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Biomedical subjects

A R Janssens

Publications and source records attributed to A R Janssens.

At least 19 recordsLinked to original sources
PubMed1992

Metallothionein concentration in the liver of patients with Wilson's disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer.

In patients with primary biliary cirrhosis and Wilson's disease liver copper concentrations become elevated during the evolution of the disorder. The accumulated copper is thought to be detoxified by metallothionein, a protein which binds copper and zinc. In liver metastasis of colorectal cancer, copper and zinc concentrations are usually decreased compared to normal liver tissue, but little is known about the concomitant metallothionein levels. In the present study metallothionein concentrations were determined in archival liver samples from patients with primary biliary cirrhosis and Wilson's disease, and in both normal and malignancy-containing liver samples from patients with metastasis from a colorectal adenocarcinoma. Twenty-seven control liver samples contained 3.98 +/- 1.55 mg metallothionein/g protein. From the 21 liver samples of patients with primary biliary cirrhosis, which had a mean metallothionein concentration of 6.06 +/- 5.03 mg/g protein, 6 were above the highest control level. Liver metallothionein concentrations for the 8 patients with Wilson's disease were significantly elevated (10.98 +/- 6.93 mg/g protein, p < 0.005 vs. controls and p < 0.05 vs. primary biliary cirrhosis). In the 11 liver metastases from colorectal adenocarcinomas metallothionein concentrations (1.17 +/- 0.90 mg/g protein) were significantly (p < 0.005) lower than surrounding normal liver tissue (4.25 +/- 1.75 mg/g protein). We conclude that in primary biliary cirrhosis and Wilson's disease increased liver metallothionein concentrations may detoxify the accumulated copper. Furthermore, liver metastasis of colorectal cancer contains less metallothionein than the surrounding normal liver tissue.

Adenocarcinoma↗
PubMed1991

Second evaluation of HEPAR, an expert system for the diagnosis of disorders of the liver and biliary tract.

HEPAR is an expert system which can be used as a supportive tool in the diagnosis of disorders of the liver and biliary tract. When consulted for a particular patient, the system assesses the patient's disorder in two stages. In the first stage, data of medical history, physical examination and routine laboratory tests are used to determine whether the disorder is hepatocellular or biliary obstructive, and whether benign or malignant features are present. In the second stage, the system produces a differential diagnosis out of a set of 80 disease categories, using the conclusions of the first stage of the assessment and the results of a restricted number of supplementary investigations, i.e. serological tests and ultrasonography. The conclusions of the two stages are ordered by the amount of evidence computed by HEPAR. The system is not yet suitable for clinical use. The system has been evaluated using data of 181 patients selected from a population of 214 consecutively admitted patients with jaundice. The patients were classified by the system as having a hepatocellular or biliary obstructive, and a benign or malignant disorder in 96% and 100% of the cases, respectively. When comparing the conclusions with strongest evidence with the final clinical diagnoses, the patients were classified correctly in 86% and 83% of the classified cases, respectively. A differential diagnosis was produced in 87% of the patients. A correspondence between the diagnosis with strongest evidence and the final clinical diagnosis was found in 78% of the classified patients.

Adolescent↗
PubMed1991

Decrease in two intestinal copper/zinc containing proteins with antioxidant function in inflammatory bowel disease.

Oxygen derived radicals contribute to tissue injury in inflammatory bowel disease. We measured the content of superoxide dismutase and metallothionein (two endogenous copper and zinc containing proteins involved in radical scavenging) in intestinal resection specimens from 29 patients with Crohn's disease and 12 patients with ulcerative colitis and compared the concentrations with those obtained in the normal mucosa of a control group of 18 patients with colorectal cancer. The superoxide dismutase content was similar in control mucosa and non-inflamed mucosa from patients with inflammatory bowel disease (mean (SEM) 2.13 (0.10) and 2.24 (0.10) mg/g protein, respectively) but was decreased in inflamed mucosa (1.87 (0.08) mg/g protein, p less than 0.005 v non-inflamed mucosa). The metallothionein content was decreased in non-inflamed inflammatory bowel disease mucosa compared with control mucosa (0.23 (0.03) and 0.36 (0.04) mg/g protein, respectively, p less than 0.02) and a further decrease was found in inflamed mucosa (0.17 (0.02) mg/g protein, p less than 0.001 v control mucosa). No differences were found between Crohn's disease and ulcerative colitis and no significant effect of medication or tissue localisation was noted. These findings might indicate a decreased endogenous intestinal protection against oxygen derived radicals in inflammatory bowel disease which could contribute to the pathogenesis of the disease.

Adolescent↗
PubMed1991

Detection of gastric erosions: comparison of biphasic radiography with fiberoptic endoscopy.

