Evaluation of commercially available third-generation anti-hepatitis C virus enzyme-linked immunosorbent assay in patients on haemodialysis

Restricted antibody reactivity to hepatitis C virus (HCV) synthetic peptides has been observed in HCV-infected patients on haemodialysis (HD). The aim of this study was to evaluate third-generation anti-HCV enzyme-linked immunosorbent assay (ELISA) test systems containing either synthetic peptide HCV antigens or recombinant HCV antigens or a combination of synthetic and recombinant antigens in screening of 69 chronic renal failure patients on HD for HCV infection. Seven patients were detected to have antibodies to HCV by the 'recombinant HCV antigens'-containing kits, of which the recombinant immunoblot assay for HCV confirmed four cases. The recombinant kits had a sensitivity of 100% and a specificity of 66%. However, the ELISA kits with only synthetic HCV antigens failed to detect antibodies in any of the cases (zero sensitivity). Hence a recombinant protein containing ELISA test system is ideal for screening of HCV infection in patients on hemodialysis.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.      

Pharmacokinetics and pharmacodynamics of cisapride in patients undergoing hemodialysis.

Twenty-two patients who were receiving hemodialysis were studied in three groups of eight subjects each to assess the pharmacokinetics during the dialysis-free interval and during hemodialysis treatment and to assess the pharmacodynamics of cisapride. Cisapride and its metabolite norcisapride were measured by use of HPLC and gas chromatography, respectively. The pharmacodynamic effect of cisapride was measured by means of radionuclide gastric emptying. After a single oral dose of 20 mg the terminal half-life of cisapride was 9.6 +/- 3.3 hours, the volume of distribution was 4.8 +/- 3.3 L/kg, the total oral plasma clearance was 380 +/- 161 ml/min, the area under the curve was 1024 +/- 447 ng.hr/ml (mean +/- SD). Norcisapride only could be detected in the dialysate (0.36 +/- 0.067 mg) and was eliminated by a hemodialysis clearance of 34.7 +/- 7.9 ml/min. Cisapride reduced gastric retention from 77.6% +/- 21.1% to 43.7% +/- 18.2% of maximum filling (40 minutes after meals) and normalized the abnormal gastric emptying time in patients receiving dialysis. Cisapride dosage adjustment or substitution after hemodialysis is not necessary.     

The pelvic digit ��eleventh finger��

Described as asymptomatic and an incidental finding on a plain x-ray film, the “pelvic digit” is a rare congenital anomaly. A 35-year-old man is of a rare symptomatic pelvic digit that warranted surgical excision. Its importance lies in its differentiation from acquired abnormalities due to trauma such as myositis ossificans and avulsion injuries of pelvis. If this entity is kept in mind, unnecessary investigations or interventions can be avoided.