[Respiratory effects of leptin].
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Biomedical subjects
Publications and source records attributed to E G Hahn.
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Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 microg ml(-1). This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated.
Massive immune reactions to certain foods may be traced back to immunological, but also to non-immunological mechanisms. The diagnostic work-up must therefore aim to distinguish an allergy from other inflammatory, neoplastic or immunoregulative disorders. The most common form of gastrointestinal-mediated allergy form are the IgE-mediated reactions of the immediate type (Type 1 allergy). The routine diagnostic investigation includes history-taking, a daily diary of foods eaten, skin tests and antibody determination. The diagnosis of an allergy is often complicated by the multitude of possible manifestation sites, a possibly localized effect, and variations in the depth of allergic processes. To confirm the diagnosis, an oral provocative test should always be performed.
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BACKGROUND: Chronic infections have been proposed to play a role in the aetiology or progression of atherosclerotic plaques. Increased risk of coronary artery disease has been suggested in patients seropositive for Helicobacter pylori. AIM: To analyse coronary specimens in patients with severe (coronary artery disease) for Helicobacter pylori specific DNA. PATIENTS AND METHODS: Atherosclerotic plaques were obtained in 46 consecutive patients (9 female, 37 male, mean age 62.7+/-9.17 years) during coronary bypass procedures. Serum was analysed for IgG -/cagA-antibodies specific for Helicobacter pylori. Polymerase chain reaction and sequence analysis were used to identify bacterial DNA. Coronary artery biopsies from 19 autopsies without coronary artery disease were examined as a control group. RESULTS: Of the 46 coronary artery disease patients, 32 (69.6%) were Helicobacter pylori seropositive. Positive results for Helicobacter pylori DNA showed 18 seropositive and 4 seronegative (with anamnesis of eradication therapy). A total of 22 patients (47.8%) of the coronary artery disease group but none of controls revealed positive DNA. In the coronary artery disease group, a correlation between DNA presence and prior myocardial infarction (p=0.008) and unstable angina (p<0.001) was found. CONCLUSION: Identification of DNA in atherosclerotic plaques of patients with severe coronary artery disease supports the hypothesis that Helicobacter pylori infection may influence the development of atherosclerosis. Our results may indicate an direct involvement of Helicobacter pylori in the progression and instability of plaques in these patients.
OBJECTIVE: Antihypertensive drugs influence the neurohumoral cardiovascular system and the concentration of hormones involved in blood pressure regulation. Little is known, however, about the extent to which various antihypertensive drugs influence cardiovascular hormone concentrations and thus disturb the differential diagnosis of hypertension in clinical practice. In this study we compare the impact of different antihypertensive medicaments on the renin-angiotensin-aldosterone system in patients with essential hypertension who are screened for primary aldosteronism. DESIGN AND SUBJECTS: We analysed serum aldosterone (SAC) and plasma renin concentration (PRC) in 37 normotensive controls, 144 hypertensive patients with essential hypertension, and 19 patients with primary aldosteronism. Patients were on different treatment regimens such as single drug or combination therapy with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II subtype 1 (AT1) receptor antagonists, calcium channel blockers, spironolactone and no treatment. RESULTS: In patients with essential hypertension, beta-blocker therapy (n = 47) led to a highly significant suppression of renin, whereas serum levels of aldosterone were not significantly altered. ACE inhibitors and AT1 receptor antagonists (n = 55) decreased aldosterone levels only to a minor extent. Calcium channel blockers (n = 23) had no significant influence on SAC or PRC. In patients with primary aldosteronism treated with spironolactone (n = 8), renin escaped suppression and reached very high levels. CONCLUSION: Beta-blockers and aldosterone antagonists have the strongest impact on the renin-angiotensin system. The decrease in renin concentration by beta-blockers leads to an increase in the ratio of aldosterone to renin, and thus to false-positive results in patients with essential hypertension. Calcium channel blockers, and probably also ACE inhibitors and AT1 receptor antagonists alone or in combination, may be continued during screening for primary aldosteronism by determination of renin and aldosterone concentration.
