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Biomedical subjects

K Borch

Publications and source records attributed to K Borch.

At least 37 records · Page 2Linked to original sources

Identification of Helicobacter in gastric biopsies by PCR based on 16S rDNA sequences: a matter of little significance for the prediction of H. pylori-associated gastritis?

The aim of the present study was to correlate molecular evidence of the presence of Helicobacter pylori in gastric biopsy samples, based on analysis of 16S rDNA, vacuolating toxin (vacA), urease A (ureA) and cagA genes, with the clinical, histological and serological findings in patients with H. pylori-associated gastritis. Fresh biopsy samples were collected from the gastric antrum and corpus of 22 asymptomatic volunteers with or without H. pylori-associated gastritis. Total DNA was extracted from the biopsy material and subjected to 16S rDNA PCR amplification, Southern blotting and 16S rDNA sequence analysis of the PCR products. The vacA, ureA and cagA genes were characterised by PCR amplification and Southern blot analysis. Based on partial 16S rDNA sequence analysis, DNA belonging to the genus Helicobacter was detected in gastric biopsy samples from 20 of 22 subjects, including seven of nine histologically and serologically normal controls. Six of 20 partial 16S rDNA sequences revealed variations within variable regions V3 and V4 that deviated from those of the H. pylori type strain ATCC 4350T and, therefore, possibly represented other species of Helicobacter. VacA genes identical with those of the type strain were found predominantly in the subjects with H. pylori gastritis, and all the patients except one were found to be cagA-positive. There was no evidence of false positive PCR reactions. In conclusion, the PCR-based molecular typing methods used here were apparently too sensitive when applied to the detection of H. pylori in human gastric tissues. The lack of quantitative analysis makes them inappropriate as clinical tools for the diagnosis of H. pylori-associated gastritis, despite the fact that they provide a qualitative and sensitive tool for the detection and characterisation of H. pylori in the gastrointestinal tract.

Adult↗

Detection of spiral and coccoid forms of Helicobacter pylori using a murine monoclonal antibody.

Helicobacter pylori is the major cause of gastritis. The aim of this investigation was to develop a specific antibody, which recognizes both coccoid and spiral forms of Helicobacter pylori and to test this antibody on gastric biopsy sections known to harbour coccoid bacteria. Murine monoclonal antibodies against glycine-acid extracts of five strains of Helicobacter pylori were raised. Immunofluorescence and immunoelectron microscopy showed that one antibody of the IgG1 subclass was specific for both the spiral and coccoid forms. It reacted with a 28 kDa protein that was present in all the five strains tested. Using this antibody in an indirect immunofluorescence assay of formalin-fixed antral and corpus biopsy specimens from Helicobacter pylori-associated gastritis patients showed that nine of the nine antral and five of six corpus specimens harboured the coccoid form of Helicobacter pylori. This technique thus provides a rapid and specific detection of both the spiral and coccoid forms.

Antibodies, Bacterial↗

Chronic endogenous hypercholecystokininemia promotes pancreatic carcinogenesis in the hamster.

In order to examine the effect of cholecystokinin on spontaneous and induced pancreatic carcinogenesis in the hamster, two sets of experiments were carried out, one involving long-term hypercholecystokininemia and one involving cancer induction during hypercholecystokininemia. The effect of hypercholecystokininemia, induced by pancreaticobiliary diversion (PBD), was studied for 8 months. Neither PBD animals nor sham-operated controls developed premalignant or malignant pancreatic lesions. However, in the PBD group the mean pancreatic weight, total protein content and DNA content were increased by 30, 29 and 27% respectively. No such increases were found in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of PBD on N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis was studied for 3 months. Putative premalignant pancreatic lesions were diagnosed in all PBD hamsters and in four of 15 sham-operated controls. Pancreatic ductular carcinoma in situ was only found in PBD animals. The [3H]thymidine labeling index of the pancreatic lesions was significantly higher in the PBD group than in the controls. No such increase was observed in PBD animals receiving a cholecystokinin-A receptor antagonist during the last 5 days of the experiment. It is concluded that chronic endogenous hypercholecystokininemia promotes early phase pancreatic carcinogenesis, but does not per se cause development of premalignant or malignant pancreatic lesions in the hamster.

