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Biomedical subjects

R T Rubin

Publications and source records attributed to R T Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Adrenal gland volume in major depression: relationship to basal and stimulated pituitary-adrenal cortical axis function.

We measured adrenal gland volume and both baseline and stimulated pituitary and adrenal cortical hormones in 35 unmedicated, major depressives and 35 individually matched normal control subjects. Mean adrenal volume in the depressives was significantly larger, by about 38%, than the adrenal volume of their matched controls. Basal plasma adrenocorticotropic hormone (ACTH)1-39 was significantly lower, and basal plasma cortisol was significantly higher, in the patients. In contrast, basal plasma ACTH determined by radioimmunoassay (RIA) was not significantly different between the two groups. The ACTH response to ovine corticotropin-releasing hormone (oCRH), whether measured specifically as ACTH1-39 or by the less-specific RIA, was highly significantly lower in the depressives than in the controls. However, neither the cortisol response to oCRH nor its response to low-dose ACTH 1-24 differed significantly between groups. In both groups of subjects, correlations between adrenal gland volume and all the hormone measures were low, and none represented more than 4% shared variance. In the patients, adrenal volume did not correlate significantly with duration of the present episode, lifetime number of episodes, melancholic subtype, Hamilton Depression Scale total score, or the Hamilton suicidality item. However, adrenal volume was significantly positively related to the somatization factor of the Hamilton scale, which was almost totally accounted for by the specific items of somatic symptoms and somatic anxiety.

Adolescent↗
PubMed1995

Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment.

We previously reported increased regional cerebral cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients with obsessive-compulsive disorder(OCD) before treatment compared to matched normal controls. In the present study, we determined whether or not these changes persisted during treatment. Single-photon emission computed tomography was used to measure regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of 99mTc-HMPAO in eight adult male OCD patients before and during treatment with chlomipramine, and in eight age-matched normal male controls. With 133Xe, there were no significant differences in rCBF between patients with OCD and their matched controls, and no significant differences in rCBF in the patients before and during treatment. Significantly increased HMPAO uptake in the orbital frontal cortex, posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in the OCD patients before treatment compared to their matched controls, and there were significant reductions of HMPAO uptake, into the normal range, in all these areas in the patients during treatment. Significantly reduced HMPAO uptake in the caudate nucleus bilaterally occurred in the patients before treatment compared to their matched controls, and these reductions persisted during treatment. This study provides additional support for the involvement of both the orbital frontal cortex and the caudate nuclei in the pathophysiology of OCD.

Adult↗
PubMed1995

Reduction of AMPA-selective glutamate receptor subunits in the entorhinal cortex of patients with Alzheimer's disease pathology: a biochemical study.

Using biochemical techniques we determined concentrations of the AMPA-selective glutamate receptor subunits GluR1 and GluR2/3 in the entorhinal cortex of patients with Alzheimer's disease pathology and age-matched controls. Tangle density was also determined in anatomically matched samples and correlated with GluR1 and GluR2/3 receptor concentration. In Alzheimer's disease brain, Western blot analysis revealed average reductions of 43% and 38% for GluR1 and GluR2/3, respectively. Based on previous immunohistochemical studies, we infer that the majority of protein reduction was due to decreases in GluR1 and GluR2/3 immunolabeled elements in the more superficial layers of the entorhinal cortex (layers II and III). These layers of the entorhinal cortex contained numerous neurofibrillary tangles in Alzheimer's disease, but neither GluR1 nor GluR2/3 protein concentration correlated significantly with tangle density. We hypothesize that the decrease in specific glutamate receptor subunits, particularly GluR2/3, may contribute to the vulnerability of neurons in the entorhinal cortex via mechanisms involving calcium conductance through AMPA-selective channels.

Aged↗
PubMed1995

Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment.

