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Biomedical subjects

N Meisler

Publications and source records attributed to N Meisler.

At least 19 recordsLinked to original sources

Implementing supported employment as an evidence-based practice.

Supported employment for people with severe mental illness is an evidence-based practice, based on converging findings from eight randomized controlled trials and three quasi-experimental studies. The critical ingredients of supported employment have been well described, and a fidelity scale differentiates supported employment programs from other types of vocational services. The effectiveness of supported employment appears to be generalizable across a broad range of client characteristics and community settings. More research is needed on long-term outcomes and on cost-effectiveness. Access to supported employment programs remains a problem, despite their increasing use throughout the United States. The authors discuss barriers to implementation and strategies for overcoming them based on successful experiences in several states.

Community Mental Health Centers↗

Procedural and methodological issues in telepsychiatry research and program development.

OBJECTIVE: The authors reviewed the literature related to telepsychiatry-applications of videoconferencing technology for mental health care-which offers hope for an affordable means of solving long-standing workforce problems, particularly in geographical areas where specialist providers are not readily available. METHODS: To conduct a comprehensive review of the telepsychiatry literature, the authors searched the MEDLINE database (1970 to February 2000), using the keywords telepsychiatry, telemedicine, and videoconferencing. Studies were selected that included the use of videoconferencing technology for the provision of any form of mental health care services. RESULTS AND CONCLUSIONS: Psychiatric interviews conducted by telepsychiatry appear to be generally reliable, and patients and clinicians generally report high levels of satisfaction with telepsychiatry. A significant limitation of the literature is the lack of empirical research on telepsychiatry, especially cost analyses and clinical outcome studies. The authors outline a research agenda addressing the procedural and methodological issues that should shape future research: study design, outcome measurement, consideration of patient characteristics, and program design.

Consumer Behavior↗

Employment outcomes for clients with severe mental illness in a PACT model replication. Program for Assertive Community Treatment.

Outcomes of clients with severe mental illness in a psychosocial and vocational rehabilitation program modeled after the Program for Assertive Community Treatment were tracked through record review to determine if clients' employment gains were sustained while they were in the program. A total of 184 clients participated in the program between December 1984 and February 1994, of whom 34 percent remained for one to four years and 33 percent remained for longer than four years. Sixty-four percent of the clients who stayed in the program a year or longer attained employment. The program maintained an average employment rate of 33 percent of all participating clients. More than half of the clients who held jobs worked part time and were employed more than half of the time that they were in the program.

Adult↗

Absence of pyridoxine-5'-phosphate oxidase (PNPO) activity in neoplastic cells: isolation, characterization, and expression of PNPO cDNA.

Major differences in the metabolism of vitamin B6 in various cancers compared to their normal cellular counterparts have been documented. In particular, pyridoxine- 5'-phosphate oxidase (PNPO), the rate-limiting enzyme in pyridoxal 5'-phosphate (PLP) biosynthesis, is absent in liver and neurally-derived tumors. We show that the expression of PNPO is developmentally regulated not only in liver but also in brain. Specifically, PNPO activity in fetal brain tissue is 7.5-fold lower than that found in adult brain tissue. Furthermore, the isolation and characterization of a PNPO cDNA are described. The isolated cDNA was verified to be the authentic PNPO cDNA on the basis of two criteria. First, the translated product from the PNPO cDNA is immunologically reactive to a polyclonal PNPO antibody. Second, PNPO negative hepatoma cell lines stably transfected with the PNPO cDNA express enzymatically active PNPO protein. The availability of these biological reagents will not only facilitate in depth investigations of the reasons for the absence of PNPO in liver and brain malignancies but also aid in an understanding of the biochemical regulation of B6 metabolism in development.

Amino Acid Sequence↗

Identification of a glucocorticoid response element in the human transforming growth factor beta 1 gene promoter.

TGF-beta 1, which has a stimulatory effect on dermal wound healing, has been implicated as the primary causative agent of fibrosis. Glucocorticoids such as dexamethasone normally inhibit wound healing and are capable of antagonizing the fibrotic effect of TGF-beta 1. Our data indicate the presence of a putative regulatory element responsive to glucocorticoids. Computer sequence analysis of the promoter region of the human TGF-beta 1 gene (Genbank Accession # J04431) revealed a consensus glucocorticoid response element, GRE (5'-AGAACA) located from (-1081) to (-1086) base pairs from the transcription start site. An oligonucleotide containing this site was obtained and labeled for use in gel mobility shift assays. The labeled oligonucleotide was found to bind both fetal rat skin nuclear extracts and purified recombinant glucocorticoid receptor. Unlabeled oligonucleotides containing a GRE from the rat procollagen type I promoter or a commercially supplied GRE competed effectively with the 32P-labeled GRE from the TGF-beta 1 promoter for binding to nuclear extracts. Addition of anti-glucocorticoid receptor revealed a supershifting of the labeled oligonucleotide-nuclear protein complex. These results indicate the presence of a putative GRE in the promoter region of the human TGF-beta 1 gene.

