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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 37 records · Page 2Linked to original sources
PubMed1999

Management strategies for the treatment of schizophrenia.

Considerable progress has been made during the past 10 years in the treatment of schizophrenia; however, the disease still represents a great challenge for the clinician. Frequently encountered problems include the patient who is only partially responsive to treatment or is treatment resistant and long-term relapse prevention. Patient compliance, long-term efficacy, drug dose, safety, and the duration of treatment are all important factors determining the degree of success of maintenance treatment in the prevention of relapse. This review discusses those aspects that should affect the clinicians' choice of treatment, including the recent introduction of atypical antipsychotics such as clozapine.

Ambulatory Care↗
PubMed1998

Guidelines for depot antipsychotic treatment in schizophrenia. European Neuropsychopharmacology Consensus Conference in Siena, Italy.

These guidelines for depot antipsychotic treatment in schizophrenia were developed during a two-day consensus conference held on July 29 and 30, 1995 in Siena, Italy. Depot antipsychotic medications were developed in the 1960s as an attempt to improve the long-term treatment of schizophrenia (and potentially other disorders benefiting from long-term antipsychotic medication). Depot drugs as distinguishable from shorter acting intramuscularly administered agents can provide a therapeutic concentration of at least a seven day duration in one parenteral dose. The prevention of relapse in schizophrenia remains an enormous public health challenge worldwide and improvements in this area can have tremendous impact on morbidity, mortality and quality of life, as well as direct and indirect health care costs. Though there has been debate as to what extent depot (long-acting injectable) antipsychotics are associated with significantly fewer relapses and rehospitalizations, in our view when all of the data from individual trials and metaanalyses are taken together, the findings are extremely compelling in favor of depot drugs. However in many countries throughout the world fewer than 20% of individuals with schizophrenia receive these medications. The major advantage of depot antipsychotics over oral medication is facilitation of compliance in medication taking. Non-compliance is very common among patients with schizophrenia and is a frequent cause of relapse. In terms of adverse effects, there are not convincing data that depot drugs are associated with a significantly higher incidence of adverse effects than oral drugs. Therefore in our opinion any patient for whom long-term antipsychotic treatment is indicated should be considered for depot drugs. In choosing which drug the clinician should consider previous experience, personal patient preference, patients history of response (both therapeutic and adverse effects) and pharmacokinetic properties. In conclusion the use of depot antipsychotics has important advantages in facilitating relapse prevention. Certainly pharmacotherapy must be combined with other treatment modalities as needed, but the consistent administration of the former is often what enables the latter.

Antipsychotic Agents↗
PubMed1998

Prospective study of tardive dyskinesia in the elderly: rates and risk factors.

OBJECTIVE: The purposes of this study were to investigate the rate (incidence) of tardive dyskinesia in elderly patients beginning treatment with antipsychotic medication and to identify risk factors for development of tardive dyskinesia in this age group. METHOD: A group of 261 neuroleptic-naive patients aged 55 or above were identified at the time they were starting antipsychotic drug treatment. This group is the complete study group; a preliminary report based on the first 160 patients was published previously. Patients were evaluated at baseline and followed up at 3-month intervals for periods ranging from 3 to 393 weeks. Assessments included abnormal involuntary movements, extrapyramidal signs, psychiatric symptoms, and medical and drug treatment histories. RESULTS: The cumulative rates of tardive dyskinesia were 25%, 34%, and 53% after 1, 2, and 3 years of cumulative antipsychotic treatment. A greater risk of tardive dyskinesia was associated with history of ECT treatment, higher mean daily and cumulative antipsychotic doses, and presence of extrapyramidal signs early in treatment. Differences in tardive dyskinesia rates between diagnostic groups found in univariate analyses were attenuated when the authors controlled for these variables. CONCLUSIONS: Tardive dyskinesia rates for patients beginning treatment with conventional antipsychotics in their fifth decade or later are three to five times what has been found for younger patients, despite treatment with lower doses. Alternative treatments need to be investigated.

Age Factors↗
PubMed1998

Clozapine reduces rehospitalization among schizophrenia patients.

