Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

Recognition and management of gastrointestinal and hepatic complications of hematopoietic stem cell transplantation has gained increasing importance as indications and techniques of transplantation have expanded in the last few years. The transplant recipient is at risk for several complications including conditioning chemotherapy related toxicities, infections, bleeding, sinusoidal obstruction syndrome, acute and chronic graft-versus-host disease (GVHD) as well as other long-term problems. The severity and the incidence of many complications have improved in the past several years as the intensity of conditioning regimens has diminished and better supportive care and GVHD prevention strategies have been implemented. Transplant clinicians, however, continue to be challenged with problems arising from human leukocyte antigen-mismatched and unrelated donor transplants, expanding transplant indications and age-limit. This review describes the most commonly seen transplant related complications, focusing on their pathogenesis, differential diagnosis and management.     

Correlation between procalcitonin and intra-abdominal pressure and their role in prediction of the severity of acute pancreatitis

Background/aimsEarly assessment of disease severity and vigilant patient monitoring are key factors for adequate treatment of acute pancreatitis (AP). The aim of this study was to determine the correlation of procalcitonin (PCT) serum concentrations and intra-abdominal pressure (IAP) as prognostic markers in early stages of AP.MethodsThis prospective observational study included 51 patients, of which 29 had severe AP (SAP). Patients were evaluated with the Acute Physiology And Chronic Health Evaluation (APACHE II) score, C-reactive protein (CRP) and PCT serum concentrations and IAP at 24 h from admission. PCT was measured three times in the 1st week of disease and three times afterward, while IAP was measured daily. PCT and IAP values correlated with each other, and also compared with APACHE II score and CRP values.ResultsPCT, IAP, CRP values and APACHE II score at 24 h after hospital admission were significantly elevated in patients with SAP. There was significant correlation between PCT and IAP values measured at 24 h of admission, and between maximal PCT and IAP values. Sensitivity/specificity for predicting AP severity at 24 h after admission was 89%/69% for APACHE II score, 75%/86% for CRP, 86%/63% for PCT and 75%/77% for IAP.ConclusionsIncreased IAP was accompanied by increased PCT serum concentration in patients with AP. PCT and IAP can both be used as early markers of AP severity.     

Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome

Movement disorders (MDs), particularly chorea, may be the presenting neurological complication of systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), but the association is not often initially recognized. Current evidence suggests an autoimmune mechanism related to antiphospholipid antibodies in these two conditions, although the antigenic target within the central nervous system has not yet been identified. Based on a comprehensive review of the literature, this article summarizes the current knowledge on MDs in SLE and APS. A high index of suspicion is required to make an early diagnosis and initiate appropriate treatment to provide symptomatic relief and to prevent other systemic complications related to the autoimmune process.     

A common polymorphism in the brain-derived neurotrophic factor gene in patients with adult-onset primary focal and segmental dystonia

Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson’s disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia.     

Radiofrequency lesioning through deep brain stimulation electrodes: A pilot study of lesion geometry and temperature characteristics

Deep brain stimulation (DBS) electrodes have been used effectively to perform radiofrequency lesions in the brain. This study aimed to characterize lesion geometry and peak tissue temperature achieved when lesioning through DBS electrodes. Fresh bovine liver was chosen for a medium as the tissue reliably changes color between 45 and 50°C. Medtronic 3387 DBS electrodes (Medtronic Sofamor Danek, Inc., Memphis, TN, USA) and the Cosman G4 Radiofrequency Generator (Cosman Medical, Inc., Burlington, MA, USA) were used for lesioning. Bipolar lesions were created at currents between 25 mA and 100 mA for 60–120 seconds. Peak tissue temperature was monitored with Cosman disposable cordotomy electrode (LCED; Cosman Medical Inc.) and recorded. Photographic analysis of the lesions was performed. Tissue impedance ranged between 800–900 Ohms, and tissue temperature was maintained at 20°C. With lesions at 25 mA for up to 120 seconds, maximal tissue temperature achieved was 36°C. This correlated with no visible lesions. At 50 mA, maximal tissue temperature exceeded 100°C, which was associated with tissue charring. Lesions created at 35 mA and 40 mA led to an increase in tissue temperature of 63°C and 75°C, respectively. Lesion size was highly reproducible, increasing from 4.5 mm × 7 mm at 35 mA, to 6 mm × 7.5 mm at 50 mA. Preliminary analysis suggests that caution should be exerted in using lesion amplitudes exceeding 40 mA (at 800 Ohms), as peak tissue temperatures in vivo could exceed 100°C. Further in vivo experiments with imaging correlates are needed to further test the safety of this technique.     

Analysis of CYP2D6 genotype and response to tetrabenazine

Tetrabenazine is effective in the treatment of the chorea associated with Huntington disease and other hyperkinetic movement disorders. Following oral administration, tetrabenazine is hepatically transformed into 2 active metabolites that are CYP2D6 substrates. There are 4 CYP2D6 genotypes: poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultrarapid metabolizers. CYP2D6 genotyping was performed on sequential subjects treated with tetrabenazine, but results were not known at the time of titration. Duration of titration to a stable dose, total daily dose, response rating scores, and adverse events were retrospectively collected and subsequently analyzed. Of 127 patients, the majority (n = 100) were categorized as extensive metabolizers, 14 as intermediate metabolizers, 11 as poor metabolizers, and 2 as ultrarapid metabolizers. Ultrarapid metabolizer patients needed a longer titration (8 vs 3.3, 4.4, and 3 weeks, respectively; P < .01) to achieve optimal benefit and required a higher average daily dose than the other patients, but this difference did not reach statistical significance. The treatment response was less robust in the intermediate metabolizer group when compared with the extensive metabolizer patients (P = .013), but there were no statistically significant differences between the various groups with regard to adverse effects. Our findings demonstrate that, aside from the need for a longer titration in the ultrarapid metabolizers, there are no distinguishing features of patients with various CYP2D6 genotypes, and therefore the current recommendation to systematically genotype all patients prescribed more than 50 mg/day of tetrabenazine should be reconsidered. © 2012 Movement Disorder Society     

Differences in the expression of mucins in various forms of cystitis glandularis

A wide spectrum of glandular epithelial metaplastic changes may be seen in the bladder. Cystitis glandularis (CG) is a well-known metaplastic lesion occurring in the presence of chronic inflammation, but there are a few data about mucin expression in its two subtypes (typical and intestinal). The purpose of the present study was to determine the expression of mucin core proteins and CD10 in the different types of CG. For this examination, we used a panel of monoclonal-specific antibodies for MUC1, MUC2, MUC5AC, and MUC6. CG of the intestinal type expressed MUC5AC both in goblet and columnar cells, and strongly expressed intestinal mucin MUC2 only in goblet cells in all cases. There was no expression of MUC1, MUC6, and CD10 in the metaplastic cells. CG of the typical type showed an expression of MUC1 similar to normal urothelium, but the CD10 expression was more intensive than in the control. The mucin expression profile in the different types of CG allows the identification of "gastric mucin" (MUC5AC) together with intestinal mucin (MUC2), while typical CG (CGTP) retains MUC1. Different and contrasting immunoprofiles were evident in various forms of CG. The absence of CD 10 in CG of the intestinal type is a finding that points towards an incomplete form of urinary bladder metaplasia.