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Biomedical subjects

S Kahl

Publications and source records attributed to S Kahl.

At least 19 recordsLinked to original sources

Modeling growth factor activity during proinflammatory stress: methodological considerations in assessing cytokine modulation of IGF binding proteins released by cultured bovine kidney epithelial cells.

The present research was conducted to model potential mechanisms through which IGFBPs might be affected by a key proinflammatory response initiating cytokine tumor necrosis factor (TNF-)-alpha. Madin-Darby bovine kidney epithelial (MDBK) cells, known to release IGFBPs in response to several stimuli, were grown under several conditions and challenged with forskolin (F) or recombinant TNF-alpha for 24h. Forskolin increased IGFBP-3 gene expression and media content of BP-3 protein. TNF-alpha increased basal and augmented F-mediated IGFBP-3 gene expression. However, TNF-alpha effects on the measurable media content of IGFBPs were influenced by culture conditions; in the absence of added protease inhibitors (PIs) or sufficient media albumin concentration (high BSA, 1mg/ml), the effect of TNF-alpha was to decrease (P<0.02) measurable IGFBPs. In the presence of PI and high BSA, media IGFBP-3 levels were shown to be increased by TNF-alpha consistent with the gene expression data. Changes in media IGFBP-3 protease activity were examined further to explain the observed effects of TNF-alpha on production and destruction of IGFBPs in media. When recombinant human IGFBP-3 (500 ng/ml) was added to PI-free, low BSA 100 microg/ml) media from TNF-treated MDBK cells, less than 10% of the BP-3 was recognizable by Western blot in 30 min; conversely, inclusion of High BSA and PI in media resulted in attenuation of the protease effect on the IGFBPs. The data suggest that the MDBK model of cellular response to proinflammatory stimulus is affected by culture conditions and that TNF-alpha affects media content of IGFBPs through effects on IGFBP gene expression coupled with degradation of IGFBPs via enhanced proteolytic enzyme release.

Animals↗

Relationships between thyroid status, tissue oxidative metabolism, and muscle differentiation in bovine fetuses.

The temporal relationships between thyroid status and differentiation of liver, heart and different skeletal muscles were examined in 42 bovine fetuses from day 110 to day 260 of development using principal component analysis of the data. Plasma concentrations of reverse-triiodothyronine (rT(3)) and thyroxine (T(4)) increased during development from day 110 to day 210 or 260, respectively, whereas concentration of triiodothyronine (T(3)) and hepatic type-1 5'-deiodinase activity (5'D1) increased from day 180 onwards. On day 260, high T(4) and rT(3) and low T(3) concentrations were observed together with a mature 5'D1 activity. Cytochrome-c oxidase (COX) activity expressed per mg protein increased at day 180 in masseter and near birth in masseter, rectus abdominis and cutaneus trunci muscles (P<0.05). Significant changes in citrate synthase (CS) activity per mg protein were observed between day 110 and day 180 in the liver and between day 210 and day 260 in the liver, the heart and the longissimus thoracis muscle (P<0.05). Muscle contractile differentiation was shown by the disappearance of the fetal myosin heavy chain from day 180 onwards. A positive correlation (r>0.47, P<0.01) was shown between thyroid status parameters (5'D1, concentrations of T(4) and T(3)) and COX activity in muscles known to be oxidative after birth (masseter, rectus abdominis) but not in liver and heart, nor in muscles known to be glycolytic after birth (cutaneus trunci, longissimus thoracis). A similar correlation was found between thyroid parameters and CS activity in liver and masseter. Results indicate that elevation of plasma T(3) concentrations in the last gestational trimester could be involved in the differentiation of oxidative skeletal muscles.

Animals↗

Early bacterial infection of the pancreas and course of disease in cerulein-induced acute pancreatitis in rats.

