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Biomedical subjects

J H Friedman

Publications and source records attributed to J H Friedman.

At least 91 records · Page 5Linked to original sources

Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Adult↗

Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group.

A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.

Activities of Daily Living↗

Gamma knife pallidotomy in advanced Parkinson's disease.

Posteroventral pallidotomy as a treatment for Parkinson's disease (PD) has been the subject of increasing interest. We treated 4 nondemented patients with advanced PD, 2 with severe bradykinesia and a declining response to medication, and 2 with marked clinical fluctuations. All patients received 180 Gy delivered in one sitting to the right posteroventral pallidum site, used by Laitinen and colleagues, adjusted as needed, to avoid the optic tract. Only 1 patient changed significantly. Dyskinesia completely resolved on the side contralateral to the lesion in this patient. This same patient also became transiently demented and psychotic. The other 3 patients suffered no clearly identifiable beneficial or harmful effects. Follow-up magnetic resonance imaging scans of the brain at 1 year revealed lesions exactly where targeted although of unequal sizes. Our negative experience forces us to conclude that either larger volumes of tissue must be ablated, that physiologic monitoring is required for placing a lesion, that our subjects were poor candidates for the procedure, or that surgical ablation and radiation cause tissue damage of different types with different results.

Aged↗

Suicidal behavior in schizophrenia and its relationship to awareness of illness.

OBJECTIVE: Suicidal behavior is prevalent in individuals with schizophrenia. Although a relationship between greater awareness of illness and suicidal behavior has been posited, the question has not been systematically studied. The purpose of this study was to examine the relationship between suicidal behavior and various aspects of insight in 218 patients with schizophrenia. METHOD: Patients who were participating in the DSM-IV field trial for schizophrenia were assessed with the Scale to Assess Unawareness of Mental Disorder and an instrument that was developed for the field trial study that measured multiple aspects of psychopathology, including suicidal behavior. RESULTS: The prevalence of suicidal thoughts and behavior found in this study was consistent with previous published reports. Schizophrenia patients with recurrent suicidal thoughts and behavior were generally more aware of their negative symptoms and delusions than were nonsuicidal patients. Contrary to expectations, general awareness of having a mental disorder did not predict suicidal behavior. CONCLUSIONS: The notion that insight may be associated with greater suicidality was partially supported.

Adult↗

The gonadal axis in men with schizophrenia.

The typical onset of schizophrenia during late adolescence and early adulthood has stimulated interest in the potential contribution of hypothalamo-pituitary-gonadal (HPG) axis abnormalities to this disorder. Previous investigations of reproductive hormone function in men with schizophrenia suggest diminished activity of the HPG axis. These studies have been hampered, however, by methodologic limitations. We have attempted to address these limitations by rigorous determination of gonadotropin and gonadal hormone levels, and attention to demographic and diagnostic variables. In contrast to prior studies, our results indicate that schizophrenic patients do not show statistically significant differences from healthy volunteers with respect to luteinizing hormone pulsatility, response to gonadotropin-releasing hormone challenge, and testosterone secretion. Due to the small number of subjects, however, these findings must be regarded as preliminary and warrant further study.

Adult↗

An introduction to multivariate adaptive regression splines.

Multivariate Adaptive Regression Splines (MARS) is a method for flexible modelling of high dimensional data. The model takes the form of an expansion in product spline basis functions, where the number of basis functions as well as the parameters associated with each one (product degree and knot locations) are automatically determined by the data. This procedure is motivated by recursive partitioning (e.g. CART) and shares its ability to capture high order interactions. However, it has more power and flexibility to model relationships that are nearly additive or involve interactions in at most a few variables, and produces continuous models with continuous derivatives. In addition, the model can be represented in a form that separately identifies the additive contributions and those associated with different multivariable interactions. This paper summarizes the basic MARS algorithm, as well as extensions for binary response, categorical predictors, nested variables and missing values. It presents tips on interpreting the output of the standard FORTRAN implementation of MARS, and provides an example of MARS applied to a set of clinical data.

Algorithms↗

Risperidone versus clozapine in the treatment of psychosis in six patients with Parkinson's disease and other akinetic-rigid syndromes.

BACKGROUND: We report six cases of psychosis in patients with akinetic-rigid syndromes who were treated with risperidone. RESULTS: Five of the six patients experienced intolerable exacerbation of parkinsonism. Four subsequently did well on clozapine therapy. One patient required nursing home placement and a feeding gastrostomy as a result of the worsening parkinsonism during risperidone treatment, but was able to return home and have the gastrostomy removed after switching from risperidone to clozapine. Two of the five patients who worsened motorically also developed encephalopathy during risperidone treatment; the encephalopathy resolved when the patients were switched to clozapine treatment. Only one patient, the youngest, did well on risperidone therapy. CONCLUSION: We believe that risperidone is not a substitute for clozapine in treating psychosis in parkinsonian patients and should be used with caution.

Aged↗

Clozapine treatment of psychosis in patients with tardive dystonia: report of three cases.

Among the tardive dyskinesia syndromes, dystonia can be the most difficult to treat. It may be severe to the point of being disabling, yet the patients may require antipsychotic medications for an even more disabling psychosis. Clozapine, an atypical neuroleptic drug that lacks extrapyramidal effects, may be the drug of choice for such patients. This report describes three patients with significant dystonia, previously disabled by their psychoses, who have been successfully managed with clozapine plus other agents for > 3 years.

Adult↗

Smooth pursuit eye movement abnormality in severe major depression: effects of ECT and clinical recovery.

Smooth pursuit eye movement (SPEM) dysfunction is a putative genetic marker for schizophrenia, but it has also been described in major depression. The authors longitudinally evaluated effects of clinical state on SPEM quality in patients with depression. Prior to ECT, SPEM abnormality characterized 42% of 24 severely depressed patients, 60% of 30 schizophrenia patients, and 5% of 20 control subjects. SPEM was significantly correlated to Hamilton Rating Scale for Depression scores (r = 0.49, P = 0.02) in the depressed patients. Although SPEM was transiently disrupted by an acute ECT treatment, it improved during the treatment course. This improvement of SPEM quality with clinical recovery suggests that SPEM abnormality may be a state marker in severe major depression, in contrast to its invariable trait nature in schizophrenia.

Adult↗

Odor discrimination deficits in schizophrenia: association with eye movement dysfunction.

Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory.

Adult↗

Ataxia without telangiectasia.

Ataxia telangiectasia (AT) is an autosomal recessive hereditary disorder characterized by onset in infancy or childhood of a cerebellar and later extrapyramidal disorder associated with telangiectasias and an immune deficit. Only a handful of cases have been described in which the features were not stereotypic. This report describes a case that is classic except for the absence of telangiectasias through age 17. This and other cases suggest that a new, more inclusive term be used to describe the syndrome of ataxia with immune deficit until the genetic abnormalities in these disorders become identifiable.

Adolescent↗