Biomedical subjects
Publications and source records attributed to A Gerken.
It is important to choose appropriate topics for audit in order to produce satisfactory results and maintain interest and enthusiasm. A trail of incomplete audit cycles is unhelpful and demoralizing. The audit should be carefully designed and a vital stage is choosing appropriate standards upon which to measure current performance. An agreed policy provides a practical standard against which to audit the use of antibiotics.
The effects of the optically active enantiomers of oxaprotiline (OXP), R(-) OXP and S(+) OXP, on depressive symptomatology and the sleep EEG were investigated in two separate exploratory studies. In addition, the neuroendocrine profile of both compounds was characterized in normal controls. In the patients treated with a daily oral dose of 150 mg S(+) OXP we found a Hamilton depression score that decreased from 29.1 +/- 1.8 (SEM) on day 0 to 14.7 +/- 3.2 on day 28 (P < 0.01). Six patients were judged to be full responders (HAMD score 0-7 points), three were improved (HAMD score 8-15) and four were nonresponders (HAMD score > 16). The therapeutic effect achieved with 150 mg R(-) OXP daily was less pronounced: the HAMD score decreased from 27.8 +/- 2.5 on day 0 to 19.4 +/- 3.2 on day 28 (P < 0.05). There were two full responders, one improved patient and seven nonresponders. The sleep EEG scoring revealed a marked suppression of REM sleep among patients treated with S(+) OXP but not with R(-) OXP. In the normal controls, a single oral dose of 75 mg S(+) OXP prompted an increase in the secretion of cortisol and growth hormone, whereas 75 mg R(-) OXP did not. Neither enantiomer influenced the secretion of testosterone or prolactin.
In order to verify the hypothesis of a strict relationship between clinical improvement and extrapyramidal side-effects, especially micrographia, twenty-two acutely ill schizophrenics were treated with perphenazine in a controlled prospective 28-day trial. During the study period, psychopathometric data, prolactin plasma levels, and handwriting samples were collected. According to the remission criteria fixed before the study began (both BPRS less than or equal to 25 and GAS greater than or equal to 80 points), 45.5% (10/22) of the total patient sample were classified as treatment responders. Handwriting tests were quantified in 21 patients. "Positive" handwriting results, i.e., a reduction of at least 13% in the overall area of 50% or more of the handwriting samples collected during the trial, were demonstrable in three of nine responders (33%) and nine of twelve nonresponders (75%). These results show that there is no positive correlation between clinical response and reduction in handwriting area. Consequently, the handwriting test is unable to predict clinical response. It is only one of a number of parameters with which to monitor the neurological side-effects of neuroleptic treatment. Outcome parameters show that psychopathological remission can be achieved with low neuroleptic dosages and few or virtually no extrapyramidal side-effects.
A community outbreak of 36 cases of Cryptosporidium infection which occurred during Spring 1986 in Great Yarmouth and Waveney is described. A period prevalence study suggested that there was a more widespread outbreak of diarrhoeal illness in the locality although only 3/68 stool samples obtained at a median time interval of 38 days from the onset of symptoms contained Cryptosporidium oocysts. The distribution of cases of cryptosporidiosis in time and place suggested person to person spread rather than a common vehicle. A retrospective matched case-control study provided no evidence of water borne spread.
A single dose of 80 mg fluoxetine induced a slight increase in cortisol secretion when compared to placebo in an acute endocrine challenge test including assessment of prolactin, growth hormone, luteinizing hormone, follicle stimulating hormone, testosterone. This pretreatment with 80 mg fluoxetine did not change the ACTH release after blockade of the feed-back regulation of peripheral corticosteroids on ACTH secretion by metyrapone. Sleep-EEG revealed reduction of rapid-eye-movement sleep. Nocturnal penile tumescence activity was unaltered.
According to severity of depressive symptomatology 14 inpatients with major depressive disorder (RDC) were assigned to 2 groups of 7 patients each with 6 of them receiving fluoxetine 60-80 mg/day and 1 receiving placebo in each group in a double-blind manner. After the treatment period of 35 days clinical improvement as assessed by standardized rating scales was more pronounced in the moderately depressed patients. There were no substantial side-effects in the 2 groups. These findings corroborate previous results from outpatient studies in more heterogeneous patient samples demonstrating safety and antidepressive efficacy of fluoxetine.
In an open clinical trial the authors treated 18 hospitalized patients suffering from endogenous depression with brofaromine (CGP 11305A), a competitive, selective, and short-acting inhibitor of type A monoamine oxidase (MAO). Four patients were defined as good responders, as they had a final HAMD score of between 0 and 7 points. Four patients were judged as improved, with final HAMD scores of between 8 and 15 points, while the remaining eight patients failed to respond (final HAMD score greater than or equal to 16 points). The major observations were a beneficial influence on drive in most patients, while paranoid symptoms worsened markedly, rendering the substance contraindicated in psychotic depression. Brofaromine appears to be safe and well tolerated and largely free of side effects. As objectified by the tyramine pressor test, dietary restrictions during brofaromine treatment require less stringency than is the case with conventional MAO inhibitors. The specificity of brofaromine to inhibit deamination is limited to MAO-A, since no reduction in platelet MAO activity was measurable. Sleep EEG recordings in a subset of patients reveals that the amount of rapid eye movement (REM) sleep is significantly reduced during brofaromine treatment.
