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Biomedical subjects

D R Rubinow

Publications and source records attributed to D R Rubinow.

At least 55 records · Page 3Linked to original sources
PubMed1997

Response to clomiphene citrate challenge test in normal women through perimenopause.

OBJECTIVE: To identify the physiological changes that discriminate subgroups of women along the reproductive continuum. METHODS: This prospective study was carried out at the outpatient facility of George Washington University Medical Center and the outpatient clinic of the National Institutes of Health Clinical Center. Twenty-five female subjects were divided into 4 biologically distinct groups: group 1 (n = 4) regular menstrual cycles and under age 35; group 2 (n = 11) regular cycles and over age 35; group 3(n = 6) irregular cycles and over age 35, and group 4(n = 4) menopausal. Measurements of basal and stimulated gonadotropins (immunoactive LH, LH-I; bioactive LH, LH-B; immunoactive FSH, FSH-I) and E2 were obtained before and after administration of clomiphene citrate. Basal and stimulated gonadotropins and E2 were analyzed to discriminate between subject groups 1-4. The relationship of menstrual cyclicity to hormone levels was evaluated. RESULTS: Basal levels of LH-I, LH-B, FSH-I could discriminate only group 4 vs. groups 1-3. Stimulated levels of FSH-I and E2 were significantly different for group 2 vs. 3 and group 2 vs. 4. Group 1 was similar to group 2. Both stimulated FSH-I and stimulated LH-I and LH-B differentiated group 4 vs. groups 1-3. The LH-B:LH-I (B:I) ratio was not discriminatory after the clomiphene citrate challenge test (CCCT). CONCLUSIONS: Baseline hormone values were useful in distinguishing only group 4. CCCT unmasked differences in FSH and E2 between irregularly and regularly cycling older women; these differences were not scen with LH-B or B:I ratio. Stimulated FSH was the most useful hormone parameter and paralleled menstrual cycle regularity as a useful discriminator in older women.

Adult↗
PubMed1997

Premenstrual syndrome: evidence for symptom stability across cycles.

OBJECTIVE: This study assessed cycle to cycle symptom stability in women with premenstrual syndrome (PMS). METHOD: Symptom ratings obtained prospectively over three or more symptomatic cycles from 16 women with PMS were analyzed. Measures of symptom severity and change were used to generate a coefficient of variation and an intraclass correlation coefficient (ICC) for each one of 14 symptoms across all cycles. In addition, symptoms were divided into three clusters, and the stability of the rank order of severity of symptoms within clusters and the correlation between symptom clusters were also calculated. RESULTS: In the 65 cycles studied, mood symptoms were the most prevalent. Mood symptoms--anxiety, irritability, and mood lability--had the lowest coefficients of variation but also the lowest ICCs of all symptoms. Within their respective symptom clusters, both physical and mood symptoms showed remarkable stability across cycles of their rank order of severity, but only the mood symptom cluster was highly correlated with functional impairment. CONCLUSIONS: Three mood symptoms--anxiety, irritability, and mood lability--were the most stable symptoms in this group of women with PMS. Mood and not somatic symptoms accounted for most of the functional impairment in this group of women. It is concluded that PMS is a stable syndrome that may best be viewed as part of the spectrum of recurrent mood disorders.

Adult↗
PubMed1997

Effects of leuprolide-induced hypogonadism and testosterone replacement on sleep, melatonin, and prolactin secretion in men.

The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a controlled experimental design. We used leuprolide acetate, with and without testosterone replacement, to study the role of testosterone in the regulation of sleep and of melatonin, PRL, and TSH secretion in men. Results from 10 men revealed significant decreases in 24-h PRL levels and in the percentage and time of stage 4 sleep in the hypogonadal state compared with testosterone replacement. There were no differences in melatonin or TSH secretion or in the timing or duration of sleep between the two hormonal conditions. These results indicate that testosterone has relatively specific and discrete effects on sleep and hormonal rhythms in men.

Adolescent↗
PubMed1997

Effect of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonin agonist m-chlorophenylpiperazine in women with premenstrual syndrome and controls.

To evaluate the potential role of serotonin in the premenstrual syndrome (PMS), we investigated the effects of menstrual cycle phase on neuroendocrine and behavioral responses to the serotonergic agent m-chlorophenylpiperazine (m-CPP) in women with PMS and controls. A single oral dose of m-CPP (0.5 mg/kg) was administered to 10 PMS patients and 10 healthy controls during the follicular and luteal phases of the menstrual cycle. We observed the following. m-CPP administration during the luteal phase resulted in an acute improvement of PMS symptoms; the plasma cortisol and ACTH responses to m-CPP were blunted in both menstrual cycle phases in PMS patients compared with controls. These data provide evidence for the acute efficacy of m-CPP in the treatment of PMS. Although there is additional evidence for dysregulation of either the hypothalamic-pituitary-adrenal axis or serotonin control of the hypothalamic-pituitary-adrenal axis in women with PMS, there is little evidence for luteal phase-specific serotonergic dysfunction. These findings, nonetheless, implicate the serotonin system as a modulating (not causal) factor in PMS.

