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Biomedical subjects

E F Stange

Publications and source records attributed to E F Stange.

At least 91 records · Page 5Linked to original sources
PubMed1998

Treatment of unresectable carcinoma of the esophagus or the gastroesophageal junction by mesh stents with or without radiochemotherapy.

The palliative treatment of malignant stenoses of the upper gastrointestinal tract by self-expanding metal stents is a novel procedure with effective relief of dysphagia in most patients. There is little follow-up information with respect to the factors influencing clinical outcome and survival rates. Survival rates of 40 consecutive patients treated with 53 mesh stents were analyzed with regard to their degree of dysphagia (grades 0-3), quality of life (Karnofsky score), and the effect of additional radiation and chemotherapy. Following stent placement dysphagia improved in 36 of 40 patients. Endoscopic reinterventions for worsening of dysphagia were necessary in 23 patients during a median follow-up period of 74 days (range 51-149). There was a trend towards superior survival time in younger patients (<60 years) with high Karnofsky score ( 70). Patients receiving concurrent radiation and chemotherapy (n=12) experienced prolonged survival (median 318 days after diagnosis, 225 days after stent) compared with patients of equal tumour staging, but without additional therapy (n=17; median 157 days after diagnosis, p<0.001; 138 days after stent, p<0.05). The combination of endoscopic stenting with additional radiation and chemotherapy was associated with improved survival. A randomized trial is warranted.

Adult↗
PubMed1998

["Therapy of Crohn disease" guideline. German Society of Digestive and Metabolic Diseases].

During a consensus conference of the German Society for Digestive and Metabolic Diseases, seven working groups gathered in Halle (Saale) covering the topic "Therapy of Crohn's Disease". The goal of this conference was to establish standard recommendations for the conservative, dietary, surgical and psychosomatic treatment of intestinal and extraintestinal manifestations. These recommendations are based on the personal experience of the experts involved as well as the literature. In preparation of the conference, questionnaires were developed which were answered by all nearly 100 physicians specializing in internal medicine and gastroenterology. These were analysed by the chairmen of the working groups which wrote a consensus proposal in Halle. This was discussed, modified and passed by the plenary session and subsequently published in the Zeitschrift für Gastroenterologie (German J Gastroenterology) with a comment and the relevant literature. The guideline became a standard in German gastroenterology. Unfortunately, only half of the recommendations are supported by controlled trials and other representatives of the health care system were not involved. Currently an update of this guideline is prepared via internet (www.prous.com/ts).

Crohn Disease↗
PubMed1997

Clathrin-mediated endocytosis of high density lipoprotein3 in human intestinal Caco-2 cells. A post-embedding immunocytochemical study.

The mechanism by which high density lipoprotein (HDL) removes excess cholesterol from intracellular sites has been the subject of much controversy. There is some evidence that HDL binds to specific cell surface receptors without internalization. Other evidence suggests that HDL is taken up by endocytosis, enters a pathway of endosomal trafficking and is resecreted from the cells (retroendocytsosis). In the present study, we investigated the distribution of apolipoprotein AI, the major protein constituent of HDL, in cultured intestinal Caco-2 cells employing post-embedding immunocytochemistry on LR White-embedded material. Cells grown under control conditions showed label for apolipoprotein AI in the endoplasmic reticulum. After incubation with native apolipoprotein E-free high density lipoprotein3 (HDL3) additional label for apolipoprotein AI was found in endosomes. These endosomes were observed near lipid droplets and in the basolateral cytoplasm. Further, it was demonstrated that label for apolipoprotein AI was colocalized with label for clathrin on the basolateral membrane. Our results support the concept that HDL3 is internalized and subsequently processed in an endosomal pathway in Caco-2 cells besides de novo synthesis of apolipoprotein AI.

Apolipoprotein A-I↗
PubMed1997

The contribution of newly synthesized cholesterol to biliary cholesterol in healthy humans.

