Familial risk in testicular cancer as a clue to a heritable and environmental aetiology

We used the nation-wide Swedish Family-Cancer Database to examine the risk for testicular cancer in offspring through parental and sibling probands. Among 0-68-year-old offspring, 4082 patients had testicular cancer in years 1961-2000, among whom 68 (1.67%) had an affected father/brother. Standardized incidence ratios (SIRs) for familial risk were four-fold when a father and nine-fold when a brother had testicular cancer. Histology-specific risks (for the testicular cancer) were similar for sons of affected fathers, but were higher among brothers for teratoma and seminoma than for mixed histologies. Standardized incidence ratios for either histology depended on the age difference between the brothers: 10.81 when the age difference was less than 5 years compared to 6.69 for a larger age difference. Parental colorectal, pancreatic, lung and breast cancer and non-Hodgkin's lymphoma and Hodgkin's disease were associated with seminoma among sons. Seminoma risk was also increased when a sibling had melanoma. Teratoma was associated with parental lung cancer and melanoma. The high familial risk may be the product of shared childhood environment and heritable causes. Familial cases of fraternal pairs with an early-onset teratoma represent a challenge for gene identification

Guidelines for follow-up of women at high risk for inherited breast cancer: Consensus statement from the Biomed 2 Demonstration Programme on Inherited Breast Cancer

Protocols for activity aiming at early diagnosis and treatment of inherited breast or breast-ovarian cancer have been reported. Available reports on outcome of such programmes are considered here. It is concluded that the ongoing activities should continue with minor modifications. Direct evidence of a survival benefit from breast and ovarian screening is not yet available. On the basis of expert opinion and preliminary results from intervention programmes indicating good detection rates for early breast cancers and 5-year survival concordant with early diagnosis, we propose that women at high risk for inherited breast cancer be offered genetic counselling, education in ‘breast awareness’ and annual mammography and clinical expert examination from around 30 years of age. Mammography every second year may be sufficient from 60 years on. BRCA1 mutation carriers may benefit from more frequent examinations and cancer risk may be reduced by oophorectomy before 40–50 years of age. We strongly advocate that all activities should be organized as multicentre studies subjected to continuous evaluation to measure the effects of the interventions on long-term mortality, to match management options more precisely to individual risks and to prepare the ground for studies on chemoprevention

The marine epilithic diatom Melosira brandinii sp. nov. (Bacillariophyta) from Elephant Island, Antarctic Peninsula, with comments on some related species

Uma nova espécie de diatomácea eplítica é descrita sob microscopia eletrônica, a partir de amostras coletadas próximo à Ilha Elefante, Península Antártica. As células de Melosira brandinii sp. nov. encontram-se reunidas em cadeias filamentosas através de longos tubos mucilaginosos. As valvas são circulares, com superfície valvar provida de lóculos pentagonais arranjados irregularmente. Cada lóculo possui 6-12 poros na superfície externa, abrindo-se para o interior através de aréolas do tipo rota. A corona é composta exclusivamente por grânulos grosseiros, os quais estão mais concentrados na borda do manto. Comparações com as espécies próximas Melosira arctica, M. moniliformis e M. nummuloides foram realizadas. Adicionalmente, são fornecidas fotomicrografias de M. arctica provenientes do material tipo e do Mar de Barents (Ártico), e de M. moniliformis de estuários do Sul do Brasil.A new species of epilithic diatom is described from samples collected near Elephant Island, Antarctic Peninsula. The cells of Melosira brandinii sp. nov. are joined in filamentous chains and attached by means of long mucilaginous stalks. The valves are circular with the valvar surface composed of irregularly arranged pentagonal Ioculi. Each loculus bears 6-12 pores on the external surface, opening to the innerside through rotae. The corona is only composed of coarse granules. A mantle is well developed, presenting rimoportulae and bearing coarse granules, which are more concentrated at the mantle edge. Comparisons with the related species Melosira arctica, M. moniliformis and M. nummuloides are made. Additionally, photomicrographs of M. arctica from the type material and Barents Sea, and of M. moniliformis from estuaries of Southern Brazil are included

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms

Flow propagation velocity is not a simple index of diastolic function in early filling. A comparative study of early diastolic strain rate and strain rate propagation, flow and flow propagation in normal and reduced diastolic function

BACKGROUND: Strain Rate Imaging shows the filling phases of the left ventricle to consist of a wave of myocardial stretching, propagating from base to apex. The propagation velocity of the strain rate wave is reduced in delayed relaxation. This study examined the relation between the propagation velocity of strain rate in the myocardium and the propagation velocity of flow during early filling. METHODS: 12 normal subjects and 13 patients with treated hypertension and normal systolic function were studied. Patients and controls differed significantly in diastolic early mitral flow measurements, peak early diastolic tissue velocity and peak early diastolic strain rate, showing delayed relaxation in the patient group. There were no significant differences in EF or diastolic diameter. RESULTS: Strain rate propagation velocity was reduced in the patient group while flow propagation velocity was increased. There was a negative correlation (R = -0.57) between strain rate propagation and deceleration time of the mitral flow E-wave (R = -0.51) and between strain rate propagation and flow propagation velocity and there was a positive correlation (R = 0.67) between the ratio between peak mitral flow velocity / strain rate propagation velocity and flow propagation velocity. CONCLUSION: The present study shows strain rate propagation to be a measure of filling time, but flow propagation to be a function of both flow velocity and strain rate propagation. Thus flow propagation is not a simple index of diastolic function in delayed relaxation

High penetrances of BRCA1 and BRCA2 mutations confirmed in a prospective series

Penetrances of BRCA1 and BRCA2 mutations have been derived from retrospective studies, implying the possibility of ascertainment biases to influence the results

Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging

<p>Abstract</p> <p>Background</p> <p>Non-ischemic dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide, with significant mortality. Correct evaluation of the patient's myocardial function has important clinical significance in the diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM patients. This study evaluated the feasibility of three-dimensional speckle tracking imaging (3D-STE) for assessment of the left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy (DCM).</p> <p>Methods</p> <p>Apical full-volume images were acquired from 65 patients with non-ischemic DCM (DCM group) and 59 age-matched normal controls (NC group), respectively. The following parameters were measured by 3D-STE: the peak systolic radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of each segment. Then all the parameters were compared between the two groups.</p> <p>Results</p> <p>The peak systolic strain in different planes had certain regularities in normal groups, radial strain (RS) was the largest in the mid region, the smallest in the apical region, while circumferential strain (CS) and longitudinal strain (LS) increased from the basal to the apical region. In contrast, the regularity could not be applied to the DCM group. RS, CS, LS were significantly decreased in DCM group as compared with NC group (<it>P </it>< 0.001 for all). The interobserver, intraobserver and test-retest reliability were acceptable.</p> <p>Conclusions</p> <p>3D-STE is a reliable tool for evaluation of left ventricular myocardial strain in patients with non-ischemic DCM, with huge advantage in clinical application.</p