Biomedical subjects
Publications and source records attributed to M Philipp.
Arylboronic acids were found to be strong competitive inhibitors of subtilisin and chymotrypsin. The binding constants are strongly pH dependent and give a Hammett-type plot with a slope of -0.885. The pH dependence, the Hammett plot, and nmr model-system studies indicate that inhibition is due to electron-pair donation by the active site histidine to the bound inhibitor.
Primary enduring negative symptoms (PENS) were studied in 26 patients with DSM-III-R schizophrenia and in 94 patients with unipolar major depressive episodes 5 years after the index episode. PENS were assessed with the Schedule for Deficit Syndrome (SDS). Negative symptoms were also assessed with the Scale for Assessment of Negative Symptoms (SANS) and subclassified into primary and secondary according to the SDS. The frequency of PENS did not differ significantly between schizophrenics and non-schizophrenic patients. Enduring negative symptoms (regardless of whether primary or not) were more frequently observed in schizophrenia (65% according to the SDS, and 88% according to the SANS) than in patients who had major depressive episodes (29% according to the SDS and 32% according to the SANS). By applying the SDS criteria for PENS, their frequency decreased in a manner which would probably affect the availability of patients samples for testing antinegative drugs. The results suggest that neither the negative symptomatology nor the primary enduring subtype ("deficit") is specific for schizophrenia. This finding might imply potential advantages of non-nosological, functional approaches for research into PENS.
111 consecutively admitted in-patients with a depressive syndrome received a dexamethasone suppression test (DST) after all known factors which might confound the test results had been carefully excluded. Plasma concentrations of cortisol, corticosterone and dexamethasone were compared with several diagnostic evaluations (RDC, DSM-III, ICD-9) in a controlled study. The positive predictive value of nonsuppressed corticosteroid levels was only moderate for each diagnostic category. Diagnostic specificities were 84.6% for major depression, endogenous subtype (RDC), 71.2% for melancholia (DSM-III) and 86.8% for endogenous depression (IDC-9) when using a post-DST cortisol value above 50 ng/ml (5 micrograms/dl) as the referent value to define DST nonsuppression. Combined determination of cortisol and corticosterone as an index of dexamethasone-induced suppression raised the sensitivity rate considerably at the cost of the predictive value for major diagnostic categories. Dexamethasone plasma levels were reciprocally correlated with cortisol levels and neglect of samples with low plasma dexamethasone contents improved the diagnostic performance for endogenous depression according to RDC and ICD-9, but not for DSM-III melancholia. Although it would be speculative to suppose that the observed low dexamethasone levels are involved in DST nonsuppression, the present findings emphasize that multisteroid analysis which includes dexamethasone is important in future studies designed to explore the clinical utility of the DST.
In a sample of 173 depressed in-patients, the sources of disagreement between the clinical ICD-9 diagnosis of endogenous depression (ED) and the corresponding operational definitions of RDC and DSM-III were analyzed. The RDC definition of ED gave a significantly higher degree of concordance with the ICD-9 diagnosis of ED, than that of DSM-III. This difference was mainly due to the algorithm used in DSM-III. When empirically derived algorithms were applied to the diagnostic criteria of DSM-III and RDC, both criteria lists reached a higher degree of concordance with the ICD-9 diagnosis of ED. When the criteria lists of RDC and DSM-III were supplemented with cross-sectional criteria (psychotic features, incapacitation) and by course-related criteria (recurrence, bipolarity, primary episode, adequate personality, no precipitating stress), this did not result in significant enhancement of the degree of concordance.
The Hamilton Anxiety Scale (HAM-A) was tested for reliability and validity in two different samples, one sample (n = 97) defined by anxiety disorders, the other sample (n = 101) defined by depressive disorders. The reliability and the concurrent validity of the HAM-A and its subscales proved to be sufficient. Internal validity tested by latent structure analysis was insufficient. The major problems with the HAM-A are that (1) anxiolytic and antidepressant effects cannot be clearly distinguished; (2) the subscale of somatic anxiety is strongly related to somatic side effects. The applicability of the HAM-A in anxiolytic treatment studies is therefore limited. More specific anxiety scales are needed.
Experimental study is dedicated to mechanisms of interaction of pentagastrin and monoamines (noradrenaline and dopamine) at the level of single neurones of the rabbits lateral hypothalamus under alimentary motivation and under saturation. It is shown that pentagastrin can modulate the effects of noradrenaline and dopamine on neuronal impulse activity in hungry and fed up animals, and the character of its action depends on the rabbits initial state. It is suggested that pentagastrin is a factor initiating alimentary motivational excitation, while noradrenaline maintains the latter at the definite level up to obtaining useful result by the animal, when dopaminergic mechanisms participating in the process of reinforcement join the noradrenergic ones.
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