Hypersecretion of biliary cholesterol appears to be the key defect in the pathogenesis of cholesterol gallstones, and this may be due to an enhanced synthesis of cholesterol. To measure fractional syntheses of biliary and plasma cholesterol, five male and 3 female healthy humans with an intact enterohepatic circulation were infused intravenously with [1-13C]acetate for 15 h. Samples of duodenal bile and blood were taken hourly and an enteral formula diet was given. Free cholesterol mass distribution was analyzed by gas chromatography mass spectrometry. The Mass Isotopomer Distribution Analysis (MIDA) technique allowed to calculate fractional synthesis. After 6 hours of infusion, the [13C]label of the cytosolic acetate pool reached a plateau of approximately 12%. Individual fractional cholesterol synthesis is plasma and bile correlated significantly (6-15 h) and amounted to 4.2% and 5.3% after 15 h, respectively. It may be concluded from this study, that newly synthesized cholesterol is secreted into bile to a higher extent than into plasma.

Acetates↗
PubMed1997

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Adjuvants, Pharmaceutic↗
PubMed1997

Crohn's disease and sarcoidosis: systemic granulomatosis?

We report an unusual case of severe Crohn's disease with involvement of the lung. In 1993 at age 21 a male patient experienced a Helicobacter-negative duodenitis. A routine chest radiograph revealed spotted opacities in the right upper lobe without discomfort and normal pulmonary function except for a reduced diffusion capacity. Bronchoalveolar lavage showed mild lymphocytosis and biopsies from the macroscopically normal bronchi displayed non-caseating granulomas. In 1995 he had symptoms of peptic ulcer disease with a gastric outlet stenosis. He underwent Billroth I resection with only temporary improvement. Three months later the symptoms had recurred and a stenosing inflammatory process of the duodenum was seen on endoscopy suggesting Crohn's disease. A chest radiograph demonstrated infiltrations in parts of the left lung and bronchoalveolar lavage again revealed alveolar lymphocytosis (CD4/CD8 ratio 3.1). Both the gastrointestinal and pulmonary affections responded to corticosteroids but the duodenal stricture had to be resected. The association of Crohn's disease and pulmonary disorders is discussed.

Adrenal Cortex Hormones↗
PubMed1997

Newly synthesized cholesterol in human bile and plasma: quantitation by mass isotopomer distribution analysis.

The purpose of this study was to quantitate the contribution of newly synthesized cholesterol to bile and plasma in humans. Eight healthy volunteers were intravenously infused with 0.125 mmol of [1-(13)C]acetate per kilogram per hour for 15 h. During continuous enteral nutrition, plasma aliquots and samples of duodenal bile were collected hourly. The trimethysilylether of unesterified cholesterol was analyzed by gas chromatography-mass spectrometry for quantitation of the mass fragments M(+0) [mass-to-charge ratio (m/z) 368], M(+1) (m/z 369), M(+2) (m/z 370), M(+3) (m/z 371), and M(+4) (m/z 372). The fractional syntheses of plasma and biliary cholesterol were determined using mass isotopomer distribution analysis. After 6 h of infusion, the 13C enrichment of the acetate pool remained constant at 12%. The fractional synthesis increased continuously during [13C]acetate infusion and reached 4.2% and 5.3% in cholesterol of plasma and bile, respectively. Both were highly correlated, but the fractional synthesis of biliary cholesterol exceeded that of plasma (P < 0.05). It may be concluded that the contribution of de novo cholesterol synthesis to bile exceeds that to plasma but is minor in humans.

Adult↗
PubMed1997

Evidence for central nervous effects of corticotropin-releasing hormone on gastric acid secretion in humans.