Animals↗

Effect of chronic endogenous hypergastrinaemia on pancreatic growth and carcinogenesis in the hamster.

BACKGROUND: To examine the effect of gastrin on spontaneous and induced pancreatic carcinogenesis in the hamster. METHODS AND RESULTS: Two sets of experiments were carried out, one involving long term hypergastrinaemia and one involving cancer induction during hypergastrinaemia. The effect of hypergastrinaemia accomplished by gastric fundectomy was studied for eight months. Neither fundectomised hamsters nor sham operated controls developed premalignant or malignant pancreatic lesions. In the fundectomy group, the mean pancreatic weight, total protein content, and DNA content was increased by 28%, 25%, and 25% respectively. No such increases were found in fundectomised animals receiving a cholecystokinin-B receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of fundectomy on N-nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for three months. There were no significant differences in the incidence or [3H]-thymidine labelling index of focal pancreatic lesions between fundectomised and sham operated control animals. CONCLUSIONS: Fundectomy with chronic hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N-nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster. The increases in growth were inhibited by a cholecystokinin-B receptor antagonist, indicating that the trophic effect of fundectomy is mediated by gastrin.

Animals↗

Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis.

BACKGROUND: It is not known whether plasma chromogranin analysis could be a complement to histology for detection and grading of gastric fundic mucosal endocrine cell proliferation in hypergastrinemic (type-A) atrophic gastritis. METHODS: Gastric biopsy sections (body and antrum) from 43 patients with type-A gastritis (9 with gastric carcinoid) were examined for density and micronodules of argyrophil endocrine cells. Fasting blood samples were analyzed for chromogranin A and B, gastrin, and somatostatin. RESULTS: All patients with carcinoid and 17 of the 34 without carcinoid had micronodules in the gastric fundic mucosa. The median plasma chromogranin A concentration was 5.7 (3.5-40.0) nmol/l in patients with carcinoid, 4.5 (3.0-9.5) nmol/l in patients with micronodules, and 3.7 (0.8-6.0) nmol/l in patients without micronodules. Overall, chromogranin A concentrations correlated to endocrine cell densities in the fundic mucosa (r = 0.64, P < 0.001) and to gastrin concentrations (r = 0.71, P < 0.001). Plasma somatostatin and chromogranin B concentrations did not differ significantly between the groups. CONCLUSION: In type-A gastritis, analysis of plasma chromogranin A may be a useful complement to histology in estimating the endocrine cell mass. Moreover, subclinical type-A gastritis may be a source of error when chromogranin A analysis is used in the search for neuroendocrine neoplasia.

Aged↗

Increased gastric absorption of polyethylene glycols in atrophic gastritis.

Atrophic gastritis increases the risk of developing gastro-intestinal tumours. An impaired barrier function of the gastric mucosa could contribute to this risk. The absorption of polyethylene glycols (molecular weights 414-766), expressed as recovery in 6-hour urine, was studied both after oral and duodenal loads in patients with atrophic gastritis (n = 18) and compared with controls without gastritis (n = 9). The patients had a higher absorption after oral than after duodenal load for molecular weights 502-546. The differences in absorption after oral and duodenal loads were correlated with the severity of the atrophy in the antrum. No differences were found in the controls. Absorption after the duodenal load did not differ between the study groups. The increased gastric absorption of polyethylene glycols in patients with atrophic gastritis may be caused by a permeability disturbance of the gastric mucosa.

Administration, Oral↗

Value of routine intraoperative cholangiography in detecting aberrant bile ducts and bile duct injuries during laparoscopic cholecystectomy.

A prospective study was performed to determine the frequency and type of bile duct abnormalities, and to determine whether routine use of intraoperative cholangiography during laparoscopic cholecystectomy might aid in the prevention of bile duct injuries. Overall, anatomical aberrations of the bile ducts were found in 98 (19 per cent) of 513 cholangiograms. The most common anomalies were at the hepatic confluence and constituted different types of right hepatic subsegmental ducts draining separately into the biliary tree (n = 43, 8.4 per cent), either close to the cystic duct or directly into the cystic duct. Three bile duct injuries (0.5 per cent) occurred during the study period. These results show that routine intraoperative cholangiography is feasible and provides valuable information about the anatomy of the biliary tract, thereby improving the safety of laparoscopic cholecystectomy. If an injury to the biliary tract occurs early during operation, the cholangiogram allows the surgeon to detect the injury, to make a prompt repair and thereby reduce the morbidity associated with a delayed diagnosis. Routine use of intraoperative cholangiography is strongly recommended.

