Efficacy of risperidone in reducing positive and negative symptoms in medication-refractory schizophrenia: an open prospective study.

BACKGROUND: Although risperidone has been shown to be an effective antipsychotic medication in schizophrenia, the clinical studies performed for the Food and Drug Administration's approval process focused on only a mixed group of schizophrenic patients. Most of these studies did not directly address the efficacy of risperidone in chronic nonresponding schizophrenics. To better evaluate whether risperidone has a substantial degree of efficacy in schizophrenic non-responders, we conducted an open prospective study of risperidone in a sample of chronically hospitalized schizophrenic patients. METHOD: Twenty-five patients who met DSM-III-R criteria for schizophrenia or schizoaffective psychosis, who were chronically hospitalized at a tertiary care state facility, and who had not responded to conventional neuroleptics were evaluated before and during treatment with risperidone by using several standard rating scales and adjunctive assessments. RESULTS: Endpoint analysis showed that 36% (N = 9) of the patients were classified as responders on the basis of at least a 20% decrease in total Brief Psychiatric Rating Scale score at final evaluation. A higher percentage of patients were classified as responders when other rating scale criteria were used. Reductions in psychopathology scores were seen in scales reflecting positive symptoms but not in scores of negative symptoms. High baseline negative symptom scores were correlated with poorer response to risperidone as indicated by the decrease in positive symptom scores. CONCLUSION: This study offers evidence that risperidone may reduce positive symptoms of schizophrenia for a subgroup of chronically hospitalized schizophrenic patients who have not responded to conventional neuroleptics. The comparative evaluation of the efficacy of risperidone versus that of clozapine in these types of patients requires further study.

Oxidative bioconversion of toluene to 1,3-butadiene-1,4-dicarboxylic acid (cis,cis-muconic acid).

Pseudomonas sp. strains, isolated from soil, utilized toluene as their sole carbon source through ameta cleavage pathway. Strains metabolizing toluene through anortho cleavage pathway were selected from the wild typemeta strain. Theortho pathway strains were subjected to chemostat selection to obtain a fast-growing strain with doubling time reduced from 14 to 1.2 h. Benzoale and antibiotics enrichment selection procedures were utilized to select a blocked mutant. The blocked mutant grew on acetate as its sole carbon source and oxidatively converted toluene tocis, cis-muconic acid. Double-blocked and muconate-permeable mutants were also selected to reduce reversion frequency and to enhance muconic acid production. In shake-flask experiments, muconic acid at 3.5 g/l was obtained after 2 days of fermentation. In a 14 l fermenter, muconic acid was produced at 45 g/l in 4 days of controlled fed-batch fermentation. The oxidative bioconversion process was also demonstrated in a 1500 l fermenter.