A number of studies have reported reduced rehospitalization for patients on clozapine. This article adds to that literature by mining the clozapine database at Hillside Hospital. The sample consisted of 81 schizophrenia patients who entered Hillside on a typical neuroleptic and then had their medication changed to clozapine. We ascertained the number of inpatient hospitalizations before starting clozapine and compared this with the number of hospitalizations after starting clozapine. We also followed an age- and gender-matched comparison group of other schizophrenia patients who entered Hillside at approximately the same time. Results indicate that the mean number of rehospitalizations while on a typical neuroleptic was 2.03 (1.93)/year, whereas it was only .56 (.97/year after the commencement of clozapine treatment; t(80) = 5.78, p < .001. A 95% confidence interval for the superiority of clozapine over standard neuroleptic treatment as measured in rehospitalizations/year is (1.0, 2.0). The decrease in hospitalization rate of .4 (1.6)/year (pre-index date minus post-index date) for the comparison group was also statistically significant [t(80) = 2.3, p < .03]; the 95% confidence interval for this decrease over time is (.1, .8). The pre-post change was much greater for the clozapine patients than comparison patients. A 2 x 2 repeated measures analysis of variance (ANOVA) contrasting the comparison group to the clozapine patients both before and after the index date indicates a significant time by group interaction (F(1.80) = 22.35, p < .001), thus documenting the greater relative decrease in rehospitalization rate in the clozapine group.

Adult↗
PubMed1998

Sertindole: a review of clinical efficacy.

Schizophrenia is the most serious and disabling form of psychiatric disorder, and affects 1% of people worldwide. Until recently, treatment has relied heavily on the use of conventional antipsychotic drugs. These drugs do help schizophrenic patients, but have severe limitations. Conventional antipsychotic drugs are not effective in all patients, and even in patients who respond to treatment, the improvement in negative symptoms is often minimal. In fact, these drugs can increase negative symptoms through the production of severe neurological side effects. In recent years, novel antipsychotics have been developed which have superior efficacy and safety profiles. Sertindole is a novel antipsychotic which has been tested in large clinical trials in North America and Europe; the results showed that this drug has efficacy against both the positive and negative symptoms of schizophrenia, while causing adverse neurological events at a similar level to that observed in patients taking placebo. The Positive and Negative Symptom Scale used in these trials showed that sertindole was as effective as haloperidol in controlling positive symptoms, and was superior to placebo in reducing negative symptoms, whereas haloperidol was not. These trials also confirmed that sertindole does not cause the neurological side effects common to the conventional antipsychotics.

Antipsychotic Agents↗
PubMed1997

The rationale and ethics of medication-free research in schizophrenia.

Schizophrenia research is receiving intense scrutiny from an ethical perspective. Medication-free protocols present a most vexing dilemma in that they greatly enhance the opportunity for advancing knowledge but also raise the prospect of withholding known effective treatment. In this article, we discuss the purpose of medication-free protocols in new drug development and nontreatment research. Potential benefits and risks associated with drug discontinuation are evaluated, and methods for minimizing risk and increasing benefits are proposed as guidelines for the protection of individual subjects. The complex problem of informed consent also is addressed. Medication-free research in schizophrenia is difficult, but it can be conducted relatively, safely with freely consenting, competent subjects. Assurance that studies meet this standard is required. We believe that such investigations can meet high standards of ethics and subject protection, and that a radical revision of procedures for research review and implementation is not indicated.

Acute Disease↗
PubMed1997

Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Adolescent↗
PubMed1997

Is esophagectomy following upfront chemoradiotherapy safe and necessary?

OBJECTIVE: To examine the safety and necessity of esophagectomy following upfront chemoradiotherapy (CRT) in patients with potentially resectable esophageal cancer. DESIGN: Cohort analytic study during a 4-year period. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients who completed CRT and underwent esophagectomy as compared with 30 patients who underwent esophagectomy alone without pretreatment during the same period. MAIN OUTCOME MEASURES: Resection-related events, perioperative morbidity and mortality, response to CRT, site of residual disease following CRT, and survival of partial responders. RESULTS: Patients receiving CRT followed by esophagectomy were similar to patients who underwent esophagectomy alone for operative characteristics, postoperative course, and perioperative morbidity and mortality. Of the 33 patients who achieved an objective response to CRT, 23 had residual tumor in the resection specimen. Of the 18 patients alive with no evidence of disease at a median follow-up of 30 months, 50% had residual tumor following CRT. CONCLUSIONS: Upfront CRT did not adversely affect resection-related outcome and may facilitate resection by downstaging disease. A considerable number of patients had prolonged survival after esophageal resection despite having residual tumor present following treatment with upfront CRT. Therefore, esophagectomy following upfront CRT can improve locoregional control of disease and should remain a critical component of any multimodality regimen.

