Familial risks of aortic aneurysms among siblings in a nationwide Swedish study.

PURPOSE: Aortic aneurysms have a high fatality rate that could be reduced with control of risk factors and use of available screening methods for detection of early changes in aortic walls. The available data on familial risks, a potential indication for screening, are mainly limited to abdominal aortic aneurysms. METHODS: A nationwide Swedish cohort was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register and the Cause of Death Register for data on aortic aneurysms from years 1987 to 2001. Standardized incidence ratios (SIRs) were calculated for affected siblings by comparing with those whose siblings had no aneurysm. RESULTS: A total of 71 affected siblings were identified with a familial SIR of 8.71; when one sibling was diagnosed before age 50 years, the SIR was 19.69. For concordant thoracic or concordant abdominal aneurysms, the SIRs were 21.68 and 13.06, respectively. For brothers, the risk of abdominal aneurysms was 14.63, and 49.50 for diagnosis before age 50 years. Familial risks and the effects of early diagnostic age were shared by the anatomic subtypes of aneurysms. Within limits of the sample size, no gender differences could be observed. Affected siblings constituted 2.2% of all diagnosed patients. CONCLUSIONS: A family history of any aortic aneurysms and age groups younger than 50 years should be considered in recommendations for screening. The high familial risks are likely to be the result of heritable genes, the identification of which would allow gene testing and preventive counseling.     

Maternal origin of transferrin receptor positive cells in venous blood of pregnant women

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti-CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti-alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.     

Maternal eating disorders influence sex ratio at birth

We explored sex ratio at birth, defined as the proportion of male live births, in women with anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorders not otherwise specified-purging type (EDNOS-P) relative to a referent group in a large population-based sample of 38,340 pregnant women in Norway. Poisson regressions were adjusted for mother's age, pre-pregnancy BMI, lifetime smoking status, maternal education, income, marital status, gestational age, and parity. Lower proportions of male live births were observed in the anorexia and bulimia groups, while binge eating disorder and EDNOS-P were associated with a higher proportion of male births. These data suggest that maternal eating disorders may influence offspring sex and that the direction of effect may vary by eating disorder subtype. If confirmed, this finding could provide evidence in formulating hypotheses regarding the consequences of eating disorders and determinants of sex ratio at birth.     

Modified two-stage basilic vein transposition for hemodialysis access

Background

Various techniques for basilic vein transposition have been described, including endovascular, 1-stage, and 2-stage transposition. However, none of these 2-stage techniques include a new arteriovenous anastomosis during the second stage. This study adds to the current literature as well as introducing a new and innovative technique for hemodialysis access.

Methods

Forty-nine basilic vein transpositions were performed. Data were collected retrospectively. Primary and secondary patency was calculated using life table methods. Complications and interventions were recorded.

Results

Primary patency was 72% at 1 year, 54% at 2 years, and 54% at 3 years. Secondary patency was 95%, 80% and 65% at 1, 2, and 3 years, respectively. Twenty-nine patients experienced complications related to the fistula, and 15 required intervention to maintain patency. Patency was achieved in 100% of the procedures using percutaneous techniques.

Conclusions

This 2-stage procedure should be strongly considered when planning brachial basilic fistulas for hemodialysis access.     

Adenoma Recurrences After Resection of Colorectal Carcinoma: Results From the Southwest Oncology Group 9041 Calcium Chemoprevention Pilot Study

Background: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC).Methods: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates.Results: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P = .01). Lower stage was associated with higher adenoma recurrence rates (P = .04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates.Conclusions: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.     

Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression

Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers— SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.     

Activated mast cells increase the level of endothelin-1 mRNA in cocultured endothelial cells and degrade the secreted Peptide

Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism.