Adverse effects of intrathecal methotrexate in children with acute leukemia in remission

A toxic syndrome characterized by fever, headache, and vomiting, lasting 2-5 days, occurred in 61% of 39 children with acute leukemia in complete remission, receiving central nervous system prophylaxis with intrathecal methotrexate, and in 14% of 34 children receiving the same plus cranial radiation. The syndrome was accompanied by pleocytosis with lymphocytes, monocytoid cells, and neutrophils. There was evidence of cumulative Mtx toxicity, since the toxic syndrome occurred mostly after the third and fourth dose and did not recur with longer intervals between doses. The incidence of the syndrome was significantly reduced by the use of Elliott's B solution as Mtx diluent, rather than water or normal saline. The occurrence of pleocytosis and toxic clinical syndrome was also significantly reduced in patients receiving concomitant cranial radiation, probably due to the lympholytic action of radiotherapy and the depressed cellular response of irradiated tissues. The use of Elliott's B solution as diluent for IT Mtx and an appropriate interval between Mtx doses are suggested for prevention of this toxic syndrome.     

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Psychosocial Correlates of Suicidal Ideation in Rural South African Adolescents

Suicide is a prevalent problem among young people in Southern Africa, but prevention programs are largely absent. This survey aimed to identify the behavioral and psychosocial correlates of suicidal ideation among adolescents in Limpopo. A two-stage cluster sample design was used to establish a representative sample of 591 adolescents. Bivariate correlations and multiple linear regression analyses were conducted. Findings show that suicidal ideation is prevalent among adolescents. The psychosocial factors perceived social support and negative feelings about the family and the behavioral factors forced sexual intercourse and physical violence by the partner were found to increase the risk of suicidal ideation. Depression mediated the relationship between these psychosocial and behavioral risk factors and suicidal ideation. This study increased our understanding of the psychosocial and behavioral predictors of adolescent suicidal ideation. The findings provide target points for future intervention programs and call for supportive structures to assist adolescents with suicidal ideation.     

cAMP regulates DEP domain-mediated binding of the guanine nucleotide exchange factor Epac1 to phosphatidic acid at the plasma membrane

Epac1 is a cAMP-regulated guanine nucleotide exchange factor for the small G protein Rap. Upon cAMP binding, Epac1 undergoes a conformational change that results in its release from autoinhibition. In addition, cAMP induces the translocation of Epac1 from the cytosol to the plasma membrane. This relocalization of Epac1 is required for efficient activation of plasma membrane-located Rap and for cAMP-induced cell adhesion. This translocation requires the Dishevelled, Egl-10, Pleckstrin (DEP) domain, but the molecular entity that serves as the plasma membrane anchor and the possible mechanism of regulated binding remains elusive. Here we show that Epac1 binds directly to phosphatidic acid. Similar to the cAMP-induced Epac1 translocation, this binding is regulated by cAMP and requires the DEP domain. Furthermore, depletion of phosphatidic acid by inhibition of phospholipase D1 prevents cAMP-induced translocation of Epac1 as well as the subsequent activation of Rap at the plasma membrane. Finally, mutation of a single basic residue within a polybasic stretch of the DEP domain, which abolishes translocation, also prevents binding to phosphatidic acid. From these results we conclude that cAMP induces a conformational change in Epac1 that enables DEP domain-mediated binding to phosphatidic acid, resulting in the tethering of Epac1 at the plasma membrane and subsequent activation of Rap.     

One-year hemodynamic comparison of Perimount Magna with St Jude Epic aortic bioprostheses

Introduction

Cardiac surgeons are using more bioprosthetic valves due to the ageing population as well as to improvements that have been made to these implants. We sought to compare the 1-year hemodynamics of two commercially available valves by echocardiographic parameters.

Material and methods

Retrospective review of our institutional database revealed 69 patients who received either Perimount Magna (n = 33) or St Jude Epic (n = 36) valves in the aortic position with no other valve surgery between June 2004 and March 2006. All patients received transthoracic echocardiography at 1 year. Comparisons between groups were made at baseline and at 1-year follow-up. In addition, a pairwise comparison was performed in each patient to determine the change in echocardiographic parameters between baseline and follow-up.

Results

Mean implanted valve size was similar (Magna 24.3 ±2.0 mm vs. Epic 24.1 ±2.2 mm). Pre- and intraoperative patient variables were similar between the two groups. There were lower peak and mean pressure gradients in the Magna group, both at discharge and one year after surgery. This correlated with a larger indexed effective orifice area (Magna 0.8 ±0.2 cm²/m² vs. Epic 0.67 ±0.2 cm²/m², p = 0.02). In spite of these findings, left ventricular mass regression was not different.

Conclusions

These findings suggest that in a series with relatively low indexed effective orifice areas, the peak and mean gradients obtained were acceptable. More clinical follow-up of these patients is required to assess the true impact of prosthesis patient mismatch.     

Unconscious thought reduces intrusion development: A replication and extension

Background and ObjectivesIntrusive images after a traumatic event, a hallmark feature of post-traumatic stress disorder, are suggested to develop because the trauma memory is disorganized and not integrated into autobiographical memory. Unconscious Thought Theory predicts that information can be conceptually organized after a period of unconscious thought (UT), more so than after conscious thought (CT). We aimed to test the hypothesis that UT decreases intrusions and increases conceptual organization in memory.MethodsParticipants were shown a stressful film and were required to perform an UT task, a CT task, or a distraction task. Intrusions of the film, intrusion qualities, and sequence memory were measured afterwards.ResultsWe confirmed our hypothesis that UT (versus CT or mere distraction) leads to fewer intrusions, thereby replicating earlier research. Contrary to prediction, we found no difference between the conditions on sequence memory. In addition, conscious thought appeared to increase intrusion nowness and arousal.LimitationsThe analogue design and healthy participant sample prevent from generalizing results to other populations. Intrusion frequency and qualities were assessed immediately after the film thereby prohibiting us from drawing conclusions about any long-term effects.ConclusionsEngaging in unconscious thought after a stressful film can reduce intrusion frequency. This has potential implications for clinical interventions to prevent initial stress symptoms. The underlying mechanism remains unclear for now and provides an avenue for future research.