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Biomedical subjects

H Goebell

Publications and source records attributed to H Goebell.

At least 37 records · Page 2Linked to original sources

Bone loss in patients with inflammatory bowel disease is less than expected: a follow-up study.

BACKGROUND: In spite of the accumulating evidence of an increased prevalence of osteopenia and osteoporosis in patients with inflammatory bowel diseases (IBD), the time course of bone loss is not well described, and there is little knowledge about factors indicating an increased risk of rapid bone loss. METHODS: We conducted a follow-up study in 80 IBD patients (45 men and 25 premenopausal and 10 postmenopausal women), 19 with ulcerative colitis and 61 with Crohn disease, with a mean follow-up time of 568 +/- 60 days, to assess bone loss, risk factors of rapid bone loss, and value of bone markers to predict bone loss. Bone mineral density was measured by dual-energy X-ray absorptiometry, bone formation by bone alkaline phosphatase (BAP), and bone resorption by N-terminal telopeptide of type-I collagen (NTX) and free deoxypyridinoline (DPD). RESULTS: Bone density changes per year were 0.46% +/- 3% at the spine, 0.06% +/- 5.1% at the femoral neck, -1.1% +/- 7.7% at the triangle of Ward, and -0.52% +/- 1.86% at total body level. Type and duration of disease, sex, age, and level of NTX, DPD, and BAP at base line did not show significant differences between patients who lost and those who did not lose bone mass. Bone loss was significantly higher in patients with (n = 28) than in those without steroids (n = 52) at the femoral neck and Ward triangle but not at the spine and total body. CONCLUSIONS: Change in bone mass in IBD patients during short-term follow-up is low on average, but there is great heterogeneity within the population, which cannot be explained by the use of steroids alone. Bone loss cannot be predicted by analysis of bone markers.

Adult↗

Factor XIII modulates intestinal epithelial wound healing in vitro.

BACKGROUND: An acquired deficiency of blood coagulation factor XIII has been proposed to cause an impairment of intestinal wound healing and hemostasis in patients with inflammatory bowel diseases. Substitution of factor XIII seems to result in a rapid improvement of intestinal wound healing. Our aim was therefore to characterize the role of factor XIII in the modulation of intestinal wound healing in vitro. METHODS: Factor XIII was added to subconfluent cultures of two non-transformed small-intestinal epithelial cell lines (IEC-6, IEC-18) and three human colon cancer-derived epithelial cell lines (T84, CaCo-2, HT-29) with subsequent assessment of cell proliferation with a colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenylformazan (MTT) assay. The effects on epithelial cell migration in vitro were assessed with an in vitro wounding model of confluent IEC-6 cell monolayers. RESULTS: Factor XIII caused a modest inhibition of proliferation of IEC-6 and IEC-18 cells. However, factor XIII significantly stimulated proliferation of T84, CaCo-2. and HT-29 cell lines. In addition, thrombin-activated factor Xill promoted intestinal epithelial cell restitution in vitro on average 2.5-fold. The modulatory effects of factor XIII could not be significantly blocked by anti-transforming growth factor beta (TGFbeta). CONCLUSIONS: Factor XIII may promote intestinal epithelial wound healing by enhancement of epithelial cell restitution through a TGFbeta-independent pathway. This may explain previously described beneficial effects of factor XIII in the treatment of active ulcerative colitis.

Animals↗

Time trends in the incidence and disease location of Crohn's disease 1980-1995: a prospective analysis in an urban population in Germany.

To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period.

Adolescent↗

Helicobacter pylori and the risk of colonic adenomas. Colorectal Adenoma Study Group.

AIMS: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. METHODS: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. RESULTS: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76-2.6) compared with hospital controls and 2.1 (1.1-3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80-3.4) compared with hospital controls and an RR of 2.6 (1.3-5.4) compared with population controls, the latter association being statistically significant. CONCLUSION: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.

Adenomatous Polyposis Coli↗

Incidence of ulcerative colitis, 1980-1995--a prospective study in an urban population in Germany.

A prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995 to determine the incidence of ulcerative colitis in an urban area in Germany. Patients with proctitis were excluded from this analysis. 74 (1980-84) and 76 (1991-95) patients newly diagnosed with ulcerative colitis were identified. A slight rise in the age- and sex-standardized incidence rate from 2.4/10(5) in 1980-84 (95% CI 1.8/10(5) to 3.0/10(5)) to 3.0 (95% CI 2.4/10(5) to 3.7/10(5)) in 1991-95 was primarily due to a significant increase of the disease in young woman. A male preponderance in the earlier time period was hereby leveled out. There were no differences in the extent of the disease and the severity of symptoms. However, the time from onset of symptoms to diagnosis was reduced from a median of nine months in the 1980s to two months in the more recent period.

Adolescent↗

[Significance of galenic preparations for luminal release of 5-aminosalicylic acid in human small intestinal lumen].

BACKGROUND: Sufficient intraluminal concentrations of 5-aminosalicylic acid (ASA) within inflamed regions of the intestine are required for therapeutic efficacy in inflammatory bowel disease. Various oral delayed release preparations have been developed to ensure that 5-ASA is set free in those parts of the gut, which are most frequently affected. However, resulting intraluminal concentrations within the small bowel are unknown. Therefore, we determined and compared 5-ASA release within different segments of the small bowel from an Eudragit L coated 5-ASA preparation (Salofalk) and from an ethylcellulose coated microsphere preparation (Pentasa). METHODS: Twelve healthy subjects were intubated with an oro-ileal multilumen-tube for marker perfusion, duodenal, jejunal and ileal aspiration of chyme and intestinal manometry. Each subject received 500 mg 5-ASA (Salofalk, n = 6, or Pentasa, n = 6) together with a semiliquid test meal. Intestinal aspirates, blood and urine samples were obtained in regular intervals for 7 to 10 hours and were analysed for 5-ASA and its main metabolite acetyl-5-ASA by HPLC. RESULTS: With Salofalk, gastric emptying of 5-ASA did not take place in the digestive, but in the subsequent interdigestive period. Luminal delivery of 5-ASA and acetyl-5-ASA increased from the duodenum (3% of dose) to the ileum (30% of dose). 10% of the dose administered were excreted in urine and about 90% reached the colon unreleased or solubilised. By contrast, with Pentasa, 5-ASA was delivered to the duodenum together with the test meal and released continuously throughout the small intestine (about 20% of dose solubilised at each intestinal site). Only 3.5% of the dose administered were excreted in urine. Deliver of 5-ASA to the colon was equal to Salofalk. CONCLUSIONS: From both preparations, considerable amounts of 5-ASA are released during small intestinal transit thus explaining therapeutic efficacy in small intestinal Crohn's disease. Because of specific release patterns, Salofalk may be of use especially in terminal ileal disease, where as patients with extensive small intestinal disease including the proximal small intestine might benefit from Pentasa.

Biological Availability↗

Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease.

Patients with chronic inflammatory bowel diseases (IBD) are at increased risk to develop osteopenia and osteoporosis. New parameters for the assessment of bone formation and especially bone resorption have significantly improved the diagnostic procedures to characterize bone metabolism. Biochemical characterization of bone turnover in IBD patients may provide important information about the pathogenesis of osteoporosis in this patient population. A cross-sectional study was performed. One hundred forty-nine patients (77 men, 52 premenopausal, and 20 postmenopausal women) with IBD (104 with Crohn's disease [CD] and 45 with ulcerative colitis [UC]) underwent clinical, osteodensitometric, and metabolic bone assessment. Bone mineral density was determined by dual energy X-ray absorptiometry. Bone formation (bone alkaline phosphatase), bone resorption (N-terminal telopeptide of type-I collagen, free desoxypyridinoline, total pyridinoline, and desoxypyridinoline), vitamin D, and parathyroid hormone were assessed. Thirty-six percent of patients with CD and 32% with UC showed osteopenia, 15% with CD and 7% with UC showed osteoporosis. Bone resorption was significantly increased in IBD patients compared to normal controls, whereas bone formation did not show a compensatory increase. Bone formation was even more suppressed in the subset of patients currently treated with corticosteroids. Our data confirm the high prevalence of osteopenia and osteoporosis reported in IBD patients. Furthermore, we provide evidence for an increased bone resorption accompanied by low bone formation in IBD patients. This imbalance of bone metabolism is likely to be one of the reasons for increased bone loss in IBD patients.

