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M Colla

Publications and source records attributed to M Colla.

16 recordsLinked to original sources
PubMed2004

Open-label non-randomized versus double-blind randomized antidepressive treatment: what are the advantages of clinical decision over randomization?

OBJECTIVE: To study, whether and how the results from open and double-blind randomized trials on antidepressants differ. METHODS: Seventy-one patients were included in a study comparing open, non-randomized, standardized treatment with paroxetine (PAROX) and amitriptyline (AMI) after a minimum of six drug-free days (OPEN). A second group of 56 patients received the same treatment under blind-randomized conditions (BLIND-RANDOM). The course of psychopathology as assessed by the Hamilton Depression Rating Scale was compared using repeated measurements ANOVA-(rm). RESULTS: While the rate of adverse events was higher in the BLIND-RANDOM compared to the OPEN condition, completer-analyses revealed no differences in psychopathological outcome. CONCLUSIONS: With similar clinical outcome BLIND-RANDOM trials of antidepressants may expose depressed patients to an increased risk of adverse events, when compared to OPEN conditions. However, the clinical outcome in study completers did not differ between the BLIND-RANDOM and the OPEN condition. Thus, the psychiatrist's choice may have impact on adverse events rather than on clinical outcome of antidepressant treatment.

Adult↗
PubMed2001

Increased platelet aggregability in major depression?

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.

Adult↗
PubMed2001

The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system in elderly subjects.

There is preclinical evidence that CRH is released in response to a glutamatergic stimulation. However, it is not clear, whether glutamate plays a role in the physiological stress response. We tested whether the antiglutamatergic drug riluzole dampens the response of the hypothalamus-pituitary-adrenocortical (HPA) system to both a mental and a physical stressor. Nine male elderly healthy subjects received placebo and 150 mg riluzole for 2 days in a randomized balanced order. Blood was withdrawn every 15 min for estimation of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, the subjects were subjected to a cognitive challenge paradigm. Further, between 19.02 and 19.15 an individually adapted physical stress test was performed. After riluzole treatment, baseline ACTH and cortisol concentrations were unchanged when compared to placebo treatment. Also, after the mental stressor, there was no difference between both treatment conditions. In contrast, the cortisol (riluzole vs. placebo: 148 +/- 60 vs. 183 +/- 98 nmol/l) and ACTH response (20.2 +/- 11.9 vs. 40.7 +/- 61.9 pmol/l) to the physical stressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system activity under baseline and cognitive-stress-induced conditions in elderly subjects. However, a trend for dampening the endocrine response to physical stress emerged.

Adrenocorticotropic Hormone↗
PubMed2000

Testosterone, androstenedione and dihydrotestosterone concentrations are elevated in female patients with major depression.

Hyperactivity of the HPA-system in major depression is reflected by an increased secretion of adrenal hormones especially cortisol and dehydroepiandrosterone (DHEA). In women for whom androgenicity is associated with cardiovascular disorders the dominant source of androstenedione and testosterone secretion are the adrenal glands. To date, there is only sparse information about the regulation of androstenedione, testosterone and dihydrotestosterone (DHT) concentrations in women with severe major depression.Therefore, 11 pre- and postmenopausal, severely depressed, hypercortisolemic women (Hamilton Depression Scale, 31.3+/-5.9; age, 28-77 yrs; mean, 48. 1+/-18.1 yrs) and 11 age-matched healthy female controls (age, 24-81 yrs; mean, 47.9+/-21.5 yrs) underwent a 24 hour (h) blood sampling starting at 0800 h with 30-minute sampling intervals. By applying multivariate analysis of covariance with age as covariate, androstenedione, testosterone and DHT plasma levels at 0900 h show a trend for elevated concentrations in depressed women compared to controls (F(1,19)=2.7; P=0.057). Univariate F tests reveal a significant difference between the groups for androstenedione (4. 19+/-1.571 vs 2.584+/-1.257 nmol/l; P<0.05) testosterone (1.110+/-0. 278 vs 0.833+/-0.347 nmol/l; P<0.05) and DHT (0.656+/-0.207 vs 0. 483+/-0.242 nmol/l; P<0.05). Mean ACTH (16.4+/-10.4 vs 10.4+/-2.4 pmol/l; P=0.89), LH (13.5+/-11.8 vs 8.9+/-9.2 IU/l; P=0.12), FSH (35. 2+/-33.1 vs 31.3+/-35.7 IU/l; P=0.67) and estradiol (135.4+/-157.4 vs 82.2+/-85.1 pmol/l; P=0.20) plasma levels did not differ between patients and controls. Further, there was a trend towards an age related decline in testosterone secretion in healthy controls (r=-0. 24; P=0.08) which did not occur in depressed patients (r=0.17; P=0. 96), while the calculated ratio of DHEA to testosterone was similar in both groups (0.2+/-0.14 vs 0.13+/-0.7; P=0.21, unpaired t-test). In conclusion, androstenedione, testosterone and DHT concentrations all were increased in hypercortisolemic women with severe major depression. These findings are best explained as a consequence of an overstimulation of the adrenal glands through pituitary and hypothalamic sites of the HPA-system.

