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Biomedical subjects

P S Teglbjaerg

Publications and source records attributed to P S Teglbjaerg.

At least 19 recordsLinked to original sources

Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis.

BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. AIMS: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. PATIENTS: Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.

Adult↗

Medical risk factors for small-bowel adenocarcinoma with focus on Crohn disease: a European population-based case-control study.

BACKGROUND: Crohn disease and biliary diseases have been associated with small-bowel adenocarcinoma (SBA). We examined how medical conditions affect the risk of SBA. METHODS: A population-based European multicentre case-control study during the period 1995-97 including 95 histologically verified cases of SBA along with 3335 population controls; 70 cases (74%) and 2070 (62%) controls were interviewed about previous medical conditions. RESULTS: Crohn disease was identified in two SBA cases (both located in ileum) and two controls; odds ratio (OR) 53.6 (6.0-477) (95% CI in parentheses). Only one case and no controls had had long-standing Crohn disease. Coeliac disease was associated with SBA (2 cases, 0 controls), but one of the cases was diagnosed at the same time as the SBA. Overall, people with a history of gallstones had no increased risk of SBA. The OR was exclusively increased during the 3-year period preceding the SBA diagnosis. Previous gallstone surgery, which may be a sign of severe gallstone disease, was not associated with SBA. Liver cirrhosis, hepatitis or medical treatments with radioactive substances or corticosteroid tablets were not associated with this disease. Cases with SBA had an increased prevalence of anaemia; OR 15.3 (2.5-92.1). An association between low educational level and SBA was found; OR 1.75 (1.0-3.0). CONCLUSION: This study supports Crohn disease and coeliac disease being strong but rare risk factors for SBA. Previous gallstones were unrelated to SBA, and detection bias may account for the findings in earlier studies.

Adenocarcinoma↗

Helicobacter pylori-negative duodenal ulcers: prevalence, clinical characteristics, and prognosis--results from a randomized trial with 2-year follow-up.

OBJECTIVE: The proportion of Helicobacter pylori-negative duodenal ulcer disease appears to be increasing. Data on clinical outcome and prognosis in this subgroup are lacking. METHODS: Two hundred seventy-six duodenal ulcer patients randomized, irrespective of H. pylori status, to either eradication therapy or maintenance omeprazole (double-blind, double-dummy design) for 1 yr were studied. Patients were followed up for a total of 2 yr, with visits performed every 2 months the first year and every 6 months the following year. Endoscopies for assessment of ulcer relapse were done at 6 and 12 months or in the event of symptomatic relapse. H. pylori status was assessed by culture, immunohistochemistry, and urea breath test at entry, at 6, 12, and 24 months or at failure. The primary endpoint was discontinuation, irrespective of reason. Patients were considered H. pylori negative if all three tests were negative. Patients were considered H. pylori-positive if any of the three diagnostic tests were positive. Study staff were blinded to H. pylori results. RESULTS: Thirty-two (12%) patients were H. pylori negative at entry. There were no differences according to H. pylori status for a number of clinical and demographic characteristics. However, H. pylori-negative patients had a shorter history of ulcer symptoms and were more likely to be NSAID users (19% vs 1%, p < 0.001). Only 28% of the H. pylori-negative patients completed the study, as compared with 40% of H. pylori-positive patients (p = 0.0005). The main reasons for the poorer prognosis in H. pylori-negative patients were relapse of ulcer/ulcer not healed (35% vs 26%) and relapse of severe dyspepsia symptoms without ulcer relapse (16% vs 7%). H. pylori-negative patients randomized to eradication therapy left the study early compared with H. pylori-negative patients randomized to long-term omeprazole therapy. Outcome in omeprazole-treated patients did not differ according to H. pylori status (p = 0.3). CONCLUSIONS: Clinical characteristics in H. pylori-negative and positive duodenal ulcer patients differ little. Clinical outcome over 2 yr is significantly poorer in H. pylori-negative patients, especially if treated empirically with eradication therapy. These results suggest that H. pylori infection should be assessed in all duodenal ulcer patients before treatment is decided.

Adult↗

Diagnostic examination of human intestinal spirochetosis by fluorescent in situ hybridization for Brachyspira aalborgi, Brachyspira pilosicoli, and other species of the genus Brachyspira (Serpulina).

