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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 109 records · Page 6Linked to original sources
PubMed1992

Clinical efficacy of clozapine in treatment-refractory schizophrenia: an overview.

The treatment of patients with schizophrenia who fail to respond to antipsychotic medications remains a challenge. Despite numerous attempts to establish effective somatic treatment approaches for this population, clozapine appears to be the only well established alternative. Depending upon trial duration and response criteria, between 30% and 60% of previously unresponsive patients appear to derive clinically significant benefit from clozapine. Clozapine also has important advantages in terms of its reduced propensity to produce extrapyramidal side-effects. Agranulocytosis remains an important risk, so strategies to improve the benefit-to-risk ratio should be explored. Issues such as trial duration, dosage, blood levels and predictors of response require additional study.

Agranulocytosis↗
PubMed1992

Synthesis and pharmacology of 3-aryl-5,6-dihydro-6-oxo-1(4H)-pyridazineacetic acid derivatives.

The title compounds were prepared by alkylation of 6-aryl-4,5-dihydro-3(2H)-pyridazinones with esters of alpha-bromoacetic acid. Hydrolysis of these esters afforded the corresponding carboxylic acids which were coupled with various amines yielding 6-oxo-1(4H)-pyridazineacetamides. A number of these derivatives showed weak anticonvulsant and weak analgesic activities, while nearly all displayed a sedative profile.

Analgesics↗
PubMed1992

Psychopharmacological screening criteria. APA Committee on Research on Psychiatric Treatments.

This chapter includes a revision of psychopharmacological screening criteria originally developed in 1977-78 by the American Psychiatric Association (APA) and the National Institute of Mental Health (NIMH). This recent revision by the APA Committee on Research on Psychiatric Treatments provides criteria that are of considerable help in carrying out drug usage evaluations. Also included are useful suggestions for medical record documentation of specific classes of drugs, as well as for identification of adverse drug reactions. Thresholds for review are suggested.

Ambulatory Care↗
PubMed1991

Prospective study of tardive dyskinesia incidence in the elderly.

OBJECTIVES: To investigate the incidence of tardive dyskinesia in elderly individuals beginning treatment with antipsychotic drugs and to identify risk factors for the development of tardive dyskinesia in the elderly. DESIGN: A cohort of previously neuroleptic-naive patients was identified at the time of initiation of antipsychotic drug treatment. Patients were evaluated at baseline and followed up at 3-month intervals for periods ranging from 3 to 119 weeks. SETTING: Subjects were recruited from the psychiatric and geriatric medical services of two medical centers, a geriatric institute, and three nursing homes in the metropolitan area of New York City, NY. PATIENTS: Two hundred fifteen individuals older than 55 years have entered the study thus far. Preliminary data are presented for 160 patients who were followed up for at least 1 month. Their age range was 57 to 99 years (mean, 77 years). Seventy-two percent were women and 87% were white. Sixty-seven percent of patients had a diagnosis of organic mental syndrome and 42% had a psychiatric diagnosis. INTERVENTIONS: A naturalistic, longitudinal, repeated assessment paradigm was employed. Assessments included abnormal involuntary movements, extrapyramidal signs, psychiatric symptoms, and medical and drug treatment histories. MAIN OUTCOME MEASURE: The incidence of tardive dyskinesia was determined using a standardized rating instrument and survival analysis. RESULTS: The incidence of neuroleptic-induced dyskinesia was 31% (95% confidence interval, 20%, 42%) after 43 weeks of cumulative neuroleptic treatment. Psychiatric (as opposed to organic) diagnosis and presence of extrapyramidal signs early in treatment were associated with increased tardive dyskinesia vulnerability.

Age Factors↗
PubMed1991

Considerations on "organic" exclusion criteria for schizophrenia.

Given the variety of "organic" or "toxic" conditions that may produce, precipitate, or exacerbate psychotic disorders, it is important to attempt to clarify existing nosologies and to highlight the need for research strategies that may help to validate relevant distinctions. This review provides a brief discussion of some of those issues.

Humans↗
PubMed1991

A selective review of biological markers in schizophrenia.

