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Biomedical subjects

H Lochs

Publications and source records attributed to H Lochs.

At least 127 records · Page 7Linked to original sources
PubMed1998

Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation.

BACKGROUND: Concentrations of pro-inflammatory cytokines are increased in the intestinal mucosa of patients with active inflammatory bowel disease (IBD). Polymorphonuclear neutrophil granulocytes (PMN) are the most abundant cell type in intestinal lesions in IBD. Interleukin 10 (IL-10) is an important contra-inflammatory cytokine which induces downregulation of pro-inflammatory cytokines. AIMS: To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro-inflammatory cytokines and can be regulated by IL-10. METHODS: Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT-PCR) of pro-inflammatory cytokines (IL-1 beta, TNF-alpha) and of IL-1 receptor antagonist were assessed in peripheral PMN. RESULTS: PMN from patients with IBD are primed to secrete enhanced amounts of pro-inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL-10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSIONS: PMN are an important source of pro-inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL-10.

Adolescent↗
PubMed1998

Adaptation of gastric mucosa to stress. Effect of ranitidine.

Gastric mucosal adaptation to injury by repeated application of stress is a well known phenomenon. This study was designed to determine the effect of gastric acid inhibition by ranitidine on gastric adaptation to repeated exposures to stress. In this study stress 3.5 h of water immersion and restraint stress (WRS) was provoked once in rats with and without pretreatment of ranitidine (40 mg/kg/s.c.) and gastric adaptation was examined by repeated exposures to 3.5 h of WRS applied every other day for up to 8 days with pretreatment with vehicle (control), with pretreatment with ranitidine (40 mg/kg/s.c.) and with withdrawal of ranitidine prior to the last exposure to WRS. Luminal acidity, mean lesion number, histology and cell proliferation (PCNA-labeling index) were determined and the expression of EGF and TGF alpha was assessed by immunohistochemistry. Pretreatment with ranitidine increased significantly luminal acidity and WRS applied once with ranitidine pretreatment resulted in a significant decrease of number of lesions. Gastric mucosa adapted to repeated WRS did show a reduction in the mean lesion number by about 60% as compared to that induced by WRS applied once. About 3 fold increase in the expression of EGF was observed in the group adapted to repeated WRS. Expression of TGF alpha was not significantly different from that in intact rats. We conclude that gastric adaptation to stress leads to a decrease in gastric lesions and to an increase in expression of EGF. Pretreatment with ranitidine that induces achlorchydria results in additional reduction in the number of stress lesions.

Adaptation, Physiological↗
PubMed1997

Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial.

BACKGROUND: Anemia often complicates Crohn disease and affects quality of life. OBJECTIVE: To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease. DESIGN: Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase. SETTING: University-based gastroenterology outpatient clinic. PATIENTS: 40 patients with Crohn disease and a hemoglobin concentration of 10.5 g/dL or less. INTERVENTION: All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo. MEASUREMENTS: Response was defined as an increase in hemoglobin concentration of 2 g/dL or more. RESULTS: 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03). CONCLUSIONS: Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.

Adolescent↗
PubMed1997

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Adjuvants, Pharmaceutic↗
PubMed1997

Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease.

Adult↗
PubMed1997

Increased gastric and intestinal permeability in patients with Crohn's disease.

OBJECTIVES: Patients with Crohn's disease exhibit marked changes in intestinal permeability that can be assessed by lactulose and mannitol. Sucrose is a novel marker for gastric permeability. We combined these three sugars to investigate whether patients with Crohn's disease demonstrate changes in gastric permeability and if so, whether these changes are matched with altered intestinal permeability. METHODS: Fifty patients with Crohn's disease and 30 healthy subjects each drank a solution containing 20 g of sucrose, 10 g of lactulose, and 5 g of mannitol. Patients' and subjects' 5-h sugar urinary excretion levels were determined by high performance liquid chromatography and an enzymatic method (sucrose). Furthermore, patients with Crohn's disease underwent endoscopy of the upper GI tract and were grouped according to endoscopic and histological findings. RESULTS: Patients with Crohn's disease showed higher gastric and intestinal permeability compared with healthy control subjects. Gastric permeability was correlated with intestinal permeability. Patients with granuloma had more pronounced changes in both gastric and intestinal permeability than patients with various endoscopic and histological lesions. Patients with normal mucosa had normal permeability. CONCLUSIONS: Alterations in gastric mucosa caused by Crohn's disease are reflected by changes in gastric permeability and can be used to noninvasively screen for Crohn's disease involvement of the upper GI tract.

Adolescent↗
PubMed1996

Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.