OBJECTIVES: Insulin-treated patients with diabetes are at a higher risk than the general population in causing traffic accidents due to hypoglycaemias. Preceding investigations focused on insulin-treated patients and hypoglycaemia-induced accidents as "end-points". We studied the incidence of symptomatic hypoglycaemia and hypoglycaemia-induced accidents during driving and put it in relation to the different treatment modes of insulin therapy (Conventional Insulin Treatment = CT, Intensified Conventional Insulin Treatment = ICT, Continuous Subcutaneous Insulin Infusion = CSII) as well as to patients treated with oral hypoglycaemia-inducing agents and the two main types of diabetes mellitus. DESIGN SUBJECTS AND SETTING: We investigated 450 patients (122 treated with sulphonylureas, 151 with CT, 143 with ICT and 34 with CSII) by an anonymous questionnaire at different locations to avoid bias. A total of 176 persons had type 1 diabetes, 243 persons had type 2 diabetes, 31 subjects could not be classified. RESULTS: Symptomatic hypoglycaemias during driving were rare events with an occurrence of 0.19-8.26 (minimal and maximal mean, depending on the mode of treatment), if given as hypoglycaemias per 100 000 km on one treatment regimen, or 0.02-0.63, if given as events per year driven. Their incidence increased significantly with the degree of "strictness" between the treatment groups, except between the patients treated with ICT and CSII. Hypoglycaemia-induced accidents are rare with 0.01-0.49, if given as events per 100 000 km and 0.007-0.01, if given as events per year driven. These differences were not significant. Significant confounders influencing the traffic safety of the patients were age, duration of diabetes and concomitant antihypertensive medication. Analysing the data in accordance with the type of diabetes revealed a significantly higher rate of hypoglycaemic events in patients with type 1 diabetes. The number of hypoglycaemia-induced accidents was considerably higher in this group, but failed slightly to reach statistical significance. CONCLUSIONS: Hypoglycaemias during driving are rare events, their occurrence is significantly influenced by the treatment regimen and type of diabetes. Hypoglycaemia-induced accidents are extremely rare, presumably as a positive effect of patient education in our group.
The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.
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AIM: This pilot study examines the question whether the transit time of an ultrasound echo enhancer, measured between the hepatic artery and the liver vein, can be used to differentiate between patients with and without liver metastases. METHOD: The hepatic transit time of an ultrasound echo enhancer (Optison(R)) was determined using the pulse-inversion mode in patients suffering from gastrointestinal tumours. A group with histologically verified liver metastases was compared to a group without liver metastases. RESULTS: 24 patients have been included in the study so far. 7 patients had liver metastases from a still existing primary tumour (group A). Five patients showed liver metastases after removal of the primary tumour (group B). Six patients had a primary tumour, but no liver involvement (group C), and six patients had neither a primary tumour nor any liver disease. The mean hepatic transit time in group A and B came to 7.4 seconds. Group C and D had a transit time of 16 and 15.5 seconds, respectively. This shows a significant difference in hepatic transit time between patients with liver metastases (groups A and B) compared to those without (groups C and D). The presence of a primary tumour did not influence hepatic transit time. CONCLUSION: In this first pilot study using the measurement of hepatic transit time it was possible to differentiate between patients with and without liver metastases.
Radio-Frequency-Tissue-Ablation (RFTA) for the treatment of primary and secondary tumours of the liver has been used for several years, but this minimally invasive treatment is not limited to the liver. A patient suffering from symptomatic postmenopausal osteoporosis, additionally having primary hyperparathyroidism since 1995, refused a surgical resection of the adenoma of the parathyroid gland. Sonographically a 16 mm hypoechoic tumour dorsal of the right upper pole of the thyroid gland was detected. Osteodensitometry: severe osteoporosis of the lumbar spine (88 % of the norm for this age group). Blood check: Elevation of serum calcium level (3.1mmol/l) and serum parathormone level 274 pg/dl (N: 10-50). A percutaneous ultrasound guided RFTA of the adenoma of the thyroid gland was carried out. After RFTA the serum parathormone levels and the serum calcium levels dropped back to normal. The patient was followed-up for one year. For the first time a sufficient therapy for osteoporosis comprising calcium, etidronate and cholecalciferol could be carried out. The osteodensitometry carried out one year after treatment showed an increase in bone density. For the treatment of symptomatic primary hyperparathyroidism RFTA can be a therapeutic alternative for patients with contraindications for surgery.
