Search PubMed⌕ Search

Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 181 records · Page 10Linked to original sources
PubMed1992

A phase I trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that both folinic acid and interferon may enhance the efficacy of 5-fluorouracil (5-FU) in colorectal carcinoma. We therefore initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of the combination of recombinant interferon (IFN) alpha-2b with folinic acid (FA) and 5-FU. Seventeen patients with colorectal cancer who failed local chemotherapy received 5-FU as a 4-hour infusion, preceded by a bolus of FA and IFN. The 5-FU dose was escalated over the range of 400 to 650 mg/m2/d for a period of 7 days. Folinic acid was administered as a bolus in a fixed dose of 200 mg/m2/d and IFN as 5 million U/d subcutaneously on days 1 to 7. A total of 89 courses of therapy were completed for the 17 patients, of which there were 10 paired courses with a combination of 5-FU and IFN or 5-FU alone, being performed to analyze the pharmacokinetics and modulation of 5-FU by IFN. The maximum tolerated dose of 5-FU using this combination and a 4-hour schedule was 600 mg/m2/d for 7 days. The dose-limiting toxicity of this regimen was diarrhea. Mucositis and myelosuppression was not a marked problem at dose levels of 400 and 500 mg/m2/d for 7 days. However, at a dose level of 600 to 650 mg/m2/d for 7 days, grade 3 and 4 (WHO) leukopenia occurred in 50% and mucositis occurred in 33%. At a given dose of 5 million U, IFN did not significantly influence 5-FU serum levels. Mean steady-state serum levels of 5-FU at 500 mg/m2 given as a 4-hour infusion were 16.55 +/- 9.34 mumol/L and 18.23 +/- 12.77 mumol/L with and without IFN, respectively. Mean area under the curve (mumol/L x min) was 4,008 +/- 2,133 and 5,114 +/- 2,567 with and without interferon, respectively. Objective responses were seen in one of 17 of these heavily pretreated patients and stable disease was seen in seven of 17 patients. The recommended dose of 5-FU for use of phase II studies is 500 mg/m2/d for 7 days. We conclude that the toxicity of 5-FU plus FA with and without IFN alpha-2b can be reduced by using a 4-hour infusion instead of a bolus.

Adult↗
PubMed1991

AIDS enteropathy.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Intestinal microsporidiosis in a German patient with AIDS.

Since intestinal microsporidiosis might be of importance in the pathogenesis of gastrointestinal symptoms in patients infected with HIV, we examined duodenal biopsies of HIV-infected patients by electron microscopy. Enterocytozoon bieneusi infection of the small intestine was found in one of 23 patients studied, which gives a 95% confidence interval for the prevalence rate between 0.1% and 22%. The infected patient was a 24-year-old homosexual male with AIDS who underwent upper endoscopy because of acute epigastric pain, nausea, and vomiting. These symptoms were obviously due to mesenterial Kaposi's sarcoma obstructing the duodenal passage, as was later revealed at autopsy. However, microsporidiosis might have caused the patient's eight-