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Biomedical subjects

E G Hahn

Publications and source records attributed to E G Hahn.

At least 217 records · Page 12Linked to original sources
PubMed2000

Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer.

BACKGROUND: Tumors arising in the stomach have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in causation of this disease. The HP discovery, which is considered as the greatest advance of gastroenterology at the dawn of 3rd millennium, is accompanied by hypergastrinemia, which seems to play a key role in gastric cancerogenesis but no study was undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the eicosanoids production. AIMS: Since gastrin is recognized as a effective gastric mitogen, it could be capable to induce COX-2, a potent tumor growth promoting and angiogenic factor, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric cancer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) in gastric cancer, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication. MATERIAL AND METHODS: The trial material included 20 patients with gastric cancers and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 was examined using RT-PCR with GAPDH as a reference and employing Western blot for COX-2 expression, while gastrin was measured by RIA. RESULTS: The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric cancers than in controls. Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in the cancer tissue and similarly COX-2 mRNA and protein were found in most of cancers and in the HP infected antral mucosa but not in HP eradicated patients in whom only cancer tissue but not gastric mucosa expressed COX-2. The gastric cancer tissue contained 20 times more of immunoreactive gastrin than the HP infected antral gastric mucosa and following HP eradication the gastrin content in the tumor and antrum showed a marked and significant reduction. No significant change in CCK(B)-R expression was noticed before and after HP eradication in the tumor and the corpus mucosa. CONCLUSIONS: 1). Gastric carcinoma coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may contribute to gastric cancerogenesis via gastrin andCOX-2 that may account for the stimulation of tumor growth, angiogenesis, and reduction in apoptosis 3) HP positive patients developing gastric cancer should be considered for HP eradication to reduce the HP provoked hypergastrinemia and COX-2 overexpression in the tumor tissue.

Aged↗
PubMed2000

Involvement of cyclooxygenase (COX)-2 products in acceleration of ulcer healing by gastrin and hepatocyte growth factor.

Ulcer healing involves expression of various growth factors including hepatocyte growth factor (HGF) at the ulcer margin and the rise in plasma gastrin but the effects of locally applied HGF and gastrin, which are known to act as trophic factors for the gastric mucosa, with or without neutralizing antibodies against HGF and gastrin or COX-1 and COX-2 inhibitors on ulcer healing and the expression of cyclooxygenase (COX)-1 and COX-2 during this healing have been little studied. Rats with gastric ulcers induced by serosal application of acetic acid (ulcer area 28 mm2) received a submucosal injection of either: 1)vehicle (saline), 2) HGF and 3) gastrin with or without neutralizing antibodies against HGF and gastrin or treatment with indomethacin (2 mg/kg-d i.p.), a non-specific inhibitor of COX, or NS-398 (5 mg/kg-d i.g.) and Vioxx (10 mg/kg-d i.g.), both highly specific COX-2 inhibitors. Each growth factor and specific antibodies against HGF and gastrin (100 ng/100 microl each) were injected just around the ulcer immediately after ulcer induction and this local application was repeated at day 2 following anesthesia and laparotomy. At day 13 and 21, the area of ulcers was determined by planimetry, the gastric blood flow (GBF) at ulcer margin was examined by H2-gas clearance technique and mucosal generation of PGE2 and the expression of COX-1 and COX-2 mRNA in the non-ulcerated and ulcerated gastric mucosa was analyzed using RT-PCR. The gastric ulcers healed progressively within 21 days and this effect was accompanied by significant increase in the GBF at the ulcer margin and expression of COX-2 mRNA and COX-2 protein at the ulcer area. Treatment with HGF and gastrin significantly accelerated the rate of ulcer healing and raised GBF at ulcer margin causing further significant upregulation of COX-2 mRNA and COX-2 protein (but not of COX-1 mRNA ) in the ulcerated mucosa. The upregulation of COX-2 mRNA induced by HGF was significantly attenuated by the concurrent local treatment with antibody against this growth peptide. Indomethacin and both COX-2 inhibitors significantly prolonged the ulcer healing, while suppressing the generation of PGE2 in non-ulcerated and ulcerated gastric mucosa and the GBF at ulcer margin. The acceleration of ulcer healing by HGF and gastrin and accompanying rise in the GBF at ulcer margin were significantly attenuated by the concurrent treatment with indomethacin or NS-398 and Vioxx. HGF injections produced a significant rise in the plasma gastrin levels and this was significantly attenuated by the cotreatment with NS-398. We conclude that 1) neutralization of HGF and gastrin by their specificantibodies delays ulcer healing due fall in the microcirculation around the ulcer and a decrease in the COX-2 expression, 2) COX-2 derived prostaglandins may play an important role in acceleration of the ulcer healing by various growth factors including HGF and gastrin, 3) enhancement of the local pool for growth factors such as HGF and gastrin at the ulcer site could offer a new modality for treatment of gastric ulcer.

