Search PubMed⌕ Search

Biomedical subjects

S E Mason

Publications and source records attributed to S E Mason.

At least 19 recordsLinked to original sources

Safe sex and first-episode schizophrenia.

The need for educating patients about the dangers of unprotected sexual activity is well documented in the literature. Using clinical examples, the authors describe safe-sex strategies for patients experiencing their first episode of schizophrenia. Interventions are based on a 2-year experience of working in a hospital-based treatment and research project with 68 patients. Strategies that begin in the healing phase of schizophrenia take place in both individual and group sessions. First-episode patients are encouraged to speak explicitly about their sex-related behaviors, and HIV testing is suggested when needed. The goal of this approach is to emphasize safe-sex/HIV prevention strategies within a framework of good clinical practice.

Acquired Immunodeficiency Syndrome↗

Use of the ornithine decarboxylase promoter to achieve N-MYC-mediated overexpression of a rabbit carboxylesterase to sensitize neuroblastoma cells to CPT-11.

Overexpression of specific transcription factors by tumor cells can be exploited to regulate expression of proteins that induce apoptosis or activate prodrugs, thereby producing tumor-selective toxicity. A majority of advanced-stage neuroblastomas overexpress the transcription factor N-MYC, and this overexpression is associated with poor prognosis. This study describes regulation of expression by N-MYC, via the ornithine decarboxylase (ODC) promoter, of a rabbit liver carboxylesterase (CE) that activates the prodrug CPT-11. Chloramphenicol acetyltransferase reporter assays and CE activity assays in transiently transfected neuroblastoma cell lines (SJNB-1, SJNB-4, NB-1691) and rhabdomyosarcoma cell lines (JR1neo20, JR1Nmyc6, JR1Nmyc9) support this approach as a potential method for sensitizing tumor cells to CPT-11. Clonogenic assays with IMR32 human neuroblastoma cells which express N-MYC and that had been stably transfected with a plasmid containing an ODC promoter/CE cassette corroborated results of enzyme activity assays. Specifically, IMR32.ODC.CE cells expressed approximately eightfold more CE activity than IMR32.CMV.neo cells; and 5 microM CPT-11 reduced the clonogenic potential of IMR32.ODC.CE cells to zero, while 50 microM CPT-11 was required to produce the same effect with IMR32.CMV.neo cells. Current experiments focus on adenoviral delivery of an ODC promoter/CE cDNA cassette for potential virus-directed enzyme prodrug therapy applications.

Animals↗

Phase-specific psychosocial interventions for first-episode schizophrenia.

Phase-specific psychosocial interventions for first-episode schizophrenia are outlined and described using examples from clinical practice with 68 patients. These interventions are based on the unique aspects of the first episode and patients' clinical states. Although schizophrenia may run an uneven and often unpredictable course, most patients experience three distinct phases: (1) the acute phase, (2) the healing phase, and (3) the maintenance phase. The timeliness of phase-specific interventions is crucial in helping both patients and families understand the illness, evaluate options, accept treatment, and adjust to changes in functioning and expectations.

Acute Disease↗

Clinical trials and tribulations: implementation processes in schizophrenia research outcome.

This article focuses on an area in clinical drug trials for new antipsychotic medications for the treatment of schizophrenia which has not received sufficient attention in the literature: the day-to-day implementation tasks performed by research staff which have potential effects on study results. Implementation tasks are viewed as dynamic processes involving interactions among research and nonresearch staff, patients, families, and pharmaceutical company staff. Research-related demands and possible sources of stress for all participants in the process, such as recruiting and maintaining patients in studies, are discussed. Suggestions are offered for increasing the ease of participation. Further investigation is called for in several areas including variability in the effectiveness of research teams and in the rarely discussed interactions between site staff and pharmaceutical company personnel, as they may affect research outcomes. It is posited that increased knowledge about implementation processes in schizophrenia drug development is needed to more fully understand study results and to enhance patients' and their families' willingness to participate.

