Biomedical subjects
Publications and source records attributed to G Charles.
25-aminolanostenol 1 and 25-aminocholesterol 2 were hemisynthesized from natural sterols and tested in vitro against Candida albicans. The biological activity of compound 1 was rather weak, whereas 2 exhibited in vitro antifungal activity with MIC value of 4 microM.
delta 7-5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover delta 5-unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6 beta-aminocholestanol is a potent antifungal agent.
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The hypothesis that lithium is the most appropriate and efficacious pharmacological treatment in the therapy of manic-depressive illness was examined in a meta-analysis. The efficacy of lithium was compared with that of the antiepileptics, carbamazepine and valproic acid. Data sources include the Medline database and relevant references from articles. Only randomised controlled clinical trials with a double-blind assessment of outcomes were included. Lithium levels were required to be within the therapeutic range of 0.4-1.5 mmol/l. The effect sizes were measured by the odds ratio using the Mantel-Haenszel method. No significant difference was observed between the treatment effect of the 3 drugs compared. While the efficacy of the 3 treatments was identical, there is a general tendency in favour of the antiepileptics in the treatment of manic depression with regard to adverse events and treatment tolerance. The impact and importance of this study seriously question the relevance of today's practice of prescribing lithium in the acute management of manic-depressive illness.
Prolactinoma is the most frequent of secreting pituitary adenomas. It is often discovered among women of childbearing-age presenting an association of amenorrhea and galactorrhea. Data in the literature from large series indicate the current risks of interaction between prolactinoma and pregnancy. Risks have been overestimated in the past and it is now recognized that pregnancy can be allowed providing strict follow-up is assured. Dopaminergic drugs have no teratogenic side-effects and are known to allow tumoral control and recovery of fertility in the majority of cases. The use of these medications explains the reduction of indications for surgery. Microprolactinomas are highly influenced by pregnancy and can even lead to tumor retrogression. Macroprolactinomas give complications more often, and require a good tumor control and a rigorous follow-up.
We have shown that clonidine, infused i.v. during the second non-REM period, was significantly less REM sleep suppressant in depressed patients than in control subjects. We have named this procedure the 'clonidine REM suppression test (CREST)'. In this report, we compare in the same sample (15 patients with primary major affective illness, 10 normal controls, 15 patients with minor depression and 15 patients with generalized anxiety) the efficacy of the CREST to separate the major depressed patients from the control subjects with the efficacy of three currently proposed biological markers of depression, i.e., the latency of REM sleep, the dexamethasone suppression test and the clonidine growth hormone stimulation test. We found that the CREST had the highest efficacy and suggest that further studies with independent and larger samples of patients and controls are needed to confirm those preliminary results and establish if the CREST could provide a new biological marker of major affective disorders.
In the present study, P300 has been recorded in 26 subjects (15 women) 1 month after an aggression without organic complications. Among our sample, 16 subjects fulfilled DSM-III-R criteria for posttraumatic stress disorder (PTSD) and 10 did not. P300 amplitude was significantly lower in the 16 PTSD subjects as compared to the 10 subjects without PTSD. This study supports information processing disturbances in PTSD.
Pelvic congestion syndrome is encountered in three pathological situations: premenstrual syndrome, intermenstrual syndrome, chronic pelvic congestion syndrome. The first two syndromes, with a range of physical and/or psychological symptoms, are cyclical. Their pathogenesis is multifactorial. Hormonal and circulatory factors are essentially blamed. Treatment is most often based upon combinations of progestogens and venotonics. The third syndrome, that of chronic pelvic congestion, is characterised by long term pelvic pain and raises etiopathogenic problems which remain only partially solved and in which a vascular role may sometimes be recognised. Endovaginal ultrasonography with colour-coded Doppler and celioscopy sometimes reveal pelvic varicose veins and indicate their responsibility for such pain, after having eliminated specific pelvic pathology (post-infectious or post-operative inflammatory sequelae of pelvic tissue, rupture of the broad ligaments, endometriosis, etc.). Treatment is above all medical, based upon hormone therapy acting upon venous receptors, venotonics which decrease the consequences of stasis, intermittent courses of anti-inflammatory agents and antibiotics when there is inflammation secondary to local infection. These various types of treatment may be combined. Surgical treatment should be restricted to certain carefully assessed cases only.
The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.