BACKGROUND: Bacterial infection of the pancreas aggravates the course of acute pancreatitis. Since bacterial translocation from the gut is likely to be an early event, in an animal model of pancreatitis, we investigated the effect of early bacterial supra-infection of the pancreas on the course of the disease. METHODS: Six hours after the induction of acute pancreatitis in male Wistar rats (n = 180) by supramaximal stimulation with cerulein (or placebo in a control group), the animals were operated and a suspension of Helicobacter pylori, Escherichia coli or saline were introduced either in the pancreatic duct or interstitium (12 groups of 15 rats each); after 24 h, animals were killed and the following parameters analysed: macroscopic and histologic appearance of the pancreas (score), wet-to-dry weight ratio, pancreas trypsinogen activation peptide level, serum amylase, interleukin-6 and phospholipase A2 activity. RESULTS: All parameters were increased in rats with cerulein-induced pancreatitis in comparison to placebo. Interstitial and intraductal application of bacteria increased the pancreatic damage. This effect was more evident with the application of E. coli in both cerulein and placebo groups. Application of E. coli but not of H. pylori determined pancreatic activation of trypsinogen, increased mortality and induced the production of interleukin-6. CONCLUSIONS: Bacterial invasion of the pancreas worsens the histologic and clinical picture of disease and induces a systemic inflammatory response.

Acute Disease↗

Diagnostic and therapeutic impact of double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a new endoscopic method for examining the small intestine. Most reports of DBE have been from Japan, and very few data on this new technique have been reported by centers outside Japan. The aim of the present study was to determine the diagnostic yield of DBE, measure the frequency of management changes made on the basis of the results, and evaluate the clinical outcome for patients undergoing the procedure. PATIENTS AND METHODS: All patients undergoing DBE using a Fujinon enteroscope (length 200 cm, diameter 8 mm) during a 11-month period were studied. All of the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. They underwent small-bowel cleansing on the day before the procedure using a standard colon lavage solution. RESULTS: Seventy DBE procedures were carried out in 53 patients (34 men, 19 women; mean age 60 years, range 24 - 80) by the oral route in 46 cases and the anal route in 24. The indications for the examination were gastrointestinal bleeding (n = 29), suspected Crohn's disease (n = 6), abdominal pain (n = 4), polyp removal or evaluation in polyposis syndromes (n = 6), chronic diarrhea (n = 4), and surveillance or tumor search (n = 4). The mean duration of the procedure was 72 min (range 25 min - 3 h). The mean radiation exposure was 441 dGy/cm (range 70 - 1462), and the mean depth of small-bowel insertion was 150 cm (range 1 - 470 cm). It was possible to evaluate the entire small bowel in four patients (8 %). A new diagnosis was obtained in 26 of the 53 patients (49 %). The findings in the 70 procedures were angiodysplasia (n = 13), ulcerations or erosions (n = 5), jejunitis or ileitis (n = 5), tumors (n = 5), stenosis (n = 4), polyps (n = 5), lymphangiectasias (n = 4), Crohn's disease (n = 4), and normal (n = 17). DBE resulted in a therapeutic intervention (endoscopic, medical or surgical, excluding blood transfusions) in 57 % of the patients (30 of 53). The only complication (1.4 %) observed was one case of intraprocedural postpolypectomy bleeding, which resolved with injection of epinephrine. CONCLUSION: In almost two-thirds of the patients examined, DBE was clinically useful for obtaining a new diagnosis and starting new treatments, changing existing treatments, carrying out surgical intervention, or providing therapeutic endoscopy. DBE is a useful and safe method of obtaining tissue for diagnosis, providing hemostasis, and carrying out polypectomy.

Adult↗

Exogenous testosterone modulates tumor necrosis factor-alpha and acute phase protein responses to repeated endotoxin challenge in steers.

