Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey

A potentially traumatic event (PTE) contributes to trauma through its frequency, conditional probability of posttraumatic stress disorder (PTSD), and experience of other PTEs. A cross-sectional survey was conducted, enrolling 21,425 adults nationally representative of six European countries. Using the WHO-Composite International Diagnostic Interview, 8,797 were interviewed on 28 PTEs and PTSD. Prevalence of 12-month PTSD was 1.1%. When PTSD was present, the mean number of PTEs experienced was 3.2. In a multivariate analysis on PTEs and gender, six PTEs were found to be more traumatic, and to explain a large percentage of PTSD, as estimated by their attributable risk of PTSD: rape, undisclosed private event, having a child with serious illness, beaten by partner, stalked, beaten by caregiver.     

Effect of apelin on glomerular hemodynamic function in the rat kidney

Apelin is a vasoactive peptide identified as the endogenous ligand of an orphan G protein-coupled receptor called APJ. Apelin and its receptor have been found in the brain and the cardiovascular system. Here we show that the apelin receptor mRNA is highly expressed in the glomeruli while its level of expression is lower in all nephron segments including collecting ducts that express vasopressin V2 receptors. Intravenous injection of apelin 17 into lactating rats induced a significant diuresis. Apelin receptor mRNA was also found in endothelial and vascular smooth muscle cells of glomerular arterioles. Apelin administration caused vasorelaxation of angiotensin II-preconstricted efferent and afferent arterioles as shown by an increase in their diameter. Activation of endothelial apelin receptors caused release of nitric oxide which inhibited angiotensin II-induced rise in intracellular calcium. In addition, it appears that apelin had a direct receptor-mediated vasoconstrictive effect on vascular smooth muscle. These results show that apelin has complex effects on the pre- and post glomerular microvasculature regulating renal hemodynamics. Its role on tubular function (if any) remains to be determined.     

Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice

OBJECTIVE—NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade–based tolerance protocols have failed in prolonging islet allograft survival in NOD mice.RESEARCH DESIGN AND METHODS—To investigate the underlying mechanisms, we studied the ability of costimulation blockade to prolong islet allograft survival in congenic NOD mice bearing insulin-dependent diabetes (Idd) loci that reduce the frequency of diabetes.RESULTS—The frequency of diabetes is reduced in NOD.B6 Idd3 mice and is virtually absent in NOD.B6/B10 Idd3 Idd5 mice. Islet allograft survival in NOD.B6 Idd3 mice treated with costimulation blockade is prolonged compared with NOD mice, and in NOD.B6/B10 Idd3 Idd5, mice islet allograft survival is similar to that achieved in C57BL/6 mice. Conversely, some Idd loci were not beneficial for the induction of transplantation tolerance. Alloreactive CD8 T-cell depletion in (NOD × CBA)F1 mice treated with costimulation blockade was impaired compared with similarly treated (C57BL/6.H2^g7 × CBA)F1 mice. Injection of exogenous interleukin (IL)-2 into NOD mice treated with costimulation prolonged islet allograft survival. NOD.B6 Idd3 mice treated with costimulation blockade deleted alloreactive CD8 T-cells and exhibited prolonged islet allograft survival.CONCLUSIONS—Il2 is the Idd3 diabetes susceptibility gene and can influence the outcome of T-cell deletion and islet allograft survival in mice treated with costimulation blockade. These data suggest that Idd loci can facilitate induction of transplantation tolerance by costimulation blockade and that IL-2/Idd3 is a critical component in this process.The NOD mouse is a model of type 1–like autoimmune diabetes and is used to study costimulation blockade–based transplantation tolerance within the context of autoimmunity (1–4). However, costimulation blockade protocols fail in NOD mice. To investigate further the cellular and genetic control of costimulation blockade–induced transplantation tolerance, we used NOD Idd congenic mice that have small introgressed regions of genetic intervals derived from diabetes-resistant C57 stocks. These mice exhibit varying degrees of protection from autoantibodies, insulitis, and diabetes (5). Using Idd congenic NOD mice, we have observed that islet allograft survival is improved by the addition of the diabetes-protective Idd3 locus (6,7).Idd3 modulates infiltration of autoreactive lymphocytes into the islets (8), and there is compelling evidence that Idd3 is the interleukin (IL)-2 gene (9). In vivo stimulated NOD T-cells produce twofold less IL-2 mRNA than cells from NOD congenic mice having protective alleles at Idd3 (9,10). Neutralizing antibodies to IL-2 lead to accelerated disease in NOD mice (11), and targeted genetic disruption of IL-2 accelerates type 1–like autoimmune diabetes (9). Treatment with exogenous IL-2 inhibits diabetes development in NOD mice and improves T regulatory (Treg) function (12). IL-2 is also known to have a nonredundant role in CD8 T-cell activation–induced cell death via the CD95 (Fas) pathway (13), is required for the development of self-tolerance (14), and is essential for the induction of allograft tolerance by costimulation blockade (15). However, IL-2 is a double-edged sword, since administration of IL-2 in vivo can either enhance or depress a cytotoxic T lymphocyte (CTL) response (16).In this study, we show that costimulation blockade fails to delete alloreactive CD8 T-cells in NOD mice. Genetic replacement of IL-2 in NOD.B6 Idd3 mice enhances alloreactive CD8 T-cell deletion and improves islet allograft survival. Finally, we show that Idd3 synergizes with genes within the Idd5 interval, leading to permanent islet allograft survival in a majority of NOD.B6/B10 Idd3 Idd5 mice treated with costimulation blockade.     