The authors measured pituitary adrenocortical responses to human corticotropin-releasing hormone (CRH) in 10 patients with a major depressive episode and 10 matched control subjects. Depressed patients had a significantly lower aldosterone and ACTH release, but cortisol and corticosterone responses were not different between groups.
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Twenty-two subjects (11 patients with major endogenous depression and 11 controls) received an intravenous test dose of 100 micrograms human corticotropin-releasing hormone (h-CRH). Corticotropin (ACTH), but not cortisol, responses were blunted in depressives. Basal cortisol secretion was higher in depressives than in controls and was negatively correlated to the corticotropin response following h-CRH. This finding indicates the integrity of the glucocorticoid-dependent negative feedback regulation in depression and supports the view that hypercortisolism in depression is primarily due to a suprapituitary disturbance. Comparison of ACTH responses after h-CRH with thyrotropin (TSH) output following thyrotropin-releasing hormone (TRH) revealed a positive correlation (r = 0.65, p less than 0.001). The concordance between ACTH and TSH responses after specific challenges suggests that regulation of both systems is at least in part under a common control.
A dexamethasone suppression test (DST) was performed in 45 patients during depressive illness and after recovery. Thirty-one samples from patients in whom plasma cortisol was resistant to the suppressive action of dexamethasone contained significantly lower mean (+/- SD) concentrations of the test drug (0.63 +/- 0.39 ng/ml vs 1.10 +/- 0.53 ng/ml) during illness than after recovery and normalization of the DST. In a control group of 14 patients who exhibited adequate DST suppression during the depressive state and after recovery, the dexamethasone concentrations were unchanged (1.54 +/- 0.91 ng/ml vs. 1.30 +/- 0.92 ng/ml). To investigate further the influence of bioavailability or pharmacokinetics of the test drug on DST results, we conducted a catheter study during sleep in 11 endogenously depressed patients who received an oral 1.5 mg dose of dexamethasone at 11 p.m. The half-life of dexamethasone was markedly lower in five DST nonsuppressors (t1/2 = 160 +/- 33 minutes) than in six DST suppressors (t1/2 = 422 +/- 172 minutes). These preliminary results indicate that metabolism of dexamethasone should be controlled in studies evaluating the clinical utility of the DST.
The current study was designed to investigate whether glucocorticoid output after syn-ACTH stimulation is different in depression associated with dexamethasone suppression test (DST) nonsuppression from the euthymic state and DST suppression. We gave 28 depressives a DST and an adrenocortical challenge with synthetic ACTH. Fourteen patients were nonsuppressors on the DST. After successful drug treatment, the subjects were reinvestigated by both tests; all DSTs revealed plasma cortisol concentrations below the criterion value of 50 ng/ml. Cortisol and corticosterone responses after syn-ACTH tended to be higher during depression. After clinical remission, higher cortisol and corticosterone responses occurred in those patients who were DST nonsuppressors during depression. This finding suggests that patients who suffer from a depression which is linked to an abnormal pituitary--adrenocortical regulation develop an enhanced sensitivity of the adrenal cortex to ACTH.
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The results of factor analysis of HAMD are not unitary. Studying the stability in course and the independence of selection criteria for the population we rated two groups (n = 107, n = 98) of inpatients with HAMD; these groups differ in nosological selection criteria. We furthermore rated one group at different timepoints (before treatment and 3 weeks after). The one-factor-solution is the only stable one and the only one which is independent from selection criteria. In all groups the one-factor-solutions show a high similarity with other published solutions of the German version of HAMD. But there is no way to extract a general factor. Thus the ability of HAMD in judging the severity of depression is doubtful. Ways are discussed to circumvent this problem.
Synthetic ovine corticotropin releasing factor (o-CRF) was administered as an intravenous bolus (100 micrograms) to eight patients suffering from a major depressive disorder, endogenous subtype. All patients showed inadequately suppressed cortisol levels after 1 mg dexamethasone. After clinical remission and normalized dexamethasone responses, these patients were reinvestigated with o-CRF stimulation. The mean adrenocorticotropic hormone (ACTH) release from the pituitary corticotroph cells was indiscriminate at both test sessions. Cortisol and corticosterone output after o-CRF tended to be higher during depression than after recovery. The o-CRF-induced increments observed with corticosterone were more marked in comparison with cortisol. Within the limitations of the current protocol, our preliminary data lend support to the view that an increased pituitary ACTH reserve or adrenocortical steroid reserve is not likely to be responsible for the defective pituitary-adrenal regulation in some dexamethasone-resistant depressives.
Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3-4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests that psychopathological factors other than weight change participate in the development of dexamethasone resistance in depression; (3) the low dose (1 mg) version of the test requires careful control of minor medical disturbances, which can make the test result ambiguous. The data suggest that after resolution of some methodological issues the DST may serve as a valuable laboratory test to monitor clinical progress during drug treatment.
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