Through previous research, promising biological markers for schizophrenia have been identified. Abnormalities in eye movement, electrodermal activity, event-related brain potentials, attention and informational processing, and brain imaging have been reported. Studies of potential trait markers suffer from the lack of a standardized methodology, which makes comparisons of their results difficult. No one possible marker appears specific for schizophrenia. Additional studies in high-risk children and adults are needed using multiple measurements to define biologic similarities and differences between psychiatric syndromes in order to develop definitive trait markers for schizophrenia. Sufficient evidence does not exist to support the inclusion of biological markers among the DSM-IV criteria for schizophrenia, although some are sufficiently robust to merit mention among the associated features discussed in the text.

Arousal↗
PubMed1991

New developments in the pharmacologic treatment of schizophrenia: editor's introduction.

In this issue we have tried to bring together a series of reviews describing new developments in the pharmacologic management of schizophrenia. Important progress is being made not only in medication development, but also in furthering our ability to use available treatments and treatment combinations in the most effective manner. Topics discussed include: the role of blood levels; alternative somatic treatments for nonresponding patients; the role of clozapine; putative mechanisms of action of novel antipsychotics; an overview of potential antipsychotic drugs under development; new findings in maintenance treatment; a review of the impact of neuroleptic treatment on the long-term course of schizophrenia; and a discussion of obstacles which must be overcome to ensure that the promise of treatment research can be fully realized.

Antipsychotic Agents↗
PubMed1991

Update on the clinical efficacy and side effects of clozapine.

Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.

Agranulocytosis↗
PubMed1991

Obstacles to clinical research and new drug development in schizophrenia.

Enormous opportunities currently exist to develop and test new treatments for schizophrenia. Treatment research not only holds promise for alleviating the suffering and disability associated with this illness, but also in providing clues to etiology and ultimately prevention. At the same time as there are increasing opportunities for treatment development, there are also increasing challenges and obstacles to the conduct of needed research. A variety of different issues need to be addressed in facilitating appropriate research including treatment settings, reimbursement for costs of care, legal and ethical issues affecting patient participation, stable funding, and the development of clinical investigators. Adequate attention to these problems in strategic planning can help to ensure that emerging opportunities are neither wasted nor delayed.

Antipsychotic Agents↗
PubMed1991

The prevalence of tardive dyskinesia.

A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team of trained raters employing a standard examination technique and rating scale. "Spontaneous" dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% among medical geriatric inpatients and ranged from 0 to 2% among psychiatric patients never exposed to neuroleptics. For samples of neuroleptic-treated patients, prevalence rates ranged from 13.3% among patients at a voluntary psychiatric hospital to 36.1% among state hospital patients. Logistic regression analyses revealed a large effect of age on tardive dyskinesia prevalence and an interaction of age with sex. Among younger subjects, men had higher rates; among subjects over age 40, rates were higher for women. Edentulousness and presence of other neurological disorders were possible contributors to high rates for the elderly. Even with control for age, sex and duration of neuroleptic exposure, prevalence differed markedly across study site.

Adult↗
PubMed1990

HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia.

Agranulocytosis develops in approximately 1% of patients with chronic schizophrenia treated with the atypical neuroleptic drug clozapine. Previous studies have not identified the mechanism or risk factors for this adverse reaction. Because of an observed association between Jewish ethnic background and the development of agranulocytosis in our patient sample treated with clozapine for refractory symptoms, HLA typing was performed in 31 patients (19.4% of whom had developed agranulocytosis). The HLA-B38 phenotype was found in 83% of patients who developed agranulocytosis and in 20% of clozapine-treated patients who did not develop agranulocytosis. Because B38 is part of a haplotype known to occur frequently in the Ashkenazi Jewish population, the frequencies of the combined alleles HLA-B38, DR4, and DQw3 were examined. The incidence of HLA-B38, DR4, DQw3 was significantly increased in patients with agranulocytosis (five of five patients) compared with control patients of Ashkenazi Jewish ancestry (two of 17 patients). These findings indicate that genetic factors marked by major histocompatibility complex haplotypes may be associated with the susceptibility of Jewish schizophrenic patients treated with clozapine to develop agranulocytosis. We postulate that gene products contained in the haplotype may be involved in mediating drug toxicity.