In animals, corticotropin-releasing hormone (CRH) has been shown to decrease gastric acid secretion after intracerebral administration. Evidence exists that in man peptides have a direct access to the brain upon intranasal administration. This study aimed at assessing brain-mediated effects of CRH on gastric pH after intranasal administration in humans. Eleven healthy men were tested on 2 occasions in a double-blind within-subject cross-over comparison during treatment with CRH (versus placebo) administered intranasally at a dose of 20 micrograms every 10 min. Gastric pH values were measured continuously by a gastral pH tube. After 2 h of intranasal treatment, 6 micrograms/kg pentagastrin was injected subcutaneously. The subject's mood was assessed by an adjective list (EWL-N) at the end of each experimental condition. Intranasal CRH increased pH baseline values from (mean +/- SE) 1.70 +/- 0.31 to 2.62 +/- 0.53 (corresponding to 54%), whereas during intranasal treatment with placebo pH values remained unchanged (p < 0.05). After injection of pentagastrin, pH values decreased to 0.73 +/- 0.04 during placebo and to 0.93 +/- 0.14 during CRH treatment (n.s.). During treatment with CRH, subjects felt less tired (p < 0.05) and deactivated (p < 0.05). Plasma cortisol and CRH levels were not affected by intranasal CRH, excluding mediation of the CRH effects via resorption into the bloodstream, and TSH levels were slightly decreased by the end of the treatment. Results confirm the notion of a pathway for CRH from the nose to the brain, initiating, via central nervous mechanisms, inhibition of gastric acid secretion and a change of mood in humans.

Adolescent↗
PubMed1996

Reduced cholesterol esterification in CaCo-2 cells by indirect action of pravastatin.

In microsomal preparations of CaCo-2 cells pravastatin decreased cholesterol esterifying activity at 25 micrograms/ml to 82.5% and at 800 micrograms/ml to 56.2% of controls. Pravastatin reduced cholesteryl ester formation dose-dependently also in viable CaCo-2 cells. However, the maximal inhibition was by 90.4% at pravastatin concentration of 25 micrograms/ml, half maximal inhibition occurred between concentrations of 5 and 10 micrograms/ml. Addition of mevalonolactone, which serves as endogenous source of cholesterol, antagonized this effect. At 10 mM mevalonolactone (MVL) even doses up to 200 micrograms/ml of pravastatin were ineffective. On the other hand, pravastatin suppressed cholesteryl ester formation when acyl-CoA cholesterol acyltransferase (ACAT) (E.C. 2.3.1.26) activity was stimulated by addition of exogenous liposomal or Low Density Lipoprotein (LDL)-derived cholesterol. This inhibition was refractory to increasing amounts of exogenous cholesterol up to 400 micrograms/ml. Therefore we conclude that only excessive doses of pravastatin suppress ACAT activity directly. In viable cells the observed inhibition of cholesteryl ester formation is due to the block in de novo synthesis of cholesterol, causing a lack of substrate for ACAT and of non-sterol products of mevalonic acid. Furthermore pravastatin interferes with the esterification and/or intracellular transport only of exogenous cholesterol, confirming former results of a compartmentalized cholesterol metabolism in the enterocyte.

Caco-2 Cells↗
PubMed1996

Reduction of bile secretion by prostaglandins in the rat in vivo.

Bile secretion has been reported to be regulated by circulating hormones and by autonomic liver nerves. In the in situ perfused rat liver, prostaglandins reduce bile flow and bile acid secretion. The aim of this study was to investigate the regulation of bile secretion by prostaglandins in the in vivo situation. The bile duct and portal vein of anaesthetised Wistar rats were cannulated by polyethylene tubes. Bile flow was determined gravimetrically. Bile acids were quantified by the 3-alpha-hydroxy-steroid-dehydrogenase method and by high-pressure-liquid-chromatography (HPLC) separation. Administration of 1 microM prostaglandin F2 alpha into the portal vein over 5 minutes reduced bile flow from 1.57 microliter/min.g liver to 0.95 microliter/min.g liver and bile acids secretion from 148 to 81 nmol/100g/min. The administration of different doses (0.1 microM, 1 microM, 10 microM) of prostaglandin F2 alpha reduced hepatic bile secretion in a dose-dependent manner. Similar effects were observed after infusion of prostaglandin D2. However, the ratio of the bile acids (alpha-tauromuricholic acid), beta-tauromuricholic acid, taurocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid) was unchanged by prostaglandin F2 alpha. In conclusion, infusion of prostaglandin F2 alpha into the portal vein results in a reduction of bile flow and bile acid secretion in a dose-dependent manner. These results suggest that the effect is linked to canicular bile secretion.