Animals↗
PubMed1999

Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions.

In this study, ischemia-reperfusion produced in rats by clamping the celiac artery for 0.5 h followed by 1 h of reperfusion was used to develop a new model of superficial gastric erosions progressing to deeper ulcers. Ischemia alone resulted in an immediate fall in gastric blood flow but no gross mucosal lesions were observed. When ischemia was followed by reperfusion, gastric erosive lesions occurred, reached a maximum at 12 h and then declined after 24 h. These acute erosions progressed into deeper lesions 24 h after ischemia-reperfusion and reached a peak after 3 days. Gastric blood flow and the mucosal generation of prostaglandin E(2) were significantly suppressed immediately following ischemia-reperfusion, but with the healing of deeper gastric ulcers, both gastric blood flow and prostaglandin E(2) generation were gradually restored. Cyclooxygenase-1 mRNA was detected by reverse transcription-polymerase chain reaction in intact gastric mucosa and throughout the recovery of the mucosa from acute ischemia-reperfusion lesions, whereas cyclooxygenase-2 mRNA, was recorded only after ischemia-reperfusion. NS-398 and rofecoxib, selective inhibitors of cyclooxyganase-2, failed to affect prostaglandin E(2) generation in the non-ulcerated gastric mucosa but inhibited it significantly in the ulcer area. The two cyclooxygenase-2 inhibitors as well as resveratrol, a specific cyclooxygenase-1 inhibitor and indomethacin and meloxicam, non-specific inhibitors of cyclooxygenase, augmented acute gastric erosions induced by ischemia-reperfusion and delayed significantly the progression of these lesions into deeper ulcers at each time interval after ischemia-reperfusion. We conclude that prostaglandins generated by both cyclooxygenase-1 and cyclooxygenase-2 contribute to the healing of gastric lesions induced by ischemia-reperfusion.

Animals↗
PubMed1999

Photodynamic destruction of high grade dysplasia and early carcinoma of the esophagus after the oral administration of 5-aminolevulinic acid.

BACKGROUND: Photodynamic therapy (PDT) is a new local, endoscopically controlled therapeutic concept based on the selective sensitization of malignant and precancerous lesions prior to light-induced tissue destruction. 5-aminolevulinic acid (5-ALA) appears to be a promising alternative photosensitizer with a high mucosa specificity without phototoxic side effects on the skin. The authors report on their experiences with this new form of PDT in 27 patients. METHODS: Twenty-seven patients (6 females and 21 males; ages 47-79 years) with histologically proven high grade dysplasia (n = 9) and early carcinoma (normal endoultrasonography or classified as uT1N0M0; n = 19; 1 patient had 2 lesions) of the esophagus were included in this study. Approximately 4-6 hours after oral ingestion of 5-ALA in a dosage of 60 mg/kg of body weight, laser light irradiation was conducted with a dye laser system with a wavelength of 635 nanometers at a light dose of 150 J/cm(2). RESULTS: The length of the segment of the esophagus with severe dysplasia or carcinoma of the mucosa varied between 0.5-9.0 cm (mean length, 2.5 cm). High grade dysplasia was eradicated in all patients. In addition, 19 mucosal tumors in 18 patients were treated successfully in 10 of 19 cases with an average of 1.7 treatment sessions and a mean follow-up of 16.9 months (range, 3-37 months). Method-related morbidity and mortality were not observed. CONCLUSIONS: Severe dysplasia and superficial (</=2 mm) mucosal carcinoma of the esophagus can be ablated completely by 5-ALA-PDT. PDT with 5-ALA has few side effects and might offer an alternative to esophagectomy or radiochemotherapy.

Aged↗
PubMed1999

Acceleration of ulcer healing by cholecystokinin (CCK): role of CCK-A receptors, somatostatin, nitric oxide and sensory nerves.

