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Biomedical subjects

J M Kane

Publications and source records attributed to J M Kane.

At least 127 records · Page 7Linked to original sources
PubMed1990

Treatment of neuroleptic induced akathisia with the 5-HT2 antagonist ritanserin.

Akathisia is a frequent and distressing side effect of antipsychotic medication. Little is known about its pathophysiology. Treatment trials of serotonin antagonists in Parkinson's disease and neuroleptic-induced Parkinsonism have been disappointing, with the possible exception of akathisia which has been reported to respond favorably to ritanserin. We report first results of a single-blind trial of ritanserin in the treatment of neuroleptic-induced akathisia. Ten patients received a mean dose of 13.5 mg/day (SD +/- 5.8) ritanserin for 2 to 4 days. Treatment response was assessed by the Hillside Akathisia Scale (HAS). HAS baseline ratings were 16.4 (+/- 6). After 3 days of treatment, these values dropped to 7.4 (+/- 5.2). This amelioration was statistically significant (p = .0069 matched-pairs signed rank test). Two patients did not respond. These results, although preliminary in nature, are encouraging and warrant further studies.

Administration, Oral↗
PubMed1990

Needle aspiration of nonfunctioning parathyroid cysts.

Until recently, nonfunctioning parathyroid cysts were usually identified at operation for a presumed thyroid mass. Thyroid needle biopsy now allows their preoperative diagnosis and potential definitive treatment. This study reviews four patients with nonfunctioning parathyroid cysts treated during a two-year period. Three women and one man range in age from 28 to 70 years. Each presented with an asymptomatic thyroid mass ranging from 3 to 5 cm in length. None had symptoms of primary hyperparathyroidism. Serum calciums were from 9.2 to 10.7 mg/dl and serum phosphoruses were 3.2 to 4.4 mg/dl. Needle aspiration revealed 5 to 85 cc of water-clear fluid. C-terminal parathyroid hormone in three patients was 12,600, 6,500 and 61,200 pg/ml and N-terminal PTH was 1,700 pg/ml in one. All four had normal serum calcium and phosphorus on follow-up ranging from six months to two years. Two patients had resolution of their cysts with a single aspiration. One patient had recurrence but has no evidence of recurrence six months after injection with tetracycline. Another patient had a recurrence but remains well one year following reaspiration. Nonfunctioning parathyroid cysts present as a thyroid mass. Needle aspiration of water-clear fluid high in parathormone is diagnostic and, in most patients, is the therapeutic modality of choice.

Adult↗
PubMed1989

Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder.

In recent years, lower serum levels have been recommended for maintenance therapy with lithium. We studied 94 patients with bipolar disorder in a randomized, double-blind, prospective trial of two different doses of lithium for maintenance therapy: the "standard" dose, adjusted to achieve a serum lithium concentration of 0.8 to 1.0 mmol per liter, and a "low" dose, resulting in a serum concentration of 0.4 to 0.6 mmol per liter. The group medians of the patients' average serum lithium levels were 0.83 mmol per liter for the patients in the standard-range group and 0.54 mmol per liter for those in the low-range group. Six of 47 patients (13 percent) assigned to receive lithium doses that would produce serum levels in the standard range had relapses while on protocol, as compared with 18 of 47 (38 percent) assigned to the low-dose range. The risk of relapse was 2.6 times higher (95 percent confidence interval, 1.3 to 5.2) among patients in the low-range group than among those in the standard-range group. Side effects, including tremor, diarrhea, urinary frequency, weight gain, and a metallic taste in the mouth, were more frequent in the standard-range group. We conclude that doses resulting in serum lithium levels from 0.8 to 1.0 mmol per liter are more effective in treating bipolar disorder than those that result in lower serum lithium concentrations, although the higher doses are associated with a higher incidence of side effects. Recent findings about the limited nephrotoxicity of lithium, along with our observations, suggest that physicians should attempt to maintain serum lithium levels between 0.8 and 1.0 mmol per liter in most patients with bipolar disorder and that they should attempt to enhance patients' understanding of and compliance with this regimen.

Adolescent↗
PubMed1989

Treatment of tardive dyskinesia with bromocriptine. A test of the receptor modification strategy.