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BACKGROUND AND STUDY AIMS: Real-time digital video transmission (rtDVT) at an acceptable quality through networks has been possible for several years. This technique can be used for telemedical applications, such as tele-endoscopy. The hypotheses of the present study were that the quality of real-time DVT depends on the technical equipment used, and that the resulting image quality influences the usability of the system for diagnostic purposes. MATERIALS AND METHODS: An experimental network was established between two German referral endoscopy centers, using the Asynchronous Transfer Mode (ATM) protocol. At first, rtDVTs of routine gastrointestinal video endoscopies were transferred through the network for prospective evaluation of the feasibility of the technical equipment and its usability for diagnostic tele-endoscopy, based on the video image quality. Secondly, the image quality and usability for correct telemedical diagnosis were evaluated prospectively in a double-blind experimental setting in relation to variations in the methods of data compression used, transmission bandwidths, and simulated transmission errors. Fourteen endoscopists evaluated 27 variations of an endoscopic video sequence. RESULTS: Compression with the Moving Picture Expert Group 2 (MPEG2 [4 : 2 : 2]) standard, the ATM protocol, and a bandwidth of 40 megabits per second (Mb/s) were used successfully in 40 routine tele-endoscopies for practical evaluation. Doctors were able to handle the system with ease, and its availability was 100%. There were no detectable differences between the original video image and the transferred image, and the images were usable for diagnosis in all cases. The set-up used clinically was therefore considered to provide the optimal conditions for comparisons in the experimental part of the study. Experimentally, any technical variation was found to cause a reduction in the overall image quality and hence a reduction in diagnostic usability: compression algorithm (MPEG2 [4 : 2 : 2] vs. others: P = 0.001), bandwidth (> or = 8 vs. < 8 Mb/s: P = 0.001), and error rate (10 (-8) vs. 10 (-7): P = 0.001). CONCLUSIONS: rtDVT using MPEG2 [4 : 2 : 2] compression and a bandwidth of 40 Mb/s did not effectively differ from the original video images in routine tele-endoscopy. The qualitative requirements in diagnostic video endoscopy, however, are obviously much higher than previously assumed, since experienced endoscopists detected a loss of image quality and a reduction in diagnostic usability with any reduction in the technical specification. Modern methods of data compression, broadband networks and a network protocol with good quality-of-service guarantees are therefore prerequisites for diagnostic rtDVT.
BACKGROUND: Despite numerous epidemiological studies, the association between Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This study was designed to determine the seropositivity of H. pylori and cytotoxin-associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO) in a large series of GC patients and controls. METHODS: 337 GC patients (118 men and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum-amidated gastrin was determined by specific radioimmunoassay and correlated with gastric luminal pH. RESULTS: The numbers of GC patients and controls involved in the study in various age groups, ranging from 20 to > 70 years, were similar, but overall H. pylori IgG seropositivity in GC patients was significantly higher (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the calculated cut-off value (38.88 pM/L) were found in several-fold larger number in GC patients (48%) than in controls (8.3%) and. similarly, serum IL-8 values over the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH = 4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls, and strong correlation between the serum gastrin and gastric pH was found in GC but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl: 1.61-4.22) for CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have significant influence on GC formation (OR > 1 in logistic regression). CONCLUSIONS: 1. CG patients show significantly higher H. pylori IgG and CagA seropositivity than dyspeptic age- and gender-matched controls, confirming that gastric infection with CagA expressing H. pylori greatly increases the risk of GC. 2. Serum gastrin levels in GC but not in controls are correlated with the rise in intragastric pH, indicating that excessive gastrin release in GC is affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity are significantly increased in the majority of GC patients, and are the only variables in multivariable analysis to have a predominant influence on GC formation, which suggests that both these parameters may be implicated in H. pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce significantly more IL-8 than do non-GC controls, probably reflecting CagA-positive H. pylori-associated gastritis.
BACKGROUND: The trisubstituted methylxanthine derivative pentoxifylline inhibits hepatic stellate cell proliferation and collagen synthesis in vitro. The antifibrotic effect of pentoxifylline in a suitable in vivo model of chronic liver fibrogenesis remains to be tested. METHODS: Groups of adult rats (n=20-23) received oral pentoxifylline at a dose of 8 mg/kg/day from week 1 to week 6, and 16 mg/kg/day from week 1 to week 6 or week 4 to week 6 after complete bile duct occlusion. Animals who underwent sham operation that received 16 mg/kg/day pentoxifylline and untreated rats with bile duct occlusion alone served as controls. After six weeks, animals were sacrificed and parameters of fibrogenesis determined. RESULTS: Bile duct occlusion caused portal cirrhosis with a 10-fold increased hepatic collagen content in the absence of inflammation or necrosis. This was accompanied by an 11-fold elevated serum aminoterminal procollagen III peptide (PIIINP). The drug induced a dramatic eightfold downregulation of procollagen I mRNA, and suppression of the fibrogenic factors transforming growth factor beta1 and connective tissue growth factor by 60-70%. However, profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was increased twofold, resulting in only a moderate decrease in liver collagen, fibrosis score, and PIIINP. CONCLUSIONS: We conclude that targeting pentoxifylline to the fibrogenic cells, thereby avoiding upregulation of TIMP-1, could become a potent antifibrogenic tool in chronic liver disease.