Adult↗
PubMed1997

Pimozide-induced depression in men who stutter.

BACKGROUND: Neuroleptic-related dysphoric reactions are well recognized in the context of psychiatric disorders, especially in association with extrapyramidal side effects. Very few controlled data exist regarding the effects of neuroleptics on the mood of psychiatrically "normal" subjects. In this study, the depressogenic effect of the neuroleptic drug pimozide was assessed in men without psychiatric disorders. METHOD: Eight men with developmental stuttering but no past or present psychiatric illness participated in a double-blind, placebo-controlled study assessing the effect of 6 weeks of pimozide treatment on speech fluency and mood. RESULTS: Four of the seven subjects who were compliant with the treatment developed marked depressive symptoms. No clear association was found between these reactions and pimozide dose, blood level, or degree of neurologic side effects. Symptoms abated soon after drug discontinuation. CONCLUSION: Pimozide induced significant depressive symptoms in this group of psychiatrically normal men who stutter. Neuroleptic drugs may have a causal effect in the induction of depression in psychiatrically normal subjects, ostensibly independent of dose or severity of neurologic side effects.

Adolescent↗
PubMed1996

Peripheral measures of arginine vasopressin, atrial natriuretic peptide and adrenocorticotropic hormone in premenstrual syndrome.

Because of the unique combination of physical (e.g. bloating, water retention) and psychological (e.g. mood, memory) symptoms associated with premenstrual syndrome (PMS), various hypothalamic and pituitary hormones have been implicated in the pathophysiology of PMS. We measured plasma adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) across the menstrual cycle in 19 women with PMS and 12 normal women. AVP concentrations were lower throughout the menstrual cycle in symptomatic PMS patients compared with PMS patients during asymptomatic cycles and normal women. No differences in ACTH and ANP were observed between patients and controls. However, ACTH and ANP were positively and significantly correlated with each other in women with PMS but not in controls. These findings contribute to a growing list of menstrual cycle-independent findings in women with PMS and suggest that there may be an underlying neurobiological vulnerability that predisposes some women to experience somatic and mood dysregulation in the luteal phase of the menstrual cycle.

Adrenocorticotropic Hormone↗
PubMed1996

Relationship between skeletal muscle intracellular ionized magnesium and measurements of blood magnesium.

The current laboratory approach to assessing magnesium status is based on determining the concentration of total Mg ((Mg)) in serum or plasma. This strategy is problematic in that the amount of Mg in blood is less than 1% of total body Mg and does not accurately reflect (Mg) in other tissues. Furthermore, the (Mg) of blood does not distinguish biologically active, ionized Mg from the bound fraction. The goal of this study was to determine intracellular ionized Mg ((Mg++)i) of skeletal muscle in vivo and to compare results with the (Mg) of blood constituents. (Mg++)i was determined in resting skeletal muscle by using phosphorus 31 magnetic resonance (31P-MR) spectroscopy. (Mg) was measured in serum (S(Mg)), serum ultrafiltrate (UF(Mg)), mononuclear blood cells (MBC(Mg)), and red blood cells (RBC(Mg)) by using atomic absorption spectroscopy or a colorimetric assay. In a sample of 60 healthy adult subjects, skeletal muscle (Mg++)i = 557 +/- 97 mumol/L (mean +/- SD); S(Mg) = 0.78 +/- 0.09 mmol/L; UF(Mg) = 0.60 +/- 0.12 mmol/L; MBC(Mg) = 13.8 +/- 2.3 mmol/L; and, RBC(Mg) = 1.92 +/- 0.33 mmol/L. A significant negative correlation was found between (Mg++)i and S(Mg) (r = -0.43, p < 0.05). S(Mg) was significantly lower (p < 0.05) and (Mg++)i significantly higher (p < 0.05) in women than in men, but neither was related to age. These findings provide new insight into the relationship between blood Mg measures and (Mg++)i of the largest soft tissue mass of the human body.

Adult↗
PubMed1996

Basal and stimulated gonadotropin levels in the perimenopause.

OBJECTIVE: We investigated whether perimenopausal menstrual cycle irregularity is associated with increased gonadotropin immunoactivity, bioactivity, or the bioactivity/immunoactivity ratio at baseline and after short-term stimulation with gonadotropin-releasing hormone. STUDY DESIGN: Subjects consisted of four groups: (1) young regular cycling women (< 35 years old), older women (> 35 years) with (2) regular or (3) irregular menstrual cycles, and (4) postmenopausal women. Gonadotropin-releasing hormone stimulation tests (100 micrograms intravenous gonadotropin-releasing hormone) were performed in the National Institute of Mental Health outpatient clinic during the follicular phase of the menstrual cycle or randomly in postmenopausal women. RESULTS: Perimenopausal women had baseline follicle-stimulating hormone and luteinizing hormone levels and stimulated follicle-stimulating hormone levels (area under the curve) that were similar to those of postmenopausal women and significantly greater than those of control (younger and older) women. Postmenopausal women had significantly greater baseline levels of luteinizing hormone bioactivity than did the other three groups. The bioactivity/immunoactivity ratio in the postmenopausal women was significantly greater than those in the perimenopausal and older cycling women, which were similar. No change in the bioactivity/immunoactivity ratio was seen after gonadotropin-releasing hormone stimulation in any group. CONCLUSIONS: Although the perimenopause is associated with increases in baseline and stimulated gonadotropin levels similar to those seen after the menopause, significantly increased baseline luteinizing hormone bioactivity and the bioactivity/immunoactivity ratio are seen only after the menopause.