Adrenocorticotropic Hormone↗
PubMed2000

Increased diurnal plasma concentrations of cortisone in depressed patients.

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) regulates glucocorticoid activity by converting cortisol into cortisone and vice versa. Frequent signs of major depression are elevated concentrations of circulating cortisol and ACTH. However, no information is available about the activity of 11-beta-HSD in this disorder. Therefore, we compared diurnal plasma concentrations of cortisol and cortisone and their ratios, reflecting 11-beta-HSD activity, in 25 severely depressed patients (Hamilton Depression Scale, 29 +/- 6; 14 men, 11 women, age 22-77 yr; mean, 47 +/- 16) and 30 control persons (20 men, 10 women age 23-85 yr; mean, 51 +/- 19). Cortisol and cortisone were measured at 0900 h, 1100 h, 1300 h, 2000 h, 2200 h, 0100 h, 0300 h, and 0700 h with specific RIAs after extraction. Both cortisol and cortisone concentrations were significantly increased in patients compared with controls (cortisol, 251.7 +/- 113.1 vs. 160 +/- 96.6 nmol/L; cortisone, 32.8 +/- 10.9 vs. 21.9 +/- 10.9 nmol/L). The calculated ratios of cortisol to cortisone were similar in controls and patients. Similar to cortisol, the circadian variation of cortisone was flattened in patients with the ratio of maximal cortisone to minimal cortisone being 1.9-fold higher in controls than in patients. There was no gender-specific difference in cortisone values neither in patients nor in controls. We conclude that in major depression increased cortisol is not due, at least partly, to an altered 11-beta-HSD activity or to a decrease in cortisone.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Endothelin-1 plasma concentrations in depressed patients and healthy controls.

Depression and cardiovascular morbidity are known to be associated. So far, however, the pathophysiological link between these conditions is unclear. We tested the hypothesis that in depressed hypercortisolemic patients endothelin-1 (ET-1) plasma concentrations are increased and contribute to the cardiovascular risk. Diurnal plasma concentrations of cortisol and ET-1 were measured in 29 healthy controls and 22 depressed patients. ANCOVA did not reveal a significant effect of diagnosis or age upon ET-1 concentrations. However, only in depressed patients, cortisol plasma concentrations tended to be positively related to ET-1 concentrations. We conclude that ET-1 is not increased in depressed patients, but within this group, hypercortisolemia may be associated with increased ET-1 concentrations.

Aging↗
PubMed1998

Mineralocorticoid receptor also modulates basal activity of hypothalamus-pituitary-adrenocortical system in humans.

