Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response

OBJECTIVE: Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents. METHOD: After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents. RESULTS: Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone. CONCLUSIONS: The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.     

Rationally and empirically derived dimensions of children's symptomatology: Expert ratings and confirmatory factor analyses of the CBCL.

Expert ratings and confirmatory factor analyses were used to develop an alternative system for scoring the Child Behavior Checklist (CBCL; T. M. Achenbach, 1991) to measure specific dimensions corresponding to current conceptualizations of child symptomatology. Data were from a nonclinic and 2 independent clinic samples. Subscales measuring Anxiety, Attention Problems/Hyperactivity, Conduct Problems, Depression, Oppositional Defiant, Social Problems/Immaturity, and Somatization were created. Logistic regressions were conducted to evaluate the diagnostic efficiency and discrimination of the new and original approaches to scoring the CBCL. Some of the new subscales demonstrated better sensitivity, positive predictive power, and discriminant validity than the original CBCL subscales; however, subscales from both approaches demonstrated low sensitivity. Results support the use of the new subscales for specific research purposes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality and vocational interests: The relation of Holland's six interest dimensions to five robust dimensions of personality.

Relations between interest-based personality dimensions from J. L. Holland's (1985) theory of vocational personalities and 5 robust factors of personality (R. R. McCrae and O. P. John; see record 1993-01496-001) were examined. Results for 479 male and 246 female US Navy trainees imply that the 6 theoretical scales of the Vocational Preference Inventory and 20 scales of the NEO Personality Inventory share 2–4 significant factors. Social and Enterprising vocational preferences were positively correlated with Extraversion; Investigative and Artistic preferences were positively correlated with Openness; and Conventional preferences were correlated with Conscientiousness. Examinations of correlations for instruments with scales that are assumed to represent facets of 5 general personality factors usually supported these interpretations. Despite their regularity, the vocational–personality correlations were too low to suggest that either form of assessment is a dependable substitute for the other. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunotherapy for recurrent pregnancy loss: analysis of results from clinical trials

PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RSA) are thought to have an immunologic mechanism. Yet clinical trials using immunotherapy to treat women experiencing RSA have low treatment effects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyte immunization and intravenous (IV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on frequency of karyotype abnormalities in trophoblast of failing pregnancies. RESULTS: Results of two independent analyses using allogeneic leukocyte immunization as immunotherapy for all women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysis was limited to primary aborters, the live birth ratio increased to 1.46 (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88 (P = 0.04). Because of low treatment effects, confounders to treatment success of maternal age and number of previous abortions were studied. Chromosomal abnormalities have been identified in 55% of concepti from RSA. The frequency of chromosomal abnormalities remained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypically abnormal concepti (chi 2 = 4.54, P < 0.05). Risk factors for RSA also include number of previous losses. CONCLUSION: Chromosomal abnormalities are a significant confounder when evaluating efficacy of immunotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.     

The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives

Direct evidence about the effects of antihypertensive treatment on vascular disease in older patients is available from five randomized trials conducted exclusively in patients over the age of 60 years. These trials involved a total of 12,483 individuals with systolic or diastolic hypertension (mean age = 72 years, mean entry blood pressure = 181/88 mmHg). Over an average follow-up period of 4.7 years, a 15/6 mmHg difference in blood pressure between study and control groups was achieved. Among those patients assigned active treatment, stroke incidence was reduced by 34% SD6 and coronary heart disease incidence was reduced by 19% SD7. These proportional reductions were of similar size to those observed in trials in predominantly younger patients. However, the absolute benefits observed in older patients were more than twice as great as those observed in younger patients. The results suggest that over 10 years, treatment would prevent at least one major vascular event among every 10 elderly patients at similar risk to those enrolled in the trials.     

The sensitivity and specificity of the caffeine-halothane contracture test: a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS

BACKGROUND: The caffeine-halothane contracture test (CHCT) is the only recognized laboratory test to diagnose malignant hyperthermia (MH). The authors report the results of their analysis of pooled data from the North American Malignant Hyperthermia Registry database to determine the sensitivity and specificity of the CHCT. METHODS: The MH Clinical Grading Scale was used to identify 32 case subjects who were "almost certain" to be MH susceptible based on clinical criteria alone. Their CHCT results were compared with those of a group of 120 control subjects considered to be at low risk for MH. Diagnostic thresholds of the CHCT were adjusted, and its component tests were combined to generate receiver operating characteristic curves. The maximal Youden index for each component test was chosen as the diagnostic threshold indicative of MH susceptibility. RESULTS: The highest sensitivity (97%; 95% CI, 84-100%) was achieved with a two-component test with thresholds of > or = 0.5 g contracture for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of other CHCT component tests did not improve CHCT sensitivity or specificity. CONCLUSION: The CHCT achieves high sensitivity and acceptable specificity as a clinical laboratory diagnostic test when it is performed according to published standards. However, it cannot be used as a screening test because of the low prevalence of MH in the general population.     

