A novel recessive mutation in fibroblast growth factor-23 causes familial tumoral calcinosis

Gain-of-function mutations in fibroblast growth factor-23 (FGF23) are responsible for autosomal dominant hypophosphatemic rickets, a disorder of isolated renal phosphate wasting. Patients with the disorder display hypophosphatemia with normocalcemia as well as inappropriately normal 1,25-dihydroxyvitamin D [1,25(OH)2D3] concentrations. Reciprocally tumoral calcinosis (TC) patients are often hyperphosphatemic with inappropriately normal or elevated serum 1,25(OH)2D3 levels and have ectopic and vascular calcifications, a phenotype similar to that of Fgf23 null mice. Therefore, the goal of the present studies was to test whether FGF23 was a candidate gene for TC. Two sisters in a consanguineous TC family had hyperphosphatemia and normal 1,25(OH)2D3 levels with characteristic ectopic and vascular calcifications. Interestingly, these patients had low-normal intact serum FGF23 levels but demonstrated FGF23 concentrations approximately 40 times normal when assessed with a C-terminal FGF23 serum assay. Mutational analyses identified a homozygous S71G mutation in FGF23 in the TC patients, which was not found in control alleles. Finally, modeling demonstrated that the S71G mutation most likely destabilizes full-length FGF23. In summary, recessive FGF23 mutations can lead to TC. Additionally, our findings indicate that FGF23 may adopt an unstable conformation in some TC patients, possibly leading to nonfunctional FGF23 protein.     

Medical therapy of a left-sided native valve endocarditis with neurologic sequela

Infective endocarditis could present with a plethora of signs and symptoms. Among the rarity of its presentation is acute confusion associated with neurological deficits, mimicking stroke especially in the young population. We report a case of a 33-year-old young man with acute right-sided hemiparesis and confusion 2 weeks after tooth extraction. The brain CT and MRI was consistent with new infarction on the left middle and anterior cerebral arteries’ territory. Echocardiography unveiled the existence of posterior mitral valve leaflet vegetation. Blood culture grew Group B beta-haemolytic Streptococcus, sensitive to penicillin. Two weeks of intravenous gentamicin with 6 weeks of intravenous benzylpenicillin were administered. In this case report, we highlight the importance of recognition of infective endocarditis in a young patient presenting with cerebrovascular accident following tooth extraction.A wide variety of organisms have been attributed to infections of native heart valves. Among them are staphylococci, streptococci, and the group of Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella corrodens, Kingella (HACEK) organisms. Aortic or mitral valves (left-sided) accounts for the vast majority of endocarditis cases in non-intravenous drug users. Right sided infective endocarditis contributes 5-10% of all cases of endocarditis, usually among intravenous drug users.1 Emboli from left-sided valvular vegetation can become dislodged or fragmented into the brain via systemic circulation, resulting in neurological complications. In contrast with the right sided embolus, the right sided infective endocarditis may cause embolic phenomenon due to preexisting congenital heart diseases such as patent foramen ovale, atrial septal defect, or ventricular septal defect. In this case report, we highlight the importance of recognition of infective endocarditis with an embolic stroke in a young confused patient with normal cardiac valve following a simple dental extraction procedure.     

Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients

BACKGROUND: Hepatitis C virus infection (HCV) is a main health problem in end-stage renal disease (ESRD) patients. The effect of pretransplant HCV infection on survival among ESRD patients who have undergone renal transplantation is controversial. We report the results of a large monocenter study that evaluated the effect of hepatitis C on the patient, and on graft survival in renal-transplanted patients who received living donated allograft. METHODS: A historical cohort study, we investigated all 1006 patients who received a living kidney transplant at Baghiatollah Medical Center in Tehran, Iran, between March 1995 and October 2001 (up to 85 months follow up). Patients' sera had been routinely assayed for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at the time of transplantation. The HBsAg-positive patients were excluded from the survival analysis. Survivals were examined using Kaplan-Meier analysis and compared using the log-rank test. Multivariate analysis was performed using Cox's model. RESULTS: Forty-five patients (4.5%) were anti-HCV-antibody positive. Anti-HCV-antibody-positive patients spent a longer time on dialysis and had a higher rate of retransplantation. There were no differences in recipients' sex and age and donors' age between the two groups. The 7-year patient survival rate was 89.9% in the anti-HCV-antibody-positive group and 95.5% in the HCV-negative group (P = 0.74). Seven-year graft survival was 82.0% and 75.0% in the anti-HCV-antibody-positive and HCV-negative groups, respectively (P = 0.39). In the multivariate analysis, age was the only significant parameter correlated with patient survival (P = 0.02). CONCLUSIONS: HCV infection does not seem to influence patient and graft survival within a medium-time follow up in living allograft recipients, and anti-HCV-antibody positive status (alone) is not a contraindication for renal transplantation. However, further studies are needed to better define the role of HCV infection in long-term prognosis.     

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia

Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a "high" level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)-Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.     

Infantile pyknocytosis,a rare cause of hemolytic anemia in newborns: report of two cases in twin girls and literature overview

Infantile pyknocytosis is a rare cause of neonatal jaundice and hemolytic anemia. We report on two cases in twin girls that were diagnosed on peripheral blood smear reading. Pyknocytosis should be considered in cases of early unexplained severe hemolytic anemia, and systematic peripheral smear review performed. Its management consists of phototherapy and RBC transfusion.     

A Study on the Utilization of Coal Fly Ash Derived Grog in Clay Ceramics

Grog is an additive material that plays important roles in ceramic making. It improves the fabrication process of green bodies as well as the physical properties of fired bodies. Few low-cost materials and wastes have found their application as grog in recent years, thus encouraging the replacement of commercial grogs with cost-saving materials. Coal fly ash, a combustion waste produced by coal-fired power plant, has the potential to be converted into grog owing to its small particle sizes and high content of silica and alumina. In this study, grog was derived from coal fly ash and mixed with kaolin clay to produce ceramics. Effects of the grog addition on the resultant ceramics were investigated. It was found that, to a certain extent, the grog addition reduced the firing shrinkage and increased the total porosity of the ceramics. The dimensional stability of the ceramics at a firing temperature of 1200 °C was also not noticeably affected by the grog. However, the grog addition in general had negative effects on the biaxial flexural strength and refractoriness of the ceramics.