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Biomedical subjects

W Petritsch

Publications and source records attributed to W Petritsch.

At least 37 records · Page 2Linked to original sources

Short-term efficacy and long-term outcome of cyclosporine treatment in patients with severe ulcerative colitis.

Cyclosporine A (CyA) has been recommended for the treatment of severe steroid-resistant ulcerative colitis, however, long-term results are scarce. We prospectively followed a treatment plan in 14 patients with severe ulcerative colitis receiving intravenous CyA after failure to respond to at least eight days of standard therapy with prednisolone (1-1.5 mg/kg/day). CyA was delivered in a daily dose of 5 mg/kg i.v. for a mean of 14 days (range 7-28) in addition to ongoing medical therapy. CyA whole blood levels were monitored by HPLC and maintained between 100 ng/ml and 400 ng/ml. Responders were switched to oral CyA (5-7.5 mg/kg/day) for a mean of two months, and steroids were gradually tapered. Eleven patients (79%) initially responded to i.v. CyA, three patients failed to respond and underwent urgent colectomy. Time until response averaged seven days (range 3-13). Four of the eleven responders underwent colectomy because of severe relapse after one, eleven, twelve and 13 months of follow-up. The remaining seven patients were followed for a median of 48 months. During the first year of follow-up three out of seven had a severe relapse and responded to steroids (two patients) or to a further course of i.v. CyA (one patient). During CyA therapy one patient developed staphylococcal sepsis, other adverse events were mild and reversible. The results confirm that CyA is effective in severe steroid-refractory ulcerative colitis. Severe relapse and colectomy are uncommon after the first year of follow-up and the colon preserving effect of CyA can be maintained in up to 50% of patients over a period of four years.

Adult↗

[Diagnosis in chronic inflammatory bowel diseases--report of the Austrian Chronic Inflammatory Bowel Disease Study Group].

Diagnostic procedures in inflammatory bowel diseases (IBD) serve to secure the diagnosis and to optimize treatment. Upon initial diagnosis endoscopy up to the terminal ileum is mandatory including multiple step biopsies. When diagnostic guidelines are followed and adequate clinical information is available, IBD will be correctly classified in about 80 to 90% of cases upon first examination. In contrast endoscopic studies are only of limited value in monitoring treatment. The decision if and when to perform endoscopy during exacerbation of disease must be an individual one. When disease activity is evaluated, a distinction must be made between degree of activity as reflected by laboratory parameters and severity of illness as reflected by the clinical presentation with abdominal complaints, fistulas, abscesses, etc. Distinct activity indices are useful in clinical studies to obtain an objective evaluation of activity and severity of disease. At clinical routine visits questions should not only concern the basic illness but also ask for quality of life and psychosocial status. Only a small number of laboratory tests are needed for basic diagnosis and follow-up. A small bowel enteroclysis should always be performed upon primary diagnosis of Crohn's disease and during the course of disease when there is suspicion of small-bowel involvement. Double contrast barium enema should be limited to special indications as incomplete colonoscopy e.g. due to stenosis or suspected fistula. Sonography is the primary investigation when complications are suspected. CT is useful as an adjunct or when the afore mentioned methods do not show clear findings. NMR is the procedure of choice for detection of pararectal fistulas and abscesses. Transrectal endosonography is comparably good but limited to the experience of the investigators and by patient's tolerability.

Biopsy↗

Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6-hour period.

OBJECTIVE: Quantitative assessment of intestinal absorption of total and single amino acids in a hydrolysed bovine serum albumin solution over a 6-h period. DESIGN: Ten healthy volunteers underwent segmental jejunal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine serum albumin served as protein source. In one set of experiments we used a washout phase before the equilibration period to eliminate any contents present in the test segment. In another set we started directly with the equilibration period. Absorption rates of total and single amino acids were measured over a period of 6 h. RESULTS: Absorption rates remained constant throughout this period and there was no significant difference in absorption rates whether a washout phase was used or not. Absorption rates of total amino acids ranged from 6.4 +/- 1.9 (mean +/- SEM) to 10.7 +/- 0.7 g/h and 30 cm, when a washout phase was used. Percentage absorption of the perfusion load per hour was 24 +/- 7% to 40 +/- 2% with a washout phase. Although a highly concentrated perfusion load was used there was a correlation (r = 0.66, P < 0.05) between absolute concentration in the perfusion solution and the amount of individual amino acid absorbed. Individual amino acids showed a wide range of percentage absorption. Percentage absorption of 50% or more of the perfusion load was seen for alanine, phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption rate was seen for methionine with 86%, the lowest for cysteine with 3%. CONCLUSION: When hydrolysed bovine serum albumin is used, amino acid absorption is constant over a period of 6 h in the human jejunum. A washout phase has no influence on total and single amino acid absorption.

