Serum immunoreactive trypsin concentration after a Lundh meal. Its value in the diagnosis of pancreatic disease.

The changes in serum trypsin concentration have been measured in 47 subjects for up to 2 hours after a Lundh meal. In 18 healthy controls, mean fasting trypsin concentration was 285 +/- 125 ng/ml (mean +/- 2 SD). The maximum increase after the Lundh meal (the trypsin response ratio) was 6.7 +/- 7.5%. Six patients with chronic renal failure had elevated fasting serum trypsin concentrations (range 460-1100 ng/ml) but trypsin response ratios fell within the control range. Of five patients with relapsing pancreatitis, two had raised and three normal or low fasting trypsins. After stimulation two had elevated trypsin response ratios; one of the two had evidence of main duct obstruction. Eleven out of 12 patients with chronic pancreatitis (with or without insufficiency) had low fasting trypsin concentrations (range 0-120 ng/ml) Seven of the 12 also had raised trypsin response ratios. In six patients with cancer of the pancreas, fasting trypsin was low in three, normal in two, and raised in one. Both patients with a normal fasting level had a raised trypsin response ratio. The combination of a single estimation of fasting serum trypsin concentration followed by serial measurements after a Lundh meal provides a useful screening test for chronic pancreatic disease.     

Immune suppression leading to hepatitis C virus re-emergence after sustained virological response

Sustained virological response SVR is defined as undetectable HCV RNA in plasma 6 months after therapy has been discontinued. Relapse or re-emergence of viremia after SVR is rare. We report two patients that relapsed when immune suppressive therapy was given within a few weeks of achieving SVR. Patient 1 received prednisone for bronchitis and patient 2 relapsed soon after immune suppression was started post renal transplantation. These data suggest that the early phase of SVR might be associated with incomplete protective immunity. They suggest that sterilizing immunity with complete elimination of virus is unlikely. The cases also caution against the use of immune suppressive therapy in the immediate aftermath of SVR.     

Digital image analysis of the distribution of proliferating cell nuclear antigen in hepatitis C virus-related chronic hepatitis,cirrhosis, and hepatocellular carcinoma

Viral dynamic studies in chronic hepatitis C virus (HCV) infection indicate a significantly shortened survival of virus-infected cells. Since at the steady state of chronic viral infection, the rate of infected cell elimination equals new cell regeneration, this would imply a high rate of hepatocyte turnover in chronic HCV liver disease. We estimated the fraction of regenerating hepatocytes in liver biopsy sections in chronic HCV liver disease, cirrhosis, and hepatocellular carcinoma (HCC). We used antibodies to proliferating cell nuclear antigen (PCNA) to detect proliferating cell nuclei in liver biopsy specimen from controls and patients with chronic hepatitis, cirrhosis, and HCC. We also used bis-benzimide to label fluorescently all hepatocyte nuclei simultaneously. Using digital image analysis, we calculated the area occupied by PCNA-stained hepatocyte nuclei, as a fraction of the total area occupied by fluorescently labeled hepatocyte nuclei (labeling index; LI). Antibody staining was negligible in the control specimen. The mean ± SE PCNA LI increased from 0.21 ± 0.1 in chronic hepatitis to 0.63 ± 0.15 in HCC. There was no significant difference between chronic hepatitis and cirrhosis. The fraction of cells undergoing regeneration is increased in chronic HCV liver disease, HCV-related cirrhosis, and HCC. Increased hepatocyte turnover could provide the link between chronic HCV liver disease and HCC.     

Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome.

The spectrum of presentation of complications in patients with human immunodeficiency virus (HIV) disease is changing, in line with their improved survival. Infection of the colon with cytomegalovirus (CMV) is now more commonly encountered in clinical practice. We have reviewed the medical records of eleven patients with clinical and pathological evidence of CMV colitis. The clinical presentation, endoscopic and histological findings, and simultaneous infection of other organs with CMV are discussed. Diarrhoea in association with abdominal pain is the most frequent symptom complex in these patients and should raise the clinical index of suspicion for CMV colitis.     

Measurement of trypsin in duodenal juice by radioimmunoassay.

Trypsin in duodenal aspirate and pure pancreatic juice samples has been measured by both radioimmunoassay and enzymatic mathods. The radioimmunossay has been shown to be specific and to detect trypsin in the presence of aprotinin (Trasylol). In duodenal juice samples from control subjects and from patients with primary biliary cirrhosis a good correlation was obtained between both immunoreactive trypsin concentration and trypsin activity. The immunoreactive trypsinogen concentration in pure pancreatic juice also correlated well with activated trypsin activity. The mean immunoreactive trypsin concentration and the concentration of enzymatically inert immunoreactive trypsin in duodenal juice samples from patients with primary biliary cirrhosis were significantly lower than controls, suggesting pancreatic hyposecretion in this disease. After five duodenal juice samples had been stored for three months at -70 degrees C, immunoreactive trypsin concentration in samples stored without Trasylol were reduced by 12 . 0 +/- 4 . 2 (mean +/- SD) times the concentration of samples stored in Trasylol. Trypsin autodegradation continues even at -70 degrees C; Trasylol protects against this. Radioimmunoassay is a reliable method of trypsin estimation in duodenal juice and has advantages over conventional enzymatic analysis.     

Biliary immunoreactive trypsin in man

Small, but significant amounts of immunoreactive trypsin/trypsinogen (IRT) are excreted in bile, obtained via percutaneous transhepatic catheter in patients with complete distal bile duct obstruction, and thus uncontaminated with pancreatic juice. The major serum proteolytic enzyme inhibitors alpha 2-macroglobulin and alpha 1-antitrypsin are also present in very small amounts in bile. The bile-to-serum ratios of these inhibitors are much lower (approximately two orders of magnitude) than that for IRT. The role of these inhibitors and their relative importance in biliary proteolytic enzyme inhibition is unknown.