Animals↗
PubMed1996

Feedback regulation of bile acid synthesis measured by stable isotope kinetics in humans.

OBJECTIVE: To investigate the effect of a low dose of exogenous bile acids and a non-absorbable antibiotic on bile acid kinetics in healthy human subjects. METHODS: Pool size, synthesis rate and fractional turnover rate of the three main bile acids were determined simultaneously with stable isotope labelled bile acids in volunteers before and during intake of 500 mg cholic acid (n = 6), chenodeoxycholic acid (n = 6) or deoxycholic acid (n = 5) per day for 4 weeks or 1 g of paromomycin (n = 6) per day for 2 weeks. RESULTS: Administration of cholic acid nearly doubled the input and pool of deoxycholic acid; chenodeoxycholic acid synthesis was inhibited by 38% and pool size was reduced by 50%. Deoxycholic acid administration resulted in a suppression of both cholic acid and chenodeoxycholic acid synthesis by 53%; the corresponding pool sizes were reduced by 64% and 57%, respectively. The degree of suppression of chenodeoxycholic acid synthesis correlated significantly (P < 0.001) with the relative change of deoxycholic acid input and pool size. Oral chenodeoxycholic acid resulted in an inhibition of cholic acid synthesis (65%) and deoxycholic acid input (67%). The effects of the antibiotic were variable. CONCLUSION: The suppressive effect of cholic acid may be mediated by deoxycholic acid, which is nearly as effective as chenodeoxycholate.

Administration, Oral↗
PubMed1995

European trial of cyclosporine in chronic active Crohn's disease: a 12-month study. The European Study Group.

BACKGROUND & AIMS: The role of cyclosporine in Crohn's disease is controversial. This study aimed to delineate the long-term effect of cyclosporine in chronic active Crohn's disease. METHODS: One hundred eighty-two patients from 33 European centers were included. The patient cohort was stratified at entry into a stratum with low Crohn's Disease Activity Index (CDAI) ( < 200) and high CDAI ( > 200). The low-activity group continued to receive the pretrial steroid dose for 2 months, and the high-activity group received 1 mg.kg-1.day-1 prednisone initially. During months 3 and 4, the dose of steroids was reduced stepwise to 5 mg/day in all patients. Placebo and cyclosporine (5 mg.kg-1.day-1) were administered throughout the 12-month study period. The main parameter of efficacy was the CDAI, and the main end point was the number of patients in remission at month 12. RESULTS: During cyclosporine therapy, 35% (95% confidence interval [95% Cl], 25%-46%) of the patients achieved a full remission (CDAI, < 150) after 4 months compared with 27% (95% Cl, 18%-38%) in the placebo group (P > 0.05). At month 12, only 20% (95% Cl, 12%-31%) vs. 20% (95% Cl, 12%-31%) of the patients had maintained a continuous remission. No major differences between treatment groups were found within each of the two strata. CONCLUSIONS: The long-term treatment of chronic active Crohn's disease with cyclosporine plus low-dose steroids does not offer an advantage compared with low-dose steroids alone.

Adolescent↗
PubMed1995

Influence of cholesterol supply on cell growth and differentiation in cultured enterocytes (CaCo-2).

When used as treatment for hypercholesterolemia HMG-CoA reductase inhibitors will first pass through and act upon the gut mucosa. Although cholesterol availability is essential for cell growth of the intestinal mucosa adverse intestinal events are rare which is possibly due to hitherto undefined compensatory mechanisms. In the present work we therefore studied the long-term influence of mevinolin on proliferation and differentiation of CaCo-2 cells as an enterocyte model and their response upon the cholesterol supply of different origin. Mevinolin caused a marked and dose-dependent inhibition of cell proliferation, microvilli length and alkaline phosphatase. This parallel suppression was reversed by the addition of either exogenous free cholesterol, endogenous cholesterol from mevalonolactone or LDL but not HDL3. Surprisingly, sucrase activity reacted in an inverse fashion to alkaline phosphatase activity. Mevinolin induced enzyme activity and this was further enhanced by mevalonolactone supply, while cholesterol and LDL normalized sucrase to controls. In conclusion, the presence of luminal cholesterol as well as plasma LDL as the cholesterol source for the enterocyte may prevent mevinolin toxicity.

