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Biomedical subjects

O B Schaffalitzky de Muckadell

Publications and source records attributed to O B Schaffalitzky de Muckadell.

At least 19 recordsLinked to original sources
PubMed2004

Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: It seems rational to perform endoscopic retrograde cholangiopancreatography (ERCP) if the probability of endoscopic therapy is high, but to carry out magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) first if this probability is moderate or low. The aim of the present study was to develop a model describing the probability of endoscopic therapy in patients without previous biliary imaging. PATIENTS AND METHODS: The development of the model was based on stepwise multiple logistic regression applied to 2470 prospectively registered first-time ERCP procedures. The model was evaluated by application to 442 prospectively registered first-time ERCP procedures entered in the database in the following 2 years. RESULTS: Predictors selected were: age, gender, p-amylase >/= 400 U/l, ln(s-bilirubin), ln(s-alkaline phosphatase), common bile duct (CBD) stone seen on transabdominal ultrasonography, gallbladder stone seen on transabdominal ultrasonography, interaction of dilated bile ducts seen on transabdominal ultrasonography with ln(s-bilirubin), and interaction between age and male gender. The area under the receiver operating characteristic (ROC) curve was 0.875 and there was good fit of the model. A test with a probability cutoff value of 80 % had a positive predictive value (PPV) of 92.8 %. Specificity was 87.1 % and, using this test, 52.4 % of patients would have been selected for primary ERCP. In the application cohort, the frequency of therapy was higher than in the development cohort. The area under the ROC curve was 78.7 %. When used in the evaluation cohort, with a cutoff probability of 80 %, the test had sensitivity 84.0 %, specificity 49.5 %, negative predictive value (NPV) 46.6 % and PPV 85.6 %. Of the patients, 76.7 % would have been selected for ERCP. This would have identified 85.5 % of individuals needing therapeutic ERCP without use first of MRCP or EUS. Test-positive cases constituted 90.3 % of stent insertions and 86.3 % of stone extractions. CONCLUSIONS: The model is useful for selection of patients for ERCP at our center.

Adolescent↗
PubMed2004

Helicobacter pylori test and eradicate versus prompt endoscopy for management of dyspeptic patients: 6.7 year follow up of a randomised trial.

BACKGROUND: Dyspepsia is a chronic disease with significant impact on the use of health care resources. A management strategy based on Helicobacter pylori testing has been recommended but the long term effect is unknown. AIM: To investigate the long term effect of a test and treat strategy compared with prompt endoscopy for management of dyspeptic patients in primary care. PATIENTS: A total of 500 patients presenting in primary care with dyspepsia were randomised to management by H pylori testing plus eradication therapy (n = 250) or by endoscopy (n = 250). Results of 12 month follow up have previously been presented. METHODS: Symptoms, quality of life, and patient satisfaction were recorded during a three month period, a median 6.7 years after randomisation (range 6.1-7.3 years). Number of endoscopies, antisecretory medication, H pylori treatments, and hospital visits were recorded from health care databases for the entire follow up period. RESULTS: Median age was 45 years; 28% were H pylori infected. Use of resources was registered in all 500 patients (3084 person years) of whom 312 completed diaries. We found no difference in symptoms between the two groups. Median proportion of days without symptoms was 0.52 (interquartile range 0.10-0.88) in the test and eradicate group versus 0.64 (0.14-0.90) in the prompt endoscopy group (p = 0.27) (mean difference 0.05 (95% confidence interval (CI) -0.03 to 0.14)). Compared with the prompt endoscopy group, the test and eradicate group underwent fewer endoscopies (mean difference 0.62 endoscopies/person (95% CI 0.38-0.86)) and used less antisecretory medication (mean difference 102 defined daily doses/person (95% CI -1 to 205)). CONCLUSION: On a long term basis, a H pylori test and eradicate strategy is as efficient as prompt endoscopy for management of dyspeptic patients in primary care and reduces the use of endoscopy and antisecretory medication.

Adolescent↗
PubMed2002

The cystic fibrosis transmembrane conductance regulator is not a base transporter in isolated duodenal epithelial cells.