Adult↗
PubMed1996

Androgens, brain, and behavior.

OBJECTIVES: This article defines androgens (and anabolic steroids), describes their mechanisms of action, and summarizes their behavioral effects and relevance in animals and humans. METHOD: A MEDLINE-derived review of the literature on androgens and behavior was performed; pivotal earlier publications were also obtained and included in the review. RESULTS: In animals, the effects of androgens on brain structure and function are well-established and profound, with behavioral implications extending far beyond reproduction. Androgens play a prominent role in the organization or programming of brain circuits, which are subsequently activated by gonadal steroids. In humans, roles for androgens have been described, albeit inconsistently, in the regulation of sexuality, aggression, cognition, emotion, and personality. The relevance of androgens for psychiatry is further suggested by gender-related differences in pharmacokinetics/pharmacodynamics and in the prevalence, course, and treatment response characteristics of several psychiatric disorders. Direct psychoactive effects of exogenously administered androgens have been described for many years, most recently in reports of the psychotoxic effects of anabolic steroids. CONCLUSIONS: Data from both animals and humans suggest that the biological and behavioral responses to androgens are context-dependent.

Anabolic Agents↗
PubMed1995

Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus.

Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus.

Animals↗
PubMed1995

Nimodipine increases CSF somatostatin in affectively ill patients.

Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker, is effective in treating some patients with rapidly cycling affective disorders and some phases of Alzheimer's disease, i.e., two syndromes associated with transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin, respectively. CSF somatostatin (SRIF) was measured in 14 affectively ill patients while they were medication-free and during chronic nimodipine treatment. CSF somatostatin significantly increased in patients during active nimodipine treatment compared with ones in the medication-free state. The current findings raise the possibility that nimodipine-induced increases in CSF somatostatin could potentially contribute to its spectrum of efficacy on neuropsychiatric disorders associated with cognitive or affective impairment. Further clinical and preclinical studies are indicated to elucidate the potential mechanisms involved in the elevation of CSF SRIF, whether it is reflected in regional changes in brain, and its possible relevance to nimodipine's clinical actions.

Adult↗
PubMed1995

Skeletal muscle intracellular ionized magnesium measured by 31P-NMR spectroscopy across the menstrual cycle.

OBJECTIVE: The hormonal regulation of magnesium (Mg) metabolism is poorly understood. Preliminary evidence suggests that reproductive hormones may influence Mg concentrations in various tissues. The purpose of this study was to determine if Mg concentrations in blood and muscle are affected by the phase of the menstrual cycle. METHODS: Magnesium measures were obtained from 16 women over the course of one complete menstrual cycle. The principal outcome measure was intracellular ionized Mg ([Mg++]i) in skeletal muscle as measured by 31P nuclear magnetic resonance spectroscopy. Three blood measures (serum, red blood cell, and mononuclear blood cell) of total Mg ([Mg]) were also obtained. RESULTS: Mean Mg concentrations were stable across the menstrual cycle with no evidence of a menstrual cycle phase effect for any of the measures. Furthermore, skeletal muscle [Mg++]i was not correlated with any blood measure of [Mg]. CONCLUSION: These results suggest that physiologic fluctuations in reproductive hormones do not influence either blood [Mg] or skeletal muscle [Mg++]i in healthy, regularly cycling women.

Adult↗
PubMed1994

Magnesium measures across the menstrual cycle in premenstrual syndrome.

The purpose of this study was to evaluate blood magnesium (Mg) measures across the menstrual cycle in women with premenstrual syndrome (PMS) and control women. Longitudinal determinations of plasma, red blood cell (RBC) and mononuclear blood cell (MBC) Mg were made in 26 women with prospectively confirmed PMS and in a control group of 19 women. Data were analyzed using analysis of variance with repeated measures and Spearman rank correlations. Significant diagnostic group effects were observed for RBC and MBC Mg concentrations (p < 0.05). These effects reflected lower Mg concentrations in PMS patients at each sampling time. No significant effects were observed for either plasma Mg or MBC Mg content, nor were there significant time by diagnosis effects for any of the measures. Consistent with earlier studies, we found decreased RBC Mg concentrations and additionally observed decreased MBC Mg concentrations in women with PMS. However, neither of these relative deficits were confined to the luteal phase.

Adult↗