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Biomedical subjects

E F Stange

Publications and source records attributed to E F Stange.

At least 73 records · Page 4Linked to original sources
PubMed2000

The pancreas and inflammatory bowel diseases.

This article reviews the literature and gives an overview on prevalence and possible explanations for pancreatic involvement in inflammatory bowel diseases (IBD). IBD patients have a markedly elevated risk for developing acute pancreatitis as well as pancreatic insufficiency. Multiple potential causes for pancreatitis in IBD patients exist. In the majority of cases acute pancreatitis appears to be related to drug side effects or local structural complications rather than a true extraintestinal manifestation of IBD. Nevertheless, some cases of acute pancreatitis remain unexplained. Prevalence of chronic pancreatitis in IBD patients also seems to be relatively high. However, etiology of pancreatic duct changes and/or the occurrence of exocrine insufficiency remain unclear. In most cases chronic pancreatitis is clinically unapparent, although in some patients it may be accompanied by clinically relevant exocrine insufficiency.

Acute Disease↗
PubMed1999

[Consequences of galenic differences and outcome of clinical trials with budesonide and 5-aminosalicylic acids for therapy of Crohn disease].

Budesonide in both galenic forms is suitable for the treatment of a flare of Crohn's disease of up to moderate activity. The same holds true for 5-amino-salicylates, although they are less effective. Topical steroids delay but do not prevent relapses. Aminosalicylates may be used in the postoperative situation for prevention of relapse but are not significantly effective after drug-induced remission.

Anti-Inflammatory Agents↗
PubMed1999

The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to suppress biliary cholesterol secretion and saturation. It remains unproven whether this is mediated by inhibition of cholesterol synthesis. Therefore, the effect of a long-term administration of pravastatin on cholesterogenesis and on biliary lipid secretion was investigated in seven healthy volunteers. Placebo or 40 mg of pravastatin were taken daily at bedtime for 5 weeks using a double-blind crossover design. During the last week, 12 hours after the last drug intake 0.04 mmol [1-13C]acetate/kg. h and 0.5 g polyethylene glycol 4,000/h were infused intraduodenally for 15 hours. Plasma and duodenal bile samples were collected hourly. Thereafter, the decay of [13C]labeled plasma cholesterol was measured during the following 3 days. The fractional and absolute syntheses of plasma and biliary cholesterol were determined by gas chromatography mass spectrometry using mass isotopomer distribution analysis. At the end of the pravastatin period plasma total and low-density lipoprotein (LDL) cholesterol had decreased by 20% and 24%, respectively. Similarly, pravastatin suppressed biliary secretion rates of cholesterol, total bile acids and phospholipids (P <.05) by 46%, 36%, and 51%. As a consequence, cholesterol saturation index remained unchanged. However, fractional syntheses of cholesterol were comparable (P >.05) on placebo compared with pravastatin with 3.1% versus 4.0% in plasma and 4.3% versus 5.2% in bile after 15 hours, respectively. The mean absolute synthesis rates amounted to 0.3 mg/kg/h on placebo versus 0.4 on pravastatin (P >. 05). In conclusion, the pravastatin-induced reduction of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis.

Acetates↗
PubMed1999

Complex feedback regulation of bile acid synthesis in the hamster: the role of newly synthesized cholesterol.

Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol. After interruption of the enterohepatic circulation, physiological and double-physiological doses of conjugated cholate (25 or 50 micromol/100 g. h) or of unconjugated deoxycholate (6 or 12 micromol) were infused intraduodenally for 54 hours and compared with controls. De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation. Directly after depletion of the bile acid pool (6-9 hours) at nearly physiological conditions, chenodeoxycholate synthesis was significantly reduced by cholate and deoxycholate by up to 45% to 51%, whereas cholate formation decreased by approximately 22% during deoxycholate. This short-term effect was mainly mediated by reduced synthesis from preformed cholesterol. After long-term bile depletion (30-54 hours), bile acid synthesis returned to control levels during 25 micromol of cholate and of both deoxycholate doses. In contrast, only 50 micromol of cholate prevented derepression of bile acid synthesis. This long-term effect was mainly attributed to a diminished formation from de novo cholesterol exceeding the reduced synthesis from preformed cholesterol. In summary, short- and long-term regulation of bile acid synthesis in hamsters differs with respect to availabilities of preformed and de novo cholesterol.

Amino Acids↗
PubMed1999

Enhanced intestinal expression of heat shock protein 70 in patients with inflammatory bowel diseases.

