Atypical primary sclerosing cholangitis cases associated with unusual pancreatitis.

BACKGROUND/AIMS: We encountered one group of primary sclerosing cholangitis cases which met classic criteria, but demonstrated better clinical courses. METHODOLOGY: We evaluated the clinical characteristics of several cases of primary sclerosing cholangitis, especially those associated with chronic pancreatitis. RESULTS: Of a total of 25 cases, eight had a background of pancreatitis with unusual irregularly segmental or diffuse narrowing features on pancreatography. Abdominal ultrasonography and computed tomography also revealed segmental or diffuse enlargement of the pancreas. Pathological findings of surgical specimens in two cases pointed to lymphoplasmacytic sclerosing pancreatitis. The walls of the lower biliary ducts were also thickened with a similar appearance to the pancreatic ducts. In seven cases, cholangiography displayed stenosis of the lower part of the common bile duct and in one case, only the hepatic hilar region was affected. In this case both biliary and pancreatic lesions responded to steroid therapy simultaneously. One case developed hepatic hilar stenosis four months after a lesion in the lower part of the common bile duct had disappeared. The cases of primary sclerosing cholangitis with pancreatitis demonstrated better clinical courses than did typical cases of primary sclerosing cholangitis. Six cases were characterized by autoimmunological abnormalities. CONCLUSIONS: We concluded that similar etiological agents might impact on both the pancreas and biliary tract, either simultaneously or in sequence. We propose new criteria for these atypical primary sclerosing cholangitis cases.     

Changes in endocrine activities relative to obesity in patients with essential hypertension

The possible role of obesity in the development of hypertension was investigated in two study groups. In a population study of 961 subjects, 739 were found to be normotensive and 222 hypertensive. The prevalence of hypertension was 18.7 percent in the nonobese, and 33.2 percent in the obese subjects. Systolic and diastolic blood pressures increased progressively with the increase of relative body weight in both normotensive and hypertensive subjects. In addition, an endocrinologic study was made of 97 patients with essential hypertension; in 82, plasma renin activity (PRA) was inversely correlated with the increase of relative body weight but not with urinary Na excretion. Despite this decrease of PRA, the level of serum aldosterone was not influenced by relative body weight. Thus, the aldosterone/PRA ratio ratio increased progressively with the increase of relative body weight. Thiazide therapy normalized this inappropriately high ratio, and reduced body weight and blood pressure. Restriction of dietary calories and salt intake had a similar effect. With a high-salt intake in an obese subject, the aldosterone/PRA ratio is unduly increased. Apparently aldosterone contributes to the additional retention of sodium and water and thereby promotes hypertension in the presence of an expanded fluid volume.     

Production of antibody associated with non-A, non-B hepatitis in a chimpanzee lymphoblastoid cell line established by in vitro transformation with Epstein-Barr virus.

A continuous cell line of chimpanzee lymphocytes producing an antibody specifically associated with non-A, non-B hepatitis (NANB) was established. Peripheral blood lymphocytes of a chimpanzee convalescent from experimental infection with NANB hepatitis were transformed in vitro by Epstein-Barr virus infection into lymphoblastoid cell lines. Supernatants of the cell cultures were screened by immunofluorescence for antibody activity against the liver tissue of a chimpanzee with NANB hepatitis. Nineteen of the 1402 cultures were found to be positive for the activity. Ten of these 19 gave cytoplasmic reactions and the remaining 9 gave nuclear reactions in hepatocytes. One culture (48-1) stably producing the antibody was further characterized. The antibody produced in 48-1 was IgM and gave granular cytoplasmic reactions in hepatocytes. Cloning of 48-1 was performed by the soft agar method and cloned cell lines stably producing the antibody were obtained. The 48-1 antibody reacted with liver biopsy specimens from 12 chimpanzees obtained during the acute or chronic phase of hepatitis caused by five different NANB strains, but not with biopsy specimens from chimpanzees with hepatitis A or B or from normal chimpanzees. In addition, examinations of serial liver biopsy specimens obtained from 2 chimpanzees experimentally infected with NANB hepatitis demonstrated that the antibody reacted with the biopsies obtained during the preacute, acute, and chronic hepatitis, but not with those obtained before inoculation, early incubation period, or during convalescence. The present results indicate the specific association of the antibody with NANB hepatitis. Immunoelectron microscopy revealed that the antibody reacted with the microtubular aggregates identical to those previously described in a patient and chimpanzees with NANB hepatitis.     