Acute Disease↗

Extracorporeal shock-wave lithotripsy of gallbladder stones: an alternative for the selected few.

OBJECTIVE: To define selection criteria for optimal outcome of ESWL with oral litholysis (ursodeoxycholic acid) for gallbladder stones. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 145 patients with symptomatic gallbladder stones occupying a maximum of half the fasting gallbladder volume and gallbladder opacification at oral cholecystography. MAIN OUTCOME MEASURES: Three-year stone clearance rates in relation to initial stone burden, occurrence of calcified stones, and degree of gallbladder opacification at cholecystography. RESULTS: At all times clearance rates according to life table analysis were significantly higher for patients whose stone volume was < or = 4.2 ml (corresponding to one stone with a diameter of < or = 2.0 cm) (83% at 3 years) than for patients whose stone volume was > 4.2 ml (67% at 3 years), and patients with one stone had significantly higher clearance rates (88% at 3 years) than patients with multiple stones (58% at 3 years). Of all patients treated for gallbladder stones during one year, 25/194 (13%) had a stone volume of < or = 4.2 ml and 16/194 (8%) a solitary stone with volume < or = 4.2 ml. Neither the degree of gallbladder opacification nor the occurrence of calcified stones influenced clearance rates. CONCLUSION: ESWL may be an alternative to surgery in the few patients whose stone volume is roughly 4 ml or less and preferably have only one stone. Gallbladder function and patency of the cystic duct are poorly evaluated by oral cholecystography.

Adult↗

Management of bile duct stones in the era of laparoscopic cholecystectomy: appraisal of routine operative cholangiography and endoscopic treatment.

OBJECTIVE: To assess the value of preoperative or postoperative endoscopic treatment of bile duct stones and routine use of operative cholangiography (OC) for detection of unsuspected common bile duct (CBD) stones in conjunction with laparoscopic cholecystectomy. DESIGN: Prospective study. SETTING: University hospital, Sweden. MAIN OUTCOME MEASURES: Diagnostic and therapeutic yield of stones at endoscopic retrograde cholangiography (ERC) before or after laparoscopic cholecystectomy and routine operative cholangiography. RESULTS: Of 630 patients who underwent laparoscopic cholecystectomy, 84 had preoperative ERC. Of these 84, 47 (56%) had bile duct stones. Endoscopic sphincterotomy was done for all 47, of whom 3 (6%) had retained stones at OC. OC was done for 590 (94%) of the 630 patients, and 45 (7.6%) were found to have choledocholithiasis. At postoperative ERC, however, 10 of these patients were free of stones and there were two cases of false negative OC, which resulted in sensitivity and specificity of OC of 95% and 98%, respectively. Thus, 35 patients (6%) had bile duct stones discovered at OC, of whom 33 had "unsuspected" stones. Of these 35 patients, 29 were cleared endoscopically after cholecystectomy. The remaining 6 patients were cleared of stones either by open choledocholithotomy (n = 2) or by laparoscopic transcystic manipulation (n = 4). There was no mortality after diagnostic or therapeutic ERC, and morbidity was confined to two cases each of pancreatitis and cholangitis, which resulted in a complication rate of 3% (4/118). No complications resulted from IOC. CONCLUSIONS: Preoperative ERC should be done for patients with symptoms or findings indicating ductal calculi. In most patients undergoing laparoscopic cholecystectomy, OC is feasible and its routine use is strongly advocated. Bile duct stones diagnosed at OC can safely and successfully be treated endoscopically after laparoscopic cholecystectomy. Until laparoscopic bile duct exploration becomes routine and generally applicable, endoscopic management of bile duct stones both before and after cholecystectomy will be an important therapeutic option.

Cholangiography↗

Biochemical properties of cloned lipases from the Pseudomonas family.