Antipsychotic Agents↗

Instability of individual differences in the association between confidence judgments and memory performance.

There are large individual differences in the degree of association between the accuracy of memories and subjective confidence in those memories. Are these differences stable within the same test, and between alternate forms of a test? In Experiment 1, college students were tested on 3 recognition memory tasks, then retested 2 weeks later on alternate forms of the same tasks. The relationship between confidence judgments and recognition performance displayed low split-half stability and low alternate-forms stability. A second experiment with elderly adults replicated these findings. In a third experiment, college students recalled answers to general knowledge questions and rated confidence in the correctness of each answer. Individual differences in the association between confidence and recall performance were not stable across the odd- and even-numbered items on the test. These data indicate the need for the development of procedures that will produce stable estimates of individuals' metacognitive accuracy.

Adult↗

Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial.

BACKGROUND: Although recent studies have documented the benefit of adjunctive antidepressant medication for the short-term treatment of certain patients with operationally defined syndromes of postpsychotic depression, the value of maintenance adjunctive antidepressant treatment in this circumstance has not been properly established. METHODS: This study examined 24 schizophrenic or schizoaffective patients with postpsychotic depression or negative symptoms. These patients had all been benefited over the short term by the addition of adjunctive imipramine hydrochloride to their ongoing fluphenazine decanoate/benztropine mesylate regimens, and this adjunctive treatment had been successfully continued for 6 months. In a randomized double-blind protocol, treatment with adjunctive imipramine hydrochloride (mean, 233 +/- 72 mg/d) was then either maintained or tapered to placebo for an ensuing 1-year trial, while treatment with fluphenazine and benztropine continued. RESULTS: Significantly more patients who received placebo substitution relapsed into depression (P < .001). Patients who received placebo substitution were also more likely to experience relapses into psychosis (P < .02). CONCLUSIONS: These results support the clinical value of maintenance adjunctive imipramine therapy among initially responsive patients with postpsychotic depressions.

Adult↗

Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats.

The pattern of expression of fos and jun family immediate early genes following the induction of long-term potentiation (LTP) was investigated in the dentate gyrus of awake rats. Rapid, transient increases in the levels of c-jun and jun-B mRNA and protein, and in the levels of Fos-related proteins (FRAs), occurred in the dentate gyrus after LTP-inducing tetanization of the perforant path. A delayed, and more prolonged induction occurred for jun-D mRNA and protein. The induction of c-Jun, Jun-B, Jun-D and Fos-related proteins was prevented by administration of an N-methyl-D-aspartate receptor antagonist, which also blocked LTP induction, and by pentobarbital, which reduced but did not block LTP. These findings show that differential expression of fos and jun gene family members occurs in a distinct pattern following LTP in awake rats. The responsive genes may participate in the biochemical cascade leading to the long-term stabilization of synaptic modifications.

Animals↗

Histories of substance abuse, panic and suicidal ideation in schizophrenic patients with histories of post-psychotic depressions.

1. Forty patients who had had syndromally-defined episodes of post-psychotic depression at least 6 months previously were interviewed in detail for life-time histories of substance abuse, panic attacks, and suicidal ideation. 2. No relationship was found between life-time history of suicidal ideation and substance abuse. 3. Statistically significant associations were found between lifetime history of suicidal ideation and both a life-time history of panic attacks and the panic disorder syndrome.

Adult↗

Correlations between immediate early gene induction and the persistence of long-term potentiation.