Duodenal epithelial bicarbonate secretion has previously been shown to be greatly impaired in mice deficient of the cystic fibrosis transmembrane conductance regulator (CFTR). It has been proposed that transmembranal bicarbonate transport occurs through the CFTR channel itself. In the present study, the transport of acid/base equivalents across the plasma membrane of proximal duodenal epithelial cells from CFTR deficient mice was compared with that of cells from normal littermates. Mixed epithelial cells from both villi and crypts were isolated from proximal duodenum and intracellular pH was assessed by cuvette-based fluorescence spectrometry using the pH sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. The steady state intracellular pH, the acid extrusion rate and the alkaline extrusion rate were unaffected by CFTR deficiency in the presence of CO(2)/HCO(-)(3). Forskolin had no effect on acid extrusion or alkaline extrusion rates. In control experiments without CO(2)/HCO(-)(3), the intrinsic buffering capacities, the steady state intracellular pH and the acid extrusion rates were equivalent in the cells from CFTR deficient mice and normal littermates. The results are consistent with a model where acid/base transport is almost exclusively mediated by the previously described transporters in the murine duodenum (i.e. Na+/H+ exchange, Cl(-)/HCO(-)(3). exchange and Na+:HCO(-)(3). cotransport). There were no evidence for significant CFTR dependent HCO(-)(3). transport in proximal duodenal epithelial cells of mixed villus and crypt origin.

Animals↗
PubMed2002

The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.

BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported. It is unclear whether the N34S mutation is a cause of pancreatitis per se, whether it modifies the disease, or whether it is a marker of the disease. PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by pancreatitis were tested: 152 from families with HP, 108 from families with ICP, and 67 with alcohol related CP (ACP). Seven patients with ICP had a family history of pancreatitis but no evidence of autosomal dominant disease (f-ICP) compared with 87 patients with true ICP (t-ICP). Two hundred controls were also tested for the N34S mutation. The findings were related to clinical outcome. RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency 1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in 4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls). The presence of the N34S mutation was not associated with early disease onset or disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S mutation in families with pancreatitis is unexplained and points to a complex association between N34S and another putative pancreatitis related gene.

Adult↗
PubMed2001

Outbreak of Hepatitis B among injecting drug users in Denmark.

BACKGROUND: The incidence of hepatitis B is low in Denmark, but injecting drug users (IDUs) remains a high-risk group for this infection. OBJECTIVES: The aim of the study was to describe a hepatitis B outbreak among IDUs by comparing existing registers. Additionally, we wanted to analyze the genetic variation of the hepatitis B virus involved in the outbreak. STUDY DESIGN: In the County of Funen, registers of laboratory diagnosis, hospital records and reports from clinicians to the Medical Officer of Health (MOH) were compared between 1992 and 1998. HBsAg positive sera recovered from the epidemic were sequenced and compared to known HBV strains. RESULTS: We identified 648 cases of hepatitis B of which 51% (332) were acute infections. The laboratory database identified 96% (319/332) of these, 45% (150/332) were admitted to hospital and 38% (127/332) were reported to public health. By capture-recapture analysis based on MOH reports and hospital records the estimated total number of acute cases were 334 (95% C.I. 283-385). We sequenced 75 HBsAg positive samples and identified two very similar strains of genotype D (serotype ayw3) among IDUs involved in the outbreak. CONCLUSIONS: The current surveillance system did not detect the majority of acute hepatitis B cases in County of Funen. We suggest laboratory-based surveillance of hepatitis B to be implemented at a national level as this may identify new outbreaks faster and more complete than the current surveillance system.

Denmark↗
PubMed2001

Secretin in plasma: ups and downs.

