Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.     

Pediatric apheresis with a novel apheresis device with electronic interface control

BACKGROUND: Cancer in children, and specifically cancer requiring autologous stem cell transplantation, is rare. As a consequence, though, experience with pediatric stem cell apheresis collections is limited. Challenges of apheresis in small children (<20 kg) include small total blood volume, issues with venous access, concerns about tolerable anticoagulant doses, and limitations in product volumes that can safely be collected. STUDY DESIGN AND METHODS: This article presents a small series of autologous “stem cell” apheresis procedures in infants and toddlers weighing between 5.5 and 20 kg, the first ones performed with a novel leukapheresis device (Spectra Optia MNC v.3.0, Terumo BCT) to be reported. Some features of the system are described that can be used to achieve favorable apheresis outcomes in small children. RESULTS: Apheresis procedures were uneventful and successful with similar extraction efficiencies (median preapheresis collection efficiency [CE2], 36%) as in adult patients. At 58%, platelet attrition was considerable. CONCLUSION: Our data indicate that stem cell apheresis with the Spectra Optia MNC v.3.0 in very small donors is feasible, safe, and associated with very small product volumes.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.     

Serum creatinine concentration and renal interstitial volume

Summary Renal biopsies of 44 patients with endocapillary acute glomerulonephritis (gn) and 64 patients with moderately severe mesangioproliferative gn were investigated morphometrically (point-counting-method, tubulometry).In both gn's statistically significant positive correlations between relative interstitial volume and the concentration of serum creatinine at the time of biopsy were found.Despite severe glomerular lesions the serum creatinine concentration is not increased in most cases of endocapillary acute gn, providing the relative interstitial volume is not increased by more than 15%.Increased serum creatinine concentration without a markedly enlarged interstitium was found in 11 cases of endocapillary acute gn with clinically and morphologically proven acute renal failure. In these cases the glomerular function is probably impaired by the Thurau-mechanism.In all other patients, especially in those with moderately severe mesangioproliferative gn, the serum creatinine concentration rises with an enlargement of relative interstitial volume. This reduction of renal function may be explained by a decrease to the total cross-sectional area of postglomerular vessels, caused by interstitial fibrosis. That may possibly lead to diminished renal blood flow and glomerular filtration with an increase of the serum creatinine concentration.Supported by the Deutsche Forschungsgemeinschaft     

Oestradiol‐Induced Synapse Formation in the Female Hippocampus: Roles of Oestrogen Receptor Subtypes

During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ERα and β are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ERα and ERβ. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ERα induced spine synapse formation, whereas ERβ agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up‐regulation of ERβ in the hippocampus of adult female aromatase‐deficient mice is paralleled by hippocampus‐specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ERβ knockout mouse, but no effect in the adult female ERα knockout mouse. Our data suggest antagonistic roles of ERβ and ERα in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.     

Die laparoskopische Versorgung iatrogener Kolonperforation

Background

Iatrogenic colon perforation is a rare but life-threatening complication of colonoscopy. Although conservative therapy is possible in selected cases, if it fails it often leads to the necessity of more extensive operations with increased morbidity in contrast to immediate and definitive surgery. Laparoscopic colorectal surgery offers the possibility of minimizing the invasiveness and associated complications.

Patients and methods

The data of all patients who underwent laparoscopic surgery for iatrogenic colon perforation within a 10-year time period (1997–2009) were recorded prospectively and analyzed retrospectively with regard to age, sex, localization of the perforation, diagnoses and clinical symptoms, type of procedure, intra- and postoperative complications as well as postoperative course.

Results

In the observation period 24 patients with iatrogenic colon perforation were treated laparoscopically. In 17 cases the perforation was associated with therapeutic colonoscopy and in 7 cases with diagnostic colonoscopy. In 19 patients the affected part of the colon was resected and in 5 patients a simple closure by suture was performed. Four cases required conversion. The median operating time was 165 min (range: 90–420 min) and the median hospital stay 11 days (range: 7–25 days). There were no surgical complications in the postoperative course. One patient (91 years) developed cardiac decompensation leading to death.

Conclusion

Laparoscopic treatment of iatrogenic colon perforations offers a minimally invasive and definitive solution to this life-threatening complication. In the hands of an experienced surgeon a laparoscopic approach is a safe and efficient enrichment to the therapeutic options in iatrogenic colon perforation.     

Haiti earthquake 2010: a field hospital pediatric perspective

On January 12 2010, a 7.0-magnitude earthquake struck Haiti. The region had suffered an estimated 316,000 fatalities with approximately 300,000 injured and more than 1 million people who lost their houses. Following the quake, the Israeli Defense Force Medical Corps dispatched a field hospital unit to the capital city, Port au Prince. The hospital had a pediatric division which included pediatric emergency department, pediatric ward and neonatal unit. We elaborate on the various aspects of pediatric treatment that was provided by our hospital. A total of 363 pediatric patients (younger than 18 years) were admitted to our facility during its 10 days of operation. Out of this total, 272 pediatric patients were treated by the pediatric division, 79 (29%) were hospitalized and 57 (21%) required surgery. The pediatric team included seven pediatricians, one pediatric surgeon and six registered nurses. An electronic record and a hard copy file were created for each patient. Fifty-seven percent of the children presented with direct earthquake related injuries. Twelve patients required resuscitation and stabilization and three patients had died. The majority of injuries were orthopedic while infectious diseases accounted for most of the general pediatric diagnoses. In conclusion, operating a field hospital for a population affected by natural disaster is a complex mission. However, pediatric care has its own unique, challenging characteristics.     

Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 g hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.