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ABSTRACT: In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.
Transplantation Proceedings 11/2010; 42(9):3880-2. · 1.00 Impact Factor
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ABSTRACT: A 52-year-old woman was hospitalized with fever after a 3-week stay in tropical Kenya. Prophylaxis against malaria had been carried out with chloroquine.
Falciparum malaria with 28% parasitaemia at first examination, rising to 50% after 3 hours.
Treatment with quinine dihydrochloride i.v. was initiated immediately after diagnosis. In addition, in view of increasing parasitemia of up to 50%, a partial exchange blood transfusion was carried out. No clinical signs of organ damage caused by malaria were observed. Because of a drop in blood pressure the patient needed catecholamine treatment for a short time. After decrease of the parasitemia the patient rapidly recovered and complete cure was achieved.
Despite extremely high parasitemia the clinical signs were unusually mild. Standard treatment for severe malaria is intravenous administration of quinine. However, this drug is no longer sold in Germany, so that difficulty in obtaining it must be expected. A stockpiling of quinine is recommended for hospitals treating patients with malaria. Transfusion may improve outcome and must be considered if parasite counts are high or if there are clinical signs of malaria complications.
DMW - Deutsche Medizinische Wochenschrift 10/2006; 131(37):2010-2. · 0.53 Impact Factor
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08/2006: pages 389-395;
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ABSTRACT: Glucocorticoids (GC) play a major role in the attenuation of inflammation. Glucocorticoid receptor (GR) expression is an important determinant of steroid sensitivity.
To investigate whether GR mRNA expression is altered in inflammatory bowel disease, and whether GR mRNA expression correlates with disease activity and may predict response to GC therapy.
Mucosal biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24 ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and correlated to endoscopic findings, clinical activity and outcome of GC therapy. In a subset of subjects GR localisation was shown by immunohistochemistry.
In patients with inflammatory bowel disease GR expression was not different from controls. However, GR was decreased in biopsies from ulcerative colitis patients with impaired GC response. The inhibitory subtype GRbeta was expressed 100-1000 times lower than GRalpha. GR immunoreactivity was identified in immune and epithelial cells except for colonic crypts.
In inflammatory bowel disease systemic and mucosal GR mRNA expression is not altered. However, in ulcerative colitis patients, low mucosal GR expression may predict the outcome of GC therapy. The low expression of GRbeta challenges its role in steroid refractoriness in inflammatory bowel disease.
Alimentary Pharmacology & Therapeutics 02/2004; 19(1):47-61. · 3.77 Impact Factor
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ABSTRACT: Glucocorticoids are potent anti-inflammatory drugs widely used in the treatment of inflammatory bowel disease, but many patients do not benefit from glucocorticoid therapy (glucocorticoid resistance) or need inappropriately high doses to retain remission (glucocorticoid dependency). Because of the role of intestinal epithelial cells in inflammatory bowel disease we examined glucocorticoid receptor signaling and the effect of interleukin-1beta as one of the main proinflammatory cytokines in the intestinal epithelial cell lines IEC-6 and Caco-2.
Dexamethasone effects on transcriptional activation was measured by reporter gene assay using a construct containing glucocorticoid-responsive elements. The transrepressive effect was monitored by a nuclear factor (NF) kappaB inducible reporter construct. In addition in IEC-6 cells immuncytochemistry was used to monitor glucocorticoid receptor translocation.
Dexamethasone induced receptor-mediated reporter gene transcription and receptor translocation, while interleukin-1beta significantly inhibited dexamethasone effects. Dexamethasone inhibited interleukin-1beta induced, NF-kappaB driven gene transcription only in IEC-6 and not in Caco-2 cells. However, in Caco-2 cells glucocorticoid receptor overexpression resulted in a marked decrease in NF-kappaB activity even in absence of dexamethasone.
These studies demonstrate that glucocorticoid receptor driven gene regulation in intestinal epithelial cells may contribute to the anti-inflammatory effects of glucocorticoids in inflammatory bowel disease. Our data are consistent with the notion that interleukin-1beta produced during inflammatory response induces steroid resistance, which is a common clinical problem in treating patients with inflammatory bowel disease.
International Journal of Colorectal Disease 12/2001; 16(6):377-83. · 2.38 Impact Factor
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The American Journal of Gastroenterology 08/2001; 96(7):2273-4. · 7.28 Impact Factor
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ABSTRACT: A variety of speculations about the possible origin and physiological role of the neurohormone melatonin in the gastrointestinal tract exist. However, the experimental evidence supporting any of these theories is not substantial and are missing for humans. We studied the distribution of melatonin which was measured with radioimmunoassay in the following compartments and organs of the human hepatobiliary-gastrointestinal tract: bile (obtained by endoscopic retrograde cholangiopancreaticography), peripheral venous and portal venous blood (obtained from patients undergoing liver transplantation), endoscopically derived biopsies (mainly consisting of mucosa and submucosa) of stomach, duodenum, large intestine as well as in resected liver tissue. Melatonin concentrations in gastrointestinal mucosa were between 136 +/- 27 pg/100 mg (stomach) and 243 +/- 37 pg/100 mg (descending colon, each n = 5). Biliary melatonin concentrations (85 +/- 45 pg/ml) correlated well with plasma concentrations (55 +/- 38 pg/ml, each n = 14) and a considerable amount of melatonin (about 51 ng/24 hours) appears to be excreted into the gut via the bile duct. Melatonin concentrations were slightly higher in portal than in peripheral venous blood and also the liver contained higher concentrations of melatonin than the blood. In conclusion the presence and distribution of melatonin in human gut, bile, liver and portal blood and the various reports on modulatory actions of melatonin on gut and liver functions suggest that melatonin may act as a mediator of inter-organ communication between gut and liver.
