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Biomedical subjects

H Lochs

Publications and source records attributed to H Lochs.

At least 109 records · Page 6Linked to original sources
PubMed1999

Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease.

BACKGROUND: Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease. Experimental immunotherapeutic interventions with anticytokine agents in refractory Crohn's disease show that tumour necrosis factor alpha (TNF alpha) may be an important mediator of inflammation. We investigated the relation between production of TNF alpha and interleukin 1beta by mononuclear cells of the colonic lamina propria in patients with remitting Crohn's disease and the risk of relapse. METHODS: We followed up 137 patients with Crohn's disease in steroid-induced remission for 1 year. Secretion of proinflammatory cytokines (tumour necrosis factor alpha [TNF alpha] and interleukin 1beta) was assessed after short-term culture of human lamina propria mononuclear cells. FINDINGS: Increased secretion of TNF alpha and interleukin 1beta were predictive for acute relapses within the next year. Site and extent of disease, baseline demographics, and serum acute-phase proteins had little predictive value. INTERPRETATION: TNF alpha is important as a target molecule for immune interventions in Crohn's disease. The capacity to produce TNF alpha or interleukin 1beta may identify patients who would benefit from anti-inflammatory remission maintenance.

Biomarkers↗
PubMed1999

High prevalence of pulmonary diffusion abnormalities without interstitial changes in long-term survivors of liver transplantation.

Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20-147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0% predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0%), emphysematous bullae in 2/40 (5.0%) and pleural thickening in 9/40 (22.5%). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause.

Adolescent↗
PubMed1999

Health-related quality of life in patients with Crohn's disease: influence of surgical operation--a prospective trial.

Improvement of health-related quality of life (HRQOL) is a major determinant in decision-making for surgery in patients with Crohn's disease (CD). This study was designed to investigate the short- and long-term effect of surgical resection for CD on HRQOL. Sixteen patients were investigated within one week before surgery and 3, 6, and 24 months postoperatively. Besides the Crohn's disease activity index (CDAI), four instruments: the time trade-off technique (TTO), the direct questioning of objectives (DQO), the rating form of inflammatory bowel disease patients concerns (RFIPC), and the Beck depression inventory--were used for assessment of HRQOL. CDAI decreased significantly after operation and 10 patients remained in remission for 24 months. Two patients had postoperative relapses and went into remission after prednisolone treatment. Four patients developed chronic active disease. HRQOL was significantly improved in all patients three and six months postoperatively. Except for the four patients with chronic active disease, all other patients (N = 12) had also significantly improved HRQOL after 24 months. In conclusion, surgical resections in CD lead to a long-term improvement of HRQOL with the exception of patients with chronic active disease. This finding might be taken in consideration for the indication of surgery in CD.

Adult↗
PubMed1999

Production of IL-12 in gastritis relates to infection with Helicobacter pylori.

Increased production of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-8, has been demonstrated in Helicobacter pylori-associated gastric mucosal inflammation. IL-12, a newly characterized cytokine, is thought to be a key mediator in host responses to bacterial infections. The aim of this study was to investigate differences in cytokine patterns between H. pylori-positive and -negative gastritis and normal mucosa. Secretion of IL-12, TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10 was measured in 176 patients with chronic gastritis in whole biopsy cultures. Gastritis was graded for chronic inflammation or acute inflammatory activity, respectively, according to the Sydney system. Biopsies with similar scores were matched for analysis from H. pylori-infected and non-infected patients. Secretion of IL-12 was significantly increased in H. pylori-associated gastritis in comparison with H. pylori-negative gastritis (P < 0.0001). In contrast, secretion of TNF-alpha, IL-1beta, IL-6, and IL-8 correlated with the degree of inflammation but was not different between H. pylori-positive and -negative patients. Moreover, IL-10 secretion was found to be higher in H. pylori-positive than in H. pylori-negative patients. IL-12 may play a specific role in H. pylori-associated gastric disease, whereas production of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6 and IL-8 does not seem to be restricted to H. pylori-induced inflammation. The contra-inflammatory cytokine IL-10 may be a contributor to the chronicity of H. pylori-associated gastritis by impairing clearance of the pathogen.