Aged↗
PubMed1997

Chronic hepatitis C virus infection in humans: induction of hepatic nitric oxide synthase and proposed mechanisms for carcinogenesis.

Chronic inflammatory states frequently lead to the increased production of nitric oxide (NO) via inducible NO synthase (NOS-2). In addition, NO may produce mutagenesis through several mechanisms such as DNA oxidation, DNA deamination, and the formation of N-nitroso compounds. As there is a strong association between human hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), we were interested in whether human HCV hepatitis leads to induction of NOS-2 and if the mutation repair system of p53/p21 was upregulated. Reverse transcriptase-polymerase chain reaction (RT-PCR) for human NOS-2 message was performed on RNA samples from both liver biopsies and whole liver from HCV-positive and control patients (normal liver from hepatic resections for metastases). Immunohistochemistry (IHC) for p53 and Western blot analysis for p21 were also performed on the whole liver samples. From the liver biopsies, 60% of HCV-positive patients expressed NOS-2 by RT-PCR. Looking at the whole liver samples, 100% of the HCV-positive patients expressed NOS-2 vs 12.5% in the normal samples. p53 was not detected in either group but there was upregulation of p21 over baseline expression in a number of the HCV-positive patients. Human HCV hepatitis leads to consistent upregulation of hepatic NOS-2 message, but message is not predictably present in "normal" human liver. There is also induction of p21 in some patients with HCV hepatitis. Chronic expression of NO in HCV hepatitis may play a role in DNA mutagenesis and the development of HCC.

Adult↗
PubMed1997

Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties.

The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse; spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS), electrically-based (MES seizures in mice and rats, corneally-kindled seizures in rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic acid, quinolinic acid and strychnine). When compared to valproate, orally administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and showed a safety index one to three-fold greater. Following a timed intravenous administration of PTZ to mice, MDL 27,192, but not phenytoin or carbamazepine, consistently increased the latencies to first twitch and clonus. MDL 27,192 was active in a genetic model of absence epilepsy, the GAERS rat model. These data indicate that MDL 27,192 likely exerts its anticonvulsant action by affecting seizure spread and by raising seizure threshold. MDL 27,192 did not display any signs of tolerance following subchronic (15 day) administration. In tests of neuroprotective potential, MDL 27,192 reduced infarct volume in a permanent middle cerebral artery occlusion model of focal cerebral ischemia in rats and reduced the loss of hippocampal dentate hilar neurons in an animal model of unilateral head injury. In summary, MDL 27,192 possesses a broad-spectrum anticonvulsant profile. The potential for reduced tolerance and neuroprotective activity are additional positive features of MDL 27,192's preclinical profile.

Animals↗
PubMed1997

Clinical challenges in the psychopharmacology of schizophrenia.

Better pharmacological treatments for schizophrenia have elevated the expectations of patients and families and allow a wider range of therapeutic options for clinicians. At the same time, the treatment of schizophrenia has become more complex, and clinical decisions must often be made in the absence of unambiguous empirical guidelines. Under these circumstances, good patient care is based on clinical judgement informed by available clinical research. This issue of the Schizophrenia Bulletin reviews research in areas that represent major clinical challenges in the psychopharmacology of schizophrenia.

Humans↗
PubMed1997

What can we achieve by implementing a compliance-improvement program?

Efforts to improve compliance and facilitate other aspects of relapse-prevention strategies can have a profound impact on the lives of millions of people around the world as well as conserving precious health-care dollars. Simultaneous efforts to educate patients and families on the nature of the disease, its course and optimum treatment, together with efforts to educate physicians and other health-care professionals on the indications, benefits and risks of long-term treatment, are critical for improving the current state of affairs. In addition, it is imperative to educate the public at large and particularly those health-care administrators and public servants who control or influence the allocation of the resources needed.