Biphasic radiography was compared with fiberoptic endoscopy in detecting gastric erosions in a prospective, blinded study of 385 patients with dyspepsia. Because no absolute standard was available for the comparison, since histologic confirmation of all erosions was not possible, the kappa statistic was used to compare results from both modalities. Flat (incomplete) erosions were detected with endoscopy only and were considered to be present in 42 patients (11.2%). Varioliform (complete) erosions were identified with both radiography and endoscopy in 12 patients (3.2%). For the detection of varioliform erosions, a substantial agreement beyond chance between both modalities was found (kappa = 0.73; standard error, 0.12). Thus, flat erosions were detected with endoscopy only, whereas state-of-the-art radiography and endoscopy were equally sensitive for detecting varioliform erosions. Histologic confirmation of erosions was obtained in only 75% of the patients. It is unknown whether the demonstration of erosions with radiography and/or endoscopy correlates with dyspepsia.

Dyspepsia↗
PubMed1991

Villous tumors of the duodenum. Presentation of five cases.

Five cases of villous tumors of the duodenum are reported. These tumors have a predilection for the periampullary region and tend to present with jaundice or obstruction of the duodenal lumen. In four of these patients, malignant transformation was seen. Endoscopy and biopsy play a major rôle in attempting to obtain an accurate preoperative diagnosis. Unfortunately, the diagnosis of malignant degeneration is frequently missed, even when multiple biopsies are taken. For this reason villous tumors should always be resected, and the strategy of treatment must depend on pre-, intra- and postoperative histological evaluation, location in the duodenum and intra-operative findings.

Adenocarcinoma↗
PubMed1991

Plasma metallothionein concentration in patients with liver disorders: special emphasis on the relation with primary biliary cirrhosis.

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1990

Isolation, characterization, and determination of human liver (copper/zinc) metallothionein.

A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT). From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control livers and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.

Amino Acids↗
PubMed1990

Development of a radioimmunoassay for human metallothionein.

We report the development of a radioimmunoassay (RIA) for human metallothionein (MT). The MT was isolated from the liver of a patient with primary biliary cirrhosis and used to raise high titer antibodies in rabbits. The RIA was developed using Bolton-Hunter labeled MT as label and purified MT as standard. The detection limit of the assay was 0.4 ng/ml and concentrations between 0.8 and 100 ng/ml could be routinely measured. Dilutions of plasma samples containing high endogenous MT concentrations and tissue extracts in assay buffer showed parallelism with the standard curve and MT added to plasma could be fully recovered.

Humans↗
PubMed1990

[Comparison of biphasic radiologic stomach and duodenum studies with fiber endoscopy for the diagnosis of peptic ulcer and stomach carcinoma].

In a prospective, blind study of 385 patients with dyspepsia, the diagnostic value of biphasic radiological examination of stomach and duodenum was compared with endoscopy. The patients were examined for presence of peptic ulcers and gastric carcinomas. No golden standard being available, kappa values were calculated for the comparison. The kappa values were 0.67 and 0.77 for gastric and duodenal ulcers, respectively; for gastric carcinomas the value was 0.91. These values indicate good agreement. The sensitivity and specificity of both methods were high; a lower sensitivity of radiological examination for duodenal ulcers was accounted for by ulcers smaller than 5 mm; for larger ulcers, the sensitivity and specificity of both methods were practically the same. It is concluded that the two methods are of equal value for the diagnosis of peptic ulcers and gastric carcinomas. Endoscopy offers the major advantage that biopsy samples can be taken for histological examination or culturing. The biphasic radiological examination, on the other hand, is cheaper and often better tolerated by the patient.

Adolescent↗
PubMed1990

Neoplasia-related changes of two copper (Cu)/zinc (Zn) proteins in the human colon.

Cu/Zn-containing proteins have recently become of interest with regard to their relation with malignant disorders. Cu Zn-superoxide dismutase (Cu/Zn-SOD) was found increased in chemically induced tumors of the large bowel whereas metallothionein (MT), containing Zn and some Cu, was shown important for the response of tumors to chemotherapy. In the present study, we evaluated the Cu/Zn-SOD and MT content of normal human colonic mucosa and colorectal carcinomas, obtained from 20 resection specimens, and of 47 adenomatous polyps. The Cu/Zn-SOD content of polyps and carcinomas was significantly (p less than 0.01) elevated when compared to normal mucosa. In the adenomatous polyps the Cu/Zn-SOD content increased significantly with increasing grade of epithelial cell dysplasia, diameter, and presence of a villous component. In the carcinomas no relation was noticed between the Cu/Zn-SOD content and the Dukes' stage or the grade of differentiation. The MT content was significantly decreased in both adenomatous polyps and carcinomas when compared to that in normal mucosa. The MT content was not related to the grade of epithelial cell dysplasia of the polyps, and to the Dukes' stage or the differentiation of the carcinomas. In conclusion, neoplasia of the colorectum is accompanied by an increase in Cu/Zn-SOD and a decrease in MT. These findings support the association between changes in Cu/Zn proteins and malignancy.