BACKGROUND: Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels in such patients. METHODS: Thirty-four patients with inflammatory bowel disease (15 with ulcerative colitis and 19 with Crohn's disease) and anemia refractory to iron therapy (hemoglobin concentrations below 10.0 g per deciliter [6.2 mmol per liter]) were randomly assigned in a prospective, double-blind, 12-week trial to receive either oral iron (100 mg per day) and subcutaneous erythropoietin (150 U per kilogram of body weight twice per week) (n=17) or oral iron and placebo (n=17). The primary measure of efficacy was an increase in hemoglobin levels of more than 1.0 g per deciliter (0.62 mmol per liter). Additional analyses were performed with other patients with inflammatory bowel disease. RESULTS: The severity of anemia was related to clinical disease activity as well as to in vitro monocyte secretion of interleukin-1 beta, a proinflammatory cytokine. Serum erythropoietin concentrations were increased in 52 randomly selected outpatients with inflammatory bowel disease and anemia, but the concentrations were inadequate in relation to the degree of anemia. Twelve weeks of therapy with recombinant erythropoietin and oral iron increased mean (+/-SE) hemoglobin concentrations from 8.81+/-0.27 g per deciliter (5.47+/-0.17 micromol per liter) to 10.52+/-0.41 g per deciliter (6.5+/-0.25 micromol per liter), whereas hemoglobin concentrations in the placebo group decreased from 8.69+/-0.11 g per deciliter (5.4+/-0.068 micromol per liter) to 7.84+/- 0.33 g per deciliter (4.9+/-0.2 mmol per liter) (P<0.001). After 12 weeks, hemoglobin levels had increased by more than 1.0 g per deciliter in 82 percent of the patients in the erythropoietin group, as compared with 24 percent of those in the placebo group (P=0.002). There were five treatment failures in the placebo group and two in the erythropoietin group (P=0.18); treatment failure was defined as a decrease in hemoglobin levels of more than 2.0 g per deciliter (1.24 micromol per liter) to a value below 8.0 g per deciliter (4.96 micromol per liter) or any decrease to less than 6.5 g per deciliter (4.03 micromol per liter). CONCLUSIONS: In patients with inflammatory bowel disease and anemia refractory to treatment with iron and vitamins, treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels.

Adolescent↗
PubMed1996

Relationship between the use of unconventional therapies and disease-related concerns: a study of patients with inflammatory bowel disease.

We studied the use of unconventional therapies of a well-defined population of 105 patients with inflammatory bowel disease (IBD; 72 with Crohn's disease and 33 with ulcerative colitis) who were attending a university out-patient clinic. The following items were used to compare those patients who used unconventional therapies with those who did not. We compared disease-related data, sociodemographic variables, patients' disease-related concerns, and their perceived level of information about IBD. Concerns were measured with the Rating Form of IBD Patient Concerns (RFIPC), inflammatory disease activity was assessed by physicians with the Crohn's disease activity index (CDAI) and the clinical activity index (CAI). Of the 97 (92.4%) patients who answered all questions, 33 (34%) reported using unconventional therapies in addition to conventional therapy. In their level of information about IBD and in their clinical and sociodemographic data, they were not different from the IBD patients who were not using alternative treatments. In their duration of disease, there was a significant difference (p < 0.0002). The longer the disease duration, the more often patients used unconventional therapies. The most important differences between users and nonusers were the following: patients who used unconventional therapies were more concerned about having surgery (p < 0.001), being treated as different (p < 0.04), and feeling out of control (p < 0.05). We conclude that there is a relationship between the use of unconventional therapies and some disease-related concerns, which should be considered in clinical practice. This may help these patients avoid using unproven and expensive alternative therapies.

Adult↗
PubMed1996

Multiple fistulas and tracheobronchial stenoses require extensive stenting of the central airways and esophagus in squamous-cell carcinoma.

We report here on two cases of double airway and esophageal stenting in patients with multiple esophagotracheal fistulas and stenoses of the airways and esophagus due to squamous-cell carcinoma. Dumon stents and a Strecker device were used for tracheobronchial stenting. Covered Gianturco Z-stents were implanted into the esophagus. In one case, extrinsic compression of the trachea and tumor progression required recanalization by Nd:YAG laser. Clinical improvement led to discharge of the patients within two weeks after the procedure. The results show that simultaneous implantation of stents in the central airways and covered Gianturco Z-stents in the esophagus is an effective therapeutic strategy in patients with tracheal and esophageal obstructions and esophagorespiratory fistulas. Further systematic studies evaluating double stenting are warranted.

Aged↗
PubMed1996

Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn's disease. German/Austrian Budesonide Study Group.

OBJECTIVE: Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred). DESIGN: This was a prospective multicentre, randomized, double-blind, double-dummy study. METHODS: A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks. RESULTS: Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015). CONCLUSIONS: Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.

Administration, Oral↗
PubMed1995

Prospective evaluation of interferon-alpha in treatment of chronic active Crohn's disease.

