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Biomedical subjects

R E Litman

Publications and source records attributed to R E Litman.

12 recordsLinked to original sources

Clinical and biologic response to clozapine in patients with schizophrenia. Crossover comparison with fluphenazine.

Twenty-one patients with schizophrenia who met criteria for neuroleptic treatment resistance or intolerance participated in a crossover, placebo-controlled, double-blind comparison of long-term typical neuroleptic and clozapine treatment. Clozapine significantly reduced total as well as positive and negative symptoms in comparison with both fluphenazine and placebo. Of the 21 patients, eight (38%) showed clozapine superiority on the basis of prospective response criteria. High levels of extrapyramidal side effects during fluphenazine treatment and later onset of illness were clinical predictors of clozapine superiority. Clozapine and fluphenazine equally reduced plasma homovanillic acid levels in comparison with placebo, although fluphenazine but not clozapine increased plasma prolactin level. A striking biologic difference between clozapine and fluphenazine was clozapine's enhancement of indexes of noradrenergic activity. Superior clozapine response was predicted by low ratios of cerebrospinal fluid homovanillic acid to 5-hydroxyindoleacetic acid, consistent with the notion that balance between dopaminergic and serotoninergic systems is important for clozapine's mechanism of action.

Adult

Outpatient standards of care and the suicidal patient.

This article is a review of the legal and clinical literature on standards of care for nonhospitalized adult suicidal patients. The authors discuss effective assessment, management and treatment procedures that balance the need for high-quality care by a reasonable and prudent practitioner with the requirements of court-determined and statutory standards. Through a review of malpractice claims data and through an examination of the clinical literature we detail the essential guidelines for sound assessment, intervention, and management procedures. The authors specifically discuss common failure situations in outpatient care (e.g., problems in pharmacotherapy, the decision to hospitalize, inappropriate and dual relationships, the assessment of imminence and lethality, and so on). Details regarding practical considerations in developing an outpatient standard of care are provided, as are suggestions that such a standard of care must include an ongoing assessment of the therapeutic alliance.

Female

The acute effects of central- and peripheral-acting dopamine antagonists on plasma HVA in schizophrenic patients.

The short-term effects of fluphenazine on plasma HVA concentrations were compared with the effects of fluphenazine and concurrent administration of debrisoquin, a monoamine oxidase inhibitor which does not cross the blood brain barrier and is used to enhance the CNS contribution to circulating plasma HVA concentrations. Fluphenazine significantly increased plasma HVA with or without debrisoquin 24 hours following the initiation of treatment. Domperidone, a butyrophenone dopamine antagonist which acts only in the peripheral nervous system, failed to alter plasma HVA concentrations. These data suggest that the acute effects of neuroleptic drugs on plasma HVA concentrations are dependent upon interaction with CNS dopaminergic systems and provide additional support for the use of plasma HVA as a reflection of CNS dopamine system activity in clinical studies.

Adult

Correlation of Wisconsin Card Sorting Test performance with eye tracking in schizophrenia.

The authors studied the relationship between performance on the Wisconsin Card Sorting Test and on the Trailmaking-B test and measures of smooth pursuit eye movements in 12 patients with chronic schizophrenia and 12 normal volunteers. They found that performance on the Wisconsin Card Sorting Test was significantly correlated with measures of smooth pursuit eye movements in schizophrenic patients but not in normal subjects. Trailmaking-B scores, however, were unrelated to smooth pursuit eye movements in either group.

Adult

Neurochemical and neural mechanisms of positive and negative symptoms in schizophrenia.

