Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system.

Hepatitis C virus (HCV) infection induces the endogenous interferon (IFN) system in the liver in some but not all patients with chronic hepatitis C (CHC). Patients with a pre-activated IFN system are less likely to respond to the current standard therapy with pegylated IFN-alpha. Mitochondrial antiviral signaling protein (MAVS) is an important adaptor molecule in a signal transduction pathway that senses viral infections and transcriptionally activates IFN-beta. The HCV NS3-4A protease can cleave and thereby inactivate MAVS in vitro, and, therefore, might be crucial in determining the activation status of the IFN system in the liver of infected patients. We analyzed liver biopsies from 129 patients with CHC to investigate whether MAVS is cleaved in vivo and whether cleavage prevents the induction of the endogenous IFN system. Cleavage of MAVS was detected in 62 of the 129 samples (48%) and was more extensive in patients with a high HCV viral load. MAVS was cleaved by all HCV genotypes (GTs), but more efficiently by GTs 2 and 3 than by GTs 1 and 4. The IFN-induced Janus kinase (Jak)-signal transducer and activator of transcription protein (STAT) pathway was less frequently activated in patients with cleaved MAVS, and there was a significant inverse correlation between cleavage of MAVS and the expression level of the IFN-stimulated genes IFI44L, Viperin, IFI27, USP18, and STAT1. We conclude that the pre-activation status of the endogenous IFN system in the liver of patients with CHC is in part regulated by cleavage of MAVS.

Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age.

Macroscopic features such as volume, surface estimate, thickness and caudorostral length of the human primary visual cortex (Brodman's area 17) of 46 human brains between midgestation and 93 years were studied by means of camera lucida drawings from serial frontal sections. Individual values were best fitted by a logistic function from midgestation to adulthood and by a regression line between adulthood and old age. Allometric functions were calculated to study developmental relationships between all the features. The three-dimensional shape of area 17 was also reconstructed from the serial sections in 15 cases and correlated with the sequence of morphological events. The sulcal pattern of area 17 begins to develop around 21 weeks of gestation but remains rather simple until birth, while it becomes more convoluted, particularly in the caudal part, during the postnatal period. Until birth, a large increase in cortical thickness (about 83% of its mean adult value) and caudorostral length (69%) produces a moderate increase in cortical volume (31%) and surface estimate (40%) of area 17. After birth, the cortical volume and surface undergo their maximum growth rate, in spite of a rather small increase in cortical thickness and caudorostral length. This is due to the development of the pattern of gyrification within and around the calcarine fissure. All macroscopic features have reached the mean adult value by the end of the first postnatal year. With aging, the only features to undergo significant regression are the cortical surface estimate and the caudorostral length. The total number of neurons in area 17 shows great interindividual variability at all ages. No decrease in the postnatal period or in aging could be demonstrated.

Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients.

Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.

Les complications de la cirrhose hépatique: varices oesophagiennes, ascite et carcinome hépato-cellulaire [Complications of liver cirrhosis: oesophageal varices, ascites and hepato-cellular carcinoma]

The principal treatment for bleeding oesophageal varices is endoscopic ligation. Non-cardioselective beta-blockers are the gold-standard of primary prophylaxis. The principal treatment for ascites is a salt-free diet and diuretics, mainly spironolactone, if necessary associated with a loop diuretic. In refractory ascites, paracentesis or installation of a transjugular intrahepatic portosystemic shunt (TIPS) are two possible treatment options. Cirrhosis patients are at higher risk of developing hepato-cellular carcinoma. Surgery is only possible in a small number of cases. Percutaneous destruction techniques have nearly the same survival rate as that obtained by surgery and should be proposed to patients where surgery is not an option.

IRENE newsletter. Volume 1, number 1 (Spring/Summer 2007)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 1, number 2 (Fall/Winter 2007). University of Iowa

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 2, number 1 (Spring/Summer 2008). University of Iowa

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 4, number 1 (Spring/Summer 2010)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 4, number 2 (Fall/Winter 2010)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 1, number 2 (Fall/Winter 2007)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 2, number 1 (Spring/Summer 2008)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 2, number 2 (Fall/Winter 2008)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 3, number 1 (Spring/Summer 2009)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 3, number 2 (Fall/Winter 2009)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.

IRENE newsletter. Volume 5, number 1 (Spring/Summer 2010)

IRENE’s mission is to improve the health and well-being of Iowans through collaboration in practice-based research on questions important to primary care physicians and their patients. IRENE’s purpose is to create and foster a network of research collaboration between the academic medical center and primary care physicians through out the state of Iowa with a particular focus on improving rural health.