Clinical responses to some disease agents differ between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. Our objective was to determine in steers the effect of testosterone on circulating concentrations of immune response mediators (tumor necrosis factor-alpha, TNF-alpha; serum amyloid-A, SAA; haptoglobin, HG; xanthine oxidase, XO; nitric oxide, NO) after two consecutive endotoxin challenges (LPS1 and LPS2, 5 days apart; 0.25 microg/kg BW). Sixteen crossbred steers (328+/-6 kg) were assigned to control (CON, n=8) or testosterone cypionate treatment (TES, n=8; 100 mg/m2 body surface; i.m. injection 12 and 2 days before LPS1). The response to LPS was calculated as area under the timexconcentration curve (AUC) for the parameter measured. After LPS1, TNF-alpha AUC was greater in TES than CON (P<0.05). Plasma HG and SAA concentrations increased (P<0.01) after LPS1 and LPS2. In all steers SAA AUC was greater after LPS1 than LPS2 (P<0.01) but the response was augmented over CON with testosterone treatment (P<0.05). HG response to LPS1 within 24 h was not affected by testosterone. However, 5 days after LPS1 mean plasma HG concentration remained higher in TES than CON (P<0.01). HG response to LPS2 was greater in TES than CON (P<0.01). Plasma nitrate+nitrite concentration (NO production marker) and XO activity increased after each LPS challenge but responses were not affected by testosterone treatment. Results indicate that the presence of circulating testosterone increases the magnitude of the TNF-alpha response to LPS challenge as well as the subsequent increases in acute phase proteins (APP). Effects of testosterone on increases in TNF-alpha and APP may underlie a differential presentation of disease symptoms between sexes or between steers and bulls. The data also suggest a role for testosterone in the development of tolerance to repeated immune challenge through its effect on the increased magnitude and duration of HG response.

Acute-Phase Proteins↗

Echo enhanced ultrasound: a new valid initial imaging approach for severe acute pancreatitis.

AIM: This prospective study aimed to compare the accuracy of echo enhanced ultrasound with spiral computed tomography (CT) in assessing acute pancreatitis and to explore the correlation between ultrasound findings and clinical outcome. METHODS: Thirty one patients (24 men and 7 women, median age 39 years, range 19-67 years) with acute pancreatitis were investigated by contrast enhanced CT and echo enhanced ultrasound within 72 hours after admission. Echo enhanced ultrasound (with intravenous injection of 2.4 ml SonoVue, pulse inversion technique, mechanical index 0.1 to 0.2, Siemens Elegra) was performed following conventional ultrasound. Balthazar's grading system was used to measure CT and ultrasound severity indices (CTSI and USSI). Correlations between CTSI and USSI and between USSI and clinical parameters were tested by Spearman's rank correlation coefficient. RESULTS: A strong correlation was demonstrated between CTSI and USSI (r = 0.807, p<0.01). Ultrasound correlated with the following: the Ranson score (r = 0.401, p<0.05), C-reactive protein levels 48 hours after admission (r = 0.536, p<0.01), duration of hospitalisation (r = 0.422, p<0.05), and clinical outcome regarding morbidity, including local and systemic complications (r = 0.363, p<0.05). Based on CT findings as the gold standard, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for detecting severe acute pancreatitis based on imaging criteria (Balthazar score D or E and/or presence of hypoperfusion compatible with necrosis and/or SI>/=3) were, respectively, 82% (95% CI 61 to 93), 89% (95% CI 57 to 98), 95% (95% CI 75 to 99), and 67% (95% CI 39 to 86). CONCLUSION: Echo enhanced ultrasound produces excellent results in the staging of acute pancreatitis severity. The procedure is cheaper and has fewer contraindications than CT. Further multicentre studies need to be performed before including the method in the diagnostic algorithm of patients with acute pancreatitis.

Acute Disease↗

Characterization of calves exhibiting a novel inheritable TNF-alpha hyperresponsiveness to endotoxin: associations with increased pathophysiological complications.

A subpopulation of calves, herein termed "hyperresponders" (HPR), was identified and defined by the patterns of plasma TNF-alpha concentrations that developed following two challenges with endotoxin (LPS, 0.8 mug Escherichia coli 055:B5 LPS/kg(0.75) live body wt) separated by 5 days. The principle characteristic of HPR calves was a failure to develop tolerance to repeated LPS challenge that was evident in the magnitude of the TNF-alpha concentrations and prolonged severity of pathological sequellae. Whereas calves failing to develop LPS tolerance were identified on the basis of their excessive in vivo plasma TNF-alpha concentration responses, in vitro TNF-alpha responses of peripheral blood mononuclear cells isolated from each calf and challenged with LPS or PMA did not correlate or predict the magnitude of in vivo plasma TNF response of the calf. Intentional breeding to obtain calves from bulls and/or cows documented as HPR resulted in offspring displaying the HPR character when similar progeny calves were tested with LPS in vivo, with extensive controls in place to account for sources of variability in the general TNF-alpha response to LPS that might compromise interpretation of the data. Feed intake, clinical serology and hematology profiles, and acute-phase protein responses of HPR calves following LPS were significantly different from those of calves displaying tolerance. These results suggest that the pattern of plasma TNF-alpha changes that evolve from a low-level double LPS challenge effectively reveal the presence of a genetic potential for animals to display excessive or prolonged pathological response to LPS-related stress and compromised prognosis for recovery.