Hippocampal mineralocorticoid (MRs) and glucocorticoid receptors (GRs) have been demonstrated to regulate the activity of the hypothalamus-pituitary-adrenocortical (HPA) system. To elucidate the role of the hippocampal MR in the circadian activity of the human HPA system, we studied diurnal secretory profiles of corticotropin (ACTH) and cortisol in 10 healthy male humans before and after an 8-day treatment with the MR antagonist spironolactone. 24-hour blood sampling at 30-min intervals was performed for estimation of cortisol (q30) and ACTH (q120). Saliva cortisol was measured for estimation of unbound cortisol. At the end of the 24-hour sampling period a corticotropin-releasing hormone (CRH) challenge was performed. High plasma concentrations of the active metabolite canrenone were achieved (begin of sampling: 2,653 +/- 693 nmol/l; end of sampling: 747 +/- 177 nmol/l). There was a significant increase in the diurnal minima (37.1 +/- 13.3 vs. 23.7 +/- 8.9 nmol/l, p < 0.02) and mean cortisol (193.5 +/- 25.8 vs. 173.0 +/- 23. 0 nmol/l, p < 0.03) plasma concentrations. However, the diurnal peak concentrations and pulsatile secretory features were unchanged after spironolactone treatment. For saliva cortisol, the only significant treatment difference was a decrease in the diurnal amplitude of cortisol relative to the diurnal mean concentration (2.56 +/- 0.47 vs. 3.11 +/- 0.87, p < 0.03). After spironolactone treatment there was a decrease in diurnal mean ACTH concentrations (46.2 +/- 14.4 vs. 41.8 +/- 10.3 pmol/l). There was no difference in the ACTH and cortisol response after infusion of CRH before and after spironolactone treatment. CBG plasma concentrations were significantly increased (22.4 +/- 2.3 vs. 19.2 +/- 2.7 mg/l, p < 0. 01) after spironolactone treatment, which possibly contributed to the observed increase in plasma cortisol. In summary, as predicted from animal studies we found significant effects of MR antagonization to be restricted to time windows of low HPA system activity. These findings are similar to the effects of aging upon the HPA system. However, the effect of spironolactone treatment was small, suggesting that the HPA system activity in humans is modulated but not regulated by the hippocampal MR.

Adrenal Cortex↗
PubMed1998

Effects of major depression, aging and gender upon calculated diurnal free plasma cortisol concentrations: a re-evaluation study.

Depression, aging and female gender are associated with increased diurnal concentrations of total plasma cortisol. For the physical effects of hypercortisolemia, however, it is generally assumed that free rather than total plasma cortisol concentrations are of importance. Herein, we report a mathematical approach to determine free plasma cortisol concentrations on the basis of total cortisol, corticosteroid binding-globulin (CBG) and albumin plasma concentrations. This approach was used to re-evaluate two sets of data in order to estimate the effect of depression as well as the effect of aging and gender upon free plasma cortisol concentrations. Comparing male depressed patients with healthy controls, we found 24-hour free cortisol minima (MIN: 4.1 +/- 1.8 vs. 1.6 +/- 1.1 nmol/l, p < 0.0001), mean (MEAN: 25.5 +/- 6.7 vs. 10.4 +/- 2.7 nmol/l, p < 0.0001) and maximal (MAX: 85.3 +/- 23.3 vs. 45.2 +/- 15. 8 nmol/l, p < 0.0001) concentrations to be significantly increased in depressed patients. In general, the impact of depression upon total plasma cortisol were not only maintained, but stronger regarding free plasma cortisol. Also, age was associated with free plasma cortisol MIN (F1,30= 10.8, p < 0.003) and free plasma cortisol MEAN (F1,30 = 8.9, p < 0.006). All effects of age upon total plasma cortisol were generally also found in free plasma cortisol, though with less impact. No effect of gender upon any of the given free plasma cortisol outcome variables was found. Taken together, our re-evaluation clearly shows not only depression but also aging to be associated with increases in free plasma cortisol concentrations. This finding is in line with the observation that in both conditions medical problems triggered and/or maintained by glucocorticoids (e.g. osteoporosis) are frequently seen.

Adult↗
PubMed1998

[Breast carcinoma in men. The surgical treatment of a case under our observation].

A case of male breast carcinoma in a very young subject (seventeen years old) is described. Breast carcinoma in male is infrequent, and at a so young age it is really rare. The patient was subjected to "Patey" mastectomy with removing the lymph nodes of the breast with the tumor, and subcutaneous mastectomy at the opposite side breast. As agreed with the oncologist other therapy was carried out.

Adolescent↗
PubMed1997

Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration.

When administered intravenously (i.v.) in a pulsatile mode during the first half of the night to young normal controls, growth hormone-releasing hormone (GHRH) results in increased growth hormone (GH) plasma levels and slow wave sleep (SWS) and blunted cortisol release. In the present study we investigated whether GHRH has the same effects when administered in the early morning. Seven normal young male volunteers had 2 sessions each in the sleep laboratory (23.00 to 10.00 h) during which the secretion of GH, cortisol and corticotropin (ACTH) and polygraphic recording were monitored. Verum (4 bolus injections of 50 micrograms GHRH) or placebo were injected i.v. at 04.00, 05.00, 06.00 and 07.00 h. GHRH stimulated GH plasma levels significantly whereas cortisol and ACTH were not altered. In the sleep-electroencephalogram, only rapid-eye-movement density was decreased significantly during the period of active medication; all other sleep parameters were unaffected. We suggest that the physiological occurring high activity of the hypothalamic-pituitary-adrenocortical(HPA) system in the early morning prevents the effects of GHRH on cortisol plasma levels and SWS. Thus GHRH administered to healthy young men in the early morning hours has the same effect as GHRH administered during the first half of the night to patients with major depression who have HPA hyperactivity throughout the day.