Systematically derived work dimensions: Factor analyses of the Occupation Analysis Inventory.

Developed the Occupation Analysis Inventory (OAI) for use as a taxonomic tool, derived a broad set of human work dimensions (factors) based on that questionnaire, and established some degree of construct validity for the resultant dimensions. 602 OAI work elements (items) were subjected to several factor analyses based on the ratings of 1,414 jobs on the elements and ratings of the elements on their requirements for 102 defined human attributes. The resultant factors were significantly related to the tested abilities of relevant job holders. It is concluded that job-rating factors should be (a) fairly reflective of the various types of work activities and conditions extant in the world of work and (b) unique in their coverage of information relevant to occupational education and career decision making. (79 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of measuring error on the results of therapeutic trials in advanced cancer

In this study, 16 experienced oncologists each measured 12 simulated tumor masses employing their usual clinical methods. Unknown to the oncologists, two pairs of these tumors were identical in size. This permitted a total of 64 measurement comparisons of the same investigator measuring the same size mass and 1920 comparisons of different investigators measuring the same size mass. If a 50% reduction in the product of perpendicular diameters is accepted as a criterion, the objective response rate due to measuring error alone was 7.8% by the same investigator and 6.8% by different investigators. If a 25% reduction criterion is used, the respective "placebo" response rates were 19% and 25%. In the clinical setting it is recommended that the 50% reduction criterion be employed and that the investigator should anticipate an objective response rate of 5 to 10% due to human error in tumor measurement.     

North American blastomycosis: the importance of a differential diagnosis

A 1-month-old infant presented with a typical pattern of pyloric stenosis but US revealed an intense hyperechogenicity of the thickened pyloric muscle. Cholecystitis and pancreatitis were also present in this child. Familial hyperchylomicronemia was detected. Surgery confirmed the fatty infiltration of the pyloric muscular layer, which was necrotic and inflammatory. Medical management with restriction of fat in the diet led to a complete recovery. This is an exceptional case of pyloric stenosis where the particular echographic appearance of the pyloric muscle led to successful to medical treatment.     

Thematic analysis: An empirically derived measure of the effects of liberal arts education.

Describes the rationale and development of the Test of Thematic Analysis, reflecting ability for complex concept formation. 24 male college freshmen and seniors at a traditional liberal arts college were asked to formulate and articulate the differences between 2 groups of stories. Scoring categories were derived from differences in freshman and senior responses and were cross-validated on another sample. In a 2nd and larger-scale study, thematic analysis scores were significantly higher among seniors than among freshman at the traditional liberal arts colleges, but there were no significant differences in 1st and 2nd yr students at 2 more vocationally oriented colleges (2-yr colleges). (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of phenothiazine on disordered thought in schizophrenia.

Using a counterbalanced design, 24 male chronic schizophrenics were tested both while receiving phenothiazine therapy and while off drugs. The test used was a conceptual one which permitted measures of 3 kinds of errors, errors resulting from excessively broad interpretation of common concepts, errors resulting from excessively narrow interpretation of common concepts, and random errors which reflect lack of alertness and a drop in intellectual efficiency. Phenothiazine therapy reduced errors of excessive breadth of concepts (p     

The stimulation of neoangiogenesis in the ischemic human heart by the growth factor FGF: first clinical results

AtFKBP12 is an Arabidopsis cDNA that encodes a protein similar to the mammalian immunophilin, FKBP12. AtFKBP12 was used as 'bait' in a yeast 2-hybrid system to screen for cDNAs in Arabidopsis encoding proteins that bind to FKBP12. Two partial cDNAs were recovered encoding the C-terminus of a protein we have called Arabidopsis thaliana FKBP12 interacting protein 37 (AtFIP37). AtFIP37 is similar to a mammalian protein, FAP48, that also binds to FKBP12. The interaction between AtFKBP12 and AtFIP37 in the 2-hybrid system, as assessed by histidine auxotrophy and beta-galactosidase activity, was disrupted by FK506, but not by cyclosporin A, a drug that binds to cyclophilin A. AtFIP37 was also shown to bind in vitro to AtFKBP12 in GST-fusion protein binding assays. The binding was abolished by prior incubation of AtFKBP12 with FK506. These findings indicate that an Arabidopsis FKBP12 ortholog encodes a protein that binds FK506 and that the interaction between AtFKBP12 and AtFIP37 may involve the FK506 binding site of AtFKBP12. The interaction provides interesting new opportunities for controlling protein:protein interactions in vivo in plants.     