The establishment of a reliable radioimmunoassay for secretin in plasma enabled studies on the physiology of secretin. It was shown that secretin, i.e. the heptacosapeptide isolated by Jorpes and Mutt, is in fact responsible for the phenomena observed by Starling and Bayliss in 1902 when studying the stimulation of pancreatic bicarbonate secretion in response to duodenal acidification. Secretin is released in amounts considerably lower than anticipated, but these amounts are nevertheless sufficient to drive pancreatic and biliary secretion of bicarbonate. Whereas secretin in the fasting state is the most important stimulus to pancreatic secretion of water and bicarbonate, other hormones and nervous factors are essential for the majority of pancreatic postprandial secretion.

Animals↗
PubMed2001

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

Adult↗
PubMed2000

Helicobacter pylori test-and-eradicate versus prompt endoscopy for management of dyspeptic patients: a randomised trial.

BACKGROUND: Strategies based on screening for Helicobacter pylori to manage dyspeptic patients in primary care have been proposed, but the clinical consequences are unclear. We did a randomised trial to assess the efficacy and safety of a test-and-eradicate strategy compared with prompt endoscopy in the management of patients with dyspepsia. METHODS: 500 patients presenting in primary care with dyspepsia (> or = 2 weeks of epigastric pain, no alarm symptoms) were assigned H. pylori testing plus eradication therapy or endoscopy. Symptoms, quality of life, patients' satisfaction, and use of resources were recorded during 1 year of follow-up. FINDINGS: 250 patients were assigned test-and-eradicate, and 250 prompt endoscopy. The median age was 45 years and 28% were H. pylori infected. 1 year follow-up was completed by 447 patients. We found no differences in symptoms between the two groups (median registered days without dyspeptic symptoms=0.63 [IQR 0.27-0.81] in the test-and-eradicate group vs 0.67 [0.36-0.86] in the prompt endoscopy group; mean difference 0.04 [95% CI -0.01-0.10], p=0.12). Nor did we find any difference in quality of life or numbers of sick-leave days, visits to general practitioners, or hospital admissions. In the test-and-eradicate group, 27 (12%) of the patients were dissatisfied with management, compared with eight (4%) in the endoscopy group (p=0.013). After 1 year, the use of endoscopies in the test-and-eradicate group was 0.40 times (95% CI 0.31-0.51) the use in the endoscopy group, the use of H. pylori tests increased by a factor of 8.1 (5.7-13.1), the use of eradication treatments increased by a factor of 1.5 (0.9-2.7), and the use of proton-pump inhibitors was 0.89 (0.59-1.33) times the use in the endoscopy group. 43 (91% [80-98%]) of 47 peptic-ulcer patients would have been identified by endoscopy or treated by eradication therapy. INTERPRETATION: A H. pylori test-and-eradicate strategy is as efficient and safe as prompt endoscopy for management of dyspeptic patients in primary care, although fewer patients are satisfied with their treatment.

Adult↗
PubMed2000

[Diagnosis of Helicobacter pylori infections--how, when and in whom?].

Recognition of Helicobacter pylori (Hp) as the major cause of peptic ulcer disease has profoundly changed treatment and prognosis of this disease. The diagnostic tests are invasive (i.e. via the endoscopy) or non-invasive. The invasive tests are: urease test, histology, culture and PCR. Non invasive tests are: breath test, serology and Hp-antigens in faeces. The performance of the tests are almost similar. Sensitivities and specificities usually are > 90%, however the sensitivities and specificities of serological tests may be lower. Choice of diagnostic test depends on the clinical situation, sensitivity and specificity of test and the prevalence of Hp. Patients who should be examined for Hp: 1. The peptic ulcer patient who has used ASA/NSAID (urease test). 2. MALT-lymphoma, (histology). 3: The young (< 45 years) dyspeptic patient with no alarm symptoms and not taking NSAID/ASA (breath test). 4. Recurrence of upper dyspepsia after former eradication of Hp in peptic ulcer patients (if malignancy is not suspected breath test is first choice). 5. Verification of Hp eradication is necessary only in patients with MALT-lymphoma (histology) or patients with complicated peptic ulcer. Breath test will be the first choice in patients with complicated peptic ulcer when endoscopy is not performed. When endoscopy is performed, the urease test is the first choice. Diagnosis of Hp status not indicated: 1. There is no documentation that Hp eradication is of benefit in patients with non organic dyspepsia. Therefore, there is no indication for diagnosis of Hp. 2. Although there is some association between Hp positivity and chronic active gastritis and carcinoma of the stomach, there is at present no indication for diagnosis of Hp, as treatment of the infection has not proved effective in reversing atrophy or dysplasia. 3. The relationship between Hp and ASA/NSAIDs in peptic ulcer disease is far from clear. There is no indication for diagnosis and treatment of the infection prior to treatment with these medications. 4. For patients treated with longterm proton pump inhibitors there is no indication for diagnosis and treatment.

