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Biomedical subjects

K Loeschke

Publications and source records attributed to K Loeschke.

At least 37 records · Page 2Linked to original sources
PubMed1998

Inflammatory bowel disease: no association between allele combinations of the interleukin (IL) I beta and IL-I receptor antagonist gene polymorphisms.

BACKGROUND: Interleukin 1 (IL-1) and its physiological antagonist interleukin-1 receptor antagonist (IL-1 ra) play a crucial role in the pathogenesis of inflammatory bowel disease. Polymorphisms in the genes coding for these cytokines, the restriction enzyme TaqI polymorphism for IL-1 beta and the variable number of tandem repeats (VNTR) polymorphism for IL-1 ra, have been shown to influence cytokine synthesis in vitro. Recently, an association has been described for distinct allele combinations of these two polymorphisms in patients with ulcerative colitis and with Crohn's disease but not in healthy control subjects. METHODS: We studied 56 patients with ulcerative colitis, 64 patients with Crohn's disease and 196 healthy control subjects. All were unrelated Caucasians of European ancestry. After polymerase chain reaction (PCR) the amplification products were analysed on agarose gels. For the IL-1 beta polymorphism the PCR product was additionally digested using the restriction enzyme TaqI. RESULTS: The allele and genotype frequencies as well as the carriage rates of the IL-1 beta TaqI polymorphism in healthy control subjects were in agreement with previous findings in other populations. Allele and genotype frequencies of the IL-1 beta polymorphism were not different in inflammatory bowel disease patients compared with healthy control subjects. Comparing allele combinations of both polymorphisms no association could be identified either within healthy control subjects or in the groups of patients with ulcerative colitis or Crohn's disease. CONCLUSION: Thus, we could not confirm the results of a previous study reporting an association between the IL-1ra and IL-1 beta gene polymorphisms in patients with inflammatory bowel disease.

Adult↗
PubMed1998

Alpha1-antitrypsin alleles and phenotypes in patients with inflammatory bowel disease.

BACKGROUND: Several studies suggest an imbalance of protease activation and inhibition in inflammatory bowel disease. Alpha1-Antitrypsin (AAT), one protease inhibitor of paramount importance, exists in numerous subtypes, some of them representing deficient phenotypes. The present study evaluated the prevalence of AAT-alleles and phenotypes in patients with inflammatory bowel disease. METHODS: The study population comprised 74 patients with Crohn's disease and 61 patients with ulcerative colitis. Isoelectric focusing was used for AAT subtyping. The prevalence of AAT alleles and phenotypes was compared with the frequency in 752 healthy unrelated controls. RESULTS: The rare phenotype M2F was detected in one patient with ulcerative colitis. No further significant differences in the distribution of AAT alleles or phenotypes between patients with inflammatory bowel disease and the healthy controls were observed. CONCLUSION: The low prevalence of deficient AAT subtypes does not point towards a contribution of AAT deficiency in the pathophysiology of IBD.

Adolescent↗
PubMed1998

Antineutrophil and pancreatic autoantibodies in first-degree relatives of patients with inflammatory bowel disease.

BACKGROUND: Perinuclear antineutrophil antibodies (P-ANCA) are found in ulcerative colitis, and autoantibodies against exocrine pancreas (PAB) in Crohn's disease. Their potential role as genetic or pathophysiologic factors is unclear. METHODS: In 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, 105 first-degree relatives of Crohn's disease patients, and 56 healthy unrelated controls autoantibodies were detected by indirect immunofluorescence. RESULTS: Forty-six per cent of patients with ulcerative colitis (28 of 61) and 38% of patients with Crohn's disease (29 of 76) were P-ANCA- and PAB-positive, respectively. In relatives of patients with ulcerative colitis P-ANCA were found in 3% (3 of 101), and in relatives of Crohn's disease patients PAB were detected in 4% (4 of 105), which is not significantly different from the occurrence in the healthy controls. CONCLUSIONS: The frequency of P-ANCA and PAB does not suggest a role as genetic markers for inflammatory bowel disease.

Adolescent↗
PubMed1998

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease. The Budesonide Study Group.

BACKGROUND: The relapse rate after steroid induced remission in Crohn's disease is high. AIMS: To test whether oral pH modified release budesonide (3 x 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. METHODS: In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 x 1 mg budesonide (n = 84) or placebo (n = 95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. RESULTS: Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5 days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. CONCLUSION: Oral pH modified release budesonide at a dose of 3 x 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease.

Administration, Oral↗
PubMed1998

p-ANCA target antigens in ulcerative colitis.