Agranulocytosis↗
PubMed1990

The effects of a potential antidepressant, 2,4-dimethyl-5-(3-fluorophenyl)-3H-1,2,4-triazole-3-thione, in an electrophysiological model responsive to desipramine.

The effects of acute and chronic administration desipramine (DMI) and the potential antidepressant, MDL 26,479 (2,4-dimethyl-5-(3-fluorophenyl)-3H-1,2,4-triazole-3-thione) were compared on the sensitivity of Purkinje neurons in the cerebellum of the rat to iontophoretically applied norepinephrine (NE) and gamma-aminobutyric acid (GABA). Neither compound, administered acutely at 10 mg/kg (i.p.), altered the spontaneous firing rate of Purkinje neurons or the depression of the rate caused by iontophoresed NE. However, MDL 26,479 did significantly reduce the enhancement of inhibitory responses to GABA, produced by NE. Administered chronically (10 mg/kg x 21 days, i.p.), neither compound altered the slowing of Purkinje neurons evoked by NE. Chronic treatment with MDL 26,479, but not with DMI, produced a small but significant decrease in average spontaneous firing rate of Purkinje neurons. Both compounds substantially attenuated the enhancement of the inhibitory responses to GABA produced by NE, with MDL 26,479 having a more marked effect than DMI. These effects of MDL 26,479 on the activity of Purkinje neurons are consistent with the compound having antidepressant potential and further suggest, since similar effects were seen after a single dose, that the compound may have a rapid onset of antidepressant action.

Action Potentials↗
PubMed1990

2,4-Dihydro-3H-1,2,4-triazol-3-ones as anticonvulsant agents.

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazol-3-ones was evaluated for anticonvulsant activity. In general the members of this series were prepared by the alkaline cyclization of 1-aroyl-4-alkylsemicarbazides. The resulting 2-unsubstituted 3H-1,2,4-triazol-3-ones were then alkylated, yielding 2,4-dialkyl-3H-1,2,4-triazol-3-ones. Approximately one-third of the compounds examined exhibited activity against both maximal electroshock- and pentylenetetrazole-induced seizures in mice. Receptor-binding studies suggest that this activity was not a consequence of activity at either benzodiazepine or NMDA-type glutamate receptors. From this series, compound 45 was selected for further evaluation where it was also found to be active against 3-mercaptopropionic acid, bicuculline, and quinolinic acid induced seizures in mice. In addition, 45 also protected gerbils from hippocampal neuronal degeneration produced by either hypoxia or intrastriatal quinolinic acid injection.

Animals↗
PubMed1990

The pharmacologic treatment of neuroleptic-induced akathisia.

Akathisia is a frequent and distressing side effect of neuroleptic medications. The literature regarding the pharmacologic treatment of acute neuroleptic-induced akathisia is critically reviewed, including nine reports of the use of anticholinergic agents, 15 of the use of beta-blocking agents, and six of the use of benzodiazepines. Reports of trials on clonidine, amantadine, piracetam, and of a patient treated with amitriptyline are also discussed. Tentative recommendations for the management of acute akathisia are proposed.

Akathisia, Drug-Induced↗
PubMed1990

Treatment programme and long-term outcome in chronic schizophrenia.

Antipsychotic drug treatment is usually started during an acute episode or exacerbation of a pre-existing psychosis. Although the medication has marked therapeutic benefit for most patients, ther is considerable heterogeneity in drug response. A variety of factors may influence this response, but at present we have no well-established predictors which would help targeting specific pharmacological treatments. The continuation of antipsychotic drug treatment to control persistent symptoms and to prevent further exacerbations or relapse has become a mainstay in the long-term treatment of schizophrenia. There are various considerations which come into play in deciding which patients should receive such treatment, at what dose, and for how long. Research in recent years has attempted to identify strategies to minimize the risks associated with long-term treatment (particularly tardive dyskinesia). In addition, other factors influencing long-term outcome have been better studied in combination with controlled drug treatment.

Antipsychotic Agents↗