We postulate that PCO and male pattern baldness are caused by alleles of the same gene which affect androgen production or action. The different frequencies of PCO and male pattern baldness arise from differing thresholds for phenotypic expression in females and males respectively. The modifying effects of other genes is the most likely explanation of the somewhat variable phenotype.
In renal transplant patients with de novo donorspecific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-
Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.
OBJECTIVE Polycystic ovary syndrome is one of the most common endocrine disorders but its aetiology remains unknown. It is highly prevalent within families, suggesting a genetic basic for the syndrome, but the mode of inheritance is unclear. The purpose of this study was to determine the mode of inheritance of polycystic ovary syndrome, within the families of affected individuals, by classic segregation analysis. DESIGN All first degree relatives of affected individuals were screened for the presence or absence of polycystic ovaries in post-menarchal-premenopausal women and early onset male pattern baldness (MPB) in the males. In extended pedigrees, assignment of affected status in postmenopausal women was made by consideration of the clinical history alone. PATIENTS Fourteen women (probands), presenting with a variety of clinical symptoms, were identified sequentially as having polycystic ovaries (PCO) by ultrasound scan. They were examined in detail to determine their family structure, clinical and endocrine status. Ten families were found to have sufficient members for further study. MEASUREMENTS All family members had their body mass index calculated, their degree of hirsutism assessed using the Ferriman and Gallwey score and serum levels of gonadotrophins (FSH and LH), testosterone, prolactin and 17a-hydroxyprogesterone measured by radioimmunoassay. A careful reproductive history was taken for each woman and any menstrual disturbance was noted. Obese probands had their glucose and insulin response to a standard 75-9 oral glucose tolerance test determined.Each male family member was also assessed for the degree and time of onset of balding.
Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy.
Intracranial arterial calcification (IAC) is associated with ischemic stroke in the general population but this relationship has not been examined in hemodialysis patients. We examined the factors associated with IAC and its relationship with acute ischemic stroke in this population. We retrospectively studied 490 head computed tomographic scans from 2225 hemodialysis patients presenting with neurological symptoms at our center (October 2005-May 2009). Intracranial arterial calcification was graded using a validated scoring system. Multivariate regression was used to examine the factors associated with the presence of IAC, its severity, and its ability to predict acute ischemic stroke. Weibull's survival models analyzed the relationship between IAC severity and survival. Ninety-five percent of patients with ischemic stroke had IAC vs. 83% in the nonstroke group (P=0.02). Intracranial arterial calcification severity increased with age (P<0.001), hemodialysis vintage (P<0.001), serum phosphate (P<0.05), and major comorbidities. In patients with multiple computed tomographic scans during the study period, increased IAC severity at baseline was predictive of acute ischemic stroke (P=0.05) on logistic regression analysis. High-grade and not low-grade IAC was associated with worse survival (P=0.008). Intracranial arterial calcification is highly prevalent in hemodialysis patients, especially in those with acute ischemic stroke. Its severity is prognostically significant and associated with risk factors for vascular calcification and may confer a greater risk of acute ischemic stroke. The mechanisms underlying the high incidence of ischemic stroke in this patient group require further comprehensive study.
Peritubular capillary basement membrane multilayering on electron microscopy is a useful marker of early chronic antibody-mediated damage, and information can be obtained by assessing PTC with three to four layers of basement membrane in addition to those with five or more layers. This finding must be validated in a prospective study.
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