Adult↗
PubMed1999

Energy and substrate metabolism in patients with active Crohn's disease.

The aim of the study was to evaluate the possible contribution of changes in energy metabolism and substrate oxidation rates to malnutrition in Crohn's disease and to assess the effect of enteral nutrition on these parameters. Energy metabolism was evaluated by indirect calorimetry in 32 patients with active Crohn's disease and 19 age- and sex-matched healthy individuals. Measurements were done in the postabsorptive state. Seven out of 32 patients received enteral nutrition via a nasogastric tube. In these patients, resting energy metabolism was determined at d 0 (postabsorptive), 7, 14 (during full enteral nutrition) and 15 (postabsorptive). Resting energy expenditure was not significantly different between patients and controls, whereas the respiratory quotient (RQ) was lower in patients (0.78 +/- 0.05 vs. 0.86 +/- 0.05; P < 0.05). During enteral nutrition in 7 patients with Crohn's disease, the RQ increased on d 7 compared with d 0 and remained high even after cessation of enteral nutrition (d 0, 0.78 +/- 0.03; d 7, 0.91 +/- 0.04; d 15, 0. 84 +/- 0.05; P < 0.05; d 7 and 15 vs. d 0). No effects of enteral nutrition on resting energy expenditure were found. Active Crohn's disease is associated with changes in substrate metabolism that resemble a starvation pattern. These changes appear not to be specific to Crohn's disease but to malnutrition and are readily reversed by enteral nutrition. Enteral nutrition did not affect resting energy expenditure. Wasting is a consequence of malnutrition but not of hypermetabolism in Crohn's disease.

Adult↗
PubMed1999

Liver cirrhosis: rationale and modalities for nutritional support--the European Society of Parenteral and Enteral Nutrition consensus and beyond.

Evaluation of nutritional status is a major problem in patients with liver cirrhosis this is due to water retention and the effect of liver function on protein synthesis. Despite problems evaluating the patient, malnutrition has been found to be a common complication in liver cirrhosis and is associated with poorer outcome. Nutritional restrictions, like protein restriction, are no longer recommended in most patients with liver cirrhosis but are considered harmful. An intake of 1 to 1.5 g/kg protein and 25 to 40 kcal/kg body weight a day is recommended (depending on the situation of the patient). If adequate intake cannot be achieved by oral nutrition, stepwise nutritional support with the introduction of an additional late evening meal, sip feeding or tube feeding is recommended. Parenteral nutrition should be used as a second line treatment for acutely ill patients. Data indicate that improvement of nutritional status prior to liver transplantation might reduce complications.

Animals↗
PubMed1999

Clinical relevance of serum interleukin-6 in Crohn's disease: single point measurements, therapy monitoring, and prediction of clinical relapse.

OBJECTIVE: To investigate the clinical relevance of interleukin-6 (IL-6) serum levels in patients with Crohn's disease (CD), single point IL-6 measurements in sera from consecutive CD patients and healthy donors (HD), as well as longitudinal measurements during the course of steroid therapy for active CD were performed. Patients with steroid-induced remission were followed until clinical relapse. METHODS: One hundred thirty-six CD patients without steroid or other immunosuppressive treatment within 2 months and surgical procedures within 3 months before study entry were investigated; 63 patients with active CD were enrolled into the follow-up program. Clinical activity was evaluated by the Crohn's disease activity index (CDAI) and serum IL-6 levels measured by enzyme-linked immunosorbent assay. RESULTS: IL-6 serum levels were significantly elevated in CD patients compared to HD (p < 0.001). In individual patients serum IL-6 levels correlated with corresponding CDAI scores in a subgroup referred to as primarily inflammatory patients presenting without bowel stenosis, previous intestinal resection, or concomitant inflammatory disorders (r = 0.72, p < 0.001). Primarily inflammatory patients displayed higher serum IL-6 levels (median: 6.0 pg/ml; range: 1.3-25) than CD patients with bowel stenosis (median: 2.0; range: 1.3-4.9; p < 0.01) or extensive intestinal resection (median: 1.5; range: 1.3-13.7; p < 0.001). Longitudinally measured serum IL-6 levels reflected the clinical response during steroid therapy and predicted clinical relapse after steroid-induced remission at week 9 of the treatment protocol. CONCLUSIONS: Serum IL-6 is a clinically relevant parameter for CD that correlates with inflammatory activity and implies a prognostic value after steroid-induced remission.

