A novel t(2;3)(p11;q27) in a case of follicular lymphoma

Rearrangement of the BCL6 gene is found in follicular lymphomas and in diffuse large B cell lymphomas of follicular center cell origin. The breakpoints cluster mainly in a region spanning the first noncoding exon of the gene (the major breakpoint region). A second breakpoint cluster has also been identified upstream of the first BCL6 noncoding exon (the alternative breakpoint region [ABR]). To date, eight different rearrangements involving the ABR have been reported. Here, we describe a novel rearrangement involving a t(2;3)(p11;q27) translocation that affects the ABR in an unusual combination with the IGK locus.     

t(10;16)(q22;p13) and MORF-CREBBP fusion is a recurrent event in acute myeloid leukemia

Recently, it was shown that t(10;16)(q22;p13) fuses the MORF and CREBBP genes in a case of childhood acute myeloid leukemia (AML) M5a, with a complex karyotype containing other rearrangements. Here, we report a new case with the MORF-CREBBP fusion in an 84-year-old patient diagnosed with AML M5b, in which the t(10;16)(q22;p13) was the only cytogenetic aberration. This supports that this is a recurrent pathogenic translocation in AML.     

TP53 is frequently altered by methylation, mutation, and/or deletion in acute lymphoblastic leukaemia

Different mechanisms, such as chromosomal rearrangements, deletions, mutations, and methylation/demethylation of the promoter regions of genes, have been shown to be involved in acute lymphoblastic leukaemia (ALL). These genetic and epigenetic alterations lead to the activation of protooncogenes or to inactivation of tumour suppressor genes promoting cell proliferation. One of the most frequently inactivated tumour suppressor genes is TP53, which is altered in 50% of human tumours. In this study, we have analysed: (1) the complete coding region, all intron-exon junctions and noncoding regions of exons 1-11 of TP53 by lexon-DGGE; (2) the methylation status of the 5' region of TP53 and (3) the deletion of one or both alleles of the gene by fluorescence in situ hybridisation (FISH) in 57 ALL patients. Using these techniques, we have found promoter methylation in 32% of the cases, missense mutations in 8.8%, and deletion of one allele in 7.5% of the samples, with TP53 being altered in 40% of the ALL samples studied in this series.     

Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

Transgenic expression of the abnormal products of acute myeloid leukemia-associated (AML-associated) primary chromosomal translocations in hematopoietic stem/progenitor cells initiates leukemogenesis in mice, yet additional mutations are needed for leukemia development. We report here aberrant expression of PR domain containing 16 (PRDM16) in AML cells with either translocations of 1p36 or normal karyotype. These carried, respectively, relatively high prevalence of mutations in the TP53 tumor suppressor gene and in the nucleophosmin (NPM) gene, which regulates p53. Two protein isoforms are expressed from PRDM16, which differ in the presence or absence of the PR domain. Overexpression of the short isoform, sPRDM16, in mouse bone marrow induced AML with full penetrance, but only in the absence of p53. The mouse leukemias were characterized by multilineage cellular abnormalities and megakaryocyte dysplasia, a common feature of human AMLs with 1p36 translocations or NPM mutations. Overexpression of sPRDM16 increased the pool of HSCs in vivo, and in vitro blocked myeloid differentiation and prolonged progenitor life span. Loss of p53 augmented the effects of sPRDM16 on stem cell number and induced immortalization of progenitors. Thus, overexpression of sPRDM16 induces abnormal growth of stem cells and progenitors and cooperates with disruption of the p53 pathway in the induction of myeloid leukemia.     

Prenatal diagnosis and tridimensional ultrasound features of bilateral femoral hypoplasia – Unusual facies syndrome

The femoral hypoplasia – unusual facies syndrome is a rare disorder, which was described first three decades ago. It is characterised by the occurrence of short femurs with certain associated alterations mainly affecting the face, of which micrognathia is the most frequently found. Although the etiology of this condition is unknown, clear relationship with maternal insulin-dependent diabetes has often been reported, which suggests some sort of inherited component. Nevertheless, most cases occur sporadically. This entity is usually diagnosed after birth because prenatal ultrasound detection is rather difficult. Here, we report a case of prospective detection. So far, such cases have been seldom described in the literature.     

