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Biomedical subjects

W Domschke

Publications and source records attributed to W Domschke.

At least 127 records · Page 7Linked to original sources

Coincidence of cytomegalovirus retinitis and central retinal vein occlusion in a patient with hemophilia B and AIDS.

A 37-year-old man with hemophilia B, acquired immunodeficiency syndrome, and a unilateral cytomegalovirus retinitis developed a central retinal vein occlusion. This vascular complication occurred despite effective antiviral drug treatment with improvement of the fundus and despite decreased blood coagulability due to hemophilia B. Additional analyses of thrombophilic parameters did not reveal hints of systemic thrombophilia, suggesting that toxic and inflammatory effects of cytomegalovirus itself were responsible for the ophthalmologic aggravation.

AIDS-Related Opportunistic Infections↗

Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.

OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Aneuploidy↗

Helicobacter pylori as a possible bacterial focus of chronic urticaria.

BACKGROUND: Chronic urticaria is one of the most frequent skin diseases. Its cause, however, remains unsolved in a large number of cases. Recent investigations pointed to a potential role of Helicobacter pylori infection of the upper gastrointestinal tract as a possible causative agent in chronic urticaria. OBJECTIVE: The aim of this study was to examine the effect of a 14-day eradication therapy on chronic urticaria. METHODS: Thirty patients with chronic urticaria and confirmed H. pylori infection were treated with amoxicillin and omeprazole. Follow-up was conducted over a period of 6 months concerning eradication of H. pylori and remission of urticaria. RESULTS: Only 8 out of 30 patients (26.7%) showed clinical improvement or disappearance of their urticarial symptoms. CONCLUSION: Though our results do not support the preliminary data of previous studies, the role of H. pylori as a possible bacterial focus of chronic urticaria has to be further investigated.

Adult↗

Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial.

OBJECTIVE: To investigate the effectiveness and safety of mycophenolate mofetil in patients with systemic lupus erythematosus who were inadequately controlled with corticosteroids, antimalarials, and other immunosuppressive agents. METHODS: Ten patients with systemic lupus erythematosus (SLE) were treated with 1500-2000 mg mycophenolae mofetil (MMF) daily for a median observation time of 11. 2+/-2.4 (8-16) months in an open clinical trial. The effectiveness and safety of treatment were analyzed using an established disease activity score, clinical status, and laboratory parameters. RESULTS: All patients improved under treatment with no or only minor side effects. The disease activity score (SLAM) decreased statistically significantly from a median of 15.6+/-5.5 to 9.9+/-4.1 after three months (P<0.01) and to 8.0+/-3.3 after six months (P<0.01). Hematologic parameters did not change significantly whereas a reduction of inflammatory markers was observed. Four patients with SLE-nephritis already treated with cyclophosphamide pulse therapy continuously showed a slight improvement of renal function. Prednisolone dosages could be reduced significantly from a median level of 10.0+/-5.1 mg/d before treatment to 4.6+/-3.5 mg/d after six months (P<0.01). CONCLUSION: Mycophenolate mofetil is a promising option in immunosuppressive treatment of patients with moderate and severe systemic lupus erythematosus who did not show a satisfactory response to other immunosuppressives.

Adolescent↗

Standardized grey scale ultrasonography in Graves' disease: correlation to autoimmune activity.

