A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia

OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.     

Cerebral amino acid changes in an animal model of intrauterine growth retardation

As part of a series of experiments to ascertain the effects of prenatal malnutrition on brain development, we measured brain amino acids in an animal model of intrauterine growth retardation (IUGR) obtained by restriction of blood supply to the fetusin utero during the last 5 days of gestation. In the present study, amino acids were measured during development by HPLC as their O-phthaldialdehyde derivatives in cerebral cortex, cerebellum and hippocampus. In rats with IUGR, significant increase of alanine (by 20% to 50%) and taurine (by 20% to 80%) were observed prior to weaning in the cerebellum and the cerebral cortex respectively. Alanine levels were also increased in hippocampus. In control animals, at birth, activities of the GABA nerve terminal marker enzyme glutamic acid decarboxylase (GAD) were found to be 32%, 17%, and 11% of adult values in cerebellum, hippocampus and cerebral cortex respectively. Two-day-old rats with IUGR had significantly lower GAD activities in all brain regions. Thus, impairment of nutrient supply to fetal brain results in selective regional abnormalities of amino acids particularly in the cerebral cortex.     

Public views on participating in newborn screening using genome sequencing

Growing discussion on the use of whole-genome or exome sequencing (WG/ES) in newborn screening (NBS) has raised concerns regarding the generation of incidental information on millions of infants annually. It is unknown whether integrating WG/ES would alter public expectations regarding participation in universal NBS. We assessed public willingness to participate in NBS using WG/ES compared with current NBS. Our secondary objective was to assess the public''s beliefs regarding a parental responsibility to participate in WG/ES-based NBS compared with current NBS. We examined self-reported attitudes regarding willingness to participate in NBS using a cross-sectional national survey of Canadian residents recruited through an internet panel, reflective of the Canadian population by age, gender and region. Our results showed that fewer respondents would be willing to participate in NBS using WG/ES compared with NBS using current technologies (80 vs 94%, P<0.001), or perceived a parental responsibility to participate in WG/ES-based NBS vs current NBS (30 vs 48%, P<0.001). Our findings suggest that integrating WG/ES into NBS might reduce participation, and challenge the moral authority that NBS programmes rely upon to ensure population benefits. These findings point to the need for caution in the untargeted use of WG/ES in public health contexts.     

消旋棉酚拆分的研究——Ⅱ.手性α-甲基苯乙胺及α-甲基苄胺为拆分剂

本文报道用中压柱色谱快速分离S或R-α-甲基苯乙胺及S或R-α-甲基苄胺缩(±)-棉酚的方法,可得光学活性胺缩( )或(一)-棉酚非对映体,经水解分别得到( )或(一)-棉酚。并证明胺缩光学活性棉酚非对映体之间有互相转化的性质,此特性可利用于棉酚对映体的转化。     

Pulsatile gonadotrophin secretion in women with polycystic ovary syndrome after gonadotrophin-releasing hormone agonist treatment

In polycystic ovary syndrome (PCOS), increased luteinizing hormone (LH) pulse frequency has been attributed to either the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator or ovarian oestrogen feedback. To address this issue, a detailed examination of pulsatile LH secretion was undertaken during recovery from GnRH agonist (GnRHa) suppression. Each of six women with PCOS and six normal ovulatory women received daily GnRHa treatment for 14 weeks. Frequent blood samples were collected and assayed for gonadotrophins, androgens and oestrogens before, during and up to 4 weeks after treatment. Women with PCOS had higher basal LH pulse frequency and amplitude and increased serum concentrations of LH, androstenedione, testosterone and oestrone than controls. After 3 months of GnRHa treatment, all these parameters were suppressed with no differences observed between the two groups. One week after cessation of GnRHa, LH pulse frequency promptly returned to pre-treatment range with no between-group differences noted, whereas LH pulse amplitude, serum gonadotrophins and ovarian steroids remained maximally suppressed and equivalent in the two groups. Subsequent LH pulse frequency remained constant while LH pulse amplitude and circulating concentrations gradually increased in parallel with a return of serum oestrogen to pre-treatment values. Despite comparable resumption of LH secretion in the two groups, corresponding androgen concentrations in women with PCOS were greater than those of normal ovulatory women. Thus, the immediate restoration of LH pulse frequency after discontinuing GnRHa treatment is largely independent of ovarian oestrogen production and reflects primacy of the GnRH pulse generator in determining basal LH pulse frequency. Equivalent LH pulse frequency rates in the two groups during the recovery period do not suggest an intrinsic hypothalamic-pituitary hyperactivity in PCOS.