Human intestinal spirochetosis, characterized by end-on attachment of densely packed spirochetes to the epithelial surface of the large intestines as a fringe has been associated with the weakly beta-hemolytic spirochetes Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli. In this study, fluorescent in situ hybridization with oligonucleotide probes targeting 16S or 23S rRNA of B. aalborgi, B. pilosicoli, and the genus Brachyspira was applied to 40 sections of formalin-fixed, paraffin-embedded intestinal biopsy specimens from 23 Danish and 15 Norwegian patients with histologic evidence of intestinal spirochetosis. Five biopsy specimens from patients without intestinal spirochetosis and three samples from pigs with experimental B. pilosicoli colitis were examined as well. In addition, the 16S ribosomal DNAs of two clinical isolates of B. aalborgi were sequenced, and a PCR procedure was developed for the identification of B. aalborgi in cultures. The genotypic characteristics of the two clinical isolates showed very high (99.5%) similarity with two existing isolates, the type strain of B. aalborgi and a Swedish isolate. Hybridization with the Brachyspira genus-specific probe revealed a brightly fluorescing fringe of spirochetes on the epithelia of 39 biopsy specimens, whereas 1 biopsy specimen was hybridization negative. The spirochetes in biopsy specimens from 13 Danish and 8 Norwegian patients (55.3%) were identified as B. aalborgi. The spirochetes in the biopsy specimens from the other 17 patients hybridized only with the Brachyspira probe, possibly demonstrating the involvement of as-yet-uncharacterized Brachyspira spirochetes in human intestinal spirochetosis.

Adolescent↗

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case-control study.

OBJECTIVE: To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). METHODS: A population-based European multi-center case-control study was conducted from 1995 to 1997. RESULTS: After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5-8.0 and 3.4 (95% CI 1.3-9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. CONCLUSIONS: A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.

Adenocarcinoma↗

Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

BACKGROUND: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. METHODS: Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. RESULTS: Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. CONCLUSIONS: Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.

Amoxicillin↗

Occupation and small bowel adenocarcinoma: a European case-control study.

OBJECTIVES: Because of the rarity of small bowel adenocarcinoma (SBA), little is known about the aetiology of this disease. This study aimed to identify occupational clustering of cases SBA as a systematic approach to new hypotheses on the aetiology of this disease. METHODS: A European multicentre case-control study was conducted in 1995-7, inclusive. Incident cases aged 35-69 years with SBA (n=168) were recruited before acceptance by a pathologist. Altogether 107 cases and 3915 controls were accepted, of which 79 cases, 579 colon cancer controls, and 2070 population controls were interviewed. RESULTS: The strongest industrial risk factors for SBA taking account of 10 years' exposure lag were dry cleaning, manufacture of workwear, mixed farming (women), and manufacture of motor vehicles (men). A significantly increased risk of SBA (odds ratio (OR) and 95% confidence interval (95% CI)) was found among men employed as building caretakers, OR 6.7 (1.7 to 26.0) and women employed as housekeepers, OR 2.2 (1.1 to 4.9); general farm labourers, OR 4.7 (1.8 to 12.2); dockers, OR 2.9 (1.0 to 8.2); dry cleaners or launderers, OR 4.1 (1.2 to 13.6); and textile workers (sewers or embroiderers), OR 2.6 (1.0 to 6.8). For the last four groups, together with welders OR 2.7 (1.1 to 6.6) (men) an exposure-response pattern was found when calculating the ORs for jobs held 1-5 years and >5 years, with never having held the job as reference. The ORs (95% CIs) for 1-5 years and >5 years were 4.3 (0.4 to 44.0) and 3.5 (0.9 to 13.7), 3.0 (0.3 to 26.2) and 4.3 (0.9 to 21.2), 4.6 (0.4 to 48.1) and 11.0 (2.0 to 60.4), 1.3 (0.2 to 11.0) and 5.8 (2.0 to 17.2), and 2.8 (0.3 to 23.8) and 4.6 (1.3 to 16.6), respectively, for each of these occupations. Among welders, people performing semiautomatic arc welding (MIG/MAG) were identified as a high risk group (OR 5.0 (1.3 to 19.6)). CONCLUSIONS: This explorative study suggests an increased occurrence of SBA in certain occupations, which needs further evaluation.

Adenocarcinoma↗

Collagenous colitis: a long-term follow-up study.

OBJECTIVE: Collagenous colitis was first described in 1976. It is a rare disorder and the long-term course and prognosis of the disease are unknown. The aim of this study was to evaluate the course of the disease more than 5 years after the diagnosis. DESIGN: A retrospective follow-up of patients with collagenous colitis diagnosed during the period 1979-1990. METHODS: All examinations performed at the time of diagnosis were reviewed and the clinical courses of the patients were determined by evaluation of the medical records. At a follow-up visit in 1996 complete histories were obtained and conventional laboratory tests were performed. RESULTS: Two men and 22 women aged 20-82 years with collagenous colitis were identified. At the time of diagnosis, extensive investigation did not reveal other gastrointestinal diseases. At the time of follow-up, six patients had died from diseases unrelated to collagenous colitis, 10 patients suffered from chronic or intermittent diarrhoea, and four patients had been without gastrointestinal symptoms for the last 2-10 years. None of the patients developed colorectal cancer or chronic inflammatory bowel disease. Four patients were lost to follow-up. CONCLUSION: Collagenous colitis is a benign disease, most often with a chronic course. No association with other gastrointestinal diseases was found.