Adult↗
PubMed2000

Survival and incidence of colorectal cancer in patients with ulcerative colitis in Funen county diagnosed between 1973 and 1993.

BACKGROUND: The aim of the study was to determine the death rate and the risk of developing colorectal cancer in patients with ulcerative colitis in Funen County. METHODS: The medical records of 801 patients with ulcerative colitis diagnosed in 1973-93 in Funen County were scrutinized with regard to colectomy, survival, and colorectal cancer, and in 1998 a follow-up was carried out. RESULTS: The patients were managed at nine different hospitals: one university hospital, one central hospital, and seven smaller hospitals. The mean age at diagnosis was 41 years, and the mean duration of disease was 10.11 years. Sixty-one per cent of the patients were classified as having proctosigmoiditis, 21% as having left-sided colitis, and 18% as having pancolitis. In 127 patients who underwent proctocolectomy during the study period lethal complications occurred in 8 cases: 5 of 110 in Odense University hospital and 3 of 17 in the other hospitals. One hundred and twenty patients in the cohort died during the period of observation, nine of them of colitis-related causes. There was a slightly increased risk of early death in the cohort after 15 years of disease. Six colorectal cancers were found, whereas four were expected, giving a standard incidence ratio of 1.665. The cumulative cancer risk after 20 years' disease duration was 5.3% in the observed group, contrasting with an expected rate of 0.49%, and 10.1% after 25 years. CONCLUSION: In this cohort of ulcerative colitis patients the mortality and the risk of developing colorectal cancer were slightly higher than expected compared with the background population.

Adult↗
PubMed1998

[Choledocholithiasis. Endoscopic treatment of 416 consecutive patients].

Endoscopic extraction of calculi in the common bile duct has been the treatment of choice for many years. According to international standards a stone-free common bile duct should be achieved in at least 90% of the patients and with an overall complication rate below 20%. We reviewed records of 416 patients who underwent ERC for common bile duct stones between January 1990 and January 1995. The overall success rate of achieving a common bile duct free of stones was 89.0%, and in 94.7% of the patients endoscopic treatment was definitive. The overall complication rate was 9.6% and the 30-day mortality rate was 2.2%. Our study showed that with a medical staff of four to six persons (of which two were trainees), approximately 450 ERCP-examinations per year and with a catchment area of half a million inhabitants (Funen County), it was possible to achieve acceptable results.

Adult↗
PubMed1998

Randomized trial of stent placed above and across the sphincter of Oddi in malignant bile duct obstruction.

BACKGROUND: Placement of stents above an intact sphincter of Oddi might prevent migration of bacteria and deposition of organic material into the stent. In patients with malignant obstructive jaundice prolongation of function time of the stent would be expected if it is placed above the sphincter of Oddi. METHODS: Thirty-four patients were randomized to stent placement either above (n = 17) or across (n = 17) the sphincter of Oddi. Straight 10F gauge Teflon stents were used. The patients were evaluated clinically and biochemically at monthly intervals during follow-up. RESULTS: The median stent function time (i.e., the time from insertion of the stent until stent replacement, patient death, or study termination) were 110 days (25th to 75th percentiles, 61 to 320 days) for stents placed above the sphincter of Oddi and 126 days (25th to 75th percentiles, 89 to 175 days) for stents placed across the sphincter of Oddi (nonsignificant [NS]). Stent replacement rates were 58.8% (10 of 17) in patients with stents placed above the sphincter and 29.4% (5 of 17) in patients with stents placed across the sphincter (NS). Significantly more patients in the former group experienced stent migration (9 vs. 2, p = 0.026). The median time from stent insertion until replacement of the stents placed above and across the sphincter of Oddi were 82 days (25th to 75th percentiles, 31 to 185 days) and 89 days (25th to 75th percentiles, 13 to 150 days), respectively (NS). CONCLUSIONS: No significant difference in overall stent performance between the two groups was found, although more stents placed above the sphincter of Oddi migrated. The time until dysfunction of the stent might be increased if migration of stents placed inside the common bile duct could be avoided.