Absorptiometry, Photon↗

Adenine nucleotides modulate epithelial wound healing in vitro.

BACKGROUND: Adenine nucleotides have been demonstrated to enhance structural and functional regeneration in experimental renal injury in rats. The mechanism of adenine nucleotide action have not been elucidated. The aim of this study was to characterize the effects of adenine nucleotides on intestinal epithelial wound healing in vitro. METHODS: The effects of adenine nucleotides on cell migration, cell proliferation and cell adhesion were studied in the non-transformed small intestinal epithelial cell line IEC-6 using an in vitro wounding model, a colorimetric BrdU assay and a hexosaminidase adhesion assay. RESULTS: The adenine nucleotides ADP and ATP were found to significantly stimulate epithelial cell restitution (migration) in vitro. Stimulation of epithelial restitution averaged 42% for ADP and 57% for ATP. In addition, adenine nucleotides inhibited the proliferation of rat small intestinal epithelial cells, averaging 56% for ADP and 74% for ATP. Enhancement of intestinal epithelial restitution and inhibition of epithelial cell proliferation by adenine nucleotides were mediated through transforming growth factor (TGF)-beta-independent pathways. CONCLUSION: These findings suggest that adenine nucleotides exert functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis of the gastrointestinal tract and its remodeling after injury.

Adenine Nucleotides↗

Altered vagal and intestinal mechanosensory function in chronic unexplained dyspepsia.

BACKGROUND: Abnormal visceral mechanosensory and vagal function may play a role in the development of functional gastrointestinal disorders. AIMS: To assess whether vagal efferent and afferent function is linked with small intestinal mechanosensory function. METHODS: In seven patients with functional dyspepsia, six patients with a history of Billroth I gastrectomy and/or vagotomy, and seven healthy controls, intestinal perception thresholds were tested by a randomised ramp distension procedure performed with a barostat device. On a separate day, an insulin hypoglycaemia test was performed to assess the plasma levels of pancreatic polypeptide (PP) in response to hypoglycaemia, as a test of efferent vagal function. RESULTS: First perception of intestinal balloon distension occurred at significantly lower pressures in patients with functional dyspepsia (median 19.3, range 14.7-25.3 mm Hg) compared with healthy controls (median 26.0, range 21.7-43.7 mm Hg, p < 0.01). Sensory thresholds were significantly lower in patients after gastrectomy (median 12.2, range 8.0-14.7 mm Hg, p < 0.05 versus all others). In healthy controls and patients with functional dyspepsia, insulin hypoglycaemia significantly (p < 0.001) increased plasma PP levels. However, only two out of seven patients with functional dyspepsia had a more than twofold increase in PP values whereas all healthy controls had a more than twofold increase in PP levels after insulin hypoglycaemia (p < 0.05). In contrast, there was no significant PP response in the gastrectomised patients (median 2%, range -10 to +23%). PP responses and visceral sensory thresholds were significantly correlated (r = 0.65, p < 0.002). CONCLUSIONS: The diminished PP response after insulin hypoglycaemia indicates disturbed efferent vagal function in a subgroup of patients with functional dyspepsia. The data also suggest that the intact vagal nerve may exert an antinociceptive visceral effect.

Adult↗

[Carcinoid syndrome. Recurrent upper abdominal pain, diarrhea and flush in a 15-year-old girl].

BACKGROUND: A carcinoid syndrome is typically diagnosed in elderly patients, median age at diagnosis was 60 years in two large series. We describe a patient with the carcinoid syndrome at the young age of 15 years. CASE REPORT: The 15-year-old patient's history and findings on physical examination, clinical chemistry, abdominal ultrasound and liver biopsy were typical for a carcinoid with hepatic metastases. The patient's age, however, was very unusual. Because of her youth, we discussed a potentially curative treatment with resection of the primary tumor in the upper jejunum followed by liver transplantation at a second operation. This concept had to be abandoned, when the first operation revealed a tumor in the mesenterium, close to the primary, 5 cm in diameter and around the superior mesenteric artery. This tumor could not be resected. Liver transplantation therefore did not offer this young patient a chance for cure.