CCK exhibits a potent cytoprotective activity against acute gastric lesions, but its role in ulcer healing has been little examined. In this study we determined whether exogenous CCK or endogenously released CCK by camostate, an inhibitor of luminal proteases, or by the diversion of pancreatico-biliary secretion from the duodenum, could affect ulcer healing. In addition, the effects of antagonism of CCK-A receptors (by loxiglumide, LOX) or CCK-B receptors (by L-365,260), an inhibition of NO-synthase by N(G)-nitro-L-arginine (L-NNA), or sensory denervation by large neurotoxic dose of capsaicin on CCK-induced ulcer healing were examined. Gastric ulcers were produced by serosal application of acetic acid and animals were sacrificed 9 days after ulcer induction. The area of ulcers and blood flow at the ulcer area were determined. Plasma levels of gastrin and CCK and luminal somatostatin were measured by RIA and mucosal biopsy samples were taken for histological evaluation and measurement of DNA synthesis. CCK given s.c. reduced dose dependently the ulcer area; the threshold dose of CCK being 1 nmol/kg and the dose inhibiting this area by 50% being 5 nmol/kg. This healing effect of CCK was accompanied by a significant increase in the GBF at ulcer margin and the rise in luminal NO production, plasma gastrin level and DNA synthesis. Concurrent treatment with LOX, completely abolished the CCK-8-induced acceleration of the ulcer healing and the rise in the GBF at the ulcer margin, whereas L-365,260 remained without any influence. Treatment with camostate or diversion of pancreatic juice that raised plasma CCK level to that observed with administration of CCK-8, also accelerated ulcer healing and this effect was also attenuated by LOX but not by L-365,260. Inhibition of NO-synthase by L-NNA significantly delayed ulcer healing and reversed the CCK-8 induced acceleration of ulcer healing, hyperemia at the ulcer margin and luminal NO release, and these effects were restored by the addition to L-NNA of L-arginine but not D-arginine. Capsaicin denervation attenuated CCK-induced ulcer healing, and the accompanying rise in the GBF at the ulcer margin and decreased plasma gastrin and luminal release of somatostatin when compared to those in rats with intact sensory nerves. Detectable signals for CCK-A and B receptor mRNAs as well as for cNOS mRNA expression were recorded by RT-PCR in the vehicle control gastric mucosa. The expression of CCK-A receptor mRNA and cNOS mRNA was significantly increased in rats treated with CCK-8 and camostate, whereas CCK-B receptor mRNA remained unaffected. We conclude that CCK accelerates ulcer healing by the mechanism involving upregulation of specific CCK-A receptors, enhancement of somatostatin release, stimulation of sensory nerves and hyperemia in the ulcer area, possibly mediated by NO.

Animals↗
PubMed1999

Leptin in gastroprotection induced by cholecystokinin or by a meal. Role of vagal and sensory nerves and nitric oxide.

Leptin, detected recently in the stomach, is a product of the ob gene released by cholecystokinin (CCK) and plays an important role in the control of food intake but its influence on gastroprotection against the damage caused by noxious agents has not been studied. This study was designed to compare the effects of leptin and cholecystokinin-8 (CCK-8) on gastric mucosal lesions induced by topical application of 75% ethanol or acidified aspirin. Four series of Wistar rats (A, B, C and D) were used to determine the effects of: (A) suppression of prostaglandin biosynthesis by indomethacin (5 mg/kg i.p.); (B) inhibition of nitric oxide (NO)-synthase by nitro-L-arginine methyl ester (L-NAME) (5 mg/kg i.v.); (C) blockade of sensory nerves by capsaicin (125 mg/kg s.c.) and (D) bilateral vagotomy, on the gastric lesions induced by intragastric (i.g.) application of ethanol with or without pretreatment with CCK-8, a known gastroprotective substance or leptin. CCK-8 (1-100 microg/kg i.p.) and leptin (0.1-50 microg/kg i.p.) dose dependently attenuated gastric lesions induced by 75% ethanol; the dose reducing these lesions by 50% being about 10 microg/kg and 8 microg/kg, respectively. The protective effects of CCK-8 and leptin were accompanied by a significant rise in gastric blood flow (GBF) and luminal NO concentration. Leptin was also effective to attenuate aspirin-induced damage and the accompanying fall in the GBF, whereas CCK-8 dose dependently worsened aspirin damage and failed to influence GBF. CCK (1-100 microg/kg i.p.), given in graded doses, produced a dose-dependent increase in the plasma leptin level and a rise of the expression of ob messenger RNA (mRNA) in gastric mucosa, the maximum being reached at a dose of 100 microg/kg. Pretreatment with CCK-8 (10 microg/kg i.p.) or with 8% peptone, that is known to stimulate CCK release, also produced a significant rise in plasma leptin levels and up-regulation of ob mRNA while reducing significantly the gastric lesions induced by 75% ethanol to the same extent as that induced by exogenous leptin (10 microg/kg i.p.). Indomethacin, which suppressed prostaglandin generation by approximately 90%, failed to influence leptin- or CCK-8-induced protection against ethanol, whereas L-NAME attenuated significantly CCK-8- and leptin-induced protection and hyperemia but addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of both hormones. The ob mRNA was detected as a weak signal in the intact gastric mucosa and in that exposed to ethanol alone but this was further enhanced after treatment with graded doses of CCK-8 or peptone meal applied prior to ethanol. We conclude that: (1) exogenous leptin or that released endogenously by CCK or meal exerts a potent gastroprotective action depending upon vagal activity, and involving hyperemia probably mediated by NO and sensory nerves but unrelated to endogenous prostaglandins; (2) leptin mimics the gastroprotective effect of CCK and probably mediates the protective and hyperemic actions of CCK in the rat stomach.

