Carditis: a relevant marker of gastroesophageal reflux disease. Data from a prospective central European multicenter study on histological and endoscopic diagnosis of esophagitis (histoGERD trial).

The columnar-lined mucosa at the gastroesophageal junction may contain an inflammatory infiltrate, commonly referred to as carditis (or cardia gastritis). The etiology of carditis is not entirely clear since published data are conflicting. Some authors believe it to be secondary to gastroesophageal reflux disease (GERD) and others to Helicobacter pylori gastritis. This prospective study aims at clarifying the relationship between carditis and the histological, clinical, and endoscopic findings of GERD, in a large cohort of individuals negative for H. pylori infection. Eight hundred and seventy-three individuals (477 females and 396 males, median age 53 years) participated in this study. Biopsy material was systematically sampled from above and below the gastroesophageal junction. Reflux-associated changes of the esophageal squamous epithelium were assessed according to the Esohisto consensus guidelines. Grading of carditis was performed according to the Updated Sydney System, known from the histological evaluation of gastritis. In total, 590 individuals (67.5%) had chronic carditis. Of these, 468 (53.6%) had mild chronic inflammation, with 321 individuals (68.6%) showing no or minimal changes on endoscopic examination (Los Angeles Categories N and M). The presence of chronic carditis was associated with several GERD-related parameters of the esophageal squamous epithelium (P < 0.0001), and data retained statistical significance even when analysis was restricted to individuals with mild chronic carditis and/or endoscopically normal mucosa. Chronic carditis was also associated with the presence of intestinal metaplasia (P < 0.0001). In addition, chronic carditis had a statistically significant association with patients' symptoms of GERD (P = 0.0107). This observation remained valid for mild chronic carditis in all patients (P = 0.0038) and in those with mild chronic carditis and normal endoscopic mucosa (P = 0.0217). In conclusion, chronic carditis appears to be the immediate consequence of GERD, correlating with patients' symptoms and endoscopic diagnosis. These results are valid in individuals with nonerosive reflux disease, which indicates a higher sensitivity of histological diagnosis. Our findings may impact the routine assessment of reflux patients.

Standardization of two immunological HbA1c routine assays according to the new IFCC reference method.

The measurement of HbA1c is meanwhile well established as the most important parameter in clinical chemistry for monitoring the long term metabolic control of diabetic patients. However, the comparability of HbA1c values obtained by different methods in different laboratories and different countries is limited since there was no internationally agreed reference method available. Additionally the % HbA1c values, based on the most common DCCT values are too high due to well known non specificity of the DCCT standardization protocol. Recently a new reference method for the determination of HbA1c was developed and has been approved by the IFCC as the future basis for the worldwide standardization of HbA1c routine assays. The two routine methods from Roche Diagnostics (both based on the immunoturbidimetric determination of the stable glucose adduct to the N-terminal group of the hemoglobin beta chain, Roche-Hitachi/Tina-quant [a] and COBAS INTEGRA) are directly standardized against this new reference method. Both routine methods are based on a two step approach: in a first step the total Hb is quantified by a colorimetric method and in a second step the stable glucose adduct to the N-terminal group of the hemoglobin beta chain is quantified by immunoturbidity (HbA1c mass). Consequently, first the standardization of the total Hb assay was reconfirmed by method comparisons against the cyanomethemoglobin reference method. Second, the standardization of the HbA1c mass was done by running method comparisons against the new IFCC reference method. The resulting new calibrator values for HbA1c [mass] and total Hb [mass] allow a direct estimation of % HbA1c according to IFCC just by calculating the HbA1c [mass]/total Hb [mass] ratio. Good linear correlations were obtained when comparing the routine methods against the new IFCC reference, indicating the high specificity of these immunological approaches. The following correlations are obtained: Hitachi / Tina-quant [a] (Y) versus IFCC reference method (X): Y = -0.031 + 1.009 x X; r = 0.995. COBAS INTEGRA (Y) versus IFCC reference method (X): Y = -0.156 + 1.006 x X; r = 0.997. Hitachi / Tina-quant [a] (Y) versus Integra (X); (both standardized according to IFCC): Y = 0.057 + 1.003 x X; r = 0.997. The HbA1c values obtained with this new IFCC standardization are significantly lower than the well known DCCT values. Due to the specificity of the immunological approach which is very close to the analyte as defined by the IFCC reference method, no further corrections of the obtained % HbA1c values are necessary. A slope/intercept correction formula is derived which allows the transformation of IFCC values into the DCCT numbers if requested.

Primary biliary cystadenocarcinoma perforating the duodenum and left intrahepatic biliary tree--mimicking a hydatid cyst.

We report the case of a 76-year-old woman with biliary cystadenocarcinoma perforating the left biliary tree and exhibiting intra-tumoral gas bubbles resulting from invasion of the duodenum. The clinical history included subfebrile temperatures of 3 months duration, and pains associated with an abdominal mass in the right upper quadrant. Blood tests showed leucocytosis, and radiological studies revealed the features of a partially calcified septated tumor with nodular components combined with multiple gas-fluid levels, mimicking an infected hydatid cyst. Intraoperative ultrasonography, cholangiography and frozen section histology were necessary to prove the malignant nature of this cystic tumor. Provided that complete resection with strict adherence to oncological precepts is possible, the prognosis of cystadenocarcinoma is better than in hepatocellular or cholangiocellular carcinoma.

Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay.

A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia.

Results of irradiation treatment in patients with non-resectable oesophageal cancer.

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (Group A: Stage I/II, 32; Group B: Stage III/IV, 16) underwent intraluminal Iridium-192 high dose-rate afterloading therapy (5-7 Gy/session, total dose: 5-21 Gy, mean: 12.4 Gy) and external beam irradiation (Karnofsky > or = 80% 50-60 Gy/2 Gy per day; Karnofsky 60-79%: 30 Gy/3 Gy per day). Durable satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B, 6.9 months, with a 12-month survival rate of 66% (group A) and 0% (group B) (P < 0.001). Local tumour response and complication rate were significantly dose-related with a predicted response rate of 70.5%, and a complication rate of 50% at ERD 129.3 Gy.

Partial purification of rat hepatic stimulator substance and characterization of its action on hepatoma cells and normal hepatocytes.

The active principle of a cytosol extract from weanling rat liver representing a putative liver-specific growth factor was partially purified and characterized. "Hepatic stimulator substance" was extracted from the livers of 40- to 60-gm male rats by heat treatment of a homogenate in 35% (w/v) phosphate-buffered saline and subsequent ultracentrifugation. This "heat supernatant" and fractions derived from the subsequent purification steps were tested for growth stimulatory activity in two rat hepatoma cell lines. The undifferentiated, fibroblastoid-like HTC hepatoma cells did not respond to crude hepatic stimulator substance or any of the partially purified preparations. In contrast, MH1C1 cells, which display some differentiated hepatic functions and epithelial morphology, reacted to hepatic stimulator substance and the purified fractions with a dose-dependent increase of their growth rate in serum-free culture. Although insulin, glucagon and epidermal growth factor showed only a minor effect on MH1C1 cell growth on their own, they were active as permissive or potentiating factors for the expression of the maximal effect of hepatic stimulator substance. Similarly, normal adult rat hepatocytes were only sensitive to hepatic stimulator substance when cultured in the simultaneous presence of epidermal growth factor. Under such conditions, hepatic stimulator substance stimulated hepatocyte entry into the S-phase of the cell cycle 3-fold compared to epidermal growth factor alone. Hepatic stimulator substance did not affect growth of human skin fibroblasts and of the rat intestinal crypt cell line IEC-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin binding to cultured adult hepatocytes. Effects of bacitracin and chloroquine on the nature of cell-associated radioactivity.

Sephadex (G-50 fine grade)-gel chromatography and trichloroacetic acid (TCA) precipitation were used to investigate the effects of chloroquine and bacitracin on the nature of cell-associated radioactivity in studies on the binding and degradation of 125I-insulin in cultured rat hepatocytes. Sephadex peak I, eluted with the void volume, increased with hepatocyte incubation time and comprised 6% of total cell-bound radioactivity at 120 min. However, all radioactivity in this peak was due to unspecific binding. Peak II, corresponding to intact insulin, represented 95% of specifically cell-associated label at 5 min and decreased to 77% at 120 min. Peak III, containing the final low-Mr degradation products, increased with incubation time (22% of specifically bound label at 120 min). The TCA-precipitable and TCA-soluble fractions of hepatocytes extracted with 0.1% SDS were within 4-7% of the proportions of radioactivity in peaks II and III respectively. Scatchard plots based on insulin-binding data from Sephadex chromatography or TCA precipitation were identical. Dissociation studies revealed that at least 75% of the intact insulin associated with the hepatocytes was bound to receptors at the cell surface. Bacitracin increased the proportion of cell-associated intact hormone and decreased that of ligand degraded when analysed by either Sephadex chromatography or TCA precipitation. The proportion of surface-bound to internalized intact hormone remained unaltered, indicating that bacitracin acted predominantly at the cell surface. In the presence of chloroquine, which dramatically increased the contribution of peak I to specific binding, 'intact' insulin was substantially overestimated when determined as the TCA-precipitable fraction. In addition, all peak I material and 50% of cell-associated label in peak II was trapped intracellularly, thereby pointing to the lysosomal or prelysosomal site of action of this drug.

Hepatic regenerative stimulator substance in the rabbit. Relation to liver regeneration after partial hepatectomy.

The occurrence and activity of hepatic regenerative stimulator substance was investigated in the partially hepatectomized rabbit and related to biochemical and morphological parameters of liver regeneration. Male rabbits were 60% hepatectomized by excising the Spigelian, left lateral and left central lobes of the liver leaving the gallbladder in situ. [3H]Thymidine incorporation into DNA, the fraction of labelled hepatocyte nuclei, the fraction of mitoses and thymidine kinase activity rose from basal levels at 30-40 h after hepatectomy and increased up to 12-fold at 40-60 h. After 7 days, proliferation parameters returned to near prae-hepatectomy values and 82% of the initial liver mass was restored. Hepatic regenerative stimulator substance was biologically active when prepared from rabbit livers between 18-30 h after partial hepatectomy. At 12 and 30 h after intraperitoneal injection of the extract into normal rats, hepatic DNA synthesis was stimulated up to 2-fold in a dose-dependent fashion. The biological activity was protease-sensitive and thus depended on a protein component of the extract. The data demonstrate the existence of hepatic regenerative stimulator substance in regenerating rabbit liver and suggest that it is implicated in the regulation of liver growth after partial hepatectomy.