BACKGROUND: Hyperactivity of the pituitary-adrenocortical axis is the most prominent neuroendocrine abnormality in major depression. It is state-related, returning to normal with resolution of the depressive episode. Adrenal gland enlargement also has been reported in patients with major depression and has been hypothesized as an index of cumulative lifetime depression. However, whether or not adrenal enlargement decreases with successful treatment of depression has not yet been studied, to our knowledge. We, therefore, determined adrenal gland volume in patients with major depression before and after treatment and in matched normal controls, and compared adrenal size with functional indexes of pituitary-adrenocortical activity. METHODS: Adrenal volumes were measured by magnetic resonance imaging in nine adult and two adolescent patients with major depression during their illness and during full remission when medication had been stopped for at least 1 month, and in nine adult and two adolescent normal control subjects individually matched to the patients. Basal, 4 to 7 PM plasma corticotropin 1-39 and cortisol levels, and corticotropin 1-39 and cortisol responses to administration of ovine corticorelin and lowdose cosyntropin also were measured. RESULTS: Mean adrenal gland volume was significantly larger, by about 70% in the patients while depressed than after successful treatment, and it also was significantly larger, again by about 70%, than the mean adrenal gland volume of their matched controls. After treatment, the mean adrenal volume of the patients decreased and was no longer significantly different from that of their controls at baseline. The magnitude of the decrease was significantly positively correlated with the duration of the depressive episode. Basal, late-afternoon plasma corticotropin 1-39 levels were significantly lower in the patients while depressed than in their matched controls, but basal plasma cortisol levels did not differ significantly among the three groups, nor did the corticotropin 1-39 and cortisol responses to corticorelin or the cortisol response to cosyntropin. Correlations between adrenal gland volume and basal corticotropin and cortisol levels, and the corticotropin and cortisol responses to hormone challenge, were not consistently in the expected direction in any of the three groups of subjects. CONCLUSIONS: Adrenal gland enlargement occurring during an episode of major depression appears to be state-dependent, in that it reverts to the normal size range during remission after treatment. It thus does not appear to be an index of cumulative lifetime depression. The lack of a discernible relationship between adrenal volume and pituitary-adrenocortical activity remains to be explained and might be related to noncorticotropin influences on the adrenal gland, including other tropic hormones and/or neural mechanisms.

Adolescent↗
PubMed1995

Neuroendocrine aspects of primary endogenous depression--XIV. Gonadotropin secretion in female patients and their matched controls.

To determine the extent of dysregulation of gonadotropin secretion in depressed women, we measured nocturnal and diurnal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations and the responses of these hormones to gonadotropin releasing hormone (LHRH) in 20 Research Diagnostic Criteria primary, definite endogenous female depressives and in 20 individually matched female normal controls. Fourteen patients and 14 controls were premenopausal, and six patients and six controls were peri/postmenopausal or panhysterectomized. None of the latter was receiving estrogen replacement therapy. The premenopausal patients showed no significant differences in basal nocturnal or diurnal gonadotropin concentrations and no significant differences in hormone concentrations post-LHRH compared to their premenopausal matched controls. In contrast, in the postmenopausal subjects there were (1) significantly increased diurnal vs. nocturnal serum FSH concentrations in the depressives; (2) marginally increased nocturnal, diurnal, and LHRH-stimulated LH concentrations and highly significantly increased LHRH-stimulated FSH concentrations in the depressives compared to their controls; and (3) positive correlations between the LH measures and ratings of depression severity in the patients. These results suggest a dysregulation of the HPG axis in peri/postmenopausal and panhysterectomized female endogenous depressives.

Adult↗
PubMed1995

Influence of meal composition on the postprandial response of the pituitary-thyroid axis.

Ingestion of food can result in an acute decline of serum thyrotropin (TSH) concentrations, but it is not known whether meal composition and/or stomach distension are influential. Normal men and women were given a normocaloric or hypocaloric, isobulk meal at lunch and at dinner in a randomized design. The normocaloric, but not the isobulk, meal resulted in a significant decline in serum TSH at both lunch and dinner; thyroid hormones and cortisol were not affected significantly. These findings suggest that meal composition is influential in the acute postprandial decline of serum TSH in man. A possible mechanism is food-induced elevation of somatostatin and consequent suppression of TSH secretion.

Adult↗
PubMed1992

Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography.

We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Neuroendocrine aspects of primary endogenous depression: XII. Receiver operating characteristic and kappa analyses of serum and urine cortisol measures in patients and matched controls.