Adult↗

Acetorphan prevents cholera-toxin-induced water and electrolyte secretion in the human jejunum.

OBJECTIVES: Acetorphan is an orally administered inhibitor of enkephalinase in the wall of the digestive tract. It prevents inactivation of endogenous opioid peptides released by submucosal and myenteric neurons. The aim of this study was to examine the effect of acetorphan on jejunal water and electrolyte transport in healthy volunteers under basal conditions and in a state of intestinal secretion induced by a bacterial enterotoxin. DESIGN: Ten volunteers in two groups were studied in an open trial. For the experimental design an intestinal perfusion technique was used. METHODS: Cholera toxin was used to induce intestinal secretion in a model employing segmental perfusion of the human proximal jejunum. Acetorphan was given orally prior to intrajejunal administration of cholera toxin; its effect on intestinal transport was measured over a period of four hours after exposure to cholera toxin. Serum levels of methylthioether of thiorphan as the main metabolite were measured throughout three experiments to assure sufficient drug absorption. RESULTS: Acetorphan had no influence on basal water and electrolyte absorption (133 vs. 140 ml/30 cm x h). In a control group with cholera toxin alone, significant water secretion was induced (131 ml/30 cm x h). Acetorphan completely prevented this secretion by leaving an absorption rate of 27 ml/30 cm x h. Intestinal electrolyte transport was also significantly changed towards absorption by acetorphan. CONCLUSION: Acetorphan can prevent jejunal water and electrolyte secretion induced by cholera toxin. Enkephalins may thus protect the small intestine from enterotoxin-induced secretion.

Adult↗

Combination of cyclosporine, azathioprine and prednisolone for perianal fistulas in Crohn's disease.

OBJECTIVES: Fistulas in Crohn's disease remain a difficult clinical challenge. Rapid improvement with cyclosporine followed by deterioration after discontinuation of this drug has been reported. This study aimed to determine whether fast remission and long-term improvement could be achieved when cyclosporine was administered concurrently with azathioprine and low-dose prednisolone and then be discontinued. METHODS: Nine patients with fistulas were enrolled in this open study. For the first two weeks cyclosporine was administered intravenously at a dose of 5 mg/kg/day. Azathioprine and low-dose prednisolone were also given during this period. After two weeks cyclosporine was administered orally for a further ten weeks while azathioprine and a tapered dose of prednisolone were continued. Effectiveness was evaluated clinically, by a scoring system and by magnetic resonance imaging. RESULTS: With intravenous cyclosporine as part of this regimen, all nine patients went into remission within days. There were no recurrences after changing from intravenous to oral cyclosporine. Cyclosporine was terminated after three months while azathioprine and low-dose prednisolone were continued. Thereafter, four patients did not deteriorate, three deteriorated slightly, and two patients had a recurrence. The CDAI (Crohn's Disease Activity Index) improved from 200 (range 85-350) to 136 (range 26-200) by the end of the third month. Serological markers remained stable after discontinuation of cyclosporine. There were no serious side effects during this triple drug regimen. CONCLUSIONS: The combination of cyclosporine, azathioprine and low-dose prednisolone leads to marked improvement of perianal fistulas in Crohn's disease. Remission occurs quickly under cyclosporine. These remissions can be maintained with azathioprine in a majority of patients.

Adult↗

Acute Budd-Chiari syndrome with fulminant hepatic failure in a pregnant woman with factor V Leiden mutation.

Budd-Chiari syndrome during pregnancy has rarely been reported. This report presents a case of acute hepatic failure in a 20-year-old pregnant woman attributable to Budd-Chiari syndrome with underlying resistance to activated protein C caused by factor V Leiden mutation. The patient delivered a healthy girl by cesarean section in the 31st week of pregnancy. Acute hepatic failure in the 6th week postpartum was successfully treated by emergency liver transplantation, and the patient and her child were doing well at 8-month follow-up. Liver transplantation was lifesaving; normal factor V production by the transplant corrected the underlying coagulopathy. In this patient, latent thrombophilia attributable to activated protein C resistance was apparently aggravated by the hypercoagulable state of pregnancy leading to acute Budd-Chiari syndrome. Activated protein C resistance should be sought as an etiologic factor in patients with Budd-Chiari syndrome.

Adult↗

Evaluation of the pathogenesis of flatulence and abdominal cramps in patients with lactose malabsorption.