Adrenocorticotropic Hormone↗
PubMed1994

[A double-blind study of neostigmine versus placebo in paralytic ileus as a result of surgical interventions].

A fully randomized double-blind study, stratified according to diagnosis, was carried out in order to assess the effect of endonasal neostigmine in the treatment of post-laparotic paralytic ileus. A total of 40 patients (16 M, 24 F), aged between 22 and 76 years old, were admitted to the study; of these 20 were cholecystectomized and 20 had undergone emergency surgery. According to a special randomization list, 10 patients from each pathological group were treated with 6% neostigmine en (1 puff = 5.4 mg) and the other ten were treated with placebo. Both treatments were administered at a dose of 2 puffs, one per nostril, at the end of surgery and then repeated every 4 hours up to a maximum of 6 puffs/day. Treatment was continued for 4 days or until canalization of feces and gas was achieved. The mean daily dose of endonasal neostigmine found to be efficacious was 4 puffs/day, equivalent to 24.7 mg in cholecystectomized patients and 23.5 mg in patients undergoing emergency surgery. In over-all terms the canalization of gas and feces was observed in 74% of patients treated with neostigmine and in 45% of those receiving placebo and the difference was statistically significant.

Administration, Intranasal↗
PubMedDate not supplied

The role of mineralocorticoid receptors in the circadian activity of the human hypothalamus-pituitary-adrenal system: effect of age.

The purpose of this study was to test the role of the mineralocorticoid receptor (MR) in the circadian activity of the hypothalamus-pituitary-adrenal (HPA) system of elderly healthy subjects. Nine elderly subjects (age: 66.2 +/- 7.7 years) were treated for 8 days with both the MR antagonist spironolactone and a placebo in a randomized, single-blind cross-over order. After treatment, we studied the circadian profiles of ACTH, plasma cortisol and saliva cortisol. No significant change in ACTH concentrations emerged. However, there were significant increases in circadian minimal (52.4 +/- 26.7 versus 33.3 +/- 14.4 nmol/l), mean (166.2 +/- 24.9 versus 133.0 +/- 18.3 nmol/l), and maximal cortisol concentrations (389.7 +/- 57.7 versus 335.4 +/- 45.0 nmol/l). Also, in the diurnal trough, we found an increase in saliva cortisol concentrations. Compared to young healthy controls, spironolactone treatment had stronger effects in the elderly. We therefore conclude that: 1) MR is involved in the human HPA system regulation; 2) the MR participates in the regulation of circadian nadir and peak activity of the HPA system; and 3) the HPA system in the elderly is more vulnerable to dysregulation at the level of the MR.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Reduced efficacy of growth hormone-releasing hormone in modulating sleep endocrine activity in the elderly.

In aging, a decline in sleep continuity, a decreased slow wave sleep, an earlier nocturnal cortisol rise, and a blunted growth hormone (GH) secretion occur. Pulsatile administration of GH-releasing hormone (GHRH) in young controls enhanced slow wave sleep and suppressed cortisol release. We administered GHRH 4 x 50 microg or placebo i.v. to 13 healthy seniors (5 women, 8 men, mean age 69.3 y +/- 8.3 SD). We observed significantly reduced nocturnal awakenings and an increased first non-rapid-eye-movement sleep period. In a subgroup (n = 9), we found a significant activation of GH secretion but unchanged cortisol secretion. Our data underscore that GHRH is capable of promoting sleep in the elderly, but much less than in young subjects. Contrasting to young subjects, the hypothalamic-pituitary-adrenocortical system remains unaffected by GHRH in the elderly. These results provide further evidence that a decrease in the efficacy of GHRH is involved in the biological mechanisms underlying aging.

Adrenocorticotropic Hormone↗