Decreased pregnancy rate after in-vitro fertilization in HIV-infected women receiving HAART

A study on in-vitro fertilization (IVF) was conducted among HIV-infected women. In these patients, a reduced pregnancy rate after IVF was observed if the patient's own oocytes were used. However, no significant reduction in the pregnancy rate was found if donated oocytes were used. The CD4 lymphocyte count was independently associated with ovarian resistance to hyperstimulation. Subclinical hypogonadism mediated by immunosuppression may explain these observations, suggesting the need to optimize the immunological status of the patient before considering assisted reproduction treatments.     

Perinatal asphyxia may present with features of neonatal atypical hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is the consequence of platelet consumption at sites of endothelial injury. Perinatal asphyxia (PA) may cause renal failure after birth and can be associated with disseminated intravascular coagulopathy (DIC) with platelet consumption. No biological investigation permits us to distinguish clearly between neonatal HUS and DIC. We report on three neonates with renal failure due to different degrees of PA. They presented biological features compatible with HUS, such as fragmentocytes (∼2%), thrombopenia (<50,000/mm³), and anemia (<8 g/dl). One patient required peritoneal dialysis. Haptoglobin was undetectable for all three patients. Factor H and factor I, as well as components of the complement system (C3 and C4) and ADAMTS13 activity, were decreased. Two patients received daily fresh frozen plasma infusions over the first 4 weeks. Renal function improved in two patients; one patient had chronic renal failure. No neurological sequelae were noted. All blood parameters suggestive of thrombotic microangiopathy (TMA) were normal on days 12, 30, and 60. We hypothesize that endothelial cell damage concomitant with PA may lead to a vicious circle that results in consumption of platelets and plasma factors involved in hemostasis and/or fibrinolysis. In conclusion, PA, DIC and HUS are difficult to distinguish, and endothelial cell damage may be their common pathophysiological pathway.     

Impaired glomerular maturation and lack of VEGF165b in Denys-Drash syndrome

Individuals with Denys-Drash syndrome (DDS) develop diffuse mesangial sclerosis, ultimately leading to renal failure. The disease is caused by mutations that affect the zinc finger structure of the Wilms' tumor protein (WT1), but the mechanisms whereby these mutations result in glomerulosclerosis remain largely obscure. How WT1 regulates genes is likely to be complex, because it has multiple splice forms, binds both DNA and RNA, and associates with spliceosomes. Herein is described that in DDS podocytes, the ratio of both WT1 +KTS isoforms C to D differs considerably from that of normal child and adult control podocytes and more closely resembles fetal profiles. Aside from the delay in podocyte maturation, DDS glomeruli show swollen endothelial cells, reminiscent of endotheliosis, together with incompletely fused capillary basement membranes; a dramatic decrease in collagen alpha4(IV) and laminin beta2 chains; and the presence of immature or activated mesangial cells that express alpha-smooth muscle actin. Because appropriate vascular endothelial growth factor A (VEGF-A) expression is known to be essential for the development and maintenance of glomerular architecture and function, this article addresses the question of whether VEGF-A expression is deregulated in DDS. The data presented here show that DDS podocytes express high levels of the proangiogenic isoform VEGF165, but completely lack the inhibitory isoform VEGF165b. The VEGF165/VEGF165b ratio in DDS resembles that of fetal S-shaped bodies, rather than that of normal child or adult control subjects. The alteration in VEGF-A expression presented here may provide a mechanistic insight into the pathogenesis of DDS.     

Health-related quality of life in patients with osteoarthritis after total knee replacement: factors influencing outcomes at 36 months of follow-up

OBJECTIVES: (1) To evaluate health-related quality of life (HRQL) in patients with severe osteoarthritis (OA) undergoing total knee replacement (TKR) and (2) to identify the influence of sociodemographic, clinical, intra-operative and postoperative variables on HRQL at 36 months after TKR. DESIGN: Prospective study with a 36-month follow-up. Preoperative interviews were carried out with 90 in-patients. The disease-specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to measure the health status. Sociodemographic, clinical, intra-operative degree of difficulty, in-patient and postoperative data were collected. Associations were analyzed using linear regression models. RESULTS: Of the 90 potentially eligible patients, 67 (54 females, mean age 74.83, standard deviation [SD] 5.57) completed follow-up assessment. There were significant differences between preoperative and postoperative WOMAC pain, stiffness and function scores (P<0.001, P=0.005 and P<0.001, respectively). Variables retained in each of the models explained between 15% and 23% (R(2) adjusted) of the variability of each WOMAC dimension. Higher preoperative WOMAC scores were associated with greater postoperative improvement (P<0.001). Chronic musculoskeletal pain unrelated to knee OA was associated with higher WOMAC pain, stiffness and function dimension scores (P=0.004, P=0.029 and P=0.005, respectively). Severe (Class III) obesity (body mass index [BMI] 35-39.9) was associated with more pain (P=0.049). CONCLUSIONS: In patients with severe OA, HRQL significantly improved at 36 months after TKR, especially in the pain dimension. Lower preoperative WOMAC scores, chronic pain unrelated to knee OA, and severe obesity negatively influenced postoperative WOMAC scores. This disease-specific questionnaire may help to identify patients at increased risk of negative outcomes after surgery.     

Transmission dynamics of pulmonary tuberculosis between autochthonous and immigrant sub-populations

Background  

The overall incidence of tuberculosis (TB) in Western Europe has been declining since the 19^th Century. However, immigrant sub-groups from high-prevalence countries are slowing down this trend. The aim of this study was to describe how immigration influences TB transmission in Germany. For that we prospectively investigated the dynamics of TB transmission between TB high-prevalence immigrant and TB low-prevalence local populations with molecular epidemiological methods and conventional contact investigations. Besides, we assessed transmission in relation to social mixing using an innovative tool that measures the integration of immigrants into the local social environment.     

Appropriateness of therapy for active Crohn's disease: Results of a multidisciplinary international expert panel—EPACT II

The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not filled all the gaps in our knowledge and thus, in clinical practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence.MethodsA multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD.ResultsOverall, 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naïve patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R.ConclusionSteroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients.     

Plasma malondialdehyde levels and CXCR4 expression in peripheral blood cells of breast cancer patients

Introduction  Breast cancer is one of the most common neoplasms in women and is a leading cause of cancer related deaths worldwide. Chemokines and their receptors are involved in the control of lymphocyte traffic, a critical component of systemic immunity. CXCR4 mRNA could be involved in the development of variety of diseases. Lipid peroxidation, the result of nonenzymatic autooxidation of polyunsaturated fatty acids, presents numerous harmful effects on biological systems and has been implicated in diseases like cancer. This study examined CXCR4 mRNA expression in peripheral blood cells and malondialdehyde (MDA) in plasma from blood donors and breast cancer patients. Materials and methods  CXCR4 expression in peripheral blood cells from 59 breast cancer patients and 76 healthy blood donors was analyzed by real-time PCR. Plasma MDA was analyzed using high-performance liquid chromatography (HPLC). Conclusion  In all stages, MDA levels in total breast cancer patients (1.41 ± 0.11) were significantly higher (P < 0.01) than those in healthy subjects (0.34 ± 0.03). No statistically significant difference occurred between CXCR4 expression in peripheral blood cells from breast cancer patients (1.69 ± 1.05) and the normal healthy control group (1.8 ± 0.65). However, stage II samples differed statistically (4.3 ± 1.72) from control, total cancer patients and stages I, III and IV samples.