Pathophysiologic theories postulate that tardive dyskinesia arises from the development of chemical denervation supersensitivity of dopamine receptors produced by chronic long-term neuroleptic treatment. To test a dopamine receptor modification strategy, 16 patients with tardive dyskinesia were assigned to treatment with a neuroleptic plus bromocriptine (a dopamine agonist) or placebo for 10 weeks in a rising-dose design. Patients were evaluated weekly during the 10-week treatment period and for 8 weeks after medication withdrawal. No significant treatment effect was found in tardive dyskinesia response in the overall sample. When patients were classified by tardive dyskinesia subtype, patients with choreoathetoid symptoms exhibited only slight improvement with active treatment, which persisted after drug withdrawal; patients with dystonic symptoms showed moderate improvement that was drug and dose dependent. The sustained administration of substantial doses of a dopamine agonist did not produce significant adverse effects, including behavioral toxic effects. These results, although not statistically significant, are of clinical and heuristic interest.

Adolescent↗
PubMed1989

Difference in catalepsy response in inbred rats during chronic haloperidol treatment is not predictive of the intensity of behavioral hypersensitivity which subsequently develops.

An animal model was utilized to explore the observed clinical association between a history of significant neuroleptic-induced parkinsonism and an increased incidence for the subsequent development of tardive dyskinesia. Catalepsy-sensitive Fisher rats and catalepsy-resistant Brown Norway rats were treated for 14 days with haloperidol at a dose of either 1 mg/kg or 5 mg/kg daily. Following a 7-day drug withdrawal period, rats were tested for behavioral hypersensitivity to acute challenge with apomorphine and then striata were assayed for 3H-spiroperidol receptor binding. Despite significant interstrain difference in catalepsy response to either neuroleptic dose, Brown Norway rats treated with 5 mg/kg developed behavioral hypersensitivity and D-2 receptor supersensitivity equivalent to that of the similarly treated Fisher rats. Catalepsy, a possible rat analog for neuroleptic-induced parkinsonism, therefore did not predict the intensity of those subsequent behavioral and receptor changes considered to result from chronic antagonism of striatal dopamine receptors and to possibly underlie tardive dyskinesia. Further studies are required to elucidate the less than obvious relationship between extrapyramidal behavioral effects of chronic neuroleptic treatment.

Animals↗
PubMed1989

The current status of neuroleptic therapy.

Neuroleptic drugs remain a critical component of the treatment of schizophrenia. Although their use in other conditions such as bipolar disorders and organic mental disorders is also widespread, further research is necessary to validate specific indications and to assess benefit-to-risk ratios. In recent years substantial attention has been focused on establishing minimum effective dosage requirements for both acute and long-term treatment of schizophrenia. Considerable progress has been made in this area. In addition, alternative maintenance-treatment strategies such as targeted or intermittent neuroleptic therapy have been studied. The management of patients who fail to respond to an adequate trial (or trials) of neuroleptic drugs continues to be an enormous clinical challenge. Few data are available on which to base subsequent treatment decisions. Recent research with clozapine suggests that this compound may be helpful in some such individuals, but further efforts to establish other potentially effective treatment strategies for treatment-refractory patients should receive a high priority.

Antipsychotic Agents↗
PubMed1989

Demographic characteristics, treatment history, presenting psychopathology and early course in schizophrenia. Treatment Strategies in Schizophrenia Collaborative Study Group.

Subject heterogeneity increases generalizability of study findings so long as site differences do not interact with treatment effects. Of 51 baseline characteristics of 234 patients, 31 show significant site differences. Of 33 baseline demographic, treatment history, and presenting symptom items, site differences were seen on 16. This heterogeneity emphasizes the importance of examining site interactions with other effects. The first opportunity to examine such interactions is in the prediction of patient stabilization following the index acute episode. Among the 33 demographic, treatment history, and presenting symptom variables, 11 significantly predicted this short-term outcome. Only 2 of these 33 variables showed site-by-baseline interactions in predicting stabilization, most likely due to chance sampling fluctuations. Thus, site heterogeneity is adding generality without confounding the predictions.

Adult↗
PubMed1989

Clozapine: guidelines for clinical management.

The advent of antipsychotic drugs represented a milestone in psychotherapeutics. Despite their proven efficacy, antipsychotic drugs are limited by side effects and treatment resistance in some patients. Since the introduction of chlorpromazine and the subsequent development of numerous neuroleptic compounds, there have been no significant qualitative advances in the clinical efficacy of antipsychotic drugs. Clozapine is an experimental neuroleptic with atypical properties. In clinical testing, this agent has shown superior antipsychotic efficacy in treatment-refractory schizophrenics and a more favorable extrapyramidal side effect profile in comparison with standard neuroleptics. Because clozapine represents a potential contribution to our therapeutic armamentarium, this article provides an overview of its pharmacology, efficacy, and methods of clinical utilization.