Optimization of the measuring conditions for thermal analysis of casting powders and evaluation of the results by means of factor analysis

Thermal analysis is a very powerful method for investigation and characterization of casting powders. The results depend on the measuring conditions to a high degree. That was the reason for the systematic optimization of the measuring conditions of differential thermal analysis and thermogravimetry (DTA/TG) which were used for this study. Especially the temperature program was developed carefully. The factor analysis of the results gives information about the variables which influence the thermal properties of the powders. Factor analysis was also used for cluster formation and identification of casting powders.     

Karyotypic analysis and evidence of tetraploidy in the North American paddlefish, Polyodon spathula

A model chromosome number of 120 was obtained for the ancient fish. Polyodon spathula (Pisces: Chondrostei). The karyotype consists of 48 macrochromosomes and 72 microchromosomes. The microchromosomes are like those found in certain other primitive fishes as well as in reptiles and birds. The possiblity that Polyodon is a species of tetraploid origin is strongly suggested by the fact that the 120 chromosomes are easily arranged into 30 groups of four homologs each. Evolutionary comparisons are made with other primitive fish groups.     

Phase-IV multicentre clinical study of risperidone in the treatment of outpatients with schizophrenia. The RIS-CAN-3 Study Group

OBJECTIVE: Since most clinical trials of atypical antipsychotics have been conducted in hospitalized patients, a Phase-IV, multicentre, 8-week, open-label, flexible-dose study was performed to assess the efficacy and safety of risperidone in outpatients with schizophrenia. METHOD: Three hundred and thirty patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) diagnosis of schizophrenia were enrolled at 61 Canadian sites. Upon trial entry, the patients had their neuroleptic and antiparkinsonian drugs discontinued, and treatment with risperidone was initiated at a dose of 2 mg daily, then increased by 2 mg daily on each of the 2 following days until the initial target dose of 6 mg daily was reached on day 3. No further titration was allowed until day 14, after which the dose could be increased or decreased. RESULTS: During the stabilization phase (days 14-56), the dose was unchanged in 44% of the patients, increased in 24%, decreased in 23%, and titrated both up and down in 9% of the patients. In the efficacy-evaluable population (n = 292), treatment with risperidone produced substantial (-26.4) and significant (P = 0.0001) improvement in the total Positive and Negative Syndrome Scale (PANSS) score. At the end of the study (week 8), 85% of patients were classified as clinically improved according to an a priori definition (that is, 20% or more decrease from baseline in total PANSS score). On their last study visit, 75% of patients reported their experience with risperidone as better than their previous neuroleptic therapy. Risperidone was generally well tolerated. The adverse events reported by more than 5% of the patients were insomnia, nausea, headache, somnolence, dizziness, fatigue, anxiety, vomiting, and ejaculation disorder. Seventy-four percent of the reported treatment-related adverse events were recorded during the first 2 weeks of the trial, possibly because of the discontinuation of prior neuroleptic and antiparkinsonian drugs followed by immediate upward titration of risperidone. However, only 8.5% of adverse events were reported to have occurred during week 3, and only 0.8% of adverse events were reported for week 8. Risperidone treatment produced significant improvements over baseline in the incidence and severity of extrapyramidal symptoms (EPS). A slight but statistically significant increase in body weight was observed. CONCLUSIONS: The results of this open-label, Phase-IV trial in a large population of outpatients with schizophrenia found that risperidone was superior to the neuroleptics that patients had previously taken in terms of efficacy and severity of EPS. Our results suggest the use of risperidone at lower doses in outpatients with schizophrenia.     

The identification and measurement of quality dimensions in health care: focus group interview results

The identification and measurement of service quality are critical factors that are responsible for customer satisfaction. This article identifies 11 attributes that define quality of care and patient satisfaction and reveals various gaps among the patient, physician, and administrator groups in the perceived importance of those dimensions. Managerial implications for patient-focused health care are discussed.     

Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.