Several case reports suggested good effects of interferon-alpha in patients with Crohn's disease. In addition, a decreased production of interferon-alpha in Crohn's disease has been shown in vitro. Treatment with interferon-alpha may activate intestinal natural killer cells and down-regulate the overproduction of inflammatory cytokines like interleukin-6 in Crohn's disease. To evaluate the clinical efficacy of interferon-alpha, we treated 12 patients with a chronic active course of Crohn's disease with recombinant human interferon-alpha prospectively for 24 weeks. Prednisolone was continuously tapered and discontinued at week 12. The end point of the study was the prevention of worsening of clinical symptoms defined with the Crohn's disease activity index and was monitored by acute-phase proteins, interleukin-6 serum concentrations, and endoscopy. The biochemical activity of interferon-alpha was measured by 2',5'-oligo adenylate serum levels. The end point of the study was reached in four patients (33%). In these patients the final Crohn's disease activity index was above 150, which means that they did not achieve clinical remission. All other patients (66%) did not respond to interferon-alpha and had to be withdrawn prematurely. Interferon-alpha did not show any beneficial effect on interleukin-6 or acute-phase protein concentrations and on endoscopic activity. The 2',5'-oligo adenylate levels continuously increased during interferon therapy. Considerable side effects were noted. These results fail to demonstrate a therapeutic role of interferon-alpha in chronic active Crohn's disease.

Adenine Nucleotides↗
PubMed1995

Screening for celiac disease in first-degree relatives of patients with celiac disease by lactulose/mannitol test.

OBJECTIVES: In first-degree relatives of celiac patients, the risk of oligosymptomatic celiac disease is elevated. These individuals therefore also have a higher potential for malignancy or nutritional deficiencies. Lactulose/mannitol permeability is increased in untreated celiac patients and has been recommended to screen for celiac disease. We investigated the usefulness of a lactulose/mannitol home test kit for screening first-degree relatives home test kit for screening first-degree relatives of celiac patients. METHODS: The lactulose/mannitol test was performed at home by 111 first-degree relatives. These subjects received the test kit from celiac index patients, were instructed by an information sheet how to carry out the test, and were asked about their symptoms by questionnaire. When lactulose/mannitol permeability was abnormal, endomysial antibodies were tested by immunofluorescence. Any relatives with positive endomysial antibodies were then biopsied. To investigate the specificity of the lactulose/mannitol test for celiac disease, 40 patients with nonspecific gastrointestinal symptoms were tested. RESULTS: Lactulose/mannitol permeability was elevated in 34 (31%) relatives, but only nine (8%) of those relatives showed positive endomysial antibodies. Flat mucosa was found in all nine relatives after biopsy. The prevalence of celiac disease was much higher (42%) among 12 relatives who contacted the outpatient clinic themselves because of symptoms. Seventy-one percent of the remaining 21 relatives with elevated permeability demonstrated normal intestinal permeability at a control test within 1 yr. CONCLUSION: By combining the lactulose/mannitol test with endomysial antibody testing, we have developed a good strategy for use in screening for celiac disease among first-degree relatives.

Adolescent↗
PubMed1995

Budesonide in glucocorticoid dependent chronic active Crohn's disease; a pilot study.

Patients with chronic active Crohn's disease are dependent on systemic glucocorticosteroids. The aim of the study was to investigate the efficacy of budesonide, a topically selective glucocorticosteroid, as therapy in these patients. We investigated 20 patients with chronic active Crohn's disease. During the last 6 months prior to the study the patients had a median Crohn's disease activity index (CDAI) of 193 (interquartile range: 122-230) (monthly controls) with a median prednisolone dosage of 14 mg per day (9-20). Budesonide was given 3 to 6 mg daily and prednisolone was weaned within one month. The patients were seen monthly for 6 months. Treatment was considered not successful, if under budesonide therapy CDAI was above 200 and increased more than 60 points despite weaning of prednisolone. Only 5 patients remained in the study for 6 months without deterioration. All other patients (75%) dropped out. The reasons for drop out of the study were worsening in 11 cases, the occurrence of extraintestinal manifestations without signs of severe intestinal inflammation in one case and noncompliance in 3 cases. Worsening could be confirmed by an increase not only of CDAI but also of biochemical parameters of inflammation in all cases. Our data show clearly, that in the dosage investigated budesonide was not effective in chronic active Crohn's disease. Further investigations are needed to evaluate higher dosages of budesonide versus conventional glucocorticosteroids.

Administration, Oral↗
PubMed1995

Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure.

The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and N-acetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cltot) of Ala-Tyr was higher than of Gly-Tyr (3,169 +/- 214 vs. 1,780 +/- 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 +/- 29 mL/kg/min, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 +/- 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cltot of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 +/- 38.4 vs. 484.4 +/- 41.4 mL/kg/min, P < .001) and half-life (kle) was retarded from 14.4 +/- 1.4 to 90.2 +/- 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac-Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala-Tyr, for the first time, enables a simple rapid nonisotope evaluation of tyrosine kinetics for assessment of liver function.

Adult↗