Improvements in both psychosis and motor signs in Parkinson's disease, and changes in regional cerebral blood flow after electroconvulsive therapy

Purpose

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.

Methods

The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).

Results

Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t = 7.2, P = 0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t = 11.7, P < 0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.

Conclusion

We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.     

Personality traits and childhood trauma as correlates of metabolic risk factors: the Netherlands Study of Depression and Anxiety (NESDA)

Objective

Personality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover, despite their interrelatedness, personality and childhood trauma were not yet studied simultaneously. Therefore, we aimed to explore whether personality and childhood trauma are correlates of metabolic risk factors.

Methods

Among 2755 participants of the Netherlands Study of Depression and Anxiety (NESDA), we investigated through linear regression models whether Big Five personality traits (i.e., extraversion, openness, agreeableness, neuroticism and conscientiousness) and childhood trauma type (i.e., emotional neglect, and psychological, physical and sexual abuse) were correlates of metabolic risk factors (i.e., lipids, waist circumference (WC), glucose and blood pressure). Basic covariates (i.e., age, sex and income level), lifestyle, severity of depressive symptoms and years of education were taken into account.

Results

Openness was the most robust favorable correlate, and sexual abuse was the most robust unfavorable correlate of lipids and WC, and of overall metabolic risk (β = −.070; p < .001 and β = .035; p = .04, respectively).

Conclusions

People with a low openness trait and those who experienced childhood sexual abuse are at higher risk of dyslipidemia and abdominal obesity.     

Antipsychotic dose and diminished neural modulation: a multi-site fMRI study

Background

The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.

Methods

Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.

Results

Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t₇₇ = 2.01, P = 0.048).

Conclusion

The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.     

Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder

Objective

Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.

Methods

Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.

Results

In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.

Conclusions

We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.     

Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

Introduction

Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.

Materials and methods

The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.

Results

15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR = 1.02, 95% CI = 0.83 - 1.26 for G versus A and OR = 0.96, 95% CI = 0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.

Conclusion

These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development.     

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective

To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission.

Methods

Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with (n = 152) or without (n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (?50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ?50% MRS decrease, and a MRS score ? 12, respectively) were analyzed.

Results

Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation (p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received (p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone (p = 0.01).

Limitations

Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.

Conclusions

The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.     

A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect

Introduction

Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.

Methods

We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.

Results

Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p = 0.04; OR = 1.45, 95% CI = 1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p = 0.04; OR = 1.83, 95% CI = 1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR = 1.08, 95% CI = 1.05 - 1.11) in both Europeans and South Asians including Han Chinese.

Conclusions

Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect.     

Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by TPH2 gene variants

Objectives

Hopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.

Methods

Depressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.

Results

Four SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.

Conclusions

We found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability.     

Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population

Background

The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese.

Method

A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (−889C/T) and IL-1 (−511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed.

Results

The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (−511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (−889C/T) in IS patients were significantly higher than that in healthy controls (p = 0.001, p = 0.003 and p = 0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR = 1.603; 95%CI = 1.032-2.489; p = 0.036 for the CC genotype of the PDE4D (83T/C) and OR = 1.913; 95%CI = 1.621-2.375; p = 0.034 for the TT genotype of the IL-1 (−889C/T), respectively.

Conclusions

the SNPs of the PDE4D (83T/C) and IL-1 (−889C/T) were associated with increased risk for the development of IS in Northern Han Chinese.     

Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: A prospective multicenter survey

Introduction

Although supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated.

Materials and Methods

We conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively.

Results

Bleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P < 0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P < 0.001), AT dose of 3000 IU/day (OR, 1.912; P = 0.026), and age (OR, 0.985; P = 0.023) were significant factors for improved survival.

Conclusion

The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%.     

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study

Objectives

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia.

Methods

Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30 s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment.