Alkaline Phosphatase↗
PubMed1995

[Endoscopic and surgical therapy of hemorrhagic duodenal and stomach ulcer].

The aim of this prospective clinical study was to evaluate whether a combination of the endoscopic hemostasis together with fibrin sealing and consecutive conservative therapy could reduce the frequency of recurrent bleedings, thus the number of operations without adversely influencing the prognosis of the disease. 134 patients admitted to the surgical and medical hospital of the University of Ulm between 1/1990 and 1/1992 with bleeding gastroduodenal ulcers took part in this study. All patients were treated endoscopically by hypertonic saline solution plus epinephrine and fibrin sealant. If initial endoscopic hemostasis was not achieved patients were operated within 6 h after admission. Patients with successful initial endoscopic hemostasis were treated conservatively and underwent control endoscopy after 24 and 48 h. In 23 patients the initial endoscopic hemostasis was not successful, they had to be operated immediately. In 111 patients endoscopic hemostasis was achieved, 20% of these patients had acute bleeding ulcers (Forrest Ia, b), 66% showed stigmata of fresh bleedings (Forrest-IIa bleeding). Primary endoscopic hemostasis was achieved in 85.6% of all patients treated, 14.4% of patients (n = 16) developed a recurrent bleeding during the observation period verified by gastroscopy. Half of these patients had an acute bleeding at the first gastroscopy (Forrest-Ia, Forrest-Ib bleeding). Recurrent bleeding became apparent between day 1 and 6 after admission to the hospital. Two patients refused surgical intervention, the other 14 were operated immediately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Deoxycholate and cholate modulate the source of cholesterol substrate for bile acid synthesis in the rat.

In the current study, the role of the supply of preformed and newly synthesized cholesterol for the feedback control of the synthesis of different bile acids and the secretion of biliary cholesterol was investigated. To define these cholesterol fluxes and the possibility of a different modulation by bile acids with different suppressive capacities, a continuous labeling with tritiated water was used in rats with an extracorporeal bile duct receiving intraduodenal infusions of taurocholate or taurocholate plus deoxycholate. After bile acid pool depletion (6 to 9 hours) total muricholate, cholate, and chenodeoxycholate synthesis was variably increased (24% to 93%) during an infusion of 304 mumol taurocholate/kg per hour. The increase in bile acid synthesis and biliary cholesterol output was predominantly due to the utilization of preformed (unlabeled) cholesterol. The addition of 52 mumol/kg per hour of deoxycholate to 258 mumol/kg per hour of taurocholate had a comparable effect. In the late period (30 to 54 hours), the taurocholate infusion had little impact on total muricholate and chenodeoxycholate synthesis but caused by a significant increase of the proportion from performed cholesterol. Both total cholate production and its synthesis from de novo (labeled) cholesterol was inhibited by 30% (P < .05) and 64% (P < .01), respectively. The secretion rate of total and de novo biliary cholesterol was higher (65% and 72%; P < .01) compared with controls. In comparison, the combined bile acid infusion led to a further increase of total muricholate synthesis (P < .05), which was again due to an enhanced synthesis from performed cholesterol (P < .001). Similar changes were observed in chenodeoxycholate. The more pronounced suppression of total cholate synthesis by 81% (P < .05) was due to a diminished cholate synthesis from both de novo cholesterol by 72% (P < .001) and preformed cholesterol by 91% (P > .05). We conclude that the modulation of the synthesis of the various primary bile acids in the rat differs and feedback regulation of cholate synthesis by taurocholate and deoxycholate is mediated by different mechanisms of control, including inhibition of cholesterol 7 alpha-hydroxylase, HMG-CoA reductase, and uptake of lipoprotein cholesterol.

Animals↗