Interchromosomal effect in sperm of males with translocations: report of 6 cases and review of the literature

Somatic chromosomal abnormalities are frequently found in infertile men, particularly in those with low sperm count and/or seeking intracytoplasmic sperm injection. These abnormalities mostly consist of numerical sex chromosome abnormalities and translocations (Robertsonian or reciprocal). In this study, we searched for the occurrence of non-disjunction of chromosomes not involved in translocations during meiosis, phenomenon called interchromosomal effect (ICE) and first described by Lejeune (1965). Ejaculate samples of two patients carrying a Robertsonian translocation and four a reciprocal translocation patients and four controls (men with a 46,XY karyotype and normal sperm parameters) were studied in dual FISH 7-9, dual FISH 13-21 and triple FISH X-Y-18. A statistically significant increase of disomy X, Y and XY (P = 0.009, P = 0.004, P < 0.001) was found in the Robertsonian der(13;14)(q10;q10) carrier but not in the der(14;21)(q10;q10) carrier compared with controls. Among reciprocal translocation carriers, a significant increase of disomy 21 (P = 0.033) was observed in a sole patient with a t(9;22)(q21;q11.2). The increase of meiotic non-disjunction for chromosome 21 and sex chromosomes is a recurrent event found in other studies. According to our results and published data, the ICE on some specific chromosomes is likely in men carrier of a translocation, although it cannot be excluded that the aneuploidy is related to the oligoasthenoteratozoospermia usually present in these men. Moreover, this phenomenon showed interindividual variations which cannot be predicted. The risk of aneuploidy in sperm of males used for ICSI need to be evaluated. It could be superadded to that of meiotic segregation of the translocation to give a more precise and personalized risk assessment of aneuploidy in the offspring of those men.     

Adjuvant endocrine therapy for perimenopausal women with early breast cancer

Adjuvant treatment with aromatase inhibitors (AIs) improves outcomes in postmenopausal women with hormone-sensitive early breast cancer compared with tamoxifen. However, AIs should not be used in premenopausal women because they can paradoxically increase estrogen secretion and may therefore stimulate tumor progression. In perimenopausal women undergoing treatment for breast cancer, it can be difficult to determine true menopausal status because adjuvant chemotherapy, tamoxifen, and gonadotropin-releasing hormone analogues can induce transient (or permanent) ovarian suppression. How can one determine whether these women are truly postmenopausal and therefore candidates for AI therapy? A panel of experts in the field of endocrine therapy in breast cancer met in Dubrovnik, Croatia, on October 23, 2006, to discuss this clinical dilemma. This report summarizes the conclusions and recommendations that arose from this discussion.     

A new mutation in two siblings with cystinosis presenting with Bartter syndrome

Nephropathic cystinosis is a severe autosomal recessive inherited metabolic disease characterized by accumulation of free cystine in lysosomes. Cystinosis can lead to renal failure and multiorgan impairment. Only five cases of cystinosis with associated Bartter syndrome are reported in the literature, and no genetic evaluation has been reported. We describe two siblings with nephropathic cystinosis presenting with features of Bartter syndrome and their genetic pattern.     

Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.     

The Brief State Rumination Inventory (BSRI): Validation and Psychometric Evaluation

Depressive rumination is an emotion regulation strategy that is considered a major risk factor for depression and other emotional disorders. While well-established measures of trait rumination are available, a psychometrically sound measure of state rumination is lacking. We report on the development and validation of a new self-report measure, the Brief State Rumination Inventory (BSRI), in both Dutch and English. In Study 1, we report the results of a multi-group confirmatory factor analysis across three independent samples (n?=?155; n?=?141; n?=?199). The analysis supported the unidimensionality and measurement invariance of the 8-item BSRI. We also examined its construct validity, showing that scores on the BSRI were positively related to measures of negative affect, trait rumination, and symptoms of depression and anxiety. Scores were negatively related to adaptive emotion regulation strategies and to positive affect. In Study 2 (n?=?60), we demonstrated the measure’s sensitivity to an experimental manipulation of rumination. Taken together, these findings suggest that the BSRI is a quick-to-administer, valid, and reliable measure of state rumination.     

Non-coronary cardiac events,younger age,and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease

Clinical Rheumatology - Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for...     

Metformin potentiates B-cell response to high glucose: an in vitro study on isolated perfused pancreas from normal rats

This study investigated the effects of metformin on pancreatic A-B- and D-cell functions using the isolated perfused rat pancreas model. The lactate output rate following metformin infusion was also monitored. Metformin was infused at the low "therapeutic" concentration of 1.5 micrograms/ml and its effects were evaluated in three different glycaemic conditions: during a basal infusion of 4.44 mM glucose, during a moderate increase to 8.88 mM of glucose concentration, and finally during a higher 16.66 mM glycaemic stimulus. Basal insulin secretion and B-cell release during the lower hyperglycaemic stimulus were unaffected by metformin infusion. On the contrary, the drug significantly enhanced insulin response to 16.66 mM glucose, particularly by increasing the second phase of hormone release. Glucagon and somatostatin releases during metformin infusion were similar to the secretory pattern observed in the control experiments both in the basal condition and in the presence of the two different hyperglycaemic stimuli. Finally metformin did not modify the lactate output rate from perfused pancreas, irrespective of the different glycaemic conditions employed. Therefore our data suggest--at least in rats, in in vitro experiments but above all in the presence of markedly elevated hyperglycaemic conditions--that metformin may influence the glucose stimulatory effect on B-cell activity.     

Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII

Summary. The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families.
Four missense mutations located in the catalytic domain of factor VII were found. The previously reported ³⁰⁴ArgGln substitution was present in the homozygous and heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent and frequent in the Italian population. The ³¹⁰Cys Phe substitution was found in the homozygous form and in the compound heterozygous condition with the nonsense mutation ³⁵⁶Trpstop. Two missense mutations, ²⁹⁸MetIle and ³⁴²GlyArg, were found in the homozygous and in the heterozygous condition respectively.
Molecular heterogeneity was further increased by finding of the ³⁵³ArgGln polymorphism in the doubly heterozygous condition with the 304 and 342 mutations.
Plausible explanations for loss of FVII function were found by inspecting a model of the serine protease domain of factor VIIa. Inefficient activation of the catalytic site is predicted for ²⁹⁸MetIle. ³⁴²GlyArg would directly distort the geometry of the 'oxyanion hole'preventing formation of a substrate enzyme intermediate. ³¹⁰Cyshe is predicted to have an adverse effect on tissue factor interaction. These mutations point to important regions of the factor VII molecule.