Results

At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z = − 2.214, p = 0.027, positive; Z = − 2.132, p = 0.033, negative; Z = − 2.023, p = 0.043, general pathology; Z = − 2.371, p = 0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ² = 13.35, p = 0.010; χ² = 10.27, p = 0.036; and χ² = 16.50, p = 0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z = − 2.041, p = 0.041; Z = − 2.251, p = 0.024; and Z = − 2.201, p = 0.028, respectively), suggesting improvement in short-term auditory verbal memory.

Conclusions

Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.     

Clinical predictors of recurrent venous thromboembolism: a single institute experience in Korea

Introduction

Racial disparities in incidence rate as well as risk factors for venous thromboembolism (VTE) exist between Asian and Western populations. Moreover, predictors for recurrent VTE were not identified in Asians. Thus, this study was undertaken to investigate risk factors for recurrent VTE events in Korean people.

Materials and Methods

Three hundred-three patients newly diagnosed as VTE were enrolled from Seoul National University Hospital. Recurrence rate based on risk factors for VTE were investigated. Cumulative incidence of recurrent VTE was calculated by the Kaplan and Meier method. Independent predictors for VTE were determined using Cox proportional hazards model.

Results

After a median follow-up of 44 months, 24 (8%) of 303 patients relapsed for a total observation time of 1,217 patient-year. Cumulative incidences of recurrent VTE were 3% at 1 year, 10% at 5 years, and 18% at 8 years. Independent predictors for recurrent VTE were presence of residual thrombosis (hazard ratio [HR] = 3.1, 95% confidence interval [CI] 1.0-9.3; p = 0.044), antiphospholipid syndrome (APS) (HR = 4.3, 95% CI 1.0-19.0; p = 0.052), and age 50 years or younger (HR = 2.5, 95% CI 1.0-6.6; p = 0.053) by multivariate analysis. Residual thrombosis and APS remained predictive of recurrence by the anticoagulation-period stratified analysis.

Conclusions

In contrast to Western populations, Korean patients with VTE had the lower recurrent rate. Extended anticoagulation is necessary for Korean patients with residual thrombosis or APS.     

Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study

Introduction

Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the potential role of suPAR is unknown. We investigated suPAR as a possible marker of arterial stiffness in Africans and Caucasians.

Methods

This study involved 207 Africans and 314 Caucasians (aged 20-70 yrs). C-reactive protein (CRP) and suPAR were determined in fasting blood samples. We measured blood pressure, pulse wave velocity (PWV) and Windkessel arterial compliance (Cwk).

Results

Africans displayed higher suPAR, CRP, PWV and lower Cwk (p < 0.001) compared to Caucasians. SuPAR was elevated in Africans irrespective of gender and smoking. We found strong relationships between PWV and suPAR (r = 0.27; p < 0.001) and Cwk and suPAR (r = − 0.39; p < 0.001) in the whole group, but found no independent relationship of any arterial stiffness measure and suPAR in Africans after adjustment for confounders. Caucasian men indicated a weak significant independent association between Cwk and suPAR (β = − 0.09; p = 0.028).

Conclusion

Africans had higher levels of suPAR and arterial stiffness than Caucasians (p < 0.001), but there was no independent relationship between arterial stiffness and suPAR in the Africans. It is speculated that due to the inflammatory role of suPAR, it will have stronger relationships with atherosclerosis, which has not yet manifested in this relatively young population group. SuPAR may therefore not be an ideal early marker of cardiovascular dysfunction, but may rather indicate established CVD.     

High plasma nesfatin-1 level in patients with major depressive disorder

Aim

In the present study, our aim was to determine the changes in the plasma concentrations of a recently discovered peptide hormone nesfatin-1 in patients with major depressive disorder and then to make a comparison with the control group.

Method

Subjects in the patient group were randomly selected from Mustafa Kemal University, Medical School, Research and Training Hospital, Psychiatry Department, Outpatient Clinic and subjects in the control group were selected from healthy volunteers. Healthy control subjects were matched in terms of weight and body mass index. Hamilton Depression Rating Scale (HAM-D) was applied to both groups. ELISA method was used for measurement of plasma nesfatin-1 levels.

