribution in rat brain.

A sensitive and specific radioimmnunoassay has been used to measure the distribution of thyrotropin-releasing hormone (TRH) in rat brain. All areas of brain tested, except cerebellum, contained readily measurable amounts of TRH. The hypothalamus contained only 31.2 percent of the total brain content of TRH. These results support recent suggestions of central actions for TRH in addition to its hypophysiotropic functions.

Animals↗

Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine.

The rate of disappearance of intracisternally administered tritiated norepinephrine from rat brain is decreased after a single dose of the tricyclic antidepressant imipramine. During long-term administration of imipramine, however, the rate of disappearance of tritiated norepinephrine from brain gradually increases, and there is a concurrent decrease in the content of endogenous norepinephrine in brain. These findings may help to explain why antidepressant effects are observed clinically only after long-termn treatment with imipramine.

Animals↗

Adrenocortical responsiveness to the ACTH stimulation test in depressed patients and healthy volunteers.

Adrenocortical activation in depression has been postulated to result from overactivity of limbic system-hypothalamic function. However, some studies suggest the possibility that excessive secretion of cortisol might result, in part, from a heightened adrenocortical responsiveness to ACTH. To further examine this possibility, we utilized both the ACTH stimulation test and the overnight dexamethasone suppression test (DST) in 72 patients with major depression and 37 age- and gender-matched healthy volunteers. The melancholic/DST-nonsuppressor group had larger mean peak cortisol and cumulative cortisol responses (CCR) than any of the other patients groups or healthy controls. However, the differences failed to reach statistical significance as a result of a relatively large cortisol response variability. Nevertheless, the present findings are in general agreement with previous reports suggesting the possibility of an enhanced adrenocortical responsiveness to ACTH.

Adolescent↗