Aim of this study was to assess whether the interindividual differences in the development of flatulence and cramps in patients with lactose malabsorption are due to the quantity of malabsorbed lactose or gas accumulation, or if accelerated intestinal transit or increased perception of gas might play a role. Hydrogen breath tests were performed in 43 patients with lactose malabsorption after ingestion of 50 g lactose and, on a separate day, 25 g lactulose. The unabsorbed amount of lactose, small bowel transit time and colonic hydrogen accumulation were assessed in patients who did and did not develop flatulence and cramps after ingestion of lactose. The unabsorbed amount of lactose, small bowel transit time and volume and rate of colonic hydrogen accumulation were the same in patients who did or did not have symptoms after lactose. Patients with flatulence and cramps had a significantly longer time interval between the onset of the increase and peak breath hydrogen concentration (p < 0.05) and a significant correlation between the time of occurrence of peak symptoms and the time of peak breath hydrogen concentration (r = 0.75, p < 0.001). Our data suggest that subjective symptoms of lactose intolerance are not due to the amount of malabsorbed lactose or to the volume or rate of gas accumulation per se, but are related to increased perception of gas.

Adolescent↗

Assessment of the influence of hydrogen nonexcretion on the usefulness of the hydrogen breath test and lactose tolerance test.

The recognition of hydrogen nonexcretion in up to 20% of tested subjects and the large ethnic differences in the prevalence of lactose malabsorption make it necessary to reassess the diagnostic usefulness of the lactose tolerance test and the hydrogen breath test. Both tests were performed in 83 consecutive patients with suspected lactose malabsorption who ingested 50 g lactose. On a separate day a hydrogen breath test was performed after 25 g lactulose. The prevalence of hydrogen nonexcretion was 18%. The diagnostic usefulness of hydrogen breath test was influenced both by the individual threshold for hydrogen excretion and the amount of malabsorbed lactose. In addition to baseline values, breath samples for hydrogen measurements have to be taken at 30, 60, 90, 180, and 240 minutes after ingestion of lactose. For the lactose tolerance test only one measurement of serum glucose at 30 minutes is needed in addition to the baseline measurement. The combination of both tests excludes the influence of hydrogen nonexcretion, but even if a combined diagnostic approach utilizing the lactose hydrogen breath test and lactose tolerance test is used, 6% of patients presenting with symptoms suggestive of lactose intolerance cannot be classified.

Adolescent↗

Prevalence of Helicobacter pylori antibodies in the serum of gastroenterologists in Austria.

Eighty-eight endoscopists (mean age 41 years, range 29-76 years) and a control group of 100 persons of similar ages were investigated for the prevalence of antibodies (ABs) to Helicobacter pylori, using a quantitative enzyme-linked immunosorbent assay (ELISA) to IgG, two semiquantitative ELISAs to IgG and IgA, and a latex test to IgG and IgM antibodies. The prevalence of antibodies to H. pylori in endoscopists was 48% (quantitative ELISA), 56% (semiquantitative ELISA to IgG), 62% (latex test), and 57% by combined evaluation of semiquantitative ELISAS to IgG and IgA. The respective numbers in the control group were 47%, 48%, 48% and 51%. None of the differences was significant. In both groups, endoscopists and controls, there was a significantly higher H. pylori positivity in older subjects compared to younger persons, but there was no difference between the two groups. The prevalence of ABs was independent to the number of endoscopies previously performed, and independent of protective measures taken, such as wearing gloves during the procedures. Antibody titers as measured with quantitative ELISA showed a positive correlation with the length of time the subject had been active as an endoscopist, but no correlation with the total number of endoscopies performed. In conclusion, the prevalence of ABs to H. pylori in endoscopists follows the age-dependent pattern known from the general population. The regular performance of gastrointestinal endoscopies poses no additional risk of infection with H. pylori in Austria.

Adult↗

Effect of 5-hydroxytryptamine antagonists on cholera toxin-induced secretion in the human jejunum.

In rats, the combined administration of the 5-HT2 antagonist ketanserin and the 5-HT3 antagonist tropisetron inhibits cholera toxin-induced intestinal secretion. We investigated whether these agents and the 5-HT3 antagonist ondansetron can inhibit cholera toxin-induced secretion in the human jejunum using a segmental perfusion technique. In a first control period the subjects' jejunums were perfused continuously with a plasma-like electrolyte solution. In a second control period they either received a combination of tropisetron plus ketanserin, or tropisetron or ondansetron alone. Cholera toxin 6.25 micrograms was then administered intrajejunally and the experiments were continued for 4 h. Net water movements during the 4th hour after CT administration minus net water movement during the first control period was used for further calculation and was referred to as net luminal gain. In perfusion studies with tropisetron plus ketanserin resp. ondansetron the net luminal gain of water (+ 161 +/- 26 resp. 189 +/- 28 ml 30 cm-1 h-1, mean +/- SEM) was significantly higher compared to perfusion studies with cholera toxin alone (+ 94 +/- 30). Treatment with tropisetron did not change the CT-induced net luminal gain of water (+ 108 +/- 41). Movements of sodium, chloride, bicarbonate and potassium paralleled the movement of water. In agreement with these observations we found a deterioration of clinical parameters after the end of the perfusion studies in four of five subjects treated with CT 25 micrograms plus ketanserin and tropisetron.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cyclosporin for the treatment of severe ulcerative colitis.