OBJECTIVE: The authors' goal was to establish, in a large multicenter sample of patients classified according to gender and menopausal status, if the growth hormone (GH) response to clonidine discriminated patients with episodes of major depression from patients with episodes of minor depression. METHOD: The GH response to intravenous clonidine administration (150 micrograms) was compared in 71 male and 140 female patients with major depressive episodes and 47 male and 53 female patients with minor depressive episodes. These patients were diagnosed according to Research Diagnostic Criteria. RESULTS: Differences in the GH response to clonidine between diagnostic groups occurred only between male patients. These results were found in the group as a whole and in each center. The GH responses to clonidine of premenopausal women differed significantly from those of postmenopausal women in each diagnostic group. CONCLUSIONS: These results confirm that gender and menopausal status are of the utmost importance in the interpretation of the clonidine GH test.
The purpose of this study is to assess the value of MR imaging in nonpalpable breast tumors. Thirty-two women whose mammogram showed opacity, architectural distorsionor microcalcifications, underwent preoperative dynamic MR studies with quantitative evaluation of contrast enhancement. MR showed early contrast enhancement in 10/12 breast cancers (2 false-negative) and in 6/20 benign lesions (false-positive). Quantitative study of contrast enhancement does not allow clear differentiation between these lesions. Further studies are required to confirm these findings and purpose MR imaging for aid in detection of carcinomas. Multifocal sudden enhancements are possible in benign lesions and incite to limit MR to focal mammographic abnormalities.
In this Department of Veterans Affairs cooperative study, we examined predictors of in-hospital and 1-year mortality of 612 mechanically ventilated patients from 6 medical intensive care units in a retrospective cohort design. The outcome variable was vital status at hospital discharge and after 1 year. The results showed that 97% of patients were men, the mean age was 63 +/- 11 years (SD), and hospital mortality was 64% (95% confidence interval, 60% to 68%). Within the next year, an additional 38% of hospital survivors died, for a total 1-year mortality of 77% (95% confidence interval, 73% to 80%). Hospital and 1-year mortality, respectively, for patients older than 70 years was 76% and 94%, for those with serum albumin levels below 20 grams per liter it was 92% and 96%, for those with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 35 it was 91% and 98%, and for patients who were being mechanically ventilated after cardiopulmonary resuscitation it was 86% and 90%. The mortality ratio (actual mortality versus APACHE II-predicted mortality) was 1.15. Conclusions are that patient age, APACHE II score, serum albumin levels, or the use of cardiopulmonary resuscitation may identify a subset of mechanically ventilated veterans for whom mechanical ventilation provides little or no benefit.
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OBJECTIVE: The Cruzan case and the Patient Self-Determination Act will encourage patients to specify in advance which life-sustaining treatments they would want if they become mentally incompetent. However, strictly following such advance directives may not always be in a patient's best interests. We sought to determine whether patients differ in how strictly they want advance directives followed. DESIGN: Interview study. SETTING: Seven outpatient chronic dialysis centers. PARTICIPANTS: One hundred fifty mentally competent dialysis patients. INTERVENTION: Using a structured questionnaire, we asked the subjects whether they would want dialysis continued or stopped if they developed advanced Alzheimer's disease. We then asked how much leeway their physician and surrogate should have to override that advance directive if overriding were in their best interests. Subjects granting leeway were also asked what factors should be considered in making decisions for them. RESULTS: Subjects varied greatly in how much leeway they would give surrogates to override their advance directives: "no leeway" (39%), "a little leeway" (19%), "a lot of leeway" (11%), and "complete leeway" (31%). Subjects also varied in how much they wanted various factors considered in making decisions, such as pain or suffering, quality of life, possibility of a new treatment, indignity caused by continued treatment, financial impact of treatment on family members, and religious beliefs. CONCLUSIONS: Strictly following all advance directives may not truly reflect patients' preferences. To improve advance directives, we recommend that physicians explicitly ask patients how strictly they want their advance directives followed and what factors they want considered in making decisions.
Clonidine hydrochloride, administered intravenously (2 micrograms/kg) during the second non-rapid eye movement period, was significantly less suppressant of rapid eye movement sleep in 10 depressed patients with primary major affective illness, according to Research Diagnostic Criteria, than in three groups of matched subjects (10 normal controls, 10 patients with minor depression, and 10 patients with generalized anxiety). These results suggest that depressed patients with major primary affective illness have down-regulated alpha 2-adrenergic receptors. These findings are consistent with the cholinergic-aminergic balance hypothesis of depression and support the aminergic side of the concept. Finally, the rapid eye movement sleep response to clonidine could provide a new biological marker of affective illness.
We report a non-significantly higher growth hormone (GH) response to intravenous clonidine administration (150 micrograms) in 10 male patients with panic disorder who had never received antidepressant therapy than in 10 matched controls. These results are consistent with data suggesting a normal or increased adrenergic receptor sensitivity in panic disorder patients.