Adenocarcinoma↗
PubMed1989

Relationship between the metabolism of antipyrine, hexobarbital and theophylline in patients with liver disease as assessed by a 'cocktail' approach.

Antipyrine (AP), hexobarbital (HB) and theophylline (TH) were administered simultaneously ('cocktail' design) to 24 patients with various types of liver disease. Clearance (Cl) of AP, HB and TH and formation clearance of the AP-metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA) and 4-hydroxyantipyrine (OHA) were determined and correlation coefficients and orthogonal least-squares regression lines calculated between the clearance and formation clearance parameters. The results were compared with those obtained in a study in which the same 'cocktail' was administered to 26 healthy control subjects. In the patients ClAP, ClHB and ClTH were 23.0 +/- 14.3 ml min-1, 206 +/- 128 ml min-1 and 39.9 +/- 26.1 ml min-1 respectively. All values were considerably lower than those found in the control subjects. With regard to AP metabolism preferential impairment of NORA formation was observed. Relatively high correlation coefficients were found between ClAP, ClHB and ClTH, which suggests, like the results of orthogonal regression analysis, a strong correlation between total metabolism of these probe drugs. Therefore it is likely that impairment in oxidation in patients with liver disease not only leads to reduction in clearance but also to reduced substrate selectivity of cytochrome P-450 isozymes.

Adult↗
PubMed1989

HEPAR: an expert system for the diagnosis of disorders of the liver and biliary tract.

The HEPAR system is a medical expert system intended as a supportive tool for the diagnosis of disorders of the liver and biliary tract. In the system, the role of information from the medical interview, physical examination, and simple non-invasive diagnostic methods, such as ultrasonography, is emphasized in order to reduce the number of diagnostic procedures to be applied. Medical diagnosis is modelled in the system using the formalism of if-then rules. Based on patient data available, the system determines whether the data indicate a hepatocellular or a biliary obstructive disorder, and whether or not benign or malignant features are present. Moreover, the system produces a subset of possible diagnoses out of a set of more than 70 diagnostic categories. The system is still under development. In a preliminary study, the HEPAR system has been evaluated using data from 94 jaundiced patients. Conclusions with respect to the hepatocellular or biliary obstructive nature of the disorder, the benign or malignant nature of the disorder, and the final diagnosis, were reached in 95%, 65%, and 80% of the cases, respectively. These conclusions were correct in 85%, 92%, and 80% of the classified cases, respectively. The system was shown not to be sensitive to incompleteness of information.

Adult↗
PubMed1988

Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives.

Peliosis hepatis, a condition characterized by the presence of blood-filled lacunar spaces in the liver, has been described primarily in patients on androgenic steroid medication and patients with tuberculosis. It has never been reported as a complication of the use of oral contraceptives, except in association with and localized in contraceptive-induced hepatic tumors. The present report concerns a 43-yr-old woman with generalized peliosis hepatis that developed during long-term use of oral contraceptives. Extensive examination did not reveal a hepatic tumor. Liver cirrhosis and portal hypertension developed, although the oral contraceptives had been withdrawn. She finally underwent successfully an orthotopic liver transplantation.

Adult↗
PubMed1987

Highly symptomatic adult polycystic disease of the liver. A report of fifteen cases.

Fifteen patients were evaluated because of highly symptomatic adult polycystic liver disease. All of them had abdominal pain, two patients had obstructive jaundice, one had ascites and a large right-sided pleural effusion, and one had oesophageal varices. In 4 patients percutaneous aspiration of the largest cysts was performed, but this form of treatment only provided temporary relief. In 9 patients a fenestration operation was carried out. One of these patients died per-operatively due to irreversible shock. The abdominal complaints disappeared post-operatively in 7 of the other 8 patients, although a decrease of the liver span was uncommon. In the two patients with obstructive jaundice the serum bilirubin level normalized after the operation, and in the patient with oesophageal varices this abnormality disappeared post-operatively. Biochemical analysis of cyst fluid was performed in 7 of the cases. The mean ratios of the levels of most of the non-protein-bound inorganic ions and other small molecules in cyst fluid and serum were about 1, whereas those of all proteins and protein-bound constituents were generally far below 1.

Cysts↗