Characterization of VHL promoter variants in patients suspected of Von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which carriers are at an increased risk of developing a variety of tumors in multiple organ systems. A clinical diagnosis of VHL is determined by the presence of specific clinical manifestations while a molecular genetic diagnosis results from a pathogenic variant in the VHL gene. The majority of mutations occur in VHL coding exons and DNA analysis of these regions has a reported sensitivity of nearly 100%. However, rare variants in the VHL gene promoter may be detected in some cases of suspected VHL disease. We report two cases where VHL promoter variants were detected and describe the role of multi-step mRNA and protein analysis in the diagnostic evaluation of these cases.     

Allocation to Matched Related or Unrelated Donor Results in Similar Clinical Outcomes without Increased Risk of Failure to Proceed to Transplant among Patients with Acute Myeloid Leukemia: A Retrospective Analysis from the Time of Transplant Approval

Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p?=?.63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p?=?.001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p?=?.54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p?=?.83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.     

Periapical and endodontic status of type 2 diabetic patients in Catalonia, Spain: a cross-sectional study

Introduction

The aim of this study was to investigate radiographically the prevalence of apical periodontitis (AP) and endodontic treatment in a sample of adult type II diabetic patients and control subjects.

Methods

In a cross-sectional study, the radiographic records of 50 adult patients reporting a history of well-controlled type 2 diabetes mellitus (DM) (study group) and 50 age- and sex-matched subjects who reported no history of DM (control group) were examined. Periapical status of all teeth was assessed using the periapical index score.

Results

The average number of teeth per patient in the diabetic and control groups was 21.9 and 24.6 teeth, respectively (P = .012). AP in one or more teeth was found in 37 diabetic patients (74%) and in 21 control subjects (42%) (odds ratio = 3.9, P = .002). One or more root-filled teeth were found in 35 (70%) and 25 (50%) of diabetic and control subjects, respectively (odds ratio = 2.3, P = .043). Among diabetic patients with root-filled teeth, 16 (46%) had AP affecting at least one treated tooth. Among controls with root-filled teeth, 6 (24%) had AP affecting at least one treated tooth (P > .05). Adjusting for teeth number, multivariate logistic regression analysis showed that periapical status (odds ratio = 3.3, P = .0071) and the number of root-filled teeth (odds ratio = 1.7; P = .0035) were significantly associated with diabetic status.

Conclusions

The results showed that in adult patients, type 2 DM is significantly associated with an increased prevalence of AP and endodontic treatment.     

A role of peripheral myelin protein 2 in lipid homeostasis of myelinating schwann cells

Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although Pmp2 is predominantly expressed in myelinated Schwann cells, its role in glia is currently unknown. To study its function in PNS biology, we have generated a complete Pmp2 knockout mouse (Pmp2^‐/‐). Comprehensive characterization of Pmp2^‐/‐ mice revealed a temporary reduction in their motor nerve conduction velocity (MNCV). While this change was not accompanied by any defects in general myelin structure, we detected transitory alterations in the myelin lipid profile of Pmp2^‐/‐ mice. It was previously proposed that Pmp2 and Mbp have comparable functions in the PNS suggesting that the presence of Mbp can partially mask the Pmp2^‐/‐ phenotype. Indeed, we found that Mbp lacking Shi^‐/‐ mice, similar to Pmp2^‐/‐ animals, have preserved myelin structure and reduced MNCV, but this phenotype was not aggravated in Pmp2^‐/‐/Shi^‐/‐ mutants indicating that Pmp2 and Mbp do not substitute each other's functions in the PNS. These data, together with our observation that Pmp2 binds and transports fatty acids to membranes, uncover a role for Pmp2 in lipid homeostasis of myelinating Schwann cells. GLIA 2014;62:1502–1512     

Roman Catholic beliefs produce characteristic neural responses to moral dilemmas

This study provides exploratory evidence about how behavioral and neural responses to standard moral dilemmas are influenced by religious belief. Eleven Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential neural activity between the two groups was found in precuneus and in prefrontal, frontal and temporal regions. Furthermore, a double dissociation showed that Catholics recruited different areas for deontological (precuneus; temporoparietal junction) and utilitarian moral judgments [dorsolateral prefrontal cortex (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for both types of judgment). Finally, we tested how both groups responded to personal and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and posterior cingulate cortex during utilitarian moral judgments to impersonal moral dilemmas and enhanced responses in anterior cingulate cortex and superior temporal sulcus during deontological moral judgments to personal moral dilemmas. Our results indicate that moral judgment can be influenced by an acquired set of norms and conventions transmitted through religious indoctrination and practice. Catholic individuals may hold enhanced awareness of the incommensurability between two unequivocal doctrines of the Catholic belief set, triggered explicitly in a moral dilemma: help and care in all circumstances—but thou shalt not kill.     

Lesion mimicking perianal abscess in an immunocompromised patient: Report of a case

INTRODUCTION

Ischiorrectal tumoral masses mimicking perianal abscess and abscess from uncommon microbiological origins have previously been reported.

PRESENTATION OF CASE

Unusual perianal abscess arising from an hematoma in an elderly woman with myelodysplastic syndrome: the patient presented on the emergency with gluteal pain and fever after intramuscular injection of analgesic drug. Physical examination revealed subcutaneous thickening on gluteus and perianal region, without skin changes. Magnetic resonance reported an heterogeneous mass sized 5 cm × 12 cm × 20 cm from gluteus maximus to ischioanal fat under levator ani muscle, through sciatic notch. Debridement of an staphylococceal infected hematoma through a single left lateral gluteus incision, and primary closure was performed. Proctologic examination was normal, so any perianal incision was done. The site infection progressed, so the patient required new surgery with wet cure. The patient contracted nosocomial pneumonia and died due to sepsis.

DISCUSSION

Hematological diseases can yield infectious and bleeding disorders. Intramuscular injections often cause haematomas that can lead to pyomyositis. Pyomyositis requires early debridement and continue cure.

CONCLUSION

Intramuscular administration of drugs should be avoided in patients with thrombocytopenia. Gluteal region is connected to perianal area through the sciatic notch. Usually perianal abscess in immunocompromised patients arise from proctologic origin, but other causes may be taken into account.