Adult↗

Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas.

BACKGROUND & AIMS: Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgenic mice overexpressing TGF-alpha develop tissue changes in the pancrease resembling changes found in chronic pancreatitis. The effects of systemic treatment with EGF on the porcine pancrease were investigated in this study. METHODS: Mature Goettingen minipigs were treated with solvent (n = 5), EGF (30 micrograms.kg-1.day-1; n = 6) for 4 weeks, or EGF (30 micrograms.kg-1.day-1; n = 5) for 5 weeks followed by 3 weeks of recovery. Pancreata were studied by routine histological examination and electron microscopy and were immunostained for proliferating cell nuclear antigen (PCNA). RESULTS: In the EGF-treated animals, mainly larger interlobular ducts of the pancreas appeared to be considerably hyperplastic, with an increased number of nuclei that stained for PCNA. The epithelia of these ducts were increased in height, with accumulations of glycoconjugates in the columnar cells and in an increased number of goblet cells. CONCLUSIONS: A new approach to experimentally induced hyperplastic changes of the excretory ducts of the pancreas is presented. Because ductal changes with glycoconjugate accumulations are common features of chronic pancreatitis and pancreatic cancer, the findings may be relevant to the pathogeneses of these conditions.

Animals↗

[Licorice. A basis for precautions one more time!].

A 38 year-old male was admitted to hospital with somnolence, flaccid paralysis of the extremities, arterial hypertension, oedema, severe hypokalemia and rabdomyolysis. The course was complicated with respiratory and kidney failure. It became apparent that the symptoms were caused by the ingestion of 200 g of licorice daily for ten weeks together with a thiazide diuretic for two weeks.

Adult↗

Fiber type composition of articular branches of the tibial nerve at the knee joint in man.

BACKGROUND: We examined the fiber type composition of the articular branches of the tibial nerve in human cadavers. Our primary motivation was to assess the suitability of these nerve branches for making neural recordings by using an interface, such as a nerve cuff electrode or a microelectrode array. Articular branches of the tibial nerve innervate primarily the posterior joint capsule of the knee (Gardner, 1948. Anat. Rec, 101:109-130); the main branch corresponds anatomically to the posterior articular nerve (PAN), which has been studied extensively in animals such as the cat. MATERIALS AND METHODS: By using light microscopy, we counted the numbers of myelinated fibers in articular branches of the tibial nerve removed from eight cadavers. Unmyelinated fibers were counted in the same specimens by using electron microscopy, and the percentage of unmyelinated fibers was calculated. RESULTS: We found on average 2,280 myelinated fibers in the main articular branch and 279 fibers in individual capsular ramifications. Myelinated fiber diameter histograms showed either bimodal (peaks at 3-4 and 9 microns) or unimodal (peak at 3-4 microns) distributions, depending on the specimen. These histograms were similar in appearance for both the individual capsular ramifications and the main articular branch of the tibial nerve. Numbers of unmyelinated fibers ranged from 4,176 to 5,200 in the main tibial nerve branch (average percentage of unmyelinated fibers = 69.6%) and from 750 to 2,250 in the individual capsular ramifications (average percentage of unmyelinated fibers = 78.5%). CONCLUSIONS: The percentage of unmyelinated fibers is comparable to that found in articular nerves in other species. We discovered that the main articular branch of the tibial nerve contains a branch projecting distal to the knee joint capsule; therefore, the best location for placement of a neural recording interface to record from capsular afferents appears to be the well-defined ramifications of the articular branch that penetrate the joint capsule. Branches that contain only these ramifications are 0.5-1.0 mm in diameter and, on average, have 658 myelinated axons, which should be a sufficient number from which to record.

Aged↗

Chronic systemic treatment with epidermal growth factor in pigs causes pronounced urothelial growth with accumulation of glycoconjugates.

Epidermal growth factor (EGF) is present in large amounts in the urine, but the effects of systemically administered EGF on the urinary tract have not been described previously. In the present paper, we describe a potent growth induction of EGF on the urinary tract. Goettingen minipigs were treated with solvent (n = 5), EGF 30 micrograms/kg/day (n = 6) for 4 weeks, or EGF 30 micrograms/kg/day for 5 weeks followed by 3 weeks of recovery (n = 5). The ureters and bladders were examined by routine histology and electron microscopy and were immunostained for proliferating cell nuclear antigen. Four weeks of EGF treatment increased the median cross sectional area of the ureter fourfold with growth of all wall layers. The urothelium was widened from 5 cell layers in the controls to 10 in the EGF-treated animals. Proliferating cell nuclear antigen immunostaining revealed an increased mitotic activity in the basal zone of the urothelium. In the luminal zone, glycoconjugates accumulated in goblet cells, in cells with intracytoplasmic lumina, and beneath the luminal cell membrane in the umbrella cells. Our studies present a new experimental approach to growth induction of the urinary tract. The findings implicate the EGF system in regulating urothelial growth and glycoconjugate biosynthesis.

