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Biomedical subjects

E G Hahn

Publications and source records attributed to E G Hahn.

At least 307 records · Page 17Linked to original sources

Mucosal expression and luminal release of epidermal and transforming growth factors in patients with duodenal ulcer before and after eradication of Helicobacter pylori.

BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and protection but their involvement in Helicobacter pylori associated duodenal ulcer has been little examined. AIM: To assess gastric acid secretion, plasma gastrin concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of these peptides and their receptor (EGFr) as well as salivary and gastric luminal release of EGF under basal conditions and after pentagastrin stimulation in 10 healthy subjects and in 25 H pylori positive patients with duodenal ulcer before and after two weeks of triple anti-H pylori therapy and four weeks after the termination of this therapy. RESULTS: Pentagastrin stimulation caused a significant increase in salivary and gastric release of EGF both in healthy controls and patients with duodenal ulcers but in the patients, the eradication of H pylori resulted in several fold higher gastric luminal (but not salivary) EGF release than before the anti-H pylori therapy. Mucosal contents of immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and EGFr in H pylori positive patients with duodenal ulcer were significantly higher than those in healthy H pylori negative controls and this increase persisted after eradication of H pylori. Basal plasma gastrin was significantly reduced after two weeks of triple therapy and four weeks after the H pylori eradication all ulcers were completely healed. CONCLUSIONS: (1) H pylori infection in patients with duodenal ulcer was accompanied by enhanced plasma gastrin and increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and enhancement of gastric (but not salivary) luminal release of EGF, particularly after pentagastrin stimulation; and (3) enhanced mucosal content and expression of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute to ulcer healing after eradication of H pylori.

Duodenal Ulcer↗

Antigastric autoantibodies in Helicobacter pylori infection: implications of histological and clinical parameters of gastritis.

BACKGROUND: It has recently been shown that humoral antigastric autoreactivities occur in a substantial number of Helicobacter pylori infected patients. AIMS: To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course. METHODS: Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies. RESULTS: H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer. CONCLUSION: The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.

Adolescent↗

K-RAS-2 gene mutations as predictors of metachronous colorectal adenomas.

BACKGROUND: Mutations of K-RAS-2 gene and tumour suppressor genes have been found in both colorectal adenomas and carcinomas. The aim of this study was to investigate the prognostic value of K-RAS-2 gene mutations found in initial colorectal adenomas for predicting the risk of metachronous adenomas. METHODS: Genomic DNA was extracted from formalin-fixed and paraffin-embedded adenomas larger than 5 mm in diameter removed at the initial total colonoscopy between 1980 and 1982. All patients underwent colonoscopic follow-up for at least 10 years. The sequence of exon 1 of the K-RAS-2 oncogene was amplified with the polymerase chain reaction technique and screened for mutation by single-strand conformation polymorphism analysis. All suspected mutations were confirmed by direct DNA sequencing. The predictive value of K-RAS-2 gene mutations for the risk of metachronous adenomas was assessed by chi-square testing and logistic regression analysis. RESULTS: Of 54 patients 39 (72%) were male and 15 (28%) female. At the time the initial adenoma was removed, 31 (57%) patients were younger than 60, whereas 23 (43%) were 60 years or older. Point mutations of the K-RAS-2 oncogene were found in the index adenomas of 15 (27.7%) patients. Mutations were found more frequently in large (> or = 20 mm) adenomas and in adenomas with severe dysplasia (P = 0.0011 and P = 0.0310, respectively). There were no significant associations between K-RAS-2 mutations and anatomic location, histologic type, or number of synchronous initial lesions. Mutations were found predominantly at codon 12 with transversions from GGT to GTT (57%), from GGT to GAT (36%), and from GGT to TTT (one patient). The single mutation found at codon 13 showed a transversion from GGC to GAC. There were significant associations between size (> or = 20 mm) and K-RAS-2 mutation of the initial adenomas and the size (> 5 mm) of metachronous adenomas (P = 0.0259 and P = 0.0265, respectively). However, multivariate analysis showed that K-RAS-2 mutations did not provide a significant additional contribution to the prognostic value of the size of the initial adenoma (odds ratio, 7.62; 95% confidence interval (CI), 1.68-34.48) and the amount of villous structure (odds ratio, 0.22; 95% CI, 0.05-0.90) it contained. CONCLUSIONS: Patients with large (> or = 20 mm) adenomas and adenomas with K-RAS-2 mutations found at the initial examination have a significantly higher risk of developing large (> 5 mm) metachronous adenomas during surveillance. Multivariate analysis of initial adenoma characteristics showed that the risk of metachronous colorectal adenomas can be adequately estimated by the size and the histologic type of the largest initial adenoma and that K-RAS-2 mutations are of secondary importance only. Further studies based on a larger series will have to identify the adenoma characteristics that will help to improve follow-up strategies.

Adenoma↗

Expression of epidermal growth factor and transforming growth factor alpha during ulcer healing. Time sequence study.

BACKGROUND: Growth factors such as epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) have been shown to share common receptor (EGFR) and to accelerate ulcer healing due to stimulation of cell proliferation, but the time sequence of expression of EGF and TGF alpha during ulcer healing has not been investigated. In this study the rate of cell proliferation and the gastric secretion and gene expression of mRNA for EGF and TGF alpha were determined during ulcer healing. METHODS: Gastric ulcers were induced in 150 Wistar rats by serosal application of 100% acetic acid (ulcer area, 14 mm2). Some of these animals were also equipped with a gastric fistula for the assessment of gastric secretion during ulcer healing. The animals were killed 0, 2, 4, 6, or 8 days after ulcer induction, and the ulcer area was determined. The mucosal sections with gastric ulcer were immunostained for proliferating cell nuclear antigen (PCNA) and for immunoexpression of EGF, TGF alpha, and EGFR. The expression of mRNA EGF and mRNA TGF alpha was also determined in the ulcer margin by reverse transcriptase (RT) polymerase chain reaction (PCR) using specific primers. RESULTS: Two, 4, 6, and 8 days after ulcer induction the gastric ulcer area was gradually reduced from the initial size (day 0) by 47%, 70%, 80%, and 87%, respectively, and this was accompanied by an increase in PCNA with its maximum on day 4. The gastric acid and pepsin secretion was significantly reduced by 75% and 79%, respectively, on day 2 after ulcer induction but then the secretion tended to return to normal value by day 8. The expression of EGF, TGF alpha, and EGFR was negligible on day 0 but increased significantly during the healing, reaching maximum on day 4. Expression of EGF mRNA was detected on days 2, 4, and 6, and that of TGF alpha mRNA on days 2, 4, 6, and 8 after ulcer induction, with the most intense signals for both transcripts observed on day 2. CONCLUSIONS: 1) The enhancement in cell proliferation during ulcer healing may be mediated by increased release of EGF and TGF alpha; 2) the expression of EGF and TGF alpha mRNA precedes the overexpression of these growth factors at the ulcer margin during ulcer healing; and 3) the overexpression of growth factors coincides with the inhibition of gastric secretion and increased blood flow at the ulcer margin, indicating that these factors affect gastric secretion and blood flow in the course of ulcer healing.

Animals↗

Gastroprotective activity of melatonin and its precursor, L-tryptophan, against stress-induced and ischaemia-induced lesions is mediated by scavenge of oxygen radicals.

BACKGROUND: Melatonin, a pineal hormone that is biosynthesized from L-tryptophan, is known to scavenge oxygen free radicals and to be present in the gut, but little is known about the role of this hormone and its precursor, L-tryptophan, in protecting the gastric mucosa from damage accompanied by increase in the generation of oxygen radicals. METHODS: This study was designed to determine the effects of melatonin and L-tryptophan on the formation of acute gastric lesions induced by stress and ischaemia reperfusion and, for comparison, by topical irritants such as 100% ethanol or acidified acetylsalicylic acid. RESULTS: It was found that pretreatment with melatonin in doses ranging from 1.2 to 10 mg/kg dose-dependently reduced the stress-induced gastric lesions and was accompanied by a reduction in blood-free radicals and by attenuation of the fall in gastric blood flow. L-tryptophan applied intragastrically in doses ranging from 1 to 100 mg/kg also reduced dose-dependently the lesions induced by stress; this effect too was accompanied by a rise in gastric blood flow. Pretreatment with indomethacin, to block the biosynthesis of prostaglandins, significantly augmented the lesions produced by stress and completely abolished the protective effects of melatonin or L-tryptophan. Both melatonin and tryptophan reduced the formation of acute gastric lesions provoked by ischaemia reperfusion; this was accompanied by an increase in gastric blood flow. In contrast, melatonin and L-tryptophan failed to influence acute gastric lesions induced by topical irritants such as 100% ethanol or acidified aspirin. CONCLUSIONS: Melatonin and L-tryptophan protect the gastric mucosa from damage by stress and ischaemia reperfusion, and this action is mediated, at least in part, by the limitation in the free radicals, the stimulation of mucosal generation of PG and by the increase in gastric blood flow.

Acute Disease↗

Color Doppler imaging versus phlebography in the diagnosis of deep leg and pelvic vein thrombosis.

The objective of this prospective study was to evaluate the accuracy of color Doppler imaging in comparison to phlebography in diagnosing phlebothrombosis. Five hundred and twenty-six phlebographies (reference method) were compared with 526 color Doppler sonographic examinations. Thrombosis diagnosed with color Doppler imaging showed a sensitivity of 98.0% (400 of 408). In 91.6% (482 of 526) of all examinations the extent of the thrombosis diagnosed with phlebography could also be seen with color Doppler imaging. When the clinical situation is unclear, color Doppler imaging should precede phlebography. Only when findings with ultrasonography are questionable should phlebography definitely be considered.

Adolescent↗

Expression of transforming growth factor-beta 1 and epidermal growth factor in caerulein-induced pancreatitis in rat.

Growth factors such as TGF-beta 1 and EGF are known to modulate the deposition of extracellular matrix components and tissue repair and to affect the cellular growth but their expression in the course of pancreatitis has not been studied. In this study we investigated the gene expression of TGF-beta 1 mRNA and EGF mRNA and other parameters of the pancreas including DNA synthesis, blood flow (PBF), tissue protein content and plasma amylase during the induction of acute pancreatitis. Supramaximal dose of cearulein (10 mg/kg/h s.c.) was infused for 5 h to induce pancreatitis. Animals were killed after 1, 2, 3, 4 and 5 h of infusion. The PBF was measured, blood samples were withdrawn to determine serum amylase concentration, biopsy samples were taken to measure the protein content and DNA synthesis. Expression of TGF-beta 1 and EGF mRNA was studied by reverse-transcription of polymerase chain reaction (RT-PCR). Caerulein infused caused a time-dependent decrease in DNA synthesis accompanied by gradual decrease of PBF and significant increase in pancreatic weight. The pancreatic protein content and plasma amylase showed progressive rise during 5 h of cearulein infusion. Histology revealed tissue edema, cellular vacuolization and prominent leukocyte infiltration after 3 h of cearulein infusion. TGF-beta 1 mRNA was strongly expressed at each time interval beginning from the 1 h after the start of cearulein infusion. In contrast, EGF mRNA was detected only at 5 h after induction of pancreatitis. We conclude that 1) the development of caerulein-induced pancreatitis results in the inhibition of pancreatic growth and the reduction in PBF accompanied by enhanced expression of TGF-beta 1; 2) The expression of EGF that was observed at the end of the induction of pancreatitis may indicate the initiation of pancreatic repair; 3) TGF-beta 1 seems to lead to subsequent induction of EGF that may stimulate the regeneration of injured pancreas.

Acute Disease↗

Melanosis coli--a harmless pigmentation or a precancerous condition?

UNLABELLED: Melanosis coli has long been considered as a harmless pigmentation of the colorectum associated with the use of laxatives containing anthraquinone. Recent experimental and clinical studies, however, have provided some evidence of a possible association between melanosis coli/laxative use and colorectal cancer. METHODS: In 2.229 consecutive patients we retrospectively analyzed the association of melanosis coli and laxative use with colorectal neoplasia. All the patients had undergone total colonoscopy, and the colorectal neoplasias had been examined histopathologically in accordance with the WHO classification. Information concerning laxative use, bowel habits and family history of colorectal cancer was obtained from the medical records. The statistical analysis was done using the Mantel-Haenszel-test for linear association. RESULTS: The presence of colorectal cancer was not associated with melanosis coli or laxative use. However, colorectal adenomas were found significantly more frequently in patients with melanosis coli than in those without melanosis (p = 0.0002). But adenomas associated with melanosis coli were significantly smaller than those not associated with melanosis (p < 0.0001), and were located predominantly in the proximal colon (p = 0.0002). In the patients with melanosis coli the relative risk was significantly higher for tubular (1.80; 95% CI: 1.26-2.56) and tubulovillous adenomas (2.03; 95% CI: 1.09-3.76), but not for villous adenomas. No significant differences were found in the grade of dysplasia of adenomas in patients with, and those without, melanosis coli. CONCLUSION: There appears to be no association between colorectal cancer and melanosis coli or laxative use. Colorectal adenomas are more frequently found in patients with melanosis coli. Colorectal adenomas do not contain the melanin-like pigmentation. The association of adenomas with melanosis coli can be explained by the ease of detection of even tiny polyps as white spots within a dark-colored colonic mucosa.

Adenoma↗

[Morphological changes in human colon carcinoma after chemotherapy with 5-fluorouracil--a study in the nude mouse model].

Colorectal cancer represents one of the most important challenges in the field of cancer chemotherapy. 5-fluorouracil (5-FU) is used as the first-choice chemotherapeutic agent in the treatment of advanced gastrointestinal cancer. Despite this fact very little is known about the morphological changes of colon carcinoma after treatment with 5-FU. Thymusaplastic nude mice (n = 59) with subcutaneously heterotransplanted human coloncarcinoma (tubulo-papillary adenocarcinoma, grade II-III) were treated with 5-FU (40 mg/kg/body weight i. p. for five days). The animals were sacrificed, tumors were removed at 0 h, 24 h, 36 h, 48 h, 54 h, 60 h, 66 h, 72 h, 94 h, 118 h, 240 h after chemotherapy and the tumor tissue was embedded for light-microscopic and ultrastructural examination. Hydropic mitochondria and cytoplasmatic vacuoles were observed in tumor cells as early as 0 h after chemotherapy. These changes displayed a focal pattern. Damaged tumor tissue was surrounded by tumor cells with intact ultrastructure. In some regions tumor cells were separated from the basal membrane and showed signs of necrosis. These focal changes within the tumor tissue were observed from 0-240 h after treatment. Tumor capillaries did not show any damage. Treatment with 5-FU led to focal cytotoxic effects in the tumor. The remaining intact vascular system of the tumor may be a target for new therapy modalities.

Adenocarcinoma, Papillary↗

[Interventional endoscopic therapy of chronic pancreatitis].

BACKGROUND AND AIM: Complications in chronic pancreatitis, such as duct occlusion due to stenosis or stones can be treated by interventional endoscopic procedures. The benefit of such procedures and the effect on the clinical course is still under debate. Therefore, it was the aim of this study to analyze the effect of endoscopic interventional procedures in more detail with respect to technical and clinical benefit. PATIENTS AND METHODS: 100 patients with chronic pancreatitis (cP) were studied retrospectively. In 58 patients an indication for interventional endoscopic therapy was given (45 +/- 12 yrs; 46 M, 12 F; cP 1 degree: n = 1, cP II degree: n = 8, cP III degree: n = 49). The patients were allocated to three groups: stenosis (n = 18), pancreatic duct stones (n = 18) and stenosis and pancreatic duct stones (n = 20). In two patients no visualization of the main pancreatic duct was performed due to cholestasis that was treated primarily. In total, 295 endoscopic procedures were performed (EPT, duct dilatation, plastic endoprothesis, ESWL, mechanical lithotripsy). Technical success was 95%. All stenoses could be dilated or bridged by plastic stents. Fragmentation of main pancreatic duct stones was achieved in 92%. The overall complication rate of all 319 endoscopies (fever, bleeding, stent dislocation) was 15.8%. Five patients had to undergo surgery, however, not as a direct consequence of complications from or unability of endoscopic procedures. 86% of the patients reported complete pain relief after the endoscopic-interventional procedures and 62% during the follow-up interval (7.4 +/- 6.3 months). 59% of the patients with weight loss and 58% of the patients with initially stable weight experienced a weight gain following endoscopic-interventional therapy. Individual patients showed improvement of endocrine or exocrine pancreatic function. 82% of the patients did not require inhouse treatment or emergency admission to the hospital whereas three admissions on average were recorded prior to endoscopic interventional treatment. Therefore, we conclude that a subset of patients does benefit from endoscopic interventional therapy of complications of chronic pancreatitis. However, a controlled prospective study is still mandatory.