Antipsychotic Agents↗
PubMed1997

What are the therapeutic needs in schizophrenia and how are they satisfied by new antipsychotics?

Although considerable progress has been made in the management of schizophrenia, much remains to be achieved in meeting the therapeutic needs of patients with this illness. Conventional antipsychotics have revolutionized treatment, but a substantial proportion of patients derive inadequate benefit and many suffer from adverse effects. Compliance with medication remains an enormous problem. With a number of new drugs soon to be available, it is hoped that valuable alternatives can be provided, increasing the possibility of good therapeutic response and increasing the benefit-to-risk ratio.

Antipsychotic Agents↗
PubMed1997

Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole Study Group.

OBJECTIVE: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia. METHOD: The patients were randomly assigned to one of the medication groups and received treatment for 8 weeks. Changes in Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, and Clinical Global Impression scores were used as evaluations of treatment efficacy. Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms. RESULTS: Both sertindole and haloperidol were comparably effective in the treatment of psychosis, and all dose levels were significantly more effective than placebo. For the treatment of negative symptoms, only sertindole, 20 mg/day, was significantly more effective than placebo. For all extrapyramidal symptom measures, sertindole was clinically and statistically indistinguishable from placebo, and rates of extrapyramidal symptoms were not dose related. All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole. Adverse events associated with sertindole treatment were mild in severity. CONCLUSIONS: Sertindole is a new antipsychotic agent effective for the treatment of both the positive and negative symptoms of schizophrenia, with motor side effects that are indistinguishable from those associated with placebo.

Adolescent↗
PubMed1997

Sertindole (Serdolect): preclinical and clinical findings of a new atypical antipsychotic.

This review first describes the preclinical findings with sertindole, a novel phenyl indole derivative antipsychotic agent. Second, a summary is provided of the major clinical trials conducted to date. Based on these findings, sertindole appears to be an effective antipsychotic agent for the treatment of positive and negative symptoms of schizophrenia, with efficacy that is clearly superior to placebo. Sertindole is as effective as haloperidol, however, is much better tolerated with significantly fewer adverse neurologic effects across a wide dosage range of both drugs. Sertindole is associated with a significant mean prolongation of the QT and QTc intervals of 3 - 6% from baseline in placebo-controlled studies. This potential adverse effect should be taken into account when treating specific patients with known risk factors for ventricular arrhythmias. Sertindole should prove to be a very useful addition to the therapeutic options available for the treatment of psychotic disorders.

Journal Article↗
PubMed1997

Olanzapine (Zyprexa):characteristics of a new antipsychotic.

Olanzapine is a thienobenzodiszepine antipsychotic,which exerts broad-spectrum receptor antagonism in the central nervous system.It demonstrates regionally selective dopamine antagonist activity as measured with the depolarisation block model and fos activation paradigm. Early in vivo imaging studies suggest a relatively low D2 occupancy in th striatum (69%) with a higher 5-HT2 occupancy in the cortex (84%) of 10 mg.Its pharmaco-kinetics are dose-proportional; Tmax is 5 h and the elimination half-life is 31 h (range:21-54 h). Efficacy studies show equivalent antipsychotic efficacy to haloperidol with the possibility of superior efficacy on negative symptoms and depression. Motor side-effects are minimal with mild akathisia emerging at the highest doses; non-motor side-effects are also minimal. Olanzapine is a highly effective antipsychotic drug with minimal side-effects. It will be an important new drug for treating schizophrenia.

Journal Article↗
PubMed1996

Gender differences in neuroleptic nonresponsive clozapine-treated schizophrenics.

Gender differences in neuroleptic-refractory chronic schizophrenic disorder patients were examined to determine whether a superior or equivalent antipsychotic response in women vs. men existed similar to that of the general schizophrenic population. Sixty-nine DSM-III schizophrenic patients (47 males and 22 females) were treated with clozapine using a standardized medication regime. The gender differences in these neuroleptic-nonresponsive chronic schizophrenic disorder patients differed from those previously observed in the general schizophrenic population in that an equivalent antipsychotic treatment response in females versus males was not found. These treatment-refractory women appear to be a severely ill subgroup of female schizophrenics with distinct onset of illness, course and treatment response characteristics.

Adolescent↗