Penile shortening after radical prostatectomy and Peyronie’s surgery

Penile shortening following radical prostatectomy and straightening procedures for Peyronie’s disease can be a devastating and unwelcome side effect of these operations. The majority of men undergoing radical prostatectomy for prostate cancer have a measured loss of penile length, which also can occur in men with Peyronie’s disease and may be exacerbated by surgery. Recent studies have investigated the mechanisms resulting in penile shortening, and various treatments have emerged to prevent and treat postoperative penile shortening. This article reviews the recent literature on penile length loss after radical prostatectomy and following correction of penile deformity for Peyronie’s disease.     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

Full-thickness chest wall resection for recurrent breast carcinoma: an institutional review and meta-analysis

Locoregional recurrence of breast cancer can occur in up to 30 per cent of patients and has often been considered to indicate a poor prognosis. We reviewed our experience with full-thickness chest wall resection for recurrent breast cancer and conducted a meta-analysis of the English literature to determine patient characteristics and outcomes. Twenty-two women with isolated chest wall recurrence of breast cancer were treated between 1970 and 2000 at our institution. We reviewed their preoperative demographics, operative management and outcome, and combined our results with seven other English language studies. A majority of women (90%) underwent a mastectomy as initial management of their breast cancer. Only 18 per cent of patients had metastatic disease at the time of chest wall resection, and 71 per cent of patients had an R0 resection. The 5-year disease-free survival at City of Hope National Medical Center (COH) was 67 per cent and was 45 per cent for the entire group of 400 patients. The 5-year overall survival was 71 per cent for the COH group and 45 per cent for the entire group. Several studies reported prognostic factors, the most common being a better prognosis in patients with a disease-free interval greater than 24 months. Full-thickness chest wall resection for patients with isolated local recurrence of breast cancer can provide long-term palliation and even cure in some patients.     

Mechanisms of Tolerance Induced by Donor-Specific Transfusion and ICOS-B7h Blockade in a Model of CD4+ T-Cell-Mediated Allograft Rejection

The inducible co-stimulatory molecule (ICOS) has been shown to play a critical role in T-cell activation and differentiation, and the regulation of alloimmune responses in vivo. Using an MHC class II mismatched model of CD4(+) T-cell-mediated rejection, we found that treatment of mice with DST and ICOS-B7h blockade induced long-term skin allograft survival and donor-specific transplantation tolerance. ICOS blockade, either during antigen priming or during the effector phase, previously shown to alter the outcome of the immune response, had a similar effect on graft survival. DST and anti-B7h mAb reduced the frequency of IFN-gamma-producing allospecific cells but did not produce deviation to a T(H)2 phenotype. In an adoptive transfer model using ABM TCR transgenic mice directly reactive to I-A(bm12), DST and anti-B7h mAb reduced the number of allospecific CD4(+) T cells and increased CD4(+) T-cell apoptosis. These data demonstrate that DST and anti-B7h mAb induces transplantation tolerance to MHC class II mismatched skin grafts by a reduction of the alloreactive clone size that is, at least in part, dependent on apoptosis of host alloantigen-specific CD4(+) T cells.     

Sub-inner limiting membrane haemorrhage: causes and treatment with vitrectomy

BACKGROUND: Preretinal haemorrhages usually occur at the interface between the posterior hyaloid and inner limiting membrane (ILM). Less frequently, they are located between the ILM and the retinal nerve fibre layer. Sub-ILM haemorrhages have been described in a variety of clinical settings and often lead to severe visual impairment because of their predilection for the macular region. METHODS: A consecutive series of five cases in which sub-ILM haemorrhages were clinically suspected and confirmed during early vitrectomy with ILM peeling were reviewed. RESULTS: Sub-ILM haemorrhages were clinically suspected in five patients (median age 32 years) based on the fundoscopic appearance and clinical setting of Terson's syndrome (n = 1), Valsalva retinopathy (n = 2), blood dyscrasia (n = 1) and blunt facial trauma (n = 1). Vision was severely impaired in all patients (to hand movements in four of five) because of a premacular location of the haemorrhage. All patients were treated with early pars plana vitrectomy because of insufficient spontaneous visual recovery after a median of 6 weeks. The sub-ILM location of the haemorrhage could be confirmed intraoperatively in all patients by biostaining of the membrane overlying the haemorrhage. ILM peeling and aspiration of the haemorrhage resulted in excellent visual recovery in all patients. No procedure-related complications were observed. CONCLUSIONS: Sub-ILM haemorrhages often occur in a specific clinical context and can lead to severe visual impairment in young patients. Given the excellent results and low complication rates, timely surgical intervention is justified when spontaneous resorption is insufficient.