Adolescent↗

[Nasal CPAP therapy of obstructive sleep apnea syndrome with expiratory pressure reduction: a prospective randomized study of acceptance of treatment during therapy initiation].

It is often difficult to achieve adequate acceptance of nasal continuous positive airway pressure (CPAP) therapy by patients with OSA. Many patients find it particularly inconvenient to expire against the treatment pressure. With this in mind, we have attempted to improve acceptance of CPAP therapy by using a bilevel system that reduces the treatment pressure during expiration. 52 patients were randomized either to initial treatment with CPAP therapy followed by bilevel treatment, or to treatment in reversed order. During bilevel therapy the ratio of inspiratory to expiratory pressure was fixed at 1:0.6. After each treatment the patients were interviewed on the basis of visual analogue scales to establish their subjective evaluation of such parameters as general well-being, quality of sleep, comparison of the respective treatment pressures, and possible preference for one of the two systems for long-term treatment. The minimal effective inspiratory treatment pressure during bilevel therapy (IPAP) and the minimal effective CPAP pressure were closely correlated (r = 0.89). There was no difference between the apnoea hypopnoea indices during CPAP therapy as compared with bilevel therapy. Most patients (57%) felt the treatment pressure with the bilevel system to be lower (p = 0.048). There were no differences in patients' well-being early in the morning, or in their assessment of sleep quality. The majority of patients (52%) preferred bilevel therapy for long term treatment, while 38% preferred CPAP therapy (n.s.). In a subgroup of 13 patients with a treatment pressure of > or = 10 mbar during CPAP therapy 10 patients (77%) gave preference to the bilevel system (n.s.). In a considerable number of patients the acceptance of treatment can be improved by using a bilevel system for initiation of nasal positive pressure therapy.

Adult↗

Helicobacter pylori and impaired gastric secretory functions associated with duodenal ulcer and atrophic gastritis.

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.

Adult↗

Gastric mucosal expression and luminal release of growth factors in gastric carcinoma and duodenal ulcer patients before and after eradication of Helicobacter pylori.

Epidemiological studies have consistently shown an association between infection of Helicobacter pylori (Hp) and duodenal ulcer (DU) and gastric cancer. The mechanism of the ulcerogenic effect of Hp has been related to excessive gastrin release, gastric acid hypersecretion and gastric metaplasia in duodenum. The implication of Hp in gastric carcinogenesis has not been explained. In this study, mucosal expression of EGF and TGF alpha and luminal release of EGF as well as basal and pentagastrin-stimulated acid secretion and plasma gastrin levels have been determined in healthy subjects, gastric carcinoma and DU patients. It was found that Hp positive DU patients show excessive gastrin release and gastric acid secretion combined with increased expression and luminal release of EGF and TGF alpha. These changes returned to normal values two years after the eradication of Hp. Gastric cancer patients also showed increased expression of EGF and TGF alpha and highly increased plasma gastrin but their gastric acid secretion was markedly reduced possibly due to atrophy of oxyntic mucosa. This study indicates that overexpression of growth factors in gastric mucosa may be implicated in the pathogenesis of both duodenal ulcer and gastric cancer and that Hp positive hypochlorhydric and hypergastrinemic patients may be predisposed to development of gastric cancer.

Adult↗