OBJECTIVE: Graves' disease leads to thyroid enlargement and to reduction of tissue echogenicity. Our purpose was to correlate grey scale ultrasonography of the thyroid gland with clinical and laboratory findings in patients with Graves' disease. DESIGN: Fifty-three patients with Graves'disease were included in our study, 100 euthyroid volunteers served as control group. Free thyroxine (FT(4)), TSH and TRAb (TSH receptor antibodies) values were measured and correlated with sonographic echogenicity of the thyroid gland. METHODS: All patients and control persons underwent ultrasonographical histogram analyses under standardized conditions. Mean densities of the thyroid tissues were determined in grey scales (GWE). RESULTS: Compared with controls with homogeneous thyroid lobes of normal size (25.6 +/- 2.0GWE, mean +/- S.D.) echogenicity in patients with Graves' disease was significantly lower (21.3 +/- 3. 3GWE, mean +/- S.D., P < 0.0001). Among the patients with Graves' disease significant differences of thyroid echo levels were revealed for patients with suppressed (20.4 +/- 3.1 GWE, mean +/- S.D., n=34) and normalized TSH values (22.5 +/- 3.6GWE, mean +/- S.D., n=19, P < 0.02). Significantly lower echogenicities were also measured in cases of persistent elevated TRAb levels (19.9 +/- 2.9GWE, mean +/- S.D., n=31) in comparison with normal TRAb levels (22.9 +/- 3.5 GWE, mean +/- S.D., n=22, P < 0.0015). No correlation could be verified between echogenicity and either still elevated or already normalized FT(4) values or the thyroid volume. In coincidence of hyperthyroidism and Graves' ophthalmopathy (19.7 +/- 3.5GWE, mean +/- S.D., n=23) significantly lower echogenicity was measured than in the absence of ophthalmological symptoms (22.3 +/- 3.3GWE, mean +/- S.D., n=30, P < 0.016). Patients needing active antithyroid drug treatment revealed significantly lower thyroid echogenicity (20.3 +/- 3.1 GWE, mean +/- S.D., n=40) than patients in remission (23.7 +/- 3.4 GWE, mean +/- S.D., n=13, P < 0.001). Statistical evaluation was carried out using Student's t-test. CONCLUSIONS: Standardized grey scale histogram analysis allows for supplementary judgements of thyroid function and degree of autoimmune activity in Graves' disease. Whether these values help to estimate the risk of recurrence of hyperthyroidism after withdrawal of antithyroid medication should be evaluated in a prospective study.

Adolescent↗

[Helicobacter pylori and gastric acid secretion].

Helicobacter pylori (H. pylori) infection leads to profound changes in gastric physiology. Several clinical and animal studies have been performed to clarify the influence of H. pylori on gastric acid secretion. Published data, however, are not consistent throughout. Infection of the gastric antrum, which can be observed mainly in duodenal ulcer patients, increases gastrin release and consecutively acid output. The net effect of corpus and antrum gastritis, such as in patients with gastric cancer, is to decrease acid secretion. Chronic H. pylori infection may finally promote gastric atrophy with irreversibly diminished acid secretion but in earlier stages of this infection eradication of H. pylori normalizes gastric secretory activity.

Animals↗

Budd-Chiari syndrome in a patient with factor V Leiden--successful treatment by TIPSS placement followed by liver transplantation.

The causes of Budd-Chiari syndrome (BCS) comprise several diseases leading to thrombophilia. One of the most common thrombophilic disorders is resistance against activated protein C, caused by a single point mutation of the factor V gene. In December 1993, a 22-year-old patient was given a diagnosis of subacute BCS with occlusion of all major hepatic veins. Placement of a transjugular intrahepatic portosystemic stent shunt led to rapid disappearance of ascites and hepatic encephalopathy. During the following two years, recurrent partial occlusions of the shunt were treated by balloon angioplasty. The cause of the BCS still being unknown, in October 1996 we performed extensive laboratory investigations concerning states of thrombophilia and found moderately elevated IgG anticardiolipin antibodies (19.7 U/ml) and a resistance against activated protein C caused by heterozygosity for a point mutation of the factor V gene (1691G-->A; factor V Leiden). As a consequence, oral anticoagulation with coumarin was initiated. In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. Moreover, IgG anticardiolipin antibodies have been negative since then. If BCS is caused by APC resistance, liver transplantation not only treats the chronic liver disease but also cures the state of thrombophilia since factor V is mainly synthesized in the liver.

Activated Protein C Resistance↗

[Can the function of the transjugular intrahepatic portosystemic shunt be evaluated noninvasively by Doppler sonography?].