The effect of cyclosporin was evaluated in six patients with severe ulcerative colitis not responding to at least 8 days of standard therapy with intravenous corticosteroids. Cyclosporin (5-7.5 mg/kg/day intravenously) was added while steroid therapy was continued. Five of 6 patients responded after a mean of 7 days and colectomy was not necessary. After 4 weeks three patients achieved clinical remission or had mild symptoms and were weaned from cyclosporin and corticosteroids without exacerbation within the next 7-15 months. Two patients improved and they were put on oral cyclosporin. One of them relapsed after 2 weeks and then responded to high dose corticosteroids. This patient is doing well at 8 months of followup on azathioprine and steroids. One patient stopped oral cyclosporin after 3 months abruptly and then had a relapse. He subsequently improved while refusing any medical therapy. Side effects of cyclosporin occurred in 2 patients but were mild and self limited and did not necessitate discontinuation of the drug. Cyclosporin appears to be effective in a large portion of patients with severe ulcerative colitis who failed to improve on corticosteroids and in whom colectomy would otherwise be considered.

Adult↗

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients.

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Anemia, Refractory↗

Effects of acute respiratory acidosis on water and electrolyte transport in the human ileum.

Animal experiments have shown that acute respiratory acidosis stimulates water, Na and Cl absorption and HCO3 secretion in the ileum. The aim of this study was to investigate whether the human ileum also responds to changes in systemic acid-base balance. Seven healthy volunteers (mean age 24, range 21-29 years) underwent segmental ileal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. A 30 cm test segment was perfused under steady state conditions with a plasma-like electrolyte solution containing PEG as a non-absorbable volume marker. After a control period, respiratory acidosis (blood pCO2 56.2 mmHg, pH 7.29 and [HCO3] 26.4 mmol l-1) was induced by CO2-breathing over a period of 50 min. Acute respiratory acidosis stimulated net HCO3 secretion in patients secreting HCO3 and reduced absorption in patients exhibiting net HCO3 absorption. These changes were immediate and appeared to be at least partly reversible. Net water, Na, K and Cl movement were not affected. The data suggest that HCO3 transport in the human ileum responds to acute respiratory acidosis.

Acid-Base Equilibrium↗

Effect of cholera toxin on the human jejunum.

In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.

Adult↗

[Kala-azar acquired in Croatia].

Six weeks after his return from a two-week vacation in Croatia a 52 year-old janitor from Graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. The spleen was enlarged to 16cm as measured by sonography. Laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum LDH concentration. While repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. The indirect immunofluorescent antibody test (1:128) and a haemagglutination-inhibition test (1:512) showed diagnostic elevations of titers. Therapy with pentostam led to prompt defervescence and resulted in a full recovery of the patient. After six weeks a marked decrease of antibody titers in the haemagglutination-inhibition test (1:16) could be observed. Leishmaniasis has to be considered in patients with fever of unknown origin who return from Mediterranean countries. Despite a negative bone marrow biopsy a diagnosis is possible on the basis of serological tests. This is important because effective therapy is available as illustrated by this patient and because of the fact that the disease runs a lethal course if the diagnosis is missed.

Animals↗

Effect of neuropeptide Y on jejunal water and ion transport in humans.

Neuropeptide Y is a neurotransmitter in enteric and postganglionic sympathetic neurons. In animal models of intestinal water and ion transport, neuropeptide Y decreases stimulated secretion but has no consistent effect on basal transport. In the present study, the effect of neuropeptide Y on jejunal water and electrolyte transport in healthy volunteers was investigated under basal conditions and during intestinal secretion induced by intraluminal administration of prostaglandin E2. The triple-lumen tube technique was used for perfusion of the small intestine with a plasmalike electrolyte solution containing polyethylene glycol as a nonabsorbable volume marker. After an initial control period (saline IV) neuropeptide Y was administered IV at a dose of 400 pmol.kg-1.h-1. Neuropeptide Y significantly increased net absorption of water, sodium, potassium, and chloride under basal conditions. The peptide significantly reduced the secretion of these electrolytes induced by an intraluminal prostaglandin E2 concentration of 5 mumol/L and reduced net water secretion by 36%. The results of the current study suggest that neuropeptide Y can change intestinal water and ion transport from secretion toward absorption.

Adult↗

Colobronchial fistula: a rare complication of Crohn's colitis.

A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported.

Adult↗