Acute-Phase Proteins↗

Laparoscopic-endoscopic rendezvous resection of upper gastrointestinal tumors.

BACKGROUND: Endoscopic and laparoscopic local resection of gastric tumors has increasingly been performed in recent years. This article describes the technical considerations and early results of laparoscopic-endoscopic rendezvous resection of gastric lesions. PATIENTS AND METHODS: Rendezvous resection was performed in 26 patients with submucosal gastric tumors (n = 22) and early gastric cancer (n = 4). Laparoscopic wedge resection (LWR) was performed in 16 patients with anterior wall tumors and laparoscopic intragastric resection (LIR) in 7 patients with posterior wall tumors. Conversion to open surgery was carried out in 3 cases. RESULTS: Operation times were 53 min (range 35-115) for LWR and 83 min (range 56-130) for LIR, respectively. In submucosal lesions the mean tumor size was 36 mm (range 16-47) and in early gastric cancer 17.3 mm (range 16-20). Rendezvous resection was performed with curative intent and clear resection margins in all patients without lymphatic or vessel permeation. Postoperative complications occurred in 2 patients. After a mean follow-up of 22.8 months (range 2-71), no local recurrence or metastatic disease and no tumor-related death were observed. CONCLUSIONS: When selected properly, the laparoscopic-endoscopic approach is considered to be curative and safe for resection of localized gastric tumors.

Endoscopy, Gastrointestinal↗

Endotoxin challenge increases xanthine oxidase activity in cattle: effect of growth hormone and vitamin E treatment.

In addition to its basic role in the metabolism of purine nucleotides, xanthine oxidoreductase (XOR) is involved in the generation of oxygen-derived free radicals and production and metabolic fate of nitric oxide (NO). Growth hormone (GH) and Vitamin E (E) have been shown previously to modify immune response to infection. Our objective was to determine in heifers the effect of endotoxin challenge (LPS; 3.0 microg/kg BW, i.v. bolus, Escherichia coli 055:B5) on xanthine oxidase (XO) activity in plasma and liver and the modification of this response by daily treatment with recombinant GH (0.1 mg/kg BW, i.m., for 12 days) or GH+E (E: mixed tocopherol, 1000 IU/heifer, i.m., for 5 days). In experiment 1, 16 heifers ( 348.7 +/- 6.1 kg) were assigned to control (C, daily placebo injections), GH, or GH+E treatments and were challenged with two consecutive LPS injections (LPS1 and LPS2, 48 h apart). After LPS1, plasma XO activity increased 290% (P < 0.001) at 3 h, reached peak (430%) at 24 h and returned to basal level by 48 h after LPS2. XO responses (area under the time x activity curve, AUC) were greater after LPS1 than LPS2 (P< 0.001). Total plasma XO responses to LPS (AUC, LPS1+LPS2) were augmented 55% (P < 0.05) over C with GH treatment but diminished to C responses in GH+E. There was a linear relationship (r2 = 0.605, P < 0.001) between total response in plasma XO activity and plasma nitrate + nitrate concentration. In experiment 2, 24 heifers ( 346 +/- 6 kg) were assigned to C or GH treatments and liver biopsy samples were obtained at 0, 3, 6, and 24h after a single LPS challenge. Hepatic XO activities increased 63.3% (P < 0.05) 6 h after single LPS challenge and remained elevated at 24 h (100.1%, P < 0.01) but were not affected by GH treatment. Results indicate that LPS-induced increases in plasma XO activity could be amplified by previous GH treatment but attenuated by E administration. The data also suggest that E may be effective in controlling some mediators of immune response associated with increased production of NO via the effect on XO activity and its production of superoxide anion as well as uric acid.