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment of complications due to portal hypertension. Possible shunt stenosis or shunt occlusion make periodical assessment of stent function necessary. Direct portal venography is the gold standard in morphologic and functional surveillance of TIPS. Controversially discussed is whether Doppler ultrasonography is effective in hemodynamical evaluation of TIPS and sufficient in prediction of shunt dysfunction. In 39 patients, 147 Doppler ultrasonographical examinations were performed and correlated with the results obtained by direct portal venography in TIPS follow-up, 43 of 47 hemodynamically relevant stenoses, including six shunt occlusions, were being diagnosed correctly by Doppler ultrasonography, by assessing maximal flow velocity in portal vein proximal to the TIPS (sensitivity 91.5%; specificity 97%). If Doppler ultrasonographical measurement of maximal flow velocity was performed within the proximal stent itself, sensitivity was only 70.4% and specificity 27%. In conclusion, assessment of portal maximal flow velocity more accurately represents hemodynamical TIPS function than Doppler ultrasonographical measurement within the proximal stent tract itself. Since, according to data presented. Doppler ultrasonography appears to be able to detect hemodynamically significant TIPS stenoses, it might reduce the number of invasive angiographies and thus contribute to more cost-effective follow-up of TIPS patients.

Adolescent↗

[Abrikossoff's tumor--a rare differential diagnosis in neoplastic lesions of the esophagus].

We report the case of a 49-year-old male patient who was referred to our department in February 1998. Due to his complaints of dysphagia and retrosternal pain an upper gastrointestinal endoscopy was performed showing a polypoid lesion of the lower esophagus. This lesion presenting with a wide base and indurated surface was removed by endoscopic snare and forceps biopsies. Histologic and immunohistochemical analyses revealed this lesion to be a benign granular-cell tumor (Abrikossoff's tumor) which is considered to be of neuroectodermal origin. Abrikossoff's tumor is a rare differential diagnosis of polypoid lesions of the esophagus.

Diagnosis, Differential↗

Prospective randomized trial of two different immunoadsorbers in severe systemic lupus erythematosus.

Experiences with extracorporeal therapy in systemic lupus erythematosus have been published over the last 20 years and more. In addition to plasmapheresis, specific adsorption columns have been developed to deplete pathogenic antibodies and immune complexes in the plasma of patients with SLE. We conducted a prospective randomized trial to compare the efficacy of a disposable adsorption column, which contained a specific ligand, phenylalanine (IMPH-350|Pt, Diamed, Köln, Germany) with a regenerable Ig-adsorbing column containing sheep anti-human antibodies (Ig-Therasorb|Pt, Therasorb, München, Germany). Twenty SLE patients inadequately controlled with corticosteroids, anti-malarials, azathioprine or cyclosporine A, had strong evidence of disease in general, or an organ related SLAM score. They were randomized to receive either a perfusion of IMPH-350, or Ig-Therasorb, immunoadsorbed with 2.5 ml of plasma, three times each. The treatment regime was repeated after 4 weeks when the response was limited or non-existent. Response was defined as a reduction in the SLAM score of at least 30%. SLAM scores in the IMPH group decreased from 14.3+/-5.6 to 9.2+/-6.2 after 1 month and to 9.4+/-3.9 after 6 months; corresponding scores in the Ig-Therasorb group were 18.3+/-5. 5 to 11.2+/-7.6, decreasing to 9.2+/-2.9. After 1 month, 8/10 patients in both groups showed a response; after 6 months, 5/10 patients in the IMPH-350 group and 8/10 in the Ig-Therasorb group fulfilled the response criteria. Reduction of dsDNA antibodies directly after treatment was 50.8+/-6.6% in the IMPH-350 group and 61.0+/-8.0% in the IgTherasorb group. Results indicate that immunoadsorption is an additional option in the treatment of severe SLE. Choice of type of immunoadsorber and immunosuppressive treatment has to take into account the severity and chronicity of common disease activity and organ involvement, as well as economic aspects.

Adult↗

Infection of Helicobacter pylori in gastric adaptation to continued administration of aspirin in humans.

BACKGROUND & AIMS: Involvement of Helicobacter pylori in aspirin-induced gastropathy and adaptation to aspirin remains unclear. The aim of this study was to compare gastric damage and adaptation after repeated exposures to acetylsalicylic acid in the same subjects before and after eradication of H. pylori. METHODS: Before and after H. pylori eradication, 8 volunteers were given aspirin, 2 g/day during 14 days. Mucosal damage was evaluated by endoscopy and histological analysis of biopsy samples. Gastric microbleeding, DNA synthesis, prostaglandin E2 generation, and luminal contents of transforming growth factor alpha and its immunohistochemical expression were determined on days 0, 3, 7, and 14 of aspirin course. RESULTS: In all subjects, aspirin-induced gastric damage that reached maximum on day 3. In H. pylori-positive subjects, this damage was maintained at a similar level up to day 14. After H. pylori eradication, the damage was significantly lessened both in endoscopy and histology at day 14 and accompanied by increased mucosal expression and luminal release of transforming growth factor alpha. Prostaglandin E2 generation was significantly greater in H. pylori-positive subjects than after H. pylori eradication, but aspirin treatment resulted in >90% reduction of this generation independent of H. pylori status. CONCLUSIONS: Gastric adaptation to aspirin is impaired in H. pylori-positive subjects, but eradication of this bacterium restores this process.