Life Sciences 07/2001; 69(5):543-51. · 2.53 Impact Factor
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ABSTRACT: A 34-year-old woman, being treated with oral mesalazine for colitis, developed upper abdominal pain radiating to the back one week after the drug was started, but the symptoms quickly regressed after mesalazine had been discontinued. The patient was admitted about 15 months later because of watery diarrhoea and lower abdominal pain. Physical examination revealed dehydration and pain on pressure over the lower abdomen.
Coloscopy demonstrated Crohn's disease of the colon, more marked on the left. Laboratory tests indicated inflammatory disease.
During treatment with oral prednisone and mesalazine enema the diarrhoea and laboratory parameters of inflammatory disease regressed. But 10 days after the start of treatment the patient complained of upper abdominal pain radiating to the back. Amylase and lipase levels were, respectively, four and twelve times normal. Ultrasound demonstrated an enlarged head of the pancreas, while endoscopy of the oesophagus, stomach and duodenum was unremarkable. 3 days after prednisone and mesalazine had been discontinued the symptoms had regressed and laboratory tests were normal. The symptoms did not recur when prednisone was administered again.
Mesalazine may cause an acute pancreatitis when given either orally or by rectal infusion.
DMW - Deutsche Medizinische Wochenschrift 12/2000; 125(44):1328-30. · 0.53 Impact Factor
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European Journal of Clinical Pharmacology 09/2000; 56(5):439-40. · 2.85 Impact Factor
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ABSTRACT: Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa.
Archiv für Experimentelle Pathologie und Pharmakologie 02/2000; 361(1):85-91. · 2.65 Impact Factor
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ABSTRACT: According to its different location, clinical features, treatment modalities and prognosis, intrahepatic cholangiocarcinoma should be well differentiated from proximal bile duct carcinoma. There is no therapeutic measure with curative potential apart from surgical treatment. Partial or extended hepatectomy is the treatment of choice in cholangiocarcinoma. Thereby, hilar resection in combination with hepatectomy is increasingly performed in proximal bile duct carcinomas. In most centers liver transplantation is not considered as a therapeutic option for irresectable cholangiocarcinomas.
Zentralblatt für Chirurgie 02/2000; 125(7):637-41. · 1.02 Impact Factor
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ABSTRACT: Renal-transplant patients who are immunosuppressed with cyclosporin A (CyA) are often treated with proton-pump inhibitors to prevent ulcer disease. No data are available on the effect of the novel proton-pump inhibitor pantoprazole on CyA levels.
In a controlled treatment, we investigated the effect of pantoprazole, which was administered in a pragmatic schedule for acid suppression (40 mg as single oral dose at 2200 hours) in six renal-transplant patients who received CyA (Sandimmun optoral, 50-175 mg twice daily) and prednisolone (5-7.5 mg/24 h). CyA trough levels (0730-0800 hours) were measured by immunoassay.
In the absence of pantoprazole, mean CyA trough levels measured on three consecutive days were between 164 ng/ml and 173 ng/ml (therapeutic range 120-200 ng/ml). Pantoprazole did not affect CyA trough levels during an observation period up to 3 months long.
Pantoprazole seems to be a safe drug in combination with CyA.
European Journal of Clinical Pharmacology 02/2000; 55(10):733-5. · 2.85 Impact Factor
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ABSTRACT: Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 M) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 M) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 M), somatostatin (1 M) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 M) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa.
Archiv für Experimentelle Pathologie und Pharmakologie 12/1999; 361(1):85-91. · 2.65 Impact Factor
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ABSTRACT: A 29-year-old hemophiliac with HIV infection for which he was receiving antiretroviral treatment (ART) with indinavir, zidovudine and zalcitabine reported increasing swelling of the neck. Physical examination noted a soft to doughy swelling, not sensitive to pressure, extending from the neck to between the shoulder blades.
Ultrasonography and magnetic resonance imaging revealed the swelling to consist of an accumulation of subcutaneous fat without capsule. Cytology demonstrated benign fatty tissue. Blood triglycerides totalled 667 mg/dl.