Animals↗

Bridging the gap between inpatient and outpatient providers using organizational elements of assertive community treatment.

Even among comprehensive local public mental health systems, there remain large gaps in continuity of care following discharge from inpatient settings. The authors describe a modification of the assertive community treatment (ACT) program model that links inpatients to ongoing community-based care, and provide preliminary evidence of its effectiveness as a component in a rationally organized comprehensive system of care. Given the recent trend toward managed Medicaid arrangements, there will be increased pressure to reduce clients' length of stay in ACT programs. State mental health authorities are cautioned to resist allowing managed care contractors to radically change the conditions under which ACT programs operate until there is greater evidence of the effectiveness of alternative approaches.

Academic Medical Centers↗

Impact of assertive community treatment on homeless persons with co-occurring severe psychiatric and substance use disorders.

This study evaluated the impact of an integrated (mental health/substance abuse) assertive community treatment program on homeless persons with serious mental and substance use disorders. High rates of retention in treatment, housing stability, and community tenure were attained, and all but the most severe substance users appeared to gain these benefits. While the intervention appears to be an effective means of retaining in services and monitoring such difficult-to-treat and costly populations, it did not yield high rates of abstinence and social benefits in severe users.

Adult↗

Dexamethasone abrogates the fibrogenic effect of transforming growth factor-beta in rat granuloma and granulation tissue fibroblasts.

Administration of TGF-beta, a fibrogenic inflammatory growth factor, promotes fibrosis and scarring. Dexamethasone, an anti-inflammatory steroid, inhibits wound healing and reduces fibrosis. The current studies were initiated to determine whether the co-administration of dexamethasone was able to abrogate the fibrogenic effect of TGF-beta. Polyvinyl alcohol sponges were implanted subcutaneously on the abdominal area of rats and directly injected with vehicle, dexamethasone, TGF-beta, or dexamethasone plus TGF-beta. Dexamethasone was able to block the fibrogenic effect of TGF-beta. Collagen and noncollagen protein synthesis was measured as a function of TGF-beta or dexamethasone concentrations in fibroblasts isolated from granulation tissue. Addition of dexamethasone to cultures treated simultaneously with TGF-beta blocked the fibrogenic response of TGF-beta. To study the molecular regulation of collagen gene expression by TGF-beta or dexamethasone, fibroblasts derived from granulation tissue were stably transfected with the ColCat 3.6 plasmid, which contains the rat pro alpha1(I) collagen promoter linked to the chloramphenicol acetyltransferase (CAT) gene. Dexamethasone decreased CAT activity whereas TGF-beta increased the activity of this reporter gene. The increase in CAT activity observed with TGF-beta treatment was significantly decreased when dexamethasone was added to the cultures, although CAT activity did not return to control level. Since collagen synthesis in fibroblasts treated simultaneously with dexamethasone and TGF-beta1 was found to be the same as that of untreated samples, the data indicate that there is a dexamethasone-mediated posttranscriptional regulation of pro alpha1(I) collagen mRNA. These studies demonstrate that at the in vivo level, the cellular level, and the molecular level, dexamethasone is able to block the fibrogenic effect of TGF-beta.

Animals↗

Glucocorticoids coordinately regulate type I collagen pro alpha 1 promoter activity through both the glucocorticoid and transforming growth factor beta response elements: a novel mechanism of glucocorticoid regulation of eukaryotic genes.