The duration of long-term potentiation in the dentate gyrus of awake rats was examined following systematic manipulation of the number of stimulus trains delivered. This was correlated with the induction of immediate early genes in separate groups of animals given identical stimulus regimes. Following 10 trains of stimulation, long-term potentiation decayed with a time constant of up to several days (long-term potentiation 2), and this correlated with the appearance of an increase in the messenger RNA and protein levels of zif/268. Increasing the number of stimulus trains resulted in a greater probability of eliciting long-term potentiation with a time constant of several weeks (long-term potentiation 3), as well as increasing the induction of zif/268, c-Jun, Jun-B, Jun-D and Fos-related proteins. When 10 trains were delivered repeatedly on up to five consecutive days, only the zif/268 protein levels showed associated changes. These data provide support for the hypothesis that long-term potentiation 3 involves mechanisms additional to those for long-term potentiation 2. One possible mechanism is altered gene expression, initiated by immediate early gene transcription factors such as zif/268 and possibly homo- or heterodimers of Fos and Jun family members, that then contributes to the stabilization or maintenance of long-term potentiation 3.

Animals↗

Adjunctive imipramine in substance-abusing dysphoric schizophrenic patients.

Previous controlled studies have presented evidence that adjunctive tricyclic antidepressant medication may be useful in the treatment of schizophrenic and schizoaffective patients with phenotypic post-psychotic depressions and that tricyclic antidepressants may be useful in the treatment of certain substance-abusing nonschizophrenic patients. The potential value of adjunctive antidepressant medication among substance-abusing dysphoric schizophrenic and schizoaffective patients, however, has not previously been addressed. The present report details the results of carefully controlled adjunctive antidepressant trials among 11 such substance-abusing schizophrenic or schizoaffective patients. The results of this acute treatment trial appeared to be favorable for at least some individuals and can be interpreted in the context of models that heretofore have been advanced for the understanding of this clinical situation.

Adult↗

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols. zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence, zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.

Animals↗

Adjunctive imipramine for dysphoric schizophrenic patients with past histories of cannabis abuse.

1. Twenty-one schizophrenic or schizoaffective patients with histories of cannabis abuse and operationally-defined syndromes of post-psychotic depression completed a double-blind trial of adjunctive imipramine added to their on-going medication regimen of fluphenazine decanoate and benztropine. 2. The imipramine-treated patients had superior global outcome. 3. Subscales suggested that specific improvement occurred in imipramine-treated patients in the domain of depression-like features. 4. Psychotic symptomatology was not found to be exacerbated by the imipramine.

Adolescent↗

The 10-year experience of an academically affiliated occupational and environmental medicine clinic.

Occupational and environmental diseases are underrecognized. Among the barriers to the successful diagnosis, treatment, and prevention of these conditions are inadequate consultative and information resources. We describe the 10-year clinical and training experiences of an academically affiliated referral center that has as its primary goal the identification of work-related and other environmental diseases. The University of Washington Occupational and Environmental Medicine Program has evaluated 6,048 patients in its diagnostic and screening clinics. Among the 2,841 seen in the diagnostic clinics, 1,553 (55%) had a work-related condition. The most prevalent diagnoses included asbestos-related lung disease (n = 603), toxic encephalopathy (n = 160), asthma (n = 119), other specific respiratory conditions (n = 197), carpal tunnel syndrome (n = 86), and dermatitis (n = 82). The clinics serve as a training site for fellows in the specialty training program, primary care internal medicine residents, residents from other medical specialties, and students in industrial hygiene, toxicology, and occupational health nursing. The program serves two additional important functions: providing consultative services to community physicians and training specialists and other physicians in this underserved area of medicine.

Adolescent↗

Continuation treatment with adjunctive imipramine in schizophrenia.

An open continuation treatment trial was undertaken for schizophrenic and schizoaffective patients with postpsychotic depressions who had manifested favorable responses to initial treatment with adjunctive imipramine added to their fluphenazine decanoate and benztropine regimen. Of 27 patients enrolled, none had a psychotic or depressive relapse, and 23 completed the 6-month study. The patients did well; completers' Global Assessment Scale scores improved with statistical significance during the trial. Side effects also appeared to improve during the trial. The results therefore support continuation treatment with adjunctive antidepressant medication for those patients with postpsychotic depressions who initially respond favorably to this regimen.