INTRODUCTION: Data about the nature and pathophysiological relevance of the target antigens reacting with perinuclear antineutrophil cytoplasmatic autoantibodies (p-ANCA) in ulcerative colitis are inconsistent and partly conflicting. In the majority of the previous studies only one singular potential target antigen was investigated. The present study aimed on the simultaneous assessment of five different p-ANCA subtypes in patients with ulcerative colitis and attempted to detect reactivity against one of the previously described antigens and to correlate specificity for different target antigens with clinical features of the disease. METHODS: Sera from 61 patients with ulcerative colitis and from 56 healthy controls were tested using indirect immunofluorescence and enzyme-linked immunosorbent assays specific for elastase, lactoferrin, cathepsin G, myeloperoxidase and bactericidal permeability increasing protein (BPI). p-ANCA subtypes were correlated with clinical features of ulcerative colitis like disease extent or presence of extraintestinal manifestations. Moreover, a possible correlation to current immunosuppressive therapy was evaluated. RESULTS: In 46% (28/61) of patients with ulcerative colitis and in 4% (2/56) of the controls p-ANCA were detected. p-ANCA subtypes were distributed as follows: 26% (16/61) anti-BPI. 16% (10/61) anticathepsin G, 15% (9/61) antielastase, 7% (4/61) antilactoferrin, 5% (3/61) antimyeloperoxidase. Presence of anticathepsin G antibodies was negatively correlated with immunosuppressive therapy. No further correlations between p-ANCA subtypes and clinical characteristics were observed. DISCUSSION: p-ANCA subtypes in inflammatory bowel disease react with a variety of different target antigens and are not correlated with clinical features of the disease.

Adult↗
PubMed1997

[Megaloblastic anemia due to inadequate nutrition].

HISTORY AND CLINICAL FINDINGS: Over a period of about 6 weeks a 49-year-old woman developed increasing exercise-dependent dyspnoea. Her general practitioner had diagnosed marked megaloblastic anaemia and she was hospitalised for its further elucidation. She reported to have eaten or drunk nothing but sweets, potato chips, salty pretzels, lemonade, coffee and tea over the last 2 years. Alcohol intake had been reliably denied by her and outsiders. On admission she weighed 106 kg, her height was 167 cm, and she looked anaemic, had dyspnoea and a sinus tachycardia. There was no evidence of external or internal bleeding and the physical examination was otherwise unremarkable. INVESTIGATIONS: Laboratory tests showed a haemoglobin concentration of 4.7 g/dl, as well as marked folic and vitamin B12 deficiency. The food items taken by her contain practically no cobalamine and no folic acid. Gastroscopy revealed grade 1 reflux oesophagitis. Malabsorption being excluded (normal Schilling test, no demonstrable autoantibodies against parietal cells, no evidence of exocrine pancreatic insufficiency), the lack of both vitamins and the megaloblastic anaemia caused by it could be explained only by a deficient food intake over several years. TREATMENT AND COURSE: After administration of cobalamine (1 mg intramuscularly twice weekly for 6 weeks, then 300 micrograms daily by mouth for 4 weeks) and folic acid (5 mg twice daily for 10 weeks), as well as a well-balanced diet as prescribed by a dietician, reticulocyte and erythrocyte concentrations had quickly risen to normal at a follow-up examination 2 months later. CONCLUSION: The case of an anaemia entirely caused by a deficient diet dearly illustrates the need of a well-balanced food intake even in adults.

Anemia, Megaloblastic↗
PubMed1997

Goblet cell autoantibodies in patients with inflammatory bowel disease and their first-degree relatives.

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.

Adult↗
PubMed1997

Antinuclear autoantibodies in patients with inflammatory bowel disease. High prevalence in first-degree relatives.

Crohn's disease and ulcerative colitis show a familial aggregation. The role of antinuclear autoantibodies, which occur in both diseases, remains to be defined. In 76 patients with Crohn's disease, 61 patients with ulcerative colitis, 105 first-degree relatives of patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 40 healthy unrelated controls antinuclear autoantibodies were detected by indirect immunofluorescence. Existence of autoantibodies was correlated with clinical features. Eighteen percent of patients with Crohn's disease (14/76), 43% of patients with ulcerative colitis (26/61), 13% of relatives of patients with Crohn's disease (14/105), 24% of relatives of ulcerative colitis patients (24/101), and 2% of the healthy controls (1/40) were positive for antinuclear autoantibodies. The difference between controls and patients and the first-degree relatives of patients with ulcerative colitis, respectively, was statistically significant (P < or = 0.0144). In ulcerative colitis, the existence of antinuclear autoantibodies was negatively correlated with immunosuppressive therapy or extraintestinal manifestations (P = 0.0004 and 0.0273, respectively). Antinuclear autoantibodies may represent a factor disposing to the development of ulcerative colitis.

Adolescent↗
PubMed1997

Lack of association between an interleukin-1 receptor antagonist gene polymorphism and ulcerative colitis.

