Stromal cells directly mediate the re-establishment of the lymph node compartments after transplantation by CXCR5 or CCL19/21 signalling

Lymph nodes (LN) are highly organized and have characteristic compartments. Destruction of these compartments leads to an inability to fulfil their immunological function. However, it is not yet clearly understood which mechanisms are involved in the development and maintenance of this organization. After transplantation of LN into the mesentery, the LN regenerate to fully functional LN. In this study, the question was addressed, how stromal cells in the B-cell follicles (follicular dendritic cells), which were identified by CD21/CD35, and stromal cells in the T-cell area (gp38+ cells) are involved via chemokine signalling. The gp38+ cells and CD21/CD35+ cells were detected in the transplanted LN (EGFP, plt/plt and CXCR5(-/-) mice) over a period of 8 weeks to analyse their competence to reconstruct the compartmental organization. The presence of gp38+ cells was stable during regeneration and these cells reconstructed the T-cell area within 4 weeks. After transplantation of plt/plt LN CCL19/CCL21 expression was observed leading to partial restoration of the T-cell area. In contrast, there were changes in the presence and morphology of CD21/CD35+ cells within the B-cell area during reconstruction, which was dependent on the presence of B cells and CXCL13/CXCR5 signalling. Hence, CD21/CD35+ cells and gp38+ cells are involved in the establishment of the compartmental organization of lymph nodes but using different ways to recruit lymphocytes via chemokine signalling.     

Open compared with closed haemorrhoidectomy: meta-analysis of randomized controlled trials

Aims This review compares the most popular techniques in managing the wounds after excisional haemorrhoidectomy, which are either to lay the wounds open or to close them. Methods Randomized controlled trials were identified from the major electronic databases using the search terms “hemorrhoid*” and “haemorrhoid*.” Duration of operation, pain, length of hospital stay, time off work, time for wound healing, patient satisfaction, continence, manometry findings and complications were assessed. Quantitative meta-analysis was performed as appropriate or possible. Results Six trials including 686 patients met the inclusion criteria. The median follow-up time ranged from 1.5 to 19.5 months. Quantitative meta-analysis showed that there was no significant difference in cure rates between the two techniques (relative risk, 1.4; 95% CI, 0.86 to 2.2; p=0.191). Open haemor-rhoidectomy was more quickly performed (weighted mean difference, 1.03 min; 95% CI, 0.51 to 1.54; p<0.001). Closed haemorrhoidectomy wounds showed faster healing (weighted mean difference, 1.2 weeks; 95% CI, 0.88 to 1.55; p<0.001). Hospital stay, maximum pain score, total and individual complication rates were not significantly different. Conclusions Apart from faster wound healing after closed haemorrhoidectomy, open and closed techniques appeared equally effective and safe. However, there were only a few studies which presented information in different ways, and statistical heterogeneity was high.     

Giant cell hepatitis: an unusual cause of fulminant liver failure

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 μmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 μmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.     

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

The internet as a tool for the renal community

The Internet has impacted health care. With the introduction of the personal health record (PHR), patients have an opportunity to track their physician visits, medications, and laboratory values online in a pleasant and informative learning environment. The PHR is a secure, online, Internet-accessible method of storing and easily retrieving health information about one's medical history, physician visits, laboratory values, and medications. The American Association of Kidney Patients (AAKP) has taken the leadership role in developing a PHR for patients of the kidney community. There are several barriers that patients experience when using the Web for health resources. These include inaccurate or self-serving information and marketing statements that can be misleading and dangerous. Poorly written or inappropriate information for patients can be problematic, as can an abundance of extraneous information. For the most part, the public often has no way to judge what is and is not credible based on the context of the article alone. This article gives the reader a review of several Web resources that are available for patients and also for renal professionals. They are largely from large nonprofit organizations like the AAKP, National Kidney Foundation, Medical Education Institute, American Society of Nephrology, or The Nephron Information Center (nephron.com). This article also reviews sites from The National Kidney Disease Education Program, Hypertension-Dialysis and Clinical Nephrology, National Institute of Diabetes and Digestive and Kidney Diseases, and DaVita.