HLA antigens in Omani patients with vitiligo

Fifty native Omanis with vitiligo were studied to compare the incidence of HLA ABC and DR antigens with a control population. HLA Bw6 was found in 82% of patients compared with 49% controls (P_c= 0.0009 RR = 4.56) and HLA DR7 occurred in 40% of patients and 9% in controls (P_c= 0.00075 RR = 6.17). HLA DR7 was significantly increased in those patients with acrofacial, compared to focal disease (57% vs. 24%P= 0.038). Sixty-six per cent of the patients in this study had parents who were consanguineous and a positive family history was only found in this group with an incidence of 32%. HLA Bw4 segregated 100% with patients with a positive family history compared with 48% in consanguineous patients without a positive family history (P_c= 0.011 RR = 23). Vitiligo appears to be associated with different HLA antigens in different ethnic groups.     

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1

Abstract: The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K₁ prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K₁, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K₁. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K₁ were to have a longer duration of effect than intravenous vitamin K₁. This may be because intramuscular vitamin K₁ acts as a depot preparation. The findings suggest that intravenous vitamin K₁ is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K₁ should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.     

Novel TMPRSS6 mutations associated with iron‐refractory iron deficiency anemia (IRIDA)

Mutations leading to abrogation of matriptase‐2 proteolytic activity in humans are associated with an iron‐refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. In this paper we describe 12 IRIDA patients belonging to 7 unrelated families and identify 10 (9 novel) TMPRSS6 mutations spread along the gene sequence: 5 missense, 1 non sense and 4 frameshift. The frameshift and non sense mutations are predict to result in truncated protein lacking the catalytic domain. The causal role of missense mutations (Y141C, I212T, R271Q, S304L and C510S) is demonstrated by in silico analysis, their absence in 100 control chromosomes and the high conservation of the involved residues. The C510S mutation in the LDLRA domain in silico model causes an intra‐molecular structural imbalance that impairs matriptase‐2 activation. We also assessed the in vitro effect on hepcidin promoter and the proteolytic activity of I212T and R271Q variants demonstrating a reduced inhibitory effect for the former mutation, but surprisingly a normal function for R271Q which appears a silent mutation in vitro. Based on mRNA expression studies I212T could also decrease the total amount of protein produced, likely interfering with mRNA stability. Collectively, our results extend the pattern of TMPRSS6 mutations associated with IRIDA and propose a model of causality for some of the novel missense mutation. © 2010 Wiley‐Liss, Inc.     

Acceleration of full-thickness wound healing in normal rats by the synthetic thrombin peptide, TP508

Thrombin is an essential factor in hemostasis, inflammation, and tissue repair. The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors and mimics cellular effects of thrombin at sites of tissue injury. Treatment of full-thickness excisional wounds in normal rats with a single topical application of 0.1 microg TP508 (14 pmol/cm2) reproducibly accelerates wound closure, yielding wounds that on average close 39% more than controls by day 7 (p < 0.001). Wounds treated with 1.0 microg TP508 are 35% and 43% (p < 0.001) smaller than controls on day 7 and 10, respectively. The early rate of closure is approximately 40% greater in TP508-treated than vehicle-treated wounds (20 versus 14 mm2/day) and remains higher through day 7. Breaking strength after closure is slightly greater (15-23%) in wounds treated with TP508 than with saline alone. Histologic comparisons show that TP508 enhances recruitment of inflammatory cells to the wound site within 24 hours post-injury. TP508 treatment also augments revascularization of injured tissue, as evidenced at day 7 by the larger size of functional vessels in the granulation tissue and by the directed development of blood vessels to wounds. These studies raise the possibility that TP508 may be clinically useful in management of open wounds.     

Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic cirrhosis

The relationship between the various haemodynamic abnormalities observed in cirrhosis and their prognostic value remains unclear. We report haemodynamic measurements on 96 patients with alcoholic cirrhosis (mean Childs-Pugh Score, CPS, 9.0 +/- 0.2, mean age 55.6 +/- 1.0 years) and assess their value in predicting variceal bleeding and death during a mean follow-up of 19.3 +/- 1.5 months. Baseline CPS correlated with hepatic venous pressure gradient (HVPG) (p = 0.001), azygos blood flow (p < 0.05), cardiac index (p < 0.05), and inversely with mean arterial pressure (p < 0.01) and systemic vascular resistance index (p < 0.05). Renal blood flow was not related to any haemodynamic parameter or CPS. Thirty-eight patients died during follow-up, and 16 had a variceal bleed. Death (p = 0.001) and variceal bleeding (p < 0.05) were more likely in patients with HVPG > 16 mmHg than in those with HVPG < 16 mmHg, and variceal bleeding was more likely in patients with HVPG > 12 mmHg (vs. HVPG < 12 mmHg, p < 0.05). HVPG also predicted death and variceal haemorrhage on univariate and multivariate analyses. No other haemodynamic parameter predicted death or bleeding. In alcoholic cirrhosis, severity of liver disease is related to HVPG, collateral blood flow and degree of systemic circulatory abnormalities. HVPG is a useful predictor of survival and variceal bleeding in these patients.      

Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate...     

The Phenotype of a CASQ2 Mutation in a Saudi Family with Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) manifests with episodic syncope or sudden death in young patients following physical activity or emotional stress. The autosomal recessive form of CPVT is caused by mutations in the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy. Genetic testing found the younger sibling, who had normal initial clinical screening, to be affected. Our cases underscore the importance of family screening through genetic testing to preemptively apply the appropriate medical intervention in CPVT. (PACE 2013; 36:e140–e142)     

Initial experience of using intracardiac echocardiography (ICE) for guiding balloon mitral valvuloplasty (BMV)

Background and aimsBMV is an established treatment for rheumatic mitral valve stenosis. The procedure is historically guided by fluoroscopy, and the role of intracardiac echocardiogram (ICE) guidance is not well defined. We report our initial experience of using ICE to guide BMV procedures.MethodsDuring BMV procedure, ICE catheter was inserted into the right atrium from the right femoral vein, and the septal puncture was monitored by ICE, as well as positioning of the balloon in the mitral valve. Comparisons were made between ICE, transthoracic echocardiography (TTE), and catheterization derived hemodynamic measurements (cath).ResultsSeventeen patients with mitral stenosis underwent the procedure. The mean age was 44.4 ± 21 years. The mean MV area increased from 0.9 ± 0.1 cm² to 1.7 ± 0.2 cm², P < 0.0001 and the mean gradient decreased from 12.6 ± 5.8 mmHg to 4.9 ± 1.8 mmHg, P < 0.001. Atrial septum puncture and guidance of the balloon into the MV apparatus were obtained in all patients under ICE guidance. Severe MR developed in one patient and was readily detected by ICE. ICE derived gradient measurements were comparable to those obtained by TTE, and cath.ConclusionICE guidance of BMV is feasible, and useful in monitoring safe septal puncture, optimizing balloon positioning, and in detecting complications. The hemodynamic measurements obtained were comparable to those obtained by TTE, and cath.     

Discoid menisci of the knee: MR imaging appearance

Discoid menisci of the knee are not uncommon, and the criteria for arthrographic diagnosis and the clinical symptoms are well known. Although enlarged menisci have been recognized at magnetic resonance (MR) imaging, there are no criteria for the MR imaging diagnosis. The authors describe 29 discoid menisci imaged by means of MR. A discoid meniscus was said to be present if three or more 5-mm-thick contiguous sagittal images demonstrated continuity of the meniscus between the anterior and posterior horns. High-resolution coronal images allowed more graphic depiction of the abnormally wide meniscus. In approximately one-third of the cases in which coronal images were obtained, the measurable height difference between the discoid and the opposite meniscus was greater than or equal to 2 mm. Arthroscopic correlation (obtained in 10 cases) revealed that six cases of discoid meniscus were diagnosed correctly with MR imaging, although one meniscus was considered discoid at MR imaging but was not considered discoid at arthroscopy. Of three discoid menisci seen to be torn at arthroscopy, two were seen to be torn at MR imaging.     

Effect of uremia on the membrane transport characteristics of red blood cells

Even though there is extensive evidence that uremia affects the fragility and deformability of red blood cells (RBCs), essentially all data on the RBC membrane permeability have been obtained with nonuremic blood. Permeability data were obtained for creatinine and uric acid, two metabolites of interest in hemodialysis, using a stirred ultrafiltration device with direct cell- and protein-free sampling. Experiments examined the effects of temperature and suspending phase on solute transport for both normal and uremic blood cells. Creatinine and uric acid transport from normal RBCs at 37 degrees C were characterized by saturation half-times of 40 +/- 10 minutes and 54 +/- 12 minutes, respectively. The corresponding half-times for uremic cells were significantly longer, 94 +/- 26 minutes and 180 +/- 38 minutes. Data indicated that the slower rate of creatinine transport in uremic blood was caused by an alteration in the RBC membrane, while the reduction in uric acid transport was associated with alterations in the uremic plasma. The temperature dependence of the RBC permeability was also much less pronounced for uremic cells for both solutes. These results provide important insights into the effects of uremia on the RBC membrane permeability, and have important implications for dialysis.