The majority of studies investigating the diagnostic utility of hypothalamo-pituitary-adrenal (HPA) axis measures in major depression have focused on the dexamethasone (DEX) suppression test (DST). The DST correlates well, but imperfectly, with other measures of HPA activity. Fewer studies have considered the ability of basal cortisol measures to discriminate depressives from non-depressed patients or normal subjects. We used receiver operating characteristic (ROC) analysis to examine the mean 24-hr serum cortisol concentration, our benchmark of basal HPA axis activity, compared to smaller segments of the 24-hr cortisol profile, post-DEX serum cortisol values, and pre- and post-DEX 24-hr urinary free cortisol (UFC) levels in 40 primary endogenous major depressives compared to 40 matched normal control subjects. No statistically significant differences in ROC curves were found between mean 24-hr cortisol and the other cortisol measures. The mean 24-hr, 1300h-1600h, 1600h-1900h, and 16-hr post-DEX serum cortisol concentrations and the post-DEX UFC level all appeared to be comparable estimators of HPA activity. The single 2300h pre-DEX serum cortisol concentration and the pre-DEX 24-hr UFC level performed notably poorer than did the other measures. We additionally calculated kappa statistics to determine the optimally sensitive and specific discriminators of the cortisol measures between the depressives and the normal controls. The 2300h post-DEX serum cortisol measure was optimally sensitive, and the 1500h post-DEX serum cortisol was optimally specific. The 0700h, 1500h, and 2300h post-DEX serum cortisols were very close together as the optimally efficient measures (best combination of sensitivity and specificity).

Adult↗
PubMed1992

Effects of hypothalamic peptides on the aging brain.

The hypothalamic peptide hormones, TRH, LHRH (GnRH), CRH, GHRH, and GHIRH (somatostatin), influence the release of the anterior pituitary hormones, which in turn promote the release of target endocrine gland hormones and other metabolites. These latter compounds feed back to the brain to help control the secretion of the hypothalamic hormones. This is a dynamic interaction that is influenced by the aging process: Most of these hormones systems become less responsive with advancing age, due to decreased function of peptide-containing secretory neurons, a loss of hormone receptor sensitivity, and/or a reduction in the output of the target endocrine glands. That the hypothalamic peptides themselves can influence brain function is supported by the fact that most are found in areas of the brain other than the hypothalamus and that receptors for them exist in these other areas. For example, CRH is contained in a number of central neural systems that can influence behavior, including limbic areas, the hypothalamus, locus coeruleus, median raphé nuclei, and cortical interneurons. CRH has been shown to be anxiogenic in animal models, and its effect can be blocked by CRH receptor antagonists. CRH content in the locus coeruleus is particularly increased by stress and may influence norepinephrine neurotransmitter function in this structure. In aging there is a gradual reduction of the sensitivity of the brain to the negative feedback of corticosteroids, such that CRH secretion becomes somewhat increased under basal conditions. The behavioral effects of this change are unclear, however, as is the influence of stress-related activation of CRH, ACTH, and glucocorticoid secretion on behavior in the elderly. Other hypothalamic peptides have different patterns of change with aging, and some are markedly altered in pathological conditions; for example, in Alzheimer's disease the content of CRH and somatostatin in certain brain areas is decreased. However, whether the changes in hypothalamic peptides precede or follow the pathological behavioral changes, and how they participate in the changes, is still unclear.

Aged↗
PubMed1992

Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia.

OBJECTIVE: The authors' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week, fixed-dose, double-blind, placebo-controlled, dose-response study of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic attacks, avoidance behavior, generalized anxiety, and global response. Blood samples were collected throughout the study and analyzed for alprazolam and other benzodiazepines. RESULTS: Patient compliance with the protocol was judged to be good on the basis of plasma concentrations. According to logistic regression analysis, the relationships between plasma alprazolam concentration and response, as reflected by number of panic attacks reported, phobia ratings, physicians' and patients' ratings of global improvement, and the emergence of side effects, were significant. However, there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms. CONCLUSIONS: The authors conclude that plasma concentration of alprazolam is related to treatment response, particularly in panic attacks. The alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals, highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects.

Adult↗
PubMed1992

Discontinuation of alprazolam after long-term treatment of panic-related disorders.