Heat shock protein (Hsp) 70 is stress-inducible and exhibits both protective and antigenic properties. This study investigated the mucosal expression of the constitutive (Hsp70c) and inducible form (Hsp70i) as well as antibodies against human Hsp70 in inflammatory bowel disease and controls. Biopsies were assessed by immunoblot and immunofluorescence, resection specimens by immunohistochemistry, and mucosal antibody content by isoelectric focusing. Compared to controls, expression of Hsp70 was enhanced in ulcerative colitis (P<0.05), less so in Crohn's disease and infectious colitis. Strong epithelial staining was found for Hsp70c and Hsp70i in both diseases. Mucosal and submucosal mononuclear cells showed enhanced Hsp70c expression in Crohn's disease and to a lesser degree in ulcerative colitis. Antibodies of isotypes A or M were detected in nearly all patients and controls. The different pattern of Hsp70 expression in Crohn's disease compared to ulcerative colitis points to a distinct protective and immunological function, whereas a role in autoimmunity seems unlikely.

Adult↗
PubMed1999

Long-term haemodynamic effects of octreotide on postprandial splanchnic hyperemia in humans: a placebo-controlled echo-doppler study.

BACKGROUND: Octreotide is a potent splanchnic hypotensive somatostatin analogue effective in the treatment of acute variceal bleeding. AIM: To study the effects of octreotide on basal and postprandial splanchnic and systemic haemodynamics, and hormonal changes in humans. METHODS: Twenty-four healthy volunteers were randomized to receive a liquid meal and either octreotide (OCT, 100 microg bolus) or placebo repeatedly every 4 h for 48 h. Splanchnic (Doppler ultrasound) and systemic haemodynamics (non-invasive cardiac monitoring) were assessed for 2 h on four consecutive days: one control day and after doses 1 (0 h), 7 (24 h) and 13 (48 h). RESULTS: The maximum postprandial increases in mean blood velocity of the superior mesenteric artery (SMA-Vmean +72%), portal (PBF +52%) and total hepatic blood flow (HBF +50%) observed in the placebo group, were abolished after the first dose of octreotide (SMA-Vmean -23%, P<0.01; PBF -22%, P<0.01; HBF -21%, P<0.01). Postprandial hyperemia was restored at the end of the 48-h study period, but baseline SMA-Vmean (placebo 40+/-12, OCT 29+/-11 cm/s, P<0.05) and PBF (placebo 1200+/-971, OCT 743+/-449 mL/min, P<0.05) remained significantly lower in the octreotide group. The postprandial decrease of systemic vascular resistance and increase of cardiac index were prevented by octreotide for 48 h. CONCLUSIONS: Repeated 4-hourly bolus injections of octreotide reduce splanchnic blood flow for at least 48 h, but the prevention of food-induced splanchnic hyperemia is short-lasting.

Adult↗
PubMed1999

Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.

Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.

Adolescent↗
PubMed1999

Mucosal cytokine expression, cellular markers and adhesion molecules in inflammatory bowel disease.

OBJECTIVE: To relate proinflammatory cytokines to leukocyte surface markers and adhesion molecules in the same paraffin-embedded biopsy specimen in inflammatory bowel disease (IBD) of varying activity. METHODS: Biopsies of seven cases of Crohn's disease, seven patients with ulcerative colitis, one case of intestinal infection and six control subjects were studied. We performed in situ hybridization on sections of tissue using probes specific to interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF alpha). Leucocyte markers and adhesion molecules were investigated in subsequent slides of selected specimens by immunohistochemistry. RESULTS: Cytokine mRNA was found in large numbers of cells throughout the inflamed intestine but also in some macroscopically unaffected tissue specimens. Transcripts were predominantly located within the lamina propria where immunohistochemistry of parallel sections revealed numerous macrophages and the presence of endothelial adhesion molecules. The expression of the different cytokines was closely related to each other and to histological but not to macroscopic (endoscopic) activity. CONCLUSIONS: The synthesis of IL-1beta IL-6 and TNF alpha mRNA is coordinately regulated. Cytokine production is located mostly in the lamina propria at sites that are rich in macrophages and show abundant staining of vascular adhesion molecules. This cascade of immune events is related to inflammatory cell infiltration in both Crohn's disease and ulcerative colitis.

Adult↗
PubMed1999

Mesenteric blood flow is related to disease activity and risk of relapse in Crohn's disease: a prospective follow-up study.