Animals↗

The magnified endoscopic view of cardia-type mucosa.

BACKGROUND: The interpretation of magnification endoscopy regarding metaplasia of the esophagogastric junction (EGJ) is still controversial. Histology of areas endoscopically suspected of Barrett's esophagus often reveals only cardia-type mucosa (CTM). The aim of this study was to characterize the surface structure of CTM by magnification endoscopy, in comparison with specialized intestinal metaplasia (SIM) and gastric corpus mucosa. METHODS: Magnification endoscopy was performed in 52 patients with normal EGJ and 36 patients with columnar lined lower esophagus (CLE) on endoscopic examination. Biopsies for histology were obtained from EGJ and CLE segments. In cases with CLE, biopsies were targeted after methylene blue staining. RESULTS: A gyriform or oval pattern was observed in all patients at the normal EGJ, histologically representing CTM. These patterns of CTM were easily discernible from the small pits of corpus mucosa. A gyriform or villous pattern was dominant in CLE, both in areas with CTM and those with SIM. Methylene blue staining was more frequent in SIM than in CTM, but was of insufficient specificity for SIM. CONCLUSIONS: Although magnification endoscopy allows one to differentiate CTM from gastric corpus mucosa, a clear distinction from SIM is not possible. Auxiliary methods that complement magnification endoscopy, like methylene blue staining and acetic acid contrast enhancement, should be evaluated regarding the differentiation between CTM and SIM.

Adult↗

[Skin-level gastrostomy -- long-term results from a prospective trial in gastric and jejunal application].

OBJECTIVE: The usefulness of skin-level gastrostomy tubes (button systems) for maintaining nutrition support after primary insertion of percutaneous endoscopic gastrostomy (PEG) is widely accepted. After first promising experiences with newly developed skin-level gastrostomy system (Freka-Button Gastrostomy) the safety and long-term stability of this new tube was not defined. MATERIAL AND METHODS: In a cohort study we prospectively evaluated from 2.1998 until 12.2001 for ease of use, complications, time to failure and long-term follow-up of 61 Freka button gastrostomies inserted in 50 patients (mean age 57.6 years, range 6 - 78 years, 44 men, 6 women). Mean time after primary PEG placement was 6.3 months (range 1 - 30 months). RESULTS: Correct application of all buttons (48 gastric, 2 jejunal) was easy and fast (median time 11 minutes) to perform. In 56 % we used a new Seldinger guide wire technique to improve stomal passage. Within the first ten days and during long-term follow-up (median 248, range 2 - 593 days) no major complication was seen. 11 systems had to be replaced mainly due to balloon failure (median 352, range 186 - 593 days). The total observation time were 15,128 days with a system failure rate of 0.26 per year. CONCLUSION: The Freka-button systems provides an easy-to-use, safe, and feasible alternative for long-term use of skin-level gastrostomy. First jejunal application of this new device was promising but needs further evaluation.

Adolescent↗

Biliary strictures are not the cause of pain in patients with chronic pancreatitis.

OBJECTIVE: To investigate the relationship of strictures of the common bile duct (CBD) with pain in patients with chronic pancreatitis (CP) and jaundice. METHODS: A total of 61 patients with CBD strictures caused by CP of alcoholic etiology were treated by endoscopic stent insertion for 1 year with scheduled stent exchanges. Pain was assessed using a visual analogue scale, and analgesic medication was recorded prior to and after endoscopic treatment. RESULTS: Endoscopic drainage was successful in all cases, with complete resolution of jaundice during the 1-year follow-up period. Prior to the endoscopic stent insertion, pain scores were 6.8 +/- 6.3. Following stent therapy pain scores were 7.7 +/- 7.7. Pain scores, the number of patients requiring analgesics, the required amount of analgesics, and the type of analgesic medication did not change following treatment of CBD stricture. CONCLUSION: Successful endoscopic drainage of biliary obstruction has no influence on pain pattern in patients with CP. CBD obstruction does not cause pain in patients with CP.

Abdominal Pain↗

Ablative procedures for prevention and treatment of esophageal adenocarcinoma.