BACKGROUND: Recently, the association of a polymorphism in the gene coding for the anti-inflammatory cytokine interleukin-1 receptor antagonist with ulcerative colitis has been reported. This was interpreted as a possible genetic predisposition for severity of the inflammatory response. AIMS: To examine this polymorphism in a southern German population. SUBJECTS: The study included 234 healthy controls, 57 patients with ulcerative colitis, including 31 patients with pancolitis, 44 first degree healthy relatives of patients with ulcerative colitis, and 65 patients with Crohn's disease. METHODS: Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment harbouring a variable number of tandem repeat nucleotide sequences. Amplification products were separated on a 2% agarose gel. RESULTS: The allele frequency for allele 2 was 27% in healthy controls, 28% in Crohn's disease, and 21% in patients with ulcerative colitis. The same allele frequency (21%) was found in a subgroup of patients with ulcerative colitis affecting the whole colon. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates no significant differences were found compared with controls. All allele frequencies in the control population were similar to those in earlier studies. CONCLUSIONS: No association of a polymorphism in the interleukin-1 receptor antagonist gene with ulcerative colitis could be identified in this southern German population. The findings of an earlier study reporting an increased frequency of allele 2, particularly in patients with pancolitis, could not be confirmed.

Adult↗
PubMed1997

Detection of Ki-ras mutations by PCR and differential hybridization and of p53 mutations by SSCP analysis in endoscopically obtained lavage solution from patients with long-standing ulcerative colitis.

OBJECTIVES: The goal of this study was the early detection of malignant transformation in patients with long-standing ulcerative colitis; therefore, mutations of the Ki-ras and p53 gene were analyzed in lavage solution and biopsies obtained at surveillance colonoscopy. METHODS: DNA was isolated from 14 patients (nine female, five male) with a history of pancolitis for more than 10 yr. Exon 1 of the Ki-ras gene and exons 5-8 of the p53 gene were amplified via polymerase chain reaction. Mutations of the p53 gene were detected via single-strand conformation polymorphism analysis; point mutations of the Ki-ras gene were hybridized on dot blots with oligonucleotides marked with digoxigenin. RESULTS: Wild-type Ki-ras and wild-type p53 were detected in all cases of ulcerative colitis and in four of seven control patients. In two ulcerative colitis patients, a mutation was found in the Ki-ras gene (Gly --> Asp 12 and Gly --> Val 12), and in one patient, a mutation in exon 5 of the p53 gene. Mutations were found only in the lavage fluid, whereas random biopsies were negative. CONCLUSIONS: From colonic lavage fluid, it is possible to extract DNA of sufficient quantity and quality for polymerase chain reaction-based amplification and subsequent analysis via single-strand conformation polymorphism or hybridization. Mutations were found in three of 14 patients with long-standing ulcerative colitis but were not found in controls. The method may be useful for the screening of such patients.

Aspartic Acid↗
PubMed1996

n-3 fatty acids only delay early relapse of ulcerative colitis in remission.

Relapse prevention by dietary n-3 fatty acids (5.1 g/day) was studied in a double-blind, placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids. 5-ASA compounds were stopped three months after randomization and clinical disease activity monitored for two years. Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit. Both treatment groups were well matched at start. Nine patients on placebo and eight on n-3 fatty acids stopped taking their medication prematurely. Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 (2P < 0.05-0.01), but cumulative relapse rate at two years was similar for those taking placebo (18/33 = 55%) and n-3 fatty acids (18/31 = 58%). There was also no consistent difference in clinical, macroscopic, and histologic disease activity between treatment groups. The n-3 fatty acids temporarily retard, but do not prevent, relapse of ulcerative colitis.

Actuarial Analysis↗
PubMed1996

[Osteomyelitis sicca in Crohn disease--coincidence or extraintestinal manifestation?].

In patients with Crohn's disease arthritis of the large joints, osteomalacia, osteoporosis and aseptic bone necrosis as a consequence of malabsorption and glucocorticoid intake may occur. The case of a patient with long-standing Crohn's disease is presented who subsequently developed abacterial osteomyelitis of the jaw ("osteomyelitis sicca"). The symptoms of the osteomyelitis improved under immuno-suppressive therapy. Because the etiopathogenetic concepts for Crohn's disease and osteomyelitis sicca are similar, the latter could be a rare extraintestinal manifestation in Crohn's disease, not described previously.

Adult↗
PubMed1996

[Severe protracted cholestasis after general anesthesia in a patient with Alagille syndrome].

A 27-year-old female patient with partial Alagille's syndrome (hypoplasia of the intrahepatic bile ducts, typical facial dysmorphism and skeletal anomalies) developed a marked cholestasis (total bilirubin 59 mg/dl), decrease of liver synthesis tests and ascites four weeks after gynecological surgery with general anesthesia involving propofol, isoflurane and nitrous oxide. Slow recovery could be achieved under treatment with ursodeoxycholic acid, spironolactone and substitution of fat-soluble vitamins A, D, E and K. Four months after admission the ascites had disappeared, liver synthesis had increased and the total bilirubin level had dropped to 3.8 mg/dl. Since all other possible causes were excluded during the hospital stay, the prolonged episode of cholestasis in this patient is best explained by the preceding general anesthesia with propofol which is known to be metabolized in the liver and impedes hepatic cytochrome P450 and hepatic blood flow.

Adult↗