Animals↗
PubMed1999

Are snoring medical students at risk of failing their exams?

STUDY OBJECTIVES: To compare the examination results of self-reported snoring and nonsnoring medical students DESIGN: We studied the examination scores obtained by medical students answering a multiple-choice test forming part of their final examinations. The students were asked to classify themselves as "nonsnorers," "occasional snorers," or "frequent snorers," and to state their age, sex, height and weight. SETTING: University Hospital, Erlangen, Germany PARTICIPANTS: 201 medical students (61% males/39% females; mean age 24.6 +/- 2.1 years; BMI 22.4 +/- 2.5 kg/m2) taking their final examinations in internal medicine. MEASUREMENTS AND RESULTS: Seventy-eight students (38.8%) claimed to be nonsnorers, 99 (49.3%) occasional snorers and 24 (11.9%) frequent snorers. The mean examination scores (adjusted for age, sex, and BMI) were 69.6 +/- 9.9% for the nonsnorers, 65.3 +/- 10.0% for the occasional snorers and 62.0 +/- 8.2% for the frequent snorers (p < 0.0001). 12.8% of the nonsnorers failed the exam, compared with 22.2% of the occasional snorers and 41.7% of the frequent snorers (p < 0.001). Logistic regression analysis showed an association between failing the exam and snoring (p = 0.013), but not between failure and age, BMI, or sex (relative risk for snorers adjusted for age, sex and BMI: 1.26; 95%--CI 1.01-1.57). CONCLUSIONS: In medical students, snoring seems to be associated with an increased risk of failing exams in a dose-response manner, even after controlling for age, sex and BMI. For the present, the mechanisms underlying this association must remain a matter of speculation. Snoring-related sleep fragmentation ("upper airway resistance syndrome") might be a causal factor.

Achievement↗
PubMed1999

[Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy with octreotide].

HISTORY AND FINDINGS: Magnetic resonance imaging (MRI) of the central nervous system was performed on a 72-year-old woman who was hyperthyroid without suppression of the thyroid-stimulating hormone (TSH) and had complained of a recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in diameter, in the anterior pituitary. The clinical symptoms were marked by a long-standing monosymptomatic illness of rapidly changing mood swings with depressive and manic phases. INVESTIGATIONS: Endocrinological-biochemical tests showed hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH: 2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a 5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified the mass as a retrosternal goitre. TREATMENT AND COURSE: As an operation on the anterior pituitary would have carried a high risk for the patient who was in a poor general condition and she had refused to be operated, treatment with octreotide, a long-acting somatostatin analogue, was initiated. This achieved a euthyroid state with partly suppressed TSH, and the patient's emotional swings ceased. CONCLUSION: If hyperthyroidism coexists with non-suppressed TSH levels, a TSH-producing hypophyseal adenoma should be considered in the differential diagnosis despite its rarity. Octreotide administration is an effective and safe treatment and is the method of choice, especially when there are contraindications to surgical resection of the anterior pituitary.

Adenoma↗
PubMed1999

Percutaneous ethanol injection and radio-frequency ablation for the treatment of nonresectable colorectal liver metastases - techniques and results.