Three Pseudomonas lipases, representing three subfamilies, were analysed for pH optima, destabilization by EGTA and surfactants, phospholipase and cholesterolesterase side activities. All the Pseudomonas lipases tested showed alkaline pH optima. The Pseudomonas cepacia and the P. pseudoalcaligenes lipases were totally inhibited by EGTA at pH 9, and the latter was also fully inhibited at pH 7. The lipase from P. mendocina was not inhibited by EGTA at any of the pH values tested. These findings indicate that a calcium binding site exists in some of the Pseudomonas lipases. The P. pseudoalcaligenes, P. cepacia and P. mendocina lipases were inhibited by the anionic surfactant SDS at concentrations between 0.01-0.5 mg/ml. The P. pseudoalcaligenes and P. cepacia lipases were not inhibited by the nonionic surfactant Brij35 in concentration up to 1 mg/ml, whereas the lipase from P. mendocina was inhibited at 0.1 mg/ml. The P. pseudoalcaligenes and P. cepacia lipases were found to possess high cholesterol esterase activity. P. pseudoalcaligenes lipase was further found to have high phospholipase activity. Ten Pseudomonas lipase sequences were compared by automatic sequence alignment. On the basis of sequence identity we have classified Pseudomonas lipases into five subfamilies.

Amino Acid Sequence↗

Effects of hypochlorhydria and hypergastrinemia on structure and function of gastrointestinal cells. A review and analysis.

Since hypochlorhydria can induce hypergastrinemia, and gastrin has a trophic effect on some gastrointestinal cells, states that cause elevated plasma gastrin levels are of interest in terms of effects on cell growth and function. This article reviews the relationship between gastric mucosal cells during periods of acid stimulation and inhibition and analyses the effects of hypochlorhydria and hypergastrinemia on gastric and colonic cells and tumors. Hypochlorhydria releases the inhibitory effect of antral gastrin cells, inducing them to release gastrin in the presence of peptides or amino acids in the gastric lumen or in response to antral distension. Gastrin stimulates the oxyntic mucosa, which may lead to hyperplasia of enterochromaffin-like cells, resulting in enterochromaffin-like carcinoid tumors in aged rats and, rarely, in patients with chronic atrophic gastritis or gastrinomas. In addition to hypergastrinemia, other factors appear to be required for the progression of enterochromaffin-like hyperplasia to carcinoids; genetic factors may be involved. Gastrin elevations due to antisecretory drug therapy are indirectly proportional to the degree of acid inhibition and are reversible upon cessation of therapy. The gastrin levels during omeprazole therapy are similar to those caused by gastric vagotomy. Available evidence does not support a relationship between hypergastrinemia and the occurrence or growth of gastric carcinoma or colonic tumors.

Achlorhydria↗

Effect of endogenous hypergastrinemia on gastrin receptor expressing human colon carcinoma transplanted to athymic rats.

BACKGROUND & AIMS: The effect of endogenous hypergastrinemia on growth of human colon carcinoma is not known. Our aim was to study the growth of human colon carcinoma in an animal model with endogenous hypergastrinemia. METHODS: Human colon carcinoma was transplanted to the colon of 40 athymic rats. Of these, 25 underwent gastric fundectomy to accomplish endogenous hypergastrinemia, and 15 were sham operated to serve as controls. The duration of the study was 8 weeks. During the last week, 12 fundectomized animals received a gastrin (cholecystokinin B) receptor antagonist. Metaphase arrest index, local invasion, and distant spread of the tumor were investigated. Expression of gastrin and cholecystokinin B receptor messenger RNA was examined by reverse-transcription polymerase chain reaction. RESULTS: Tumor spread by direct extension outside the colon was observed in all animals, and liver metastases were observed in 10 of the 25 fundectomized animals. Sham-operated animals showed none of these features. The metaphase arrest index of the tumor did not differ between fundectomized animals given the cholecystokinin B receptor antagonist and sham-operated animals, whereas it was significantly increased in fundectomized animals not given the antagonist. The tumor expressed both gastrin and cholecystokinin B receptor messenger RNA. CONCLUSIONS: The results indicate that endogenous hypergastrinemia may promote proliferation and spread of human colon carcinoma expressing cholecystokinin B receptor.

Aged↗