OBJECTIVE: The diagnostic significance of increased splanchnic blood flow in Crohn's disease is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. METHODS: Splanchnic flowmetry was performed in 59 patients with Crohn's disease and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Twenty-one patients measured during the active state and in clinical remission were followed-up for 6 months. Hemodynamic parameters of the superior and inferior mesenteric arteries and the portal vein were related to clinical (Crohn's disease activity index [CDAI]), laboratory (C-reactive protein), and endoscopic (Crohn's Disease Endoscopic Index of Severity) parameters of disease activity. RESULTS: The postprandial mean velocity of the superior mesenteric artery correlated closest with clinical activity (CDAI, p < 0.005) and C-reactive protein (p < 0.01), but was unrelated to endoscopic activity. All patients in remission after 6 months (9/9) showed an increase in postprandial pulsatility index of the superior mesenteric artery, compared with an initial measurement during active disease (+28%). In contrast, the majority of patients with later relapse or surgery (11/12) had decreased pulsatility index during initial remission (-20%). The positive predictive value of this index for maintenance of remission was 0.82. CONCLUSIONS: Postprandial flow measurements in the superior mesenteric artery are closely related to clinical but not endoscopic disease activity in patients with Crohn's disease. The repeated measurement of the postprandial pulsatility index allows estimation of the risk of recurrence.

Adult↗
PubMed1999

Mesenteric blood flow is related to disease activity and risk of relapse in ulcerative colitis: a prospective follow up study.

BACKGROUND: The diagnostic significance of increased splanchnic blood flow in ulcerative colitis is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. SUBJECTS/METHODS: Splanchnic flowmetry was performed in 76 patients with ulcerative colitis (47 with active disease and 29 in remission), six with infectious colitis, and 13 healthy controls during fasting and 30 minutes after ingestion of a standardised meal. Twenty seven of the patients with ulcerative colitis and all patients with infectious colitis were investigated during the active state as well as in clinical remission and followed up for six months. Flow velocity and pulsatility index (PI) of the superior (SMA) and inferior (IMA) mesenteric arteries and the portal vein were related to clinical (Truelove index), laboratory (C-reactive protein), and endoscopic (Sutherland index) parameters of disease activity. RESULTS: The mean flow velocity of the IMA correlated closest with clinical activity (Truelove, r = 0.41, p<0.005), the PI with C-reactive protein (r = 0.30, p<0.05), and endoscopic activity (r = 0.45, p<0.001). All patients in remission after six months (14/14) or with infectious colitis (6/6) showed an increase in PI of the IMA compared with the initial measurement during active disease (mean increase for ulcerative colitis +36% and for infectious colitis +77%). In contrast, most patients with later relapse or surgery (11/13) had decreased PI during initial remission (mean decrease -12%). The positive predictive value of this index for maintenance of remission was 0.77. Flow variables of the SMA and portal vein displayed weaker correlations. CONCLUSIONS: Flow measurements in the IMA are closely related to clinical and endoscopic disease activity in patients with ulcerative colitis. Repeated measurement of the PI allows estimation of the risk of recurrence.

Adolescent↗
PubMed1999

[Evidence-based medicine: context and relevance].

Currently, evidence-based medicine is subject of a controversial discussion. This review is focused on the different types of evidence in clinical medicine and elaborates the history and context of evidence-based medicine. Evidence-based medicine insists that the theoretical plausibility of a therapeutical concept alone does not substitute for the empirical proof of its efficacy. Evidence-based medicine emphasizes the necessity to complement the individual physician's clinical experience with valid external evidence. This evidence has to be obtained by laborious systematic reviews rather than the traditional fragmentary study of the literature. The Cochrane Collaboration stands for this concept. The application of evidence-based medicine links the individual patient's problems with external evidence by asking defined answerable questions and supplies criteria for the critical evaluation of the evidence found. Evidence-based medicine, however, is not devoid of problems and contradictions. Above all, it has to be subjected to its own criteria and has to prove its efficacy.

Evaluation Studies as Topic↗
PubMed1999

[Glucocorticoid-induced diabetes mellitus in gastrointestinal diseases].

Glucocorticoid excess causes insulin resistance i.e. a reduced effectiveness of insulin to suppress hepatic glucose production and to increase glucose uptake in muscle and fat tissue. Persons who cannot compensate for the resulting additional insulin need develop overt diabetes during glucocorticoid therapy. In the field of gastroenterology, glucocorticoids are mainly employed for the therapy of chronic inflammatory bowel diseases, alcoholic and autoimmune hepatitis, and after liver transplantation. The risk of developing steroid diabetes depends among other things on the genetic predisposition, the body composition, the underlying gastrointestinal disease, the age, and the steroid dose. The treatment of glucocorticoid-induced diabetes resembles essentially the treatment of type 2-diabetes. In addition to dietary measures, oral antihypoglycemic drugs and/or insulin are applied. If oral antihypoglycemic drugs are used, specific problems that might result from the gastrointestinal diseases need to be observed. In the short and medium term, the prognosis of glucocorticoid-induced diabetes is good since it is well treatable. If glucocorticoid treatment is continued for a long time, the alterations of glucose metabolism and the resulting hyperinsulinemia may lead to increased cardiovascular risk.