It is difficult to come away from review of pharmacologic and metabolite studies without concluding that dopaminergic mechanisms play a significant role in mediating both negative and positive symptoms. Nevertheless, the characteristics of dopaminergic involvement are unclear. Whereas compelling evidence continues to link the mechanism of action of neuroleptic drugs, including therapeutic effects on negative and positive symptoms, to blockade of D2 receptors, neuroleptic-induced alterations in dopaminergic function are time-dependent and may include reductions in variability as well as in net dopamine activity. Moreover, pharmacologic enhancement of dopaminergic function may at least transiently improve symptomatology (negative greater than positive) and levels of CSF HVA appear to be reduced or are negatively correlated with symptoms in some schizophrenic patients. Thus, there is support for both increased and decreased dopamine function in schizophrenia. Functional brain imaging has, after only a few years of application, made significant contributions to our understanding of the pathophysiology of schizophrenia. Studies of cerebral metabolism and regional CBF have shown remarkable consistency in their identification of abnormal function of the frontal cortex in schizophrenia. It should be pointed out, however, that agreement across studies remains largely conceptual with significant discrepancies still existing with regard to the precise localization of dysfunction and its relationship to cognitive activation. Although less well documented than 'hypofrontality' itself, negative symptomatology appears to bear some relationship to this defect. The idea that positive symptoms might be associated with increased subcortical and/or metabolism is less well supported. The recent advances in our understanding of structure and function of CNS dopaminergic systems may help to integrate these two bodies of data into more dynamic models of dopaminergic defects in schizophrenia. For example, the concept that diminished mesocortical coupled with increased subcortical dopaminergic activity might be a 'substrate' for psychosis is compatible with neurochemical evidence suggesting both diminished and enhanced dopaminergic processes as well as with metabolic hypofrontality. Better understanding of the regulatory mechanisms involved in establishing functional balance between cortical and subcortical systems might, therefore, identify new possibilities for biological dysfunction in schizophrenia. The recent study by Weinberger et al. which correlates CSF HVA levels with neuropsychologically induced frontal CBF is an example of how neurochemistry can enhance brain imaging data.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain

Smooth pursuit eye movements in schizophrenia: effects of neuroleptic treatment and caffeine.

Abnormal smooth pursuit eye movement (SPEM) has been proposed as a trait marker in schizophrenia. We utilized high resolution infra-red oculography to measure SPEM in 11 neuroleptic-treated schizophrenic patients, 10 drug-free schizophrenic patients, and 11 normals. The most characteristic abnormality was a significant increase in saccadic intrusions during SPEM in schizophrenic patients (p less than .001). SPEM gain was reduced in schizophrenic patients (p less than .005). No significant effects of neuroleptic treatment on SPEM were found, including analysis of seven patients in whom paired data was available. We also measured SPEM prior to and after caffeine ingestion (10 mg/kg) in 10 normals. We found reduced saccadic interruptions as a result of caffeine ingestion compared with placebo (p less than .05). As caffeine has been shown to selectively increase dopaminergic neurotransmission in mesocortical neurons, further study utilizing dopamine agonists during SPEM in schizophrenic patients is warranted.

Adult

Long-term treatment of chronically suicidal patients.

Chronically suicidal persons with chronic psychiatric disorders (dysthymia, recurrent depression, alcoholism/addiction, schizophrenia, personality disorders) challenge the experience and resourcefulness of psychiatrists. The author reviews his 30 years of experience with these patients and makes six recommendations for long-term treatment: (1) a team approach using consultants and ancillary therapists, (2) flexible therapeutic plans combining medication with psychotherapy, (3) care in monitoring transference and countertransference, (4) brief hospitalization at turning points in the patient's life or in the treatment, (5) decisions based on risk-benefit evaluation, and (6) appropriate record keeping. He also summarizes effective treatment approaches with patients who have chronic psychiatric disorders.

Chronic Disease

500 psychological autopsies.

Five hundred psychological autopsies on equivocal (suicide versus accident) deaths were reviewed to ascertain which factors are significant in making the determination between suicidal and accidental deaths. Factors varied in relative importance according to the method used to cause death. Significant factors included life-style, recent stress, suicidal communications, previous self-destructive behaviors, history of depression, and obvious factors from the physical evidence such as large amounts of drugs in the blood. Although the court-provided decision guideline is "a preponderance of the evidence", in practice, the assembled evidence is often used to construct a "most credible" scenario to explain the death.

Accidents