Ablation of Barrett's mucosa by endoscopic resection, photodynamic therapy or thermoablative methods in combination with adequate acid suppression leads to mucosal replacement largely by squamous epithelium. In appropriately selected cases, these methods have the potential to cure superficial Barrett's neoplasia. Endoscopic resection is an alternative to surgical resection of high-grade intraepithelial neoplasia or early esophageal adenocarcinoma, if the tumor is less than 20 mm in size, is not ulcerated, and does not exhibit differentiation grade 3 or lymph vessel infiltration on histological examination. In the presence of submucosal infiltration, the likelihood of lymph node infiltration is related to the infiltration depth. The risk of a noncurative endoscopic ablative approach has to be weighted against the general risk of surgery. With photodynamic or thermoablative treatment, the completeness of destruction of neoplastic tissue can only be judged at follow-up. These methods are therefore restricted to cases that have an increased surgical risk. Ablation of non-neoplastic Barrett's mucosa is currently not indicated.

Adenocarcinoma↗

Antigen stool test for assessment of Helicobacter pylori infection in patients with upper gastrointestinal bleeding.

BACKGROUND: Re-bleeding of Helicobacter pylori-associated peptic ulcer disease is reduced by H. pylori eradication. AIM: To validate a non-invasive test, the Premium Platinum HpSA stool test, in patients with upper gastrointestinal bleeding. METHODS: Stool samples of consecutive patients with relevant bleeding from gastric or duodenal ulcers or erosions were collected at initial endoscopy and during the following week. Samples were assessed using the HpSA test. H. pylori status was defined by three biopsy-based reference methods: culture, rapid urease test and histology. It was positive if culture was positive or if rapid urease test and histology were positive. RESULTS: One hundred and fourteen patients (mean age, 66 years) were included. In accordance with the definition, 56 (49%) were H. pylori positive. The sensitivity and specificity of the first stool sample were 84% and 90%, respectively. The respective values for two samples from consecutive days were 91% and 86%. In comparison with a serum immunoglobulin G antibody enzyme-linked immunoabsorbent assay, the HpSA test showed superior specificity. CONCLUSIONS: The diagnostic accuracy, in particular the sensitivity, of the HpSA stool test is reduced by upper gastrointestinal bleeding. The positive predictive value of 89%, however, justifies the initiation of eradication therapy on the basis of a positive stool test. A negative test result should be confirmed by a further diagnostic method.

Adolescent↗

[Endoscopic biliary drainage in patients with pancreatic cancer].

Obstructive jaundice is a common clinical sign in patients with pancreatic cancer. 52% of all patients with a potentially resectable pancreatic cancer suffer from painless obstructive jaundice. There are no prospective studies showing a beneficial effect of preoperative drainage in patients with resectable pancreatic cancer. Morbidity (53%) and mortality (15%) in patients without preoperative biliary drainage are not significantly different from those who had endoscopic drainage preoperatively (morbidity 41%; mortality 15%). However, there are some logistic reasons for preoperative drainage, especially if surgery is delayed. In cases of nonresectable pancreatic cancer endoscopic drainage for palliation of obstructive jaundice is the method of choice. The decision between metallic and plastic stents for palliation is based on expected survival time and quality of life. Implantation of metal stents is the method of choice in patients with life expectancy exceeding six months. Scheduled three months exchange of plastic stents is recommended to avoid complications. After a six months interval about 70% of patients with scheduled exchange are without symptoms, compared to about 40% of patients who had exchange of plastic stents on demand. Scheduled three months exchange of plastic stents leeds to a patency rate of plastic stents comparable to those of metallic stents.

Aged↗

A technique for endo-organ resection of gastric wall tumors using one intragastric trocar.

This report describes a new technique for combined laparoscopic and gastroscopic intragastric resection of benign gastric wall tumors. We performed this combined endo-organ procedure in five patients. Endo-organ intragastric resection is only used with posterior gastric wall tumors and tumors located near the cardia and the pylorus. For this approach, only one trocar is placed into the stomach for intragastric introduction of the endostapler. The video gastroscope allows intragastric vision. We recommend our procedure for the extirpation of small, benign, intramural gastric tumors, as a safe and very comfortable method for the patient.

Gastrectomy↗