Decreased plasma concentration of a novel anti-inflammatory protein--adiponectin--in hypertensive men with coronary artery disease

Aims: Recent studies indicate that adiponectin may have anti-inflammatory and anti-atherogenic properties, suggesting that hypoadiponectinemia can play a role in the pathogenesis of cardiovascular disease. Therefore the aim of the study was to assess plasma adiponectin concentration in hypertensive male patients with coronary artery disease (CAD). Associations of adiponectinemia with other cardiovascular risk factors were also analysed. Methods and results: The study included 99 consecutive male patients (median age 57 years) with hypertension and CAD who at the same time underwent coronary and renal angiography. The control group consisted of 62 BMI-matched healthy male blood donors (median age 48 years). Plasma adiponectin level was significantly lower in the CAD group as compared to the control group (4.01±0.18 vs. 4.88±0.24 μg/ml; p<0.01). There were no differences in plasma adiponectin concentration between hypertensive CAD patients with and without atherosclerotic renal artery stenosis. In the CAD group plasma adiponectin concentration correlated with levels of creatinine (r=0.56; p<0.001), HDL cholesterol (r=0.24; p<0.05), BMI (r=−0.33; p<0.001), glucose (r=−0.22; p<0.05) and triglycerides (r=−0.25; p<0.05). No correlation was found between plasma adiponectin and homocysteine concentrations. In a multivariate stepwise logistic regression model increasing concentrations of adiponectin were independently and significantly associated with a lower risk of CAD (OR 0.58 95% CI 0.42–0.81 p<0.001). Conclusions: Our results showed decreased plasma adiponectin concentration in the studied group of hypertensive men with CAD as compared to normotensive healthy subjects. This may suggest that decreased plasma adiponectin concentration is associated with a higher risk of CAD.     

Impaired novelty P3 potentials in multiple system atrophy--correlation with orthostatic hypotension

Although neuropsychological tests demonstrate frontal lobe dysfunction in multiple system atrophy (MSA), assessment of frontal function using event-related brain potentials (ERPs) has not been sufficiently performed in MSA. The correlation between frontal lobe dysfunction and orthostatic hypotension (OH), which is known to cause frontal hypoperfusion, remains unclear. Our objectives were to assess frontal lobe dysfunction in MSA patients using ERPs and to elucidate the relevance of OH to changes in ERPs. Nine consecutive patients with MSA and nine age- and gender-matched healthy controls were compared by performance in the Wisconsin Card Sorting Test (WCST) and somatosensory ERPs to target and novel stimuli, namely, parietal maximal P3 (target P3) and fronto-central P3 (novelty P3), respectively. The correlation between novelty P3 and OH was evaluated in the MSA group. The MSA group showed a poorer performance in categories achieved (CA), total errors (TE) and perseverative errors by Nelson's (PEN) method in the WCST compared with the control group (CA and PEN: p<0.01; TE: p<0.02). Novelty and target P3s in the MSA group showed significantly prolonged latency (novelty: p<0.05; target: p<0.01) and reduced amplitude (novelty: p<0.02; target: p<0.01) compared with the control group. There was a significant negative correlation between novelty P3 latency and a drop in systolic blood pressure (r=0.76; p<0.02). Abnormalities of novelty P3 in the MSA group might reflect frontal lobe dysfunction, namely failure of attentional set-shifting, that was identified by the WCST. OH may play a role in the development of frontal lobe dysfunction in MSA.     

Sexual dysfunction in multiple sclerosis: a MRI,neurophysiological and urodynamic study

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T₁ and T₂ lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C₂ level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=−0.63, p<0.0001), level of independence (r=−0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=−0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T₁ lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.     

Morphological and latency abnormalities of the mid-latency auditory evoked responses in schizophrenia: a preliminary report

Introduction: Evoked potential (EP) amplitude and latency abnormalities have been extensively examined in schizophrenia. Morphological abnormalities of the mid-latency auditory evoked responses (MLAERs; P50, N100, P200), on the other hand, received very little attention. Methods: Based on a priori defined set of morphological criteria, the morphology and latency of the MLAERs were blindly compared between stable outpatients with schizophrenia (N=27) and age- and gender-matched healthy control subjects (N=22). The morphology of the MLAERs was considered abnormal if one or more of the components fell outside the expected latency range, if one or more of the components were missing, or if a later occurring component was smaller in amplitude than an earlier occurring one. Results: Of the 27 schizophrenia subjects, 20 had waveforms that were deemed atypical, while only 8 from the control group were classified as atypical (χ²=5.52, p<0.02). The latencies of the P50 and N100 components, identified based on morphology, were significantly prolonged in schizophrenia patients. Conclusions: These preliminary data suggest that morphological abnormalities of the MLAERs in schizophrenia patients are significant and should be taken into consideration when examining the MLAERs of this patient population.     

中国抗精神病药物治疗精神分裂症患者P300潜伏期和波幅变化的Meta分析(英文)

背景事件相关电位研究表明,精神分裂症患者的认知功能损害与P300的潜伏期和波幅有关,但尚不清楚这些认知功能的改变是否会随着药物治疗而改变。目的汇集中国的随访研究,确定抗精神病药物治疗与P300成分改变的关系。方法手工和电子检索1982年1月至2011年12月在中国进行的、以中文或英文发表的文献,内容为抗精神病药物治疗前后精神分裂症患者P300的潜伏期和波幅变化。2位评定者对12项符合Meta分析纳入标准的研究独立进行分析。12项研究中有17个样本的P300波幅峰值具有同质性,因而采用固定效应模型计算汇集的标准化效应值(pooledstandardized effect size,PSES);但P300潜伏期数值具有异质性,因而采用随机效应模型计算PSES。采用Egger’s和Begg’s检验及倒漏斗图分析发表性偏倚。结果汇集样本的611例受试者中,治疗前后完成P300潜伏期和波幅测试的502例(82.2%)纳入Meta 分析。发现抗精神病药物治疗与P300波幅微小但显著的增加有关(PSES=0.39, 95% CI [0.26, 0.51], z=6.14, p<0.001)及P300潜伏期微小但显著的减少有关(PSES= -0.29, 95% CI [-0.51, -0.07]; z=2.58; p=0.010)。无显著的发表偏移。结论既往西方的Meta分析主要是基于横断面研究,与此不同,中国的这一精神分裂症患者治疗随访研究的Meta分析发现P300波幅和潜伏期均随药物治疗而改变。提示P300成分,特别是P300波幅,可能是精神分裂症患者药物治疗期间监测认知功能变化的有价值的生物学标记。     

Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression

The present study investigated body weight gain, food intake, open-field activity and brain histamine H1 receptor mRNA and protein expression in rats treated with three types of antipsychotics. Rats were divided into eight groups and treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (as control) for 1 or 12 weeks. Administration of olanzapine for 1 week led to a threefold increase in body weight gain and a 35% increase in fat deposits compared to controls (p<0.05). In the 12-week olanzapine treatment group, accumulative food intake was significantly higher in the first 7 weeks of treatment compared to controls (p<0.018), while body weight gain was significantly greater in the first 8 weeks compared to controls (p<0.045). Using in situ hybridization, we found that olanzapine treatment, but not aripiprazole or haloperidol treatment, significantly reduced H1 receptor mRNA expression in the arcuate hypothalamic nucleus (Arc: −18%, p=0.006, 1 week; −20%, p=0.008, 12 weeks) and ventromedial hypothalamic nucleus (VMH: −22%, p=0.006, 1 week; −19%, p=0.042, 12 weeks) compared to controls. The quantitative autoradiography data showed a reduction in VMH H1 receptor binding density after 1 (−12%, p=0.040) and 12 (−10%, p=0.094) weeks of olanzapine treatment. There were significant negative correlations between the levels of H1 receptor mRNA expression, and body weight gain and energy efficiency in the Arc and VMH after 1- and 12-week antipsychotic treatments in all groups. In addition, H1 receptor mRNA expression in the Arc showed a significant negative correlation with food intake and fat mass in all groups. Furthermore, there were negative correlations between H1 receptor binding density in the VMH and total fat mass and body weight gain after 1 week of antipsychotic treatment. The present study suggests that downregulated VMH and Arc H1 receptor expression may be a key factor contributing to olanzapine-induced obesity.     

Autoimmune diseases in the pedigrees of schizophrenic and control subjects

Autoimmune diseases aggregate in individuals and within pedigrees, and it has been postulated that autoimmune mechanisms may account for a proportion of schizophrenia. Structured questionnaires were used to interview the mothers of 121 DSM-III-R schizophrenic patients and the mothers of 116 controls in order to determine the prevalence of schizophrenia and of autoimmune diseases in their pedigrees. Patients with a schizophrenic first degree relative were significantly more likely to also have a parent or sibling with an autoimmune disease (60% vs. 20%, OR=6.1, 95% CI=2.3−16.5, p=0.0003). A significant excess of insulin dependent diabetes mellitus (IDDM) was present in the parents and siblings of schizophrenic patients (OR=9.65, 95% CI=1.3−429.2, p=0.009). These findings suggest that autoimmune mechanisms may play a role in the aetiology of schizophrenia, particularly familial schizophrenia. Associations have been established between autoimmune diseases and the HLA encoding genes of the major histocompatibility complex on chromosome six, and it may be that some of the genetic liability to schizophrenia involves these genes.     

Correlates of insight in first episode psychosis

Impaired insight is common in schizophrenia and may be related to poor treatment adherence. Few studies have examined the clinical and neurocognitive correlates of insight in early schizophrenia. Early course schizophrenia, schizoaffective, and schizophreniform disorder patients (n=535) were studied. The Positive and Negative Symptom Scale (PANSS) was used to assess psychopathology, and a broad range of neuropsychological functions was assessed. Using hierarchical stepwise multiple regression analyses, we examined the association of clinical, neurocognitive, and premorbid measures with the level of insight. Impaired insight was associated with overall symptomatology, including positive, negative, and general psychopathology and with deficits in cognitive functioning. In descending order of robustness, the significant variables were PANSS general psychopathology (p<0.0001), Rey Auditory Verbal Learning Test (p<0.0004), Clinical Global Impression (p<0.005), PANSS positive (p<0.007), and premorbid adjustment—general subscale (p=0.02). Among the PANSS general psychopathology items, unusual thought content was most robustly associated with impaired insight (p<0.00000). Insight impairment is very common in early schizophrenia, and appears to be associated with a broad range of psychopathology and deficits in multiple cognitive domains. These observations suggest that deficits in insight may be related to a generalized dysfunction of neural networks involved in memory, learning, and executive functions.     

Evaluation of a novel point-of-care enoxaparin monitor with central laboratory anti-Xa levels

Background: Measurement of enoxaparin's anticoagulant activity has been limited to specialized coagulation laboratories and has been impractical for areas needing rapid results, such as during coronary angioplasty. A new point-of-care device, Rapidpoint® ENOX®, was recently developed to measure clotting times with enoxaparin use. Objectives: To correlate ENOX times with anti-Xa levels among patients receiving enoxaparin. Methods: A total of 166 patients receiving enoxaparin for the prevention of deep venous thrombosis or as treatment during acute coronary syndromes or angioplasty were prospectively studied. Citrated and non-citrated whole-blood (CWB and NCWB) samples were obtained at baseline and peak enoxaparin activity. ENOX times were measured with whole-blood, and the Stachrom® anti-Xa assay was performed on the plasma from the remainder of the samples. The Pearson correlation coefficient was used to assess the relationship between these two assays. Results: There was a strong linear correlation between the ENOX times and the anti-Xa activities for both CWB (r=0.89, p<0.001) and NCWB (r=0.82, p<0.001) when considering all 332 samples (baseline and peak). When baseline samples were excluded, the correlation remained strong for CWB ENOX times and anti-Xa levels (r=0.84, p<0.001), but was only moderate for NCWB (r=0.73, p<0.001). A CWB ENOX time of ≤160 s corresponded to anti-Xa level of ≤0.5 IU/ml in 95% (188/197) of patients. A CWB ENOX time ≥200 s corresponded to anti-Xa levels ≥0.8 IU/ml in 96% (93/96) of patients. Conclusions: Rapidpoint® ENOX® times correlate strongly to anti-Xa activities measured by the Stachrom® Heparin Assays for citrated whole-blood samples. This novel test can be used for rapid bedside measurements of enoxaparin anticoagulant activity.     

Gestational diabetes: A case-control study of women''s experience of pregnancy, health and the child

Women with previous gestational diabetes (n = 113) and controls (n = 226) were studied retrospectively by means of questionnaires. Women with gestational diabetes reported less well-being (p<0.05), psychic health (p<0.001) and vigour (p<0.001) during pregnancy and a less positive experience of pregnancy (p<0.001) than controls. They also recalled more worry about health during pregnancy than controls (p<0.001), reported more physical health problems (p<0.05), more worry about health (p<0.05) and kept to a diet more often after pregnancy (women with gestational diabetes 34%, controls 13%, p<0.001). Although most of the women in the groups were not troubled, it was clear that the gestational diabetes influenced their experience of health negatively but motivated them to adopt a healthy lifestyle. Initial treatment with insulin seemed to be slightly more stressful than diet only.