Adaptation, Physiological↗

Immunoscopy--a technique combining endoscopy and immunofluorescence for diagnosis of colorectal carcinoma.

BACKGROUND: Colorectal carcinoma is a common malignant disease with a high mortality rate. It arises most frequently in adenomas of the colorectum with different grades of dysplasia. Endoscopy and biopsy are among the most reliable diagnostic tools currently available. Diagnosis of malignancy at an early stage is sometimes difficult. This study reports on a new method, "immunoscopy", that combines endoscopy and immunofluorescent diagnostic procedures; it is the first reported use of locally applied fluorescein-labeled antibodies for detection of colorectal carcinomas. METHODS: A monoclonal antibody against carcinoembryonic antigen was fluorescein labeled. In phase I, formalin-fixed tissue samples, and in phase II, postoperative fresh tissue samples from tumorous and nontumorous areas of resected colorectal carcinomas were studied. After being incubated for 10 minutes, specific fluorescence was visualized with a conventional endoscope whose range was increased by means of two narrow band filters. RESULTS: Because of high levels of autofluorescence, evaluation of immunoscopic investigations using formalin fixed tissue (phase I) was not carried out. Immunoscopic investigation with postoperative fresh tissue samples could differentiate between tumorous and nontumorous areas (p < 0.001). Immunoscopic results were compared with data from immunohistochemical investigations with anti-carcinoembryonic antigen on the same tissue samples. CONCLUSIONS: Immunoscopy can differentiate between malignant and benign mucosal areas in fresh tissue samples. The high sensitivity of immunoscopy could potentially make it a useful diagnostic complement to routine endoscopy.

Adenoma↗

Influence of chitosan microspheres on the transport of prednisolone sodium phosphate across HT-29 cell monolayers.

PURPOSE: The present study was performed to investigate the influence of chitosan microspheres on transport of the hydrophilic, antiinflammatory drug prednisolone sodium phosphate (PSP) across the epithelial barrier. METHODS: Microspheres were prepared using a precipitation method and loaded with PSP. Transport studies were performed in a diffusion cell chamber using the polarized human cell line HT-29B6. Porcine small intestine and fluorescence-labeled microspheres were used to investigate penetration ability of microspheres. RESULTS: It was shown that transport of PSP drug solution was not saturable across the cell monolayers (P = 8.68 +/- 8.24 x 10(-6) cm sec-1) and no sodium dependency could be established. EGTA treatment resulted in an increased permeability (P = 18.69 +/- 1.09 x 10(-6) cm sec-1). After binding of prednisolone to chitosan microspheres its permeability was enhanced drastically compared with the drug solution (P = 35.37 +/- 3.21 x 10(-6) cm sec-1). This effect was prevented by EGTA treatment (P = 15.11 +/- 2.57 x 10(-6) cm sec-1). Furthermore the supporting effect of chitosan microspheres was impaired by pH and ion composition of the medium, whereas the effect remained unchanged in cells treated with bacterial lipopolysaccharides. In vitro incubation of fluorescence-labeled microspheres in the lumen of freshly excised intestine revealed a significant amount of the spheres in the submucosa. CONCLUSIONS: Chitosan microspheres are a useful tool to improve the uptake of hydrophilic substances like PSP across epithelial layers. The effect is dependent on the integrity of the intercellular cell contact zones and the microparticles are able to pass the epithelial layer. Their potential benefit under inflammatory conditions like in inflammatory bowel disease, in order to establish high drug doses at the region of interest, remains to be shown.

Animals↗

IL-10 synergizes with IL-4 and IL-13 in inhibiting lysosomal enzyme secretion by human monocytes and lamina propria mononuclear cells from patients with inflammatory bowel disease.

Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated with enhanced monocytic lysosomal enzyme release. In this study, peripheral monocytes and lamina propria mononuclear cells (LPMNC) were isolated from IBD patients and normal controls. Cells were stimulated with lipopolysaccharide after treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using the corresponding p-nitrophenyl glycosides as substrates. Molecular forms of cathepsin D were examined to describe the mode of enzyme release. IL-10 and IL-4 strongly down-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte response was not found with combinations of IL-13 and IL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretion compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressed enzyme release by these cells. Both the precursor and mature forms of cathepsin D were elevated in IBD patients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both the precursor and mature form of cathepsin D. Our results favor the potent clinical utility of combined treatment, thus improving chances of developing effective treatments for human IBD.

Adult↗

Helicobacter pylori-positive peptic ulcer patients do not adapt to aspirin.

BACKGROUND: Recent studies indicate that eradication of Helicobacter pylori might prevent peptic ulcer formation in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). On the other hand, gastric adaptation after repeated exposures to aspirin (ASA) is well documented but the influence of H. pylori on this process remains to be elucidated. AIM: To compare gastric damage and adaptation following repeated exposures to ASA in a group of patients with H. pylori infection, before and after eradication of the bacterium, and in H. pylori-negative controls. METHODS: Eight healthy volunteers without H. pylori infection and eight patients with duodenal ulcer (DU) history and H. pylori infection before and after H. pylori eradication were given ASA 2 g/day for a period of 14 days. Mucosal damage was evaluated by endoscopy and histology of biopsy samples. Gastric microbleeding, DNA synthesis in the gastric mucosa and mucosal expression, as well as luminal content of transforming growth factor-alpha (TGFalpha) were determined on days 0, 3, 7 and 14 of the ASA course. RESULTS: In all patients aspirin-induced gastric damage reached a maximum on day 3. In H. pylori-positive patients, this damage was maintained at a similar level up to day 14, whereas in H. pylori-negative controls and H. pylori-eradicated patients this damage significantly lessened on day 14 and was accompanied by elevated DNA synthesis as well as increased mucosal expression and luminal release of TGFalpha.

Adaptation, Physiological↗

Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole--an open pilot study.

BACKGROUND: The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested. AIM: To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre outpatient care in an open pilot study. METHODS: 163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and 13C-urea breath test before starting and at least 4 weeks after completing treatment. RESULTS: 150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/ 150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by 13C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%). CONCLUSIONS: For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.

2-Pyridinylmethylsulfinylbenzimidazoles↗

IL-4, IL-10 and IL-13 down-regulate monocyte-chemoattracting protein-1 (MCP-1) production in activated intestinal epithelial cells.

Several studies have demonstrated that intestinal epithelial cells play a major role in the initiation and perpetuation of intestinal inflammation by secreting proinflammatory cytokines and chemokines. MCP-1 is suggested to be a chemokine that plays a major part during intestinal inflammation in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4, IL-10 and IL-13 have been described to exert anti-inflammatory properties on various cell types. The aim of our study was to determine the effect of Th2 cytokines on the production of MCP-1 by activated intestinal epithelial cells. We examined Caco-2 cells as well as intestinal epithelial cells which were isolated from surgical specimens. Production of the chemokine MCP-1 was determined under stimulated and non-stimulated conditions. IL-4, IL-10 and IL-13 were added to stimulated epithelial cells under various culture conditions. Supernatants were analysed for cytokine concentrations using ELISAs. Under stimulation with physiological agents like IL-1beta or tumour necrosis factor-alpha (TNF-alpha), we observed markedly increased concentrations of MCP-1 in supernatants of Caco-2 cells and intestinal epithelial cells. IL-4, IL-10 and IL-13 all had the capacity to down-regulate the production of MCP-1 in Caco-2 cells as well as in freshly isolated epithelial cells. Caco-2 cells which were primed with Th2 cytokines 24 h before stimulation were subsequently decreased in their ability to be stimulated by IL-1beta or TNF-alpha for MCP-1 production. As MCP-1 has been shown to play a major role during intestinal inflammation, the in vitro suppression of MCP-1 in enterocytes suggests the in vivo use of regulatory cytokines in patients with active IBD.

Caco-2 Cells↗