Adult↗

Antidepressant for substance-abusing schizophrenic patients: a minireview.

1. Substance abuse and post-psychotic depression are both frequently encountered concomitants of schizophrenia. 2. Substance abuse may be associated with depression-like symptomatology in the course of schizophrenia, and patients may attempt to self-medicate these symptoms with substances of abuse. 3. Antidepressant medication has been found to be a useful adjunct to treatment in at least some cases of substance abuse and some cases of post-psychotic depression. 4. Preliminary evidence exists suggesting that adjunctive antidepressant medication, added to a neuroleptic, may be useful for at least some stable dysphoric substance-abusing schizophrenic patients. 5. It is important to attempt to rule out even subtle neuroleptic-induced akinesia in such patients with a vigorous trial of antiparkinsonian medication.

Antidepressive Agents↗

The use of antidepressants for negative symptoms in a subset of schizophrenic patients.

The authors used a randomized, placebo-controlled design to assess the therapeutic efficacy of adjunctive imipramine, added to fluphenazine decanoate and benztropine, among well-stabilized, negative-symptom schizophrenia and schizoaffective disorder patients who additionally met operationalized criteria for postpsychotic depression. The outcome of the imipramine-treated group was superior in both global ratings and a specific negative-symptom scale. Exacerbation of psychotic symptomatology was not found to be problematic. The implications of this study are discussed in terms of a potential strategy for pharmacotherapy among certain negative-symptom patients and in terms of its relevance to a possible pathophysiological basis for the negative-symptom state.

Adult↗

Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats.

The dose- and time-dependent effects of N-methyl-D-aspartate receptor/channel antagonists on radial 8-arm maze performance were examined in rats. Both CPP (1.0-30 mg/kg), a competitive NMDA antagonist, and MK-801 (0.1-1.0 mg/kg), a noncompetitive NMDA antagonist, produced dose-dependent increases in the number of errors made to sample all 8 baited arms. The effective doses of both drugs produced maximal performance impairments 2 hr after IP injection, and no effects after 24 hr. In a second radial arm maze task where only 4 arms were baited, CPP (10 mg/kg) had a somewhat greater effect on the number of working memory errors than on reference memory errors. MK-801 (0.1, 0.33 mg/kg) had no effects on either this task or on a task involving a 1-hr delay between correct choices 4 and 5 on the 8 choice task. CPP (10 mg/kg), however, impaired performance on this latter task. These results indicate that doses of NMDA antagonists, sufficient to block hippocampal long-term potentiation, also disrupt radial arm maze performance.

Animals↗

Induction of Fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanesthetized rats.

Memory formation in the mammalian central nervous system may require long-lasting alterations in gene expression. However, it is not yet known whether the candidate memory mechanism long-term potentiation (LTP) requires alterations in gene expression for its maintenance, nor the extent to which the time course of LTP can be manipulated at the time of induction. In this study we influenced the time course of LTP decay for the perforant path input to the dentate gyrus in awake rats by manipulating conditions at the time of induction, and correlated the outcome with the induction of c-fos protein(s) (Fos), as measured immunohistochemically in the dentate gyrus of separate animals 2 h post-tetanization. Sodium pentobarbital, which blocks the induction of Fos-like immunoreactivity (Fos-IR), also blocked a long-duration form of LTP maintained over weeks. On the other hand, two different patterns of delivery of 50 trains, that produced similar time courses of LTP decay, produced markedly different degrees of Fos-IR induction. In addition, while stimulation consisting of only 10 trains induced a sizable Fos response, it only produced LTP lasting a few days. When the 10-train stimulation was repeated on 3 or 5 consecutive days, there appeared to be no additional Fos-IR induction, yet the LTP decay time constant was considerably prolonged. Thus there is little correlation between the degree of Fos-IR induction and the subsequent durability of LTP.

Animals↗