BACKGROUND: Percutaneous ethanol injection (PEI) and radio-frequency (RF) ablation are possible palliative treatment modalities for patients with non-resectable liver metastases of colorectal carcinomas. The different techniques are explained and reviewed. RESULTS: PEI did not show promising results for the treatment of liver metastases. RF results were more encouraging; some studies showed improved mean survival times for patients when a complete necrosis of the metastases could be achieved. The maximum diameter of the necrotic area possible in a single session is about 5 cm. CONCLUSION: PEI and RF are palliative last-line treatment strategies for patients with non-resectable liver metastases and should only be applied if chemotherapy is not sufficient or not possible. The long-term efficacy of RF ablation in this group of patients has to be evaluated.

Catheter Ablation↗
PubMed1999

Acute hepatitis induced by greater celandine (Chelidonium majus).

The hepatotoxic potential of conventional drugs is well known, but herbal medicines are often assumed to be harmless. In the last 2 years, we have observed 10 cases of acute hepatitis induced by preparations of greater celandine (Chelidonium majus), which are frequently prescribed to treat gastric and biliary disorders. The course of hepatitis was mild to severe. Marked cholestasis was observed in 5 patients, but liver failure did not occur. Other possible causes of liver disease (viral, autoimmune, hereditary, alcohol, and secondary biliary) were excluded by laboratory tests and imaging procedures, and liver biopsy specimens were consistent with drug-induced damage. After discontinuation of greater celandine, rapid recovery was observed in all patients and liver enzyme levels returned to normal in 2-6 months. Unintentional rechallenge led to a second flare of hepatic inflammation in 1 patient. Greater celandine has to be added to the list of herbs capable of inducing acute (cholestatic) hepatitis. A significant proportion of unexplained cases of hepatitis may be caused by greater celandine.

Acute Disease↗
PubMed1999

Disposable-sheath, flexible gastroscope system versus standard gastroscopes: a prospective, randomized trial.

BACKGROUND: Endoscopically transmitted infections due to inadequate disinfection are rare but well-recognized complications. A new prototype of a flexible, fiberoptic endoscope has been developed that uses a disposable sheath to cover and protect all working surfaces of the endoscope from contamination. The present study investigated the function, reprocessing, and hygienic status of this endoscope system in comparison with standard systems. METHODS: In a prospective, randomized trial, 100 upper endoscopic procedures (50 standard, 50 sheathed) were performed. Analog rating scales were used to evaluate endoscopic performance and reprocessing. Reprocessing time, procedure duration, insertion depth, total instrument downtime, and problems occurring during the procedure were recorded. Microbiologic swabs were obtained from each endoscope. RESULTS: Mean procedure duration was slightly longer with the sheathed system than with standard endoscope (9.9 vs. 8.4 min). Set up and reprocessing times, however, were significantly shorter with the Endosheath (8.9 vs. 48.4 min with the standard endoscope). The disposable-sheath endoscope system permits the rate of performance of procedures to be increased by a factor of up to 3.0. Both endoscopists and reprocessing personnel preferred the standard endoscope. No post-procedure sheath leakage or rupture was seen. CONCLUSION: Our results suggest that the "disposable endoscope" may have important advantages in terms of decreased instrument turn-around time and potentially improved safety.

Adolescent↗
PubMed1999

Endoscopic photodynamic diagnosis: oral aminolevulinic acid is a marker of GI cancer and dysplastic lesions.

BACKGROUND: Dysplasia and early cancer of the upper gastrointestinal (GI) tract often are undetected at white-light endoscopy. We describe oral administration of 5-aminolevulinic acid for the in vivo photodynamic diagnosis of premalignant and malignant lesions during endoscopy. METHODS: Four patients with known gastric adenoma (n = 1), macroscopically undetected but histologically proven esophageal squamous cell cancer (n = 1), suspected early cancer of the esophagus (n = 1), and multiple duodenal adenomas (n = 1) were sensitized with 5-aminolevulinic acid administered orally (15 mg/kg body weight). Photodynamic diagnosis was conducted after a retention time of 6 to 7 hours with a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected through the gastroscope with an image-intensifying camera. RESULTS: All malignant lesions exhibited red or bluish fluorescence during photodynamic diagnosis. Fluorescence-negative mucosal areas proved to be histologically benign. CONCLUSION: Fluorescence induced with 5-aminolevulinic acid might be useful for the endoscopic detection of dysplasia and early carcinoma in the upper GI tract. Further investigations are needed to evaluate the sensitivity and specificity of photodynamic diagnosis for different tumor entities.

Adenoma↗