Discontinuation of alprazolam after long-term treatment of 142 patients with panic-related disorders was examined in five study sites using a telephone interview. The majority (67%) of patients interviewed discontinued alprazolam for a period of at least 3 days after a gradual dosage reduction schedule over a 4-week period at the end of the long-term treatment study. A marked difference among the study sites in percentages of patients discontinuing therapy with alprazolam suggests that physician intervention played an important role in determining the ability of patients successfully to discontinue use of alprazolam: 90% and 95% of patients ceased therapy at two sites whereas only 21%, 38%, and 66% of patients discontinued therapy at the other three sites. The mean daily dosage for patients who continued using alprazolam decreased from 5.1 mg/day at the end of the long-term segment to 2.7 mg/day at the time of the poststudy interview. This decline indicates a lack of tolerance to the therapeutic effectiveness of alprazolam over an extended period of time.

Adult↗
PubMed1992

A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder.

A recently reported multinational, 8-week double-blind, placebo-controlled study assessing the efficacy of alprazolam versus placebo in the treatment of panic disorder indicated significant differences favoring alprazolam. We now report the results of a three-site, 6-week, double-blind, fixed-dose study comparing alprazolam 2 mg, alprazolam 6 mg, and placebo in 94 patients with panic disorder with or without agoraphobia. Both alprazolam treatment groups (6 mg and 2 mg) improved significantly more than did the placebo treatment group on most outcome measures. Only a few statistically significant differences between the 6 mg and 2 mg alprazolam groups were discerned, although the pattern of treatment response across measures suggested a dose effect. Dropouts in the placebo group were primarily due to lack of efficacy and in the alprazolam 6 mg group were due to side effects, which may have contributed to the limited differences between groups at study end. The findings suggest that many patients may require less than 6 mg of alprazolam per day for effective treatment of panic disorder.

Adolescent↗
PubMed1991

Adrenal gland volume determination by computed tomography and magnetic resonance imaging in normal subjects.

To compare the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) for the quantitative determination of adrenal gland size in human subjects, adrenal gland volumes were determined by both techniques in five female and five male, normal, nonstressed adult volunteers. Mean left and right adrenal volumes were slightly larger by CT, and the left adrenal volume was slightly larger than the right by both imaging techniques. Volume determinations by CT and MRI correlated +0.85 and +0.82 for the left and right glands, respectively. Body surface area was highly correlated, and sex moderately correlated, with left and right adrenal volumes by both techniques. Both CT and MRI somewhat overestimated the known volumes of a set of phantoms, CT by an average of 42% and MRI by an average of 20%. The results of this initial study suggest that MRI holds promise as a technique for in vivo adrenal gland measurements, and that the influence of both body surface area and sex should be considered in comparative studies of adrenal size.

Adrenal Glands↗
PubMed1991

Dose-dependent effects of scopolamine on nocturnal growth hormone secretion in normal adult men: relation to delta-sleep changes.

To explore the sensitivity of nocturnal GH secretion to different degrees of cholinergic blockade, we investigated the effects of two doses of the muscarinic receptor antagonist scopolamine (SCOP; 3.0 and 6.0 micrograms/kg, im) and placebo, administered in a randomized fashion at 2300 h on three nights to eight normal male volunteers. Both doses of SCOP produced significant reductions in mean nocturnal GH concentration compared to the effects of the placebo; the higher dose of SCOP reduced GH to a greater degree than the lower dose, but this difference was not statistically significant (mean, 2.3 micrograms/L after 6 micrograms/kg vs. 3.0 micrograms/L after 3 micrograms/kg). Both SCOP doses significantly shifted GH secretion into later portions of the night, with a significantly greater delay observed after the larger dose. Similarly, a significant delay in the time of the GH rise was produced by SCOP. In contrast, the effects of both doses of SCOP on delta-sleep or sleep onset were small. These data confirm earlier reports demonstrating that cholinergic muscarinic input represents a potentially important source of regulation of nocturnal GH release and suggest that the magnitude of the reduction in GH and the extent of delay in the GH rise time may reflect quantitative differences in the degree of cholinergic blockade. These data are in agreement with recent studies suggesting that the timing of GH release need not be associated with delta-sleep per se.

Adult↗