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Biomedical subjects

J F Lipinski

Publications and source records attributed to J F Lipinski.

52 records · Page 3Linked to original sources

Neuroleptic blood levels and therapeutic effect.

Studies attempting to delineate a therapeutic range of blood levels for neuroleptics have yielded conflicting results. The reasons for this are briefly reviewed and a study is described in which a correlation is sought between blood levels of thioridazine and clinical efficacy. The study employs the radioreceptor assay for neuroleptics to detect both parent drug and active metabolites in blood. The results of the study indicate that while dose is a poor predictor of blood levels of medication, blood levels of neuroleptic activity in patients on thioridazine may be very highly correlated with antipsychotic effect.

Adolescent↗

Clinical use of the radioreceptor assay for neuroleptics.

The potential clinical utility of the radioreceptor assay for neuroleptics (NRRA) was examined. The NRRA was able to detect neuroleptic activity in blood specimens from patients receiving a variety of neuroleptic medications. For each medication, mean plasma neuroleptic activity was lower in patients showing a poor response to treatment than in those showing a good response. Because the range of plasma neuroleptic activities found was quite different from drug to drug, it appears that results obtained by the NRRA must be standarized for each drug.

Antipsychotic Agents↗

"Schizoaffective disorder": an invalid diagnosis? A comparison of schizoaffective disorder, schizophrenia, and affective disorder.

The authors compared patients meeting widely accepted criteria for the diagnosis of schizoaffective disorder, manic type, with patients meeting rigorous criteria for manic disorder and schizophrenia, using three methods of validation: family history, short-term treatment response, and long-term outcome. No significant differences were found between patients with manic disorder and schizoaffective disorder. However, consistent and often highly significant differences separated patients with schizophrenia from those with manic disorder and schizoaffective disorder. The findings suggest that schizoaffective disorder, as currently defined, is not a valid and independent entity. The authors suggest that psychotic disorders not diagnosable as manic-depressive illness or schizophrenia and without apparent organic basis would best be called "undiagnosed" or "atypical" psychosis. Further, while proposals for new diagnoses or for subtyping of schizophrenia or manic-depressive illness should be encouraged, these should undergo rigorous screening for validity before being accepted into clinical use.

Antipsychotic Agents↗

Methylation hypothesis.

L-Methionine had no behavioral effects in normal humans and failed to increase concentrations of S-adenosylmethionine (methyl donor) in human or rat blood, while increasing rat liver levels more than fivefold. Methionine or S-adenosylmethionine in very high doses had almost no effect on methylation of tritiated levodopa in rodent tissues; various "methyl acceptor" molecules, including nicotinamide, guanidineacetic acid, and estradiol similarly had little effect. In rabbit lung, methionine and S-adenosylmethionine not only failed to increase production of dimethyltryptamine, but actually decreased it, possibly due to end-product inhibition by S-adenosylhomocysteine, which also strongly inhibited methylation of dopa in rat. These results fail to support several predictions of the "methylation hypothesis" concerning the pathophysiology and potential treatment of idiopathic psychotic disorders and leave the consistent clinical worsening effects of methionine in schizophrenia unexplained.

Adult↗

Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research.

Present clinical and research methods of differential diagnosis of schizophrenia and affective psychoses rely very heavily on presenting symptoms and signs, especially in acute psychosis. We have reviewed studies bearing on this issue, including studies of the phenomenology of psychotic illness, outcome, family history, response to treatment with lithium carbonate, and cross-national and historical diagnostic comparisons. We conclude that most so-called schizophrenic symptoms, taken alone and in cross section, have remarkably little, if any, demonstrated validity in determining diagnosis, prognosis, or treatment response in psychosis. In the United States, particularly, overreliance on such symptoms alone results in overdiagnosis of schizophrenia and underdiagnosis of affective illnesses, particularly mania. This compromises both clinical treatment and research.

Bipolar Disorder↗

Activities of types A and B MAO and catechol-o-methyltransferase in blood cells and skin fibroblasts of normal and chronic schizophrenic subjects.

We assayed activities of monoamine oxidase (MAO) type B in blood platelets and type A (and B) in fibroblasts cultured from punch biopsy specimens of skin, as well as of catechol-O-methyltransferase (COMT) in erythrocytes and fibroblasts. Fibroblasts contained moderate amounts of both forms of MAO (types A and B) found in human brain and large amounts of COMT activity. Activities of both enzymes correlated poorly between fibroblasts and blood cells. Comparing carefully diagnosed chronic schizophrenics with age-matched normal young men, we found no difference in these biochemical variables, nor could we distinguish patients with paranoid symptoms. In contrast, we confirmed markedly lower MAO activities in platelet samples from chronic patients provided by colleagues at the National Institute of Mental Health. Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation, with special attention to diagnosis, matching of subjects, and effects of possible spurious environmental variables.

Adolescent↗

Lithium salts: 1970-1975.

Lithium ion provides a useful and specific form of chemotherapy for manic and hypomanic episodes, although its antimanic effect may be delayed for as long as a week or more, requiring the use of an antipsychotic agent in the initial period to control the behavior of very disturbed patients. The mechanisms of action of lithium remain obscure, but probably involve effects on neuronal and hormone-target cell membranes. Lithium has interesting antithyroid and anti-antidiuretic hormone effects that are potentially useful medically. The main limitation of the use of lithium is its narrow therapeutic index and requirement of close medical supervision. The most promising aspects of the use of lithium are its encouragement of better psychiatric diagnosis and its "prophylactic" effectiveness in at least reducing the frequency and severity of manic and depressive attacks in manin-depressive illness.

Affective Symptoms↗

Do "flashbacks" represent obsessional imagery?

We describe three patients, all meeting DSM-III-R criteria for obsessive-compulsive disorder (OCD), whose vivid, intrusive obsessional images had been diagnosed by previous treatment personnel as "flashbacks" of repressed childhood trauma. All three patients had been urged to engage in psychotherapy to "uncover" their putative repressed memories. However, serotonin reuptake antagonists produced prompt remission of the images and the associated obsessional and compulsive symptoms in all cases. It may be that in some patients, so-called flashbacks instead represent the very common obsessional images of OCD.

Adult↗