Adolescent↗
PubMed1999

[Motility diagnosis in chronic constipation].

Scintigraphy is generally considered as gold-standard for the diagnosis of delayed gastric emptying. The 13C-acetate and -octanoate breath tests represent an alternative to this method, which has been extensively validated. Gastric and small bowel manometry are very important tools for the research of motility disorders. In clinical practice, this method has only few indications. Sonographic measurement of gastric emptying is a useful procedure for the diagnosis of delayed gastric emptying, provided that the investigation is done by an experienced person. It is not clear so far, whether MRI is an alternative to the methods mentioned above. If delayed gastric emptying is excluded, the H2-lactulose breath test is a simple screening test for the disorders of small bowel transit. Colonic transit time can reliably be measured with radiopaque markers. Anorectal disorders are diagnosed by manometry and defecography. MRI-defecography gives additional information compared to the conventional defecography. These methods have an important role in the evaluation of chronic constipation. The rational combination of the displayed methods is the most appropriate way to approach the patients' problems.

Chronic Disease↗
PubMed1999

Efficacy of azathioprine in the treatment of chronic active Crohn's disease: prospective one-year follow-up study. German Imurek Study Group.

Azathioprine has been found effective in chronic active Crohn's disease. The aim of this open uncontrolled trial was an efficacy analysis in hospitals and private practices versus results of controlled trials. 89 patients with active Crohn's disease (CDAI > 150) were included in a multicenter trial of azathioprine therapy during one year. Follow-up evaluations were scheduled at three, six and twelve months and included self-assessment as well as physicians assessment of disease activity using CDAI and laboratory parameters. 65 patients (73%) completed the study per protocol until twelve months. At the end of the trial 75% of patients were in remission (CDAI < 150), 22% were ameliorated and two patients (3%) deteriorated. Corticosteroid dose was dropped from 0.46 mg/kg bw to 0.18 mg/kg bw during the study. Adverse events, primarily allergy, nausea and hyperlipasemia were frequent (21%), but only two patients had to be withdrawn from the trial. Everyday use of azathioprine for the treatment of chronic active Crohn's disease in hospital and private practice is equally effective compared to results of previous controlled trials. High doses of steroids at the beginning of azathioprine therapy may be associated with higher remission rates at one year.

Adolescent↗
PubMed1998

The postprandial portal flow is related to the severity of portal hypertension and liver cirrhosis.

BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis. METHODS: Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is inversely related to the severity of portal hypertension and liver cirrhosis, and may be a valuable parameter with respect to the risk of variceal bleeding.

Adult↗
PubMed1998

Intestinal expression of human heat shock protein 90 in patients with Crohn's disease and ulcerative colitis.

Heat shock proteins are induced by several stress factors and are potential antigens in autoimmune disorders. Expression of heat shock protein 90 (HSP 90) was investigated in patients with inflammatory bowel disease and normal controls. We combined western blot analysis with laser densitometry for quantitation. Localization of HSP 90 was investigated by immunohistochemistry. Western blots showed a significant mucosal expression of HSP 90, which was comparable in patients and controls. There was also no difference between normal and inflamed mucosa in inflammatory bowel disease. In immunohistochemical staining studies, HSP 90 was detected in epithelial cells, mononuclear cells, giant cells, nerve cells, and endothelial cells of small vessels. There was no difference in the intensity of staining or localization in patients with inflammatory bowel disease compared to controls. These findings render a potential protective or immunogenic function of HSP 90 in inflammatory bowel disease unlikely.

Adult↗
PubMed1998

Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506).

OBJECTIVE: Steroid treatment failure in acute Crohn's disease and ulcerative colitis frequently necessitates surgical intervention. Several alternative therapeutic strategies have been raised. The most promising so far has been intravenous cyclosporine, but the results in the long term have been discouraging. We assessed the efficacy and safety of the new macrolide immunomodulator tacrolimus as an alternative to cyclosporine A. METHODS: Eleven patients with steroid-refractory disease (six ulcerative colitis, two indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity according to the Truelove and Witts criteria or Crohn's disease activity index > 150, respectively, were eligible for the study. All patients were treated with intravenous tacrolimus for 7-10 days followed by oral treatment over a median period of 7 months (range 0.25-16). Azathioprine and mesalamine were given concomitantly. Steroids were tapered according to clinical activity. RESULTS: Seven of 11 patients achieved remission rapidly, whereas a modest improvement was noted in two. Only two patients required an early and one a delayed colectomy. Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an improvement of pouchitis was observed. A tapering to low dose steroids was possible during oral tacrolimus therapy in all nine responders and remission was maintained in five of them (mean follow-up 9.2 months). The drug was well tolerated and side effects were managed conservatively. CONCLUSION: Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.

Adolescent↗