Early bilirubinemia after allogeneic stem cell transplantation - an endothelial complication

Hyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0-28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, interleukin (IL)18, CXCL8 and suppressor of tumorigenicity-2 (ST2) serum levels, and the endothelial activation and stress index (EASIX). Clinical correlations were validated in a sample of 388 patients transplanted in an independent institution. The EB cut off was determined at 3.6 mg/dL (61.6 mu M). EB predicted OS (HR 1.60, 95% CI 1.21-2.12, p < 0.001), and NRM (CSHR 2.14; 1.28-3.56, p = 0.004), also independent of typical endothelial complications such as veno-occlusive disease, refractory acute graft-versus-host disease, or transplant-associated microangiopathy. However, EB correlated with high Angiopoietin-2, EASIX-pre and EASIX-day 0, as well as increased levels of posttransplant CXCL8, IL18, and ST2. In summary, EB indicates a poor prognosis. The association of EB with endothelial biomarkers suggests an endothelial pathomechanism also for this posttransplant complication

Schizophrenia or frontotemporal dementia in a young Chinese female: A purview of possible diagnoses

Frontotemporal dementia (FTD) is now increasingly being recognized as one of the causes of young onset dementia (YOD). The presentation of FTD can be subtle with a broad range of symptoms. This frequently causes misdiagnosis and a delay in initiating the correct treatment. While subtle personality changes, disinhibition and problems in executive functioning are frequently encountered in FTD, frank psychotic symptoms resembling schizophrenia are unusual. This is a case of a 38 yearold Chinese female that highlights how obsessive compulsive symptoms which progressed to florid psychosis and disorganized speech and behavior can be a presenting picture in FTD. For seven years, this patient was treated as a case of schizophrenia and was thought to have poor response to electroconvulsive therapy (ECT) as well as antipsychotic medication. Her blood work and electroencephalogram (EEG) were normal. Magnetic resonance imaging (MRI) showed progressive cerebral atrophy. This case report suggests that psychosis should be investigated in detail especially when the clinical presentation is not typical of a functional disorder and more so when the patient is not responsive to conventional treatment. This report also highlights the importance of eliciting symptoms suggestive of an ``organic'' etiology, such as incontinence and disorientation. In addition, the usefulness of repeated imaging to show the rapidly progressive course of FTD has been illustrated. Other possible differential diagnoses of this patient are also discussed

Gender Influences On Psychopathology And Functionality In Schizophrenia In University Malaya Medical Centre, Kuala Lumpur, Malaysia

Numerous studies on gender differences in schizophrenia have been published to summarize the evidence from molecular to the clinical level. Female schizophrenics are found to have better skills then the males. In addition, it was described that the male schizophrenics exhibited more negative symptoms compared to the females. The aim of this study was to investigate the gender influences on psychopathology and functionality of schizophrenia patie nts in University Malaya Medical Centre. Methods: All patients diagnosed with schizophrenia who attended the outpatient psychiatric clinic during a two-month period were recruited into the study.The patients were assessed on their socio-demographic profile, clinical data, psychopathology according to Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and functionality by using Personal and Social Performance Scale (PSP). Results: A total of 76 female and 74 male patients entered the study. Both genders were matched in age, ethnic groups, educational background and duration of illness. There were more singles among the male schizophrenics. 72% of the female schizophrenics and 87% of the males were on atypical antipsychotics (p<0.05). 57% of the female and 55% of the male schizophrenics hold a job. There were no significant differences in positive, negative and general psychopathology in both genders. The mean total score of PANSS was 46.5 in the females and 48.2 in the males. There was also no significant difference of PSP total score in both gender. The mean score of PSP was 73.0 for female schizophrenics and 70.0 for the males. PANSS scores was negatively correlated with PSP scores (r = - 0.70, p<0.001). Conclusion: There were no gender differences in psychopathology and functionality among schizophrenia patients attending psychiatric outpatient clinic in University Malaya Medical Center. Both genders are functioning well and more than half are having a job

Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism

Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value = 0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value = 0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value = 0.003 and 0.002, respectively). Gene–gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P = 0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P = 0.015 and P = 0.010, for BPD and SZ, respectively) and GG (P = 0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ

Peripheral PDLIM5 expression in bipolar disorder and the effect of olanzapine administration

<p>Abstract</p> <p>Background</p> <p>One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is <it>PDLIM5</it>, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on <it>PDLIM5</it> mRNA expression in the peripheral blood leukocytes of BPD patients.</p> <p>Methods</p> <p>We measured the expression of <it>PDLIM5</it> mRNA from 16 patients with BPD Type I after 0, 4, and 8 weeks of treatment with olanzapine using quantitative real-time PCR. The Young Mania Rating Scale was used to evaluate the severity of manic symptoms in BPD patients. We also compared <it>PDLIM5</it> mRNA expression in treatment-naïve BPD patients with that in healthy control subjects.</p> <p>Results</p> <p>No significant difference was found in <it>PDLIM5</it> mRNA expression between patients before olanzapine treatment and following 4 and 8 weeks of treatment (<it>p</it>>0.05). Although we observed a significant reduction in the severity of manic symptoms in all BPD patients (<it>p</it><0.05), the effectiveness of the medication did not significantly correlate with the expression of <it>PDLIM5</it> mRNA (<it>p</it>>0.05). Interestingly, <it>PDLIM5</it> mRNA expression differed significantly between treatment-naïve BPD patients and healthy control subjects (<it>p</it>=0.002).</p> <p>Conclusion</p> <p><it>PDLIM5</it> mRNA expression did not appear to be a reflection of the efficacy of olanzapine in reducing the manic symptoms of BPD. The significant difference in expression of <it>PDLIM5</it> mRNA in the peripheral blood leukocytes of treatment-naïve BPD patients versus that of healthy control subjects, however, suggests that it may be a good biological marker for BPD.</p