Small duct cholangitis induced byn-formyll-methioninel-leucinel-tyrosine in rats

Primary sclerosing cholangitis (PSC) frequently accompanies inflammatory bowel diseases. In an attempt to increase our understanding of the pathogenesis of PSC, we studied bile duct changes in rats with colitis which had been givenn-formyll-methioninel-leucinel-tyrosine (fMLT) rectally; fMLT is one of the chemotactic peptides produced byEscherichia coli, and is secreted into the bile by hepatocytes after it enters the portal blood. Transrectal administration of fMLT induced a marked inflammation in the portal triad and mild hepatocyte necrosis on the 4th day. The infiltrating leukocytes in the portal tract were mostly mononuclear cells, which densely infiltrated around the bile ducts. These mononuclear cells appeared to attach to bile duct epithelial cells, and they were more numerous in the smaller bile ducts. Electron microscopy revealed that lymphocytes were in direct contact with bile duct lining cells and that some epithelial cells had degenerated or collapsed. These results suggest that thisE. coli-derived peptide may induce cholangitis in the small bile duct through cell-mediated mechanisms. Since these pathologic changes resemble those of the bile duct observed in the early stage of PSC, it can be concluded that bacterial chemotactic peptides may play a role in the pathogenesis of small-duct PSC.     

Elevated levels of soluble fibrin in patients with venous thromboembolism

The fibrin-related markers (FRMs), including soluble fibrin (SF), d-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, d-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for d-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 μg/ml, FDP 2.1 μg/ml and d-dimer 4.8 μg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 μg/ml, FDP was less than 1.3 μg/ml, and d-dimer was less than 0.5 μg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.     

Serotypes and antibiotic sensitivity of hemolytic streptococci isolated from clinical specimens in Hiroshima Prefecture, 1987-1989

The grouping, the typing and the drug-sensibility of hemolytic streptococci isolated from the clinical specimens taken from 4 medical centers in Hiroshima Prefecture have been examined and reviewed during the past 3 years 1987-1989. The results were summarized in this report. 1. Of 1572 strains of hemolytic streptococci, 844 strains (53.7%) were group A; 539 strains (34.3%), group B; 14 strains (0.9%), group C; 82 strains (5.2%), group G; and 93 strains (5.9%), the others. We found that group A and group B were predominant, and the incidence rate of group B was higher than it used to be. 2. The prevalent types were T-4 (37.9%), T-1 (13.6%), T-12 (12.0%), and T-28 (10.7%) in group A, while Ia (26.2%), M9 (provisional type 18.4%), and III (14.5%) in group B. 3. As far as the detection data of each month is concluded, during the summer season we could hardly detect group A which peak of occurrence during the winter season. These findings were really consistent with the occurrence pattern of those patients who suffered from streptococcal infectious disease. But this occurrence pattern couldn't be found in group B. 4. In our study, the positive frequency was throat swab greater than urine greater than sputum greater than vaginal swab greater than pus greater than ear secretion in order. Group A was mainly isolated from throat swab, while group B, from several specimens including urine. 5. We found that there was a high drug-sensibility to the beta-lactam drugs in all strains except for 3 strains of group B which were resistant to CEX.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of incontinence following low anterior resection for rectal carcinoma

PURPOSE: This study was performed to predict incontinence following low anterior resection for rectal cancer. METHODS: Preoperatively, 21 patients were evaluated via patient history and a physical examination that included anal manometric studies. Six months postoperatively, repeat manometric studies and clinical evaluations were performed to assess the level of continence. Degree of continence was graded based on severity of the dysfunction and grade of the continence score. RESULTS: The formula used for predicted postoperative resting pressure is as follows: predicted postoperative resting pressure=0.42 × preoperative resting pressure+1.56 × length of remaining rectum+12.37 (R ² =0.58;P <0.001). It was demonstrated that patients with low predicted postoperative resting pressures (<30 mmHg) had incontinence, and those with high predicted postoperative resting pressures (>35 mmHg) were continent. There were significant correlations between length of the remaining rectum and ratio of the decrease in maximum resting pressure (postoperative/preoperative maximum resting pressure;r =0.63;P <0.01). CONCLUSIONS: Continence following low anterior resection may be influenced by maximum resting pressure function of the internal anal sphincter; if it is injured during surgery, incontinence will occur. We may be able to foretell incontinence by using the predicted postoperative resting pressure formula, which is calculated by using preoperative resting pressure measurements and then determining the length of the remaining rectum.Abstract presented at the meeting of The Japanese Society of Gastroenterological Surgery, Tokyo, Japan, July 18 to 19, 1996.     

Insulin-induced activation of phosphoinositide 3-kinase in Fao cells

Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6% of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.Abbreviations PI3-kinase Phosphoinositide 3-kinase - p85 85-kDa subunit of PI3-kinase - p110 110-kDa subunit of PI3-kinase - IRS-1 insulin receptor substrate-1 - SH2 src homology 2 - SH3 src homology 3 - BCR breakpoint cluster region - PMSF phenylmethylsulphonyl fluoride - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid - PIP phosphatidylinositol phosphate - TLC thin layer chromatography - IP (in figures) immunoprecipitation with the indicated antibody - TBS Tris-buffered saline