Clinical Trials as Topic↗
PubMed1988

2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents.

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and reserpine-induced ptosis in mice. In general the more active members of this series were substituted by haloaryl groups at the 5-position of the triazole nucleus and by methyl groups at the 2- and 4-positions. Exchange of the thiocarbonyl group at the 3-position for a carbonyl group resulted in the complete loss of activity. Biochemical evaluation of the more active members of this series indicated that the aforementioned activities were not a consequence of either norepinephrine (NE) uptake or monoamine oxidase inhibition. In an attempt to determine a mechanism of action, one member of this series, compound 22, was selected for further evaluation in an electrophysiological model where it was found to reduce norepinephrine function in the cerebellum as measured by the NE augmentation of GABA inhibition of Purkinje neurons.

Animals↗
PubMed1988

The role of neuroleptics in manic-depressive illness.

Neuroleptic drugs are a common treatment for acute mania. Although lithium alone may be effective, for those patients with moderate or severe agitation neuroleptics appear to be superior. Low-potency and high-potency neuroleptics are equally effective in mania, as in schizophrenia. Patients with affective disorders, however, may be highly susceptible to the pseudoparkinsonian or extrapyramidal side effects that can occur with neuroleptics. Moderate doses of neuroleptics can be effective in most patients and can reduce the likelihood of serious side effects. Many bipolar patients have manic relapses despite adequate serum lithium levels, and many of those patients are subsequently maintained on a regimen of neuroleptic drugs in addition to lithium. Using the lowest possible dose of the neuroleptic may decrease the high, long-term risk of tardive dyskinesia. More clinical research is needed to determine the most appropriate use of neuroleptic drugs in bipolar disorder.

Antipsychotic Agents↗
PubMed1988

Epidemiological aspects of tardive dyskinesia.

Although there continues to be some debate as to the extent to which neuroleptic drug treatment is either necessary or sufficient to produce abnormal involuntary movements in various psychiatric populations, the consensus at present is that neuroleptics do play a major role in producing, precipitating or evoking abnormal involuntary movements. No doubt a variety of other factors play a critical role in predisposing particular individuals to the development of the condition. Numerous prevalence surveys have been conducted and extensively reviewed. In general, prevalence surveys have helped to identify populations at particular risk, to suggest factors which contribute to risk and to establish the overall scope of the problem. The strategy of estimating prevalence in a specific population has limitations, however, and further advances in our understanding of tardive dyskinesia (TD) will require a different type of methodology. Important progress has been made in the last several years involving prospective studies of TD development. Current estimates of incidence suggest that TD develops in about 5% of patients with each year of cumulative neuroleptic exposure. These data are derived from relatively young patients (average age 28); the incidence in older individuals is likely to be higher. Further data on the epidemiology of TD will be presented.

Dyskinesia, Drug-Induced↗
PubMed1988

Tardive dyskinesia: prevalence, incidence, and risk factors.

Despite increased attention to the problem of tardive dyskinesia (TD), many questions remain unresolved. There is a consensus that neuroleptics play a substantial role in its development, but other variables must also contribute. Prevalence surveys have helped to define the scope of the problem and suggest risk factors for further study. Their usefulness has been limited by methodological problems including the difficulty of estimating false-negative (masked) dyskinesia and false-positive (movements caused by other neuromedical conditions) rates. A recent large scale survey reported an overall rate of abnormal involuntary movements of 23.4% among neuroleptic-treated psychiatric patients; the range was from 12.3% among outpatients at a Veterans Administration hospital to 37.4% among state hospital inpatients. Rates of covert dyskinesia, obtained by withdrawing medication from 70 TD negative cases, ranged from 17% for the Veterans Administration to 67% at the state hospital (overall rate, 34%). Very few clear false-positive cases were found. The incidence of TD, based on a large prospective study of young adult patients, is 19% after 4 years of cumulative neuroleptic exposure. Higher incidence rates have been found in prospective studies of older patient samples. Age remains the risk factor most consistently associated with TD development; it may also relate to increased persistence. Female sex among older populations, diagnosis of affective disorder, and evidence of neuroleptic-induced pseudoparkinsonism also relate to increased risk. Further work is needed to elucidate the role of dosage and length of neuroleptic treatment, as well as other potential contributory factors.

Dyskinesia, Drug-Induced↗