Long chain omega-3 fatty acids intake,fish consumption and mental disorders in the SUN cohort study

Background Very long chain omega-3 fatty acids (w-3 PUFA) intake and fish consumption have been suggested as protective factors against neuropsychiatric disorders but there is scarcity of large cohort studies assessing this association. Aim of the study To assess the association between w-3-PUFA intake and fish consumption and mental disorders. Methods A prospective cohort study was performed in 7,903 participants. W-3 PUFA intake and fish consumption were ascertained through a validated semi-quantitative food frequency questionnaire. The outcomes after 2 years of follow-up were: (1) Incident mental disorder (depression, anxiety, or stress), (2) incident depression, and (3) incident anxiety. Logistic regression models and generalized additive models were fit to assess the relationship between w-3 PUFA intake or fish consumption and the incidence of these outcomes. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated. Results 173 cases of depression, 335 cases of anxiety, and 4 cases of stress were observed during 2-year follow-up. ORs (95% CI) of mental disorder for successive quintiles of energy-adjusted w-3 PUFA intake were 1 (reference), 0.72 (0.52–0.99), 0.79 (0.58–1.08), 0.65 (0.47–0.90), and 1.04 (0.78–1.40). Subjects with a moderate consumption of fish (third and fourth quintiles of consumption: median of each quintile 83.3 and 112 g/day, respectively) had a relative risk reduction higher than 30%. Conclusions A potential benefit of w-3 PUFA intake on total mental disorders is suggested, although no linear trend was apparent.     

Self-oriented perfectionism in eating disorders

OBJECTIVE: To assess perfectionism dimensions in eating disorders in comparison with other psychiatric disorders and subjects from the general population. METHOD: The Child and Adolescent Perfectionism Scale (CAPS), the Eating Disorders Inventory (EDI-2), and the Eating Attitudes Test (EAT) were administered to a group of 108 female eating-disordered patients (75 anorexia nervosa and 33 bulimia nervosa), to a group of 86 female psychiatric patients with anxiety (N = 32), depressive (N = 38), or adaptive disorders (N = 16), and to 213 healthy female participants. RESULTS: Both bulimic and anorexic patients scored higher on Self-Oriented Perfectionism (p < 0.001) than the other two groups but not on Socially-Prescribed Perfectionism (p = 0.054). Among patients with eating disorder, 17.6% obtained a score two standard deviations higher than the mean in the healthy comparison group on self-oriented perfectionism; this percentage was significantly higher than in the other two groups. The percentage of eating disorder patients with high socially-prescribed perfectionism was similar to that found in other psychiatric disorders. Moreover, self-oriented perfectionism was a predictor of an eating disorder. CONCLUSION: Self-oriented perfectionism is more specific to eating disorders than to depressive or anxiety disorders.     

Establishment of a modified surgical safety checklist for the neurosurgical patient: Initial experience in 400 cases

IntroductionAdverse events during diagnostic and therapeutic procedures and medical errors associated with them are an important source of patient morbidity. In an attempt to reduce these, the WHO has proposed a series of measures applicable to medical and surgical patients. Within these last ones is the surgical safety checklist (SSC), a brief questionnaire that does not increase healthcare costs, is accessible to all surgical centres and can be adapted to each specific environment.ObjectivesTo evaluate the effectiveness of establishing a modified WHO SSC on the safety and quality of care of the neurosurgical patient in a third-level university hospital.Material and methodsThe SSC was applied to a series of 400 scheduled surgeries between May 2009 and May 2010. During the initial 6 months, 183 surgical procedures were performed (group 1). All adverse events detected in this period were studied with a root-cause analysis methodology (RCA) and, according to its results, corrective measures were introduced. After that, 217 procedures were performed (group 2).ResultsWe recorded 51 events in 44 surgeries (11%). We were able to correct 88.23% of them before surgery was initiated, avoiding any consequence in the normal management of the case. In Group 1, incidents were noted in 15.3% of the procedures. The RCA suggested that 37.8% of the events had a human cause, followed by problems related to material resources and equipment in 29.7%, and organisational reasons in 21.6%. Incidence of events was reduced in group 2 to 7.4% (P=.01). Corrective measures prevented the appearance of perioperative events in 1 out of 13 procedures.ConclusionsThe SSC is an effective tool for improving safety in neurosurgical patients, which can be established in surgical departments of any hospital without increasing healthcare costs or operative time.