Abdominal Pain↗

Value of an extended monoethylglycinexylidide formation test and other dynamic liver function tests in liver transplant donors.

Measuring monoethylglycinexylidide (MEGX) formation after intravenous administration of lidocaine in potential organ donors (MEGX test) has been advocated as a useful test to select donor livers for transplantation, but some groups have demonstrated a low test efficacy. We, therefore, investigated the value of an extended MEGX formation test and the value of other dynamic liver function tests, in selecting suitable human donor livers. In 51 human multi-organ donors, we measured elimination of galactose, indocyanine green, and lidocaine, as well as formation of MEGX, at 15, 30, and 60 min after administration of the test substances. In the early postoperative period, the function of the transplanted liver was then classified as good or poor, as defined by a prothrombin time above or below 65% by day 4 and fibrinogen concentration above or below 300 mg/dl by day 7. Donor characteristics and preservation modalities were very similar between the two groups. Galactose, indocyanine green, and lidocaine metabolism failed to predict good or poor graft function in the early postoperative period. MEGX serum concentrations, however, were significantly higher in the group of donors whose organs functioned well in the recipients, as compared with donors whose organs functioned poorly in the recipients. This was true for MEGX concentrations at 15 min (117+/-9 vs. 90+/-9 ng/ml; P=0.03), 30 min (108+/-8 vs. 86+/-8 ng/ml; P=0.04), and 60 min (100+/-6 vs. 73+/-5 ng/ml; P=0.006). Extending the MEGX formation test from 15 to 60 min improved test efficacy. Maximal MEGX concentration in 9 or up to 12 consecutive blood samples, drawn between 3 and 120 min after lidocaine infusion, was also significantly higher in donors whose organs functioned well, than in donors whose organs functioned poorly (129+/-10 vs. 101+/-10 ng/ml; P=0.03). Although the groups with good and poor organ function differed significantly with respect to their MEGX serum concentrations, and although efficacy of the MEGX test was improved by extending the test from 15 to 60 min, the overlap in individual MEGX serum concentrations was still so wide that it is virtually impossible to predict early graft function only on the basis of the MEGX test in the donor. Therefore, the MEGX test, although of potential scientific interest, does not predict early graft function with an accuracy necessary for clinical use.

Adult↗

Ileal carbohydrates inhibit cholinergically stimulated exocrine pancreatic secretion in humans.

CONCLUSION: Ileal inhibitory effects on pancreatic enzyme output are also demonstrable during exogenous, cholinergic stimulation of exocrine pancreatic secretion. These findings support the hypothesis that direct inhibition of cholinergic systems may be involved in the ileal inhibitory effects on pancreatic enzyme secretion. Furthermore, glucagon-like peptide-1 (GLP-1) may play a role in the mediation of the ileum-induced effects. BACKGROUND: Ileal carbohydrate perfusion inhibits endogenously stimulated exocrine pancreatic secretion in humans. Our aim was to investigate if ileal perfusion of carbohydrates exerts similar effects on exogenously stimulated pancreatic enzyme output, i.e., if the inhibitory mechanisms are reproducible during direct, cholinergic stimulation of the exocrine pancreas. Furthermore, we sought to clarify the role of the potential humoral mediators (GLP-1) and peptide YY (PYY). METHODS: Eight healthy fasting volunteers were intubated with an oroileal multilumen tube system for aspiration of duodenal juice and perfusion of test solutions. Exocrine pancreatic secretion was stimulated by a continuous i.v. infusion of the cholinergic agonist carbachol. Additionally, the ileum was perfused for 15-min intervals with either carbohydrates (total load: 18 g) or saline as control. Blood samples for determination of GLP-1 and PYY were taken before the beginning of exogenous stimulation and before and after ileal perfusion. RESULTS: Exogenously stimulated pancreatic enzyme secretion was significantly inhibited by additional ileal carbohydrate perfusion (p < 0.05), whereas ileal saline had no effect. Moreover, plasma levels of GLP-1 increased significantly (p = 0.004) after ileal perfusion of carbohydrates, but not after saline. PYY plasma concentrations remained unchanged after both ileal perfusates.

Adult↗