Adult↗
PubMed1999

Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin.

BACKGROUND: Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second. PATIENTS AND METHODS: Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks. RESULTS: During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl). CONCLUSION: Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.

Adult↗
PubMed1999

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.

The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.

Antibodies, Monoclonal↗
PubMed1999

Tacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation.

A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 ng/ml) until recently, revealed an increase to toxic level of 54 ng/ml. After discontinuation of mibefradil, tacrolimus levels returned to the normal range and all symptoms and clinical changes were reversible. Mibefradil and tacrolimus both are metabolized through the cytochrome--P-450 pathway. We suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by mibefradil was responsible for these toxic effects. Therefore, special caution is recommended when administering tacrolimus with other drugs that carry the potential for pharmakokinetic interaction.

Antihypertensive Agents↗
PubMed1998

[Improvement of diabetes mellitus after excision of a parathyroid adenoma].

Disturbances of glucose metabolism with hyperinsulinism and peripheral insulin resistance are frequently observed in patients with hyperparathyroidism. The mechanism of how hyperparathyroidism affects glucose metabolism is not known. Hypercalcemia, hypophosphatemia and the parathyroid hormone itself seem to be involved. However, parathyroidectomy exerted rather variable effects on glucose metabolism: In patients with fully developed diabetes mellitus both, a complete normalisation of glucose tolerance as well as no change in the metabolic situation have been observed. We report a 64-year old female patient with primary hyperparathyroidism and diabetes mellitus. The patient had severe insulin resistance with insulin requirements of 200 IU/day. Fasting insulin and C-peptide levels were elevated. After successful operation of a parathyroid adenoma there was a marked improvement in diabetes, and the patient's insulin requirement decreased to one third of the preoperative dose. This case further illustrates the association between primary hyperparathyroidism and diabetes mellitus and the potential improvement of the metabolic situation after parathyroidectomy.

Adenoma↗
PubMed1998

Association between intraepithelial Escherichia coli and colorectal cancer.

BACKGROUND & AIMS: Although multiple studies have focused on Helicobacter pylori, little is known about the mucosa-associated flora of the colon. The aim of this study was to detect bacteria directly in colonic mucosa from patients screened for colorectal cancer. METHODS: Bacteria were quantified with the polymerase chain reaction and identified by comparative sequence analysis in colonoscopic biopsy specimens from 31 asymptomatic and 34 symptomatic controls with normal colonoscopic findings, 29 patients with colonic adenoma, and 31 patients with colorectal carcinoma. In 41 patients, intra- and extracellular location of bacteria was confirmed with the gentamicin protection assay. RESULTS: No bacteria were detected in biopsy specimens from 97% of asymptomatic and 69% of symptomatic controls. In contrast, bacterial concentrations of 10(3)-10(5) colony-forming units per microliter were detected in biopsy specimens from both malignant and macroscopically normal tissue in 90% and 93% of patients with adenoma and carcinoma, respectively. E. coli and coli-like bacteria were shown to colonize the colonic mucosa in 82% of these patients. The gentamicin protection assay indicated that E. coli was partially intracellular in 87% of patients with adenoma and carcinoma and in none of the controls. CONCLUSIONS: The colonic mucosa of patients with colorectal carcinoma but not normal colonic mucosa is colonized by intracellular E. coli.

Adenoma↗
PubMed1998

Photodynamic therapy of nonresectable cholangiocarcinoma.