The typical location, absence of a capsule and the cytological finding confirmed the clinical diagnosis of drug-induced benign symmetrical lipomatosis (BSL, also called peripheral lipodystrophy) in ART. A connection with the hyperlipoproteinaemia is supported by the observation that the patient used to have a normal fat metabolism; the onset of BSL coincided with a massive increase in triglyceride levels. The hyperglyceridaemia and clinical signs improved on a low-fat diet.
BSL can occur in the course of ART in HIV infection, when reverse-transcriptase inhibitors or protease inhibitors are being taken. Medication should not be changed, when antiretroviral treatment is adequate. To reduce the symptoms low-fat diet should be tried, as well as administration of HMG-CoA-reductase inhibitors or, if necessary, surgical liposuction.
DMW - Deutsche Medizinische Wochenschrift 01/1999; 123(50):1512-6. · 0.53 Impact Factor
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Der Internist 12/1998; 39(11):1188. · 0.30 Impact Factor
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Italian journal of gastroenterology and hepatology 07/1998; 30(3):283-4.
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ABSTRACT: The effects of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists were studied on the release of 5-HT from enterochromaffin cells of incubated strips of porcine and human small intestine. Tetrodotoxin (1 micromol/l) was present in the incubation medium to block neuronally mediated inputs to the enterochromaffin cells. The 5-HT1A receptor agonist (+)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 1 micromol/l) and the 5-HT2 receptor agonist alpha-methyl-5-HT (1 micromol/l) increased 5-HT release by 40% in about 60% of the human preparations. These agonists showed no effect on 5-HT release in porcine intestinal mucosa. The 5-HT3 receptor agonist 2-methyl-5-HT (3-100 micromol/l) increased 5-HT release in both species by 60% (pig) and 90% (man), respectively. These stimulatory effects were antagonized by tropisetron (10 nmol/l). The 5-HT4 receptor agonist 5-methoxytryptamine (0.3-30 micromol/l) reduced 5-HT release by about 50% in both species. These inhibitory effects were antagonized by tropisetron (3 micromol/l). The basal outflow of 5-HT from the intestinal mucosa was not significantly affected by tropisetron (10 nmol/l; 3 micromol/l). The specific 5-HT4 receptor antagonist GR 113808 ((1-[2-methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-ind ole-3-carboxylate) (0.1 micromol/l) which by itself did not significantly affect 5-HT release from human duodenal specimens blocked the inhibitory effect of 5-methoxytryptamine (30 micromol/l). These findings indicate that stimulatory 5-HT3 and inhibitory 5-HT4 receptors are present on enterochromaffin cells of the porcine and human intestinal mucosa. Under the present experimental conditions endogenous 5-HT does not significantly activate these receptors. Stimulatory 5-HT1A and 5-HT2 receptors may additionally be present on human enterochromaffin cells.
Archiv für Experimentelle Pathologie und Pharmakologie 06/1998; 357(5):548-52. · 2.65 Impact Factor
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ABSTRACT: The rare neoplastic cystic adenomas of the pancreas form two groups of tumors: macrocystic mucinous and microcystic serous adenomas. Both entities show specific radiologic and histologic features. Several recent case reports, however, suggest some diversity within the group of microcystic serous adenomas. We present the case of a young man operated because of epigastric pain for 12 months and a palpable microcystic tumor of the pancreatic head. Multiple cysts communicating with branches of the pancreatic duct in an alveolar-like pattern were demonstrated on endoscopic retrograde cholangiopancreatography. Histologic examination of the specimen confirmed the diagnosis of a serous adenoma of the pancreas. The tumor morphology in this case may suggest a ductal origin of microcystic serous adenomas.
HPB Surgery 02/1998; 11(1):43-9.
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DMW - Deutsche Medizinische Wochenschrift 09/1997; 122(33):1014-9. · 0.53 Impact Factor
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ABSTRACT: Human galanin (hGal) is a 30-residue non-amidated gut-brain peptide that shows considerable sequence divergence compared with galanin (Gal) forms of other species. Conflicting results have been reported with regard to the structural requirements for its modulatory action on gut motility.
We investigated the effect of human and rat Gal and substituted analogues of Gal on the contractility of longitudinal muscle strips of the human colon in vitro.
Both hGal and rGal contracted the preparations in a concentration-dependent and tetrodotoxin-resistant manner without difference in sensitivity. The NH2-terminally truncated peptides hGal (3-30) and rGal (3-29) were inactive, whereas the NH2-terminal fragments, hGal (1-21) and rGal (1-18), remained fully responsive. Single amino acid substitutions at NH2-terminal positions showed divergent results: substitution of Trp2 reduced significantly potency and efficacy, whereas substitutions at positions 1, 3, 4, or 5 did not markedly modify the bioactivity of Gal. Galantide, a high-affinity Gal antagonist in the central nervous system, is a full agonist in human colonic smooth muscle.
The COOH-terminal part of Gal contributes mainly the receptor-binding affinity of the peptide, whereas the NH2-terminal region is essential for biologic activity.
Scandinavian Journal of Gastroenterology 06/1996; 31(5):446-51. · 2.02 Impact Factor
