Determination of the cut-off value of serum alanine aminotransferase in patients undergoing hemodialysis, to identify biochemical activity in patients with hepatitis C viremia.

BACKGROUND: Elevated liver enzymes are infrequent in patients with hepatitis C virus (HCV) infection undergoing chronic hemodialysis (HD), suggesting that the alanine aminotransferase (ALT) is a poor predictor of hepatocellular damage in this population. OBJECTIVE: To establish a more appropriate cut-off value of ALT to identify biochemical activity due to HCV infection in HD patients. STUDY DESIGN: A total of 217 patients, with an average age of 51.2 years, were evaluated between January and October 2002; 130 were males (60%). Serum ALT was measured by a kinetic method in five consecutive monthly blood samples, from which an average was obtained and divided by the upper limit of normal (ULN). HCV antibodies were determined using an enzyme immunoassay, the serum HCV-RNA by nested-PCR and HCV genotype by hybridization of the amplified sequence from the 5'-non-coding region. The cut-off value of ALT was obtained from a ROC curve. RESULTS: Within the 217 patients, 18 (8.3%) were anti-HCV-positive, 17 (7.8%) of whom were also HCV-RNA-positive. Genotype distribution was: 1a=47%; 1b=18%; 3a=35%. Mean ALT/ULN (0.77+/-0.57) of the 18 anti-HCV-positive cases was higher (p<0.001) than the negative group (0.38+/-0.23). The mean ALT/ULN (0.81+/-0.57) of the 17 HCV-RNA-positive cases was also higher (p<0.0001) than the negative cases (0.37+/-0.23). The cut-off value of ALT to distinguish the anti-HCV-positive from negative patients was 0.50% or 50% of the ULN (sensitivity=67%; specificity=83%). According to the HCV-RNA, the cut-off value of ALT was 0.45% or 45% of the ULN (sensitivity=71%; specificity=80%). CONCLUSION: Reducing the cut-off of ALT by half, enables a better identification of biochemical activity in patients with HCV infection on chronic HD.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

INTRA-AORTIC BALLOON RUPTURE CAUSING FEMORAL ENTRAPMENT

Rupture of an intra-aortic balloon counterpulsator (IABCP) demands immediate removal. We report a case of thrombus formation within a Datascope IABCP secondary to IABCP rupture, necessitating surgical exploration for removal. There is a disturbing pattern of balloon ruptures with this type of IABCP.     

Pulmonary artery catheterization: a modified technique

A modified technique for catheterization of the pulmonary artery was developed. It involves the passage of a tapered, movable-core, J-tipped guide wire across the right ventricle into the pulmonary artery followed by the advancement of a straightened Grollman pigtail catheter. The technique was successful in 34 of 34 pulmonary artery catheterizations. The method avoids prolonged catheter manipulation within the right ventricle. In addition, since the catheter does not cross the tricuspid valve until the guide wire has been advanced, the occasional complication of the pigtail "hooking" on a tricuspid valve leaflet or chordae tendineae during catheter withdrawal and manipulation is prevented.