Aged↗
PubMed1998

Regulation of porcine biliary secretion by secretin.

The importance of physiological plasma levels of secretin in biliary bicarbonate secretion is not known. However, in anaesthetized pigs the substantial hepatic output of bicarbonate into the duodenum in response to low doses of secretin exceeds pancreatic bicarbonate output. The aim was therefore to study the relationship between duodenal acidification, secretin and hepatic biliary bicarbonate output in the conscious pig. Göttingen minipigs (n = 22) were cholecystectomized and the common bile duct catheterized. The biliary bicarbonate secretion in response to intraduodenal HCl, secretin or pentagastrin given intravenously, and to meal was studied. Intraduodenal HCl infusion, secretin and pentagastrin given intravenously augmented hepatic bicarbonate output and plasma secretin concentrations significantly. The secretin response to acidification was sufficient to explain the subsequent increase in biliary bicarbonate secretion. Hepatic bicarbonate secretion and concentrations of CCK and secretin in plasma increased postprandially. Exclusion of bile salts from the duodenum abolished postprandial increase in bile volume and increased release of CCK in fasting and fed pigs whereas secretin release was diminished. The results demonstrate that hepatic bicarbonate secretion is stimulated by endogenous secretin and therefore may have a physiological role in duodenal neutralization.

Animals↗
PubMed1998

Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease.

BACKGROUND: Activation of coagulation and fibrinolysis occurs in patients with inflammatory bowel disease. Our aim was to study the course of a marker for activation of the coagulation cascade, prothrombin fragment 1 + 2 (F1+2), and fibrinolysis, fibrin degradation products (FbDP), in patients with ulcerative colitis and Crohn's disease before and during therapy with glucocorticoids. METHODS: Twenty-seven patients with active ulcerative colitis and 42 with active Crohn's disease treated with glucocorticoids were studied. Plasma samples were drawn before, during, and at end of therapy or at time of treatment failure. F1+2 and FbDP were measured with commercially available enzyme immunoassays. RESULTS: Mean base-line concentrations of F1+2 were significantly increased in patients with ulcerative colitis (4.77 +/- 0.50 nmol/l; P < 0.0001) and in Crohn's disease (4.66 +/- 0.59 nmol/l; P < 0.0001) compared with healthy controls (1.57 +/- 0.09 nmol/l). Mean base-line concentrations of FbDP were significantly increased in patients with ulcerative colitis (1264 +/- 161 microg FE/l; P < 0.0001) and in Crohn's disease (491 +/- 51 microg FE/l; P < 0.0001) compared with healthy controls (194 +/- 21 microg FE/l). During treatment with glucocorticoids the plasma concentrations of FbDP decreased in patients with Crohn's disease achieving remission and in patients with ulcerative colitis avoiding surgery but remained unchanged in patients not responding to therapy. In contrast, F1+2 remained increased in patients with Crohn's disease and ulcerative colitis irrespective of outcome. CONCLUSION: The present data support the concept that coagulation cascade and fibrinolysis is activated in patients with active inflammatory bowel disease. F1+2 and FbDP correlate poorly with the clinical disease activity and acute-phase reactants. The clinical response to treatment with glucocorticoids is accompanied by a decrease in plasma concentrations of FbDP but not in F1+2. FbDP may emerge as a new marker in the assessment of disease activity in patients with inflammatory bowel disease.

Adult↗