Glucocorticoids have previously have shown to decrease Type I collagen synthesis in vivo and in fibroblast cell culture. Several studies have demonstrated that glucocorticoids decrease Type I procollagen gene expression. These latter studies have included uridine incorporation into pro alpha 1 (I) and pro alpha 2 (I) mRNAs and nuclear run-off experiments. Using the ColCat 3.6 plasmid, which contains part of the 5' flanking region of the pro alpha 1 (I) collagen gene and the reporter gene, chloramphenicol acetyltransferase, the present studies demonstrate by stable transfection of fetal rat skin fibroblasts that dexamethasone down regulates the promoter activity of the pro alpha 1 (I) collagen gene. The glucocorticoid-mediated down-regulation of procollagen gene expression was demonstrated using the ColCat 3.6, 2.4, 1.7, or 0.9 plasmid. In addition, competitive oligonucleotide transfection experiments and site specific mutation of the glucocorticoid response element (GRE) in the whole ColCat 3.6 plasmid did not eliminate the effect. The possibility existed that another cis-element in the 5' flanking region of the pro alpha 1 (I) collagen gene was also required for the collagen glucocorticoid-mediated down-regulation of procollagen gene expression, since TGF-beta has been shown to stimulate in a decrease of transforming growth factor-beta (TGF-beta) secretion into the media. Gel mobility studies demonstrated that glucocorticoid treatment of rat skin fibroblasts decreased glucocorticoid receptor binding to the GRE and TGF-beta activator protein to the TGF-beta element which were brought back to control values by coordinate exogenous TGF-beta treatment. Thus the interaction of these TGF-beta molecules with cellular membrane receptors and subsequent transduction is dramatically decreased resulting in less signals to regulate collagen gene expression. These data indicate that glucocorticoids coordinately regulate procollagen gene expression through both the GRE and TGF-beta elements. Depression of procollagen gene expression by glucocorticoids through the TGF-beta element is mediated by decreased TGF-beta secretion, possibly involving a secondary effect on regulatory protein(s) encoded by noncollagenous protein gene(s). The present studies provide the basis for a novel mechanism of glucocorticoid-mediator regulation of eukaryotic genes containing the TGF-beta element.

Animals↗

Glucocorticoid-induced down regulation of transforming growth factor-beta 1 in adult rat lung fibroblasts.

Transforming growth factor-beta 1 mRNA and transforming growth factor beta activity are decreased with exposure of normal adult rat lung fibroblasts to dexamethasone. Dexamethasone caused a decrease in transforming growth factor-beta 1 mRNA within 2 hours, which was sustained at least over a 24-hour period. The decrease in transforming growth factor-beta 1 mRNA was dose related. Dexamethasone treatment of rat lung fibroblasts also resulted in a decrease of transforming growth factor beta activity as determined by the mink lung cell growth inhibition assay. These data indicate that glucocorticoids may regulate collagen synthesis at least in part through the mediation of transforming growth factor-beta 1 in rat lung fibroblasts.

Animals↗

Research on field-based services: models for reform in the delivery of mental health care to populations with complex clinical problems.

OBJECTIVE: Clinical services for psychiatrically impaired populations have only recently been studied with scientifically valid designs to explore innovations in structure, accessibility, and financing. Health systems reform in the United States has provided the impetus for better defining clinically effective and cost-sensitive models for mental health services. This article reviews assertive community treatment, used for adults with severe mental illnesses, and multisystemic therapy, used for adolescents with serious emotional disturbances, as examples of service system innovations that have been studied with controlled clinical trial designs and have demonstrated efficacy in treating difficult and costly clinical populations. METHOD: The authors reviewed the published controlled clinical trials of assertive community treatment and multisystemic therapy, focusing on the clinical and administrative elements that distinguish them from traditional service systems. RESULTS: A qualitative assessment of these two approaches suggests that they share common elements, with important implications for mental health policy. Specifically, the use of an ecological model of behavior applied to mental health patients is critical to both systems. In addition, therapeutic principles emphasizing pragmatic (outcome-oriented) treatment approaches, home-based interventions, and individualized goals are key elements of their success. Most important, both systems embody a therapeutic philosophy demanding therapist accountability, in which personnel are rewarded for clinical outcomes and therapeutic innovation rather than for following a prescribed plan. CONCLUSIONS: As empirically tested approaches, assertive community treatment and multisystemic therapy provide a scientific foundation for continued reform and serve to illustrate critical elements in designing new community treatment initiatives for behavioral as well as medical conditions.

Adolescent↗

CNS to case manager: broadening the scope.

A clinical nurse specialist's role capitalizes on five role components: manager, clinician, consultant, educator, and researcher. Although the case manager's responsibilities also encompass these areas, priorities differ. A clear definition of both roles is essential when considering a transition from clinical nurse specialist to case manager.

Consultants↗

State mental health agency responsibility for outreach.

Historically, state mental health agencies have narrowly defined their responsibility for providing services. Recently, however, many have begun to be more assertive in managing community-based systems of care.

Community Mental Health Services↗

Clinical significance, evaluation, and management of secondary depression in schizophrenia.

Treatment of the chronic schizophrenic patient is often complicated by depressive symptoms that can be difficult to detect. Because of the association between depressive symptoms and poor outcome features, the presence of these symptoms has substantial treatment implications. Treatment issues for depressive schizophrenic patients include selecting appropriate drug therapy, overcoming high rates of noncompliance, dealing with self-doubt and social withdrawal, and protecting patients from recurrent depressive symptomatology, suicide, or psychotic relapse. Controlled studies suggest that neuroleptic therapy is the drug treatment of choice; addition of an antidepressant does not appear to enhance therapeutic efficacy and may be associated with increased adverse effects. Successful treatment also requires the use of assertive case management, community support, family support, and careful patient education.

Adult↗