Animals↗

Ureteric growth in a Goettingen minipig induced by epidermal growth factor. A case report.

We have recently discovered that prolonged systemic administration of epidermal growth factor (EGF) induces a remarkable growth of all wall layers of the urinary tract in minipigs. In the present paper, we report the most pronounced changes induced by 4 weeks of systemic EGF challenge in two pigs treated for four weeks with either solvent or EGF (30 micrograms/kg/day), respectively. The EGF treated ureter was longer and thicker with an approximately four fold increase in diameter. All wall layers were enlarged. The urothelium was increased from 5 to 10 cellular rows with basal hyperplasia and an increased number of goblet cells and cells with intracytoplasmic lumina in the luminal half. In the muscular coat, the bundles of hypertrophied cells and intervening connective tissue were enlarged. The present paper suggests a possible in vivo approach to increase the amount of tissue needed in reconstructive surgery of the urinary tract.

Animals↗

Time to loco-regional recurrence after resection of Dukes' B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis.

Factors influencing time to loco-regional recurrence were identified in a multivariate regression analysis of data from a series of 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. A number of clinical and pathological characteristics were prospectively collected and recorded. In addition, carcinoembryonic antigen (CEA) was measured within 1 week before surgery. The endpoint used was recurrence below the level of the umbilicus. All patients were followed for at least 5 years or until time of death. The two Dukes' stages B and C were analysed in two separate analyses using the Cox proportional hazards model. In patients with Dukes' B tumours, an increased risk of loco-regional recurrence was associated with perineural invasion, tumour located less than 10 cm from the anal verge, patient aged above 70 years, and small tumour size. In patients with Dukes' C tumours, the necessity to resect neighbour organs, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and large tumour size were all associated with a poor loco-regional outcome. Postoperative radiotherapy was not a significant prognosticator for loco-regional control. An update of the 5-year results of the randomised study of post-operative radiotherapy (50 Gy with 2 Gy per fraction in an overall treatment time of 7 weeks) showed no survival benefit from adjuvant radiotherapy in either Dukes' category and no statistically significant improvement in the 5-year loco-regional control rate. However, when the comparison was restricted to a group of high-risk patients there was a statistically significant benefit from radiotherapy with respect to loco-regional control (P = 0.03) but not with respect to survival (P = 0.23). The potential advantage, in terms of the required number of patients, of restricting clinical trials of intensified loco-regional therapies to the high-risk patients, is illustrated.

Adult↗

Frequency of Helicobacter pylori and gastritis in healthy subjects without gastrointestinal symptoms.

To investigate the frequency of Helicobacter pylori and gastritis in asymptomatic adults, 30 healthy volunteers underwent upper endoscopy. Biopsy specimens were obtained from the corporeal and antral mucosa of the stomach. The specimens were examined by light microscopy for gastritis and the occurrence of H. pylori. In 12 subjects signs of gastritis were noted at endoscopy, but only in 7 of them was this diagnosis confirmed histologically. No other abnormalities were observed by the endoscopist. Histologic examination was normal in 17 subjects, but in 13 subjects (43%) inflammation was found in the gastric specimens. Ten had inflammation both in the corpus and in the prepyloric specimens, and in six of these subjects H. pylori was discovered. H. pylori was only found in subjects with inflammation in both the corpus and the antrum. Subjects with gastritis were slightly older than subjects with normal gastric mucosa (median age, 47 versus 37 years; not significant). In the group of subjects with gastritis, persons with H. pylori were older than those without (median age, 53.5 versus 36 years; p = 0.05). The results of our study indicate that gastritis is present before colonization with H. pylori occurs. This could imply that H. pylori is not the cause of gastritis but that the presence of gastritis is a prerequisite for colonization of the bacterium in the stomach.

Adult↗

Blood transfusion and prognosis in Dukes' B and C colorectal cancer.

To evaluate the prognostic influence of blood transfusion in cancer patients, transfusion data were reviewed on 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. Data on whole blood and packed red blood cell transfusions were recorded together with a number of clinical, pathological and histochemical characteristics. The endpoint used was death with cancer. All patients were followed for 2-7 years or until time of death. Univariate statistical methods revealed a highly significant trend towards worsened prognosis with increasing volume of transfusion blood. However, this effect was insignificant when multivariate statistical methods were employed: patients receiving whole blood or packed red blood cell transfusions did no worse than expected from their clinico-pathological characteristics. It is concluded that in this series the observed association between transfusion status and prognosis is adequately explained by a multivariate prognostic model including well-established prognostic factors.

Aged↗