BACKGROUND & AIMS: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. METHODS: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease <50%) after endoscopic stent insertion, underwent photodynamic therapy. Two days after intravenous application of a hematoporphyrin derivate, intraluminal photoactivation was performed cholangioscopically. Serum bilirubin, quality of life, and survival time were assessed in two monthly intervals after photodynamic therapy. RESULTS: After photodynamic therapy, bilirubin serum levels declined from 318 +/- 72 to 103 +/- 35 micromol/L (P = 0.0039) with no significant increase during the two monthly follow-ups. Quality of life indices improved dramatically and remained stable (e.g., Karnofsky index from 32.2% +/- 8.13% to 68.9% +/- 6.1%; P = 0.0078). Thirty-day mortality was 0%, and median survival time was 439 days. CONCLUSIONS: This study provides clear evidence that photodynamic therapy is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas Bismuth type III and IV. Compared with published data, survival time seems to be prolonged.

Bile Duct Neoplasms↗
PubMed1998

Splanchnic oxygen transport and lactate metabolism during normothermic cardiopulmonary bypass in humans.

UNLABELLED: The effect of normothermic (36.2 degrees C +/- 0.6 degree C) nonpulsatile cardiopulmonary bypass (CPB) on splanchnic (hepatic) blood flow (SBF), splanchnic oxygen transport (DO2spl) and oxygen consumption (VO2spl), splanchnic lactate uptake and gastric mucosal pH (pHi, gastric tonometry) was studied in 12 adults (New York Heart Association class II, ejection fraction > or = 0.4) undergoing coronary artery surgery. SBF was estimated with the constant-infusion indocyanine green (ICG) technique using a hepatic venous catheter. DO2spl, VO2spl, and splanchnic lactate uptake were calculated using the Fick principle after the induction of anesthesia, during aortic cross-clamping, after CPB, and 2 and 7 h after admission to the intensive care unit (ICU). SBF, DO2spl, and VO2spl did not decrease during CPB but increased after ICU admission, whereas pHi decreased 7 h after ICU admission. Initial ICG extraction was 0.78, which decreased to 0.54 during aortic clamping and remained low thereafter. The increased arterial blood lactate concentrations were not associated with a decreased splanchnic lactate uptake. We conclude that normothermic CPB is not associated with deterioration in the global intestinal oxygen supply. The increase of blood lactate levels and the decrease in ICG extraction, as well as in pHi, are consistent with a systemic inflammatory response to CPB. IMPLICATIONS: This study demonstrated that normothermic cardiopulmonary bypass (at flows > 2.4 L.min-1.m-2) was not associated with deterioration in global intestinal oxygen delivery, which suggests that increased blood lactate concentrations and decreased gastric mucosal pH and indocyanine green extraction are manifestations of a systemic inflammatory response to cardiopulmonary bypass.

Adult↗
PubMed1998

Influence of topically and systemically active steroids on circulating leukocytes in Crohn's disease.

OBJECTIVE: Budesonide, although only topically active, is effective in the treatment of Crohn's disease. This study was performed to compare the clinical efficacies of budesonide and prednisolone in relation to the activation status of circulating leukocytes. METHODS: Twenty-four patients with active Crohn's disease were randomized to treatment with either budesonide or 6-methylprednisolone. Clinical response was monitored by the Crohn's disease activity index, C-reactive protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on neutrophils was determined by flow cytometry. The release of TNF-alpha and IL-1beta by peripheral blood mononuclear cells was measured by ELISA. RESULTS: After 2 wk of treatment a clinical response was observed in both groups, but it was more accentuated in patients treated with prednisolone. At baseline an upregulation of CD71 and CD64, but not CD25, was found in active patients. Prednisolone significantly decreased the expression of CD64 and the release of TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71. Budesonide treatment failed to exert any effect on circulating leukocytes. CONCLUSIONS: The inability of budesonide to downregulate activated circulating leukocytes may contribute to the somewhat lower clinical efficacy of this topical steroid in the treatment of active Crohn's disease.

Adult↗