Results

The average nesfatin-1 level was statistically higher in patients with major depressive disorder than in the control group (p < 0.001). A positive correlation was observed between plasma nesfatin-1 levels and HAM-D scores both in the patient group (r = 0.59, p < 0.001) and in the control group (r = 0.58, p < 0.001).

Conclusion

Our findings suggest a possible relationship between major depressive disorder and high plasma nesfatin-1 level.     

Aggression and psychopharmacological treatments in major psychosis and personality disorders during hospitalisation

Background

A number of large-scale studies have shown that there is a relationship between many psychiatric disorders and aggression or violence. As no medication is currently approved for the treatment of aggression, pharmacotherapy (often involving drug combinations) is used on a trial-and-error basis with various degrees of response.

Method

The study involved 244 in-patients aged 19-83 years (mean 41.9 ± 11.3 SD). The Modified Overt Aggression Scale (MOAS) was used to assess any aggressive or violent behaviors occurring in the week before admission and upon discharge.Psychopathology was assessed using the Brief Psychiatric Rating Scales (BPRS).

Results

All of the patients showed a significant improvement (p < 0.001) in mean weighted total MOAS scores at the end of the study, with no significant differences between the various drugs or combination therapies. The patients who received combination treatments including antidepressants showed a worsening in the weighted total MOAS score (18.46% ± 114.31% SD); the patients who did not receive antidepressants had an improvement (13.61% ± 257.36% SD) (p = 0.0069).

Conclusions

Multivariate testing of the variables age, gender, substance/alcohol abuse, the duration of hospitalisation, the administration of mood stabilisers, and the use of typical or atipical antipsychotics showed that the severity of the psychopathological picture correlated significantly with the presence of violence, whereas the effect of combined antidepressant treatment on violent behavior was only relative.     

A clinical-laboratory approach contributing to a rapid and reliable diagnosis of heparin-induced thrombocytopenia

Introduction

Heparin-induced thrombocytopenia (HIT) remains a very challenging diagnosis. The first objective of this study was to compare the performance of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA. The main purpose was to evaluate the diagnostic utility of the combination of the H/PF4 PaGIA^® with the clinical “4T's” score as a screening strategy.

Materials and Methods

102 patients with clinical suspicion of HIT were classified into risk groups using the 4T's score. The presence of HIT antibodies was assessed by two immunoassays and confirmed by a functional flow cytometric assay.

Results

Comparison of the ID-H/PF4 PaGIA^® with the Asserachrom^® HPIA ELISA demonstrated a comparable technical performance, being an excellent screening test to rule out HIT (negative predictive value or NPV = 100%). According to the 4T's score, HIT was excluded in all low risk patients (NPV = 100%). ELISA optical density levels were significantly different between all risk groups (P-values < 0.01). In contrast, due to the low positive predictive value (22%) and weak positive likelihood ratio (2.6), a positive ID-H/PF4 PaGIA^® result did not considerably increase the probability of HIT.

Conclusion

Our study confirms the combination of the 4T's score with the ID-H/PF4 PaGIA^® as a reliable strategy to rule out HIT. Yet, confirming positive ID-H/PF4 PaGIA^® results by flow cytometry within 1-2 h after blood sampling remains necessary. This novel clinical-laboratory approach can contribute in a rapid and reliable way to the definite diagnosis of HIT.     

Relationship between inflammation and metabolic syndrome following treatment with paliperidone for schizophrenia

Objective

Metabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters.

Methods

Data were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements (i.e., weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides.

Results

Among the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10³ WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24 weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference.

Conclusions

Schizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.     

Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function

Introduction

Patients with chronic kidney disease exhibit features of a hypercoagulable state and have endothelial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease.

Materials and Methods

We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X); natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1 + 2) in 66 stage 4&5 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interleukin-6) was determined.

Results

Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1 + 2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P < 0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r = 0.58; P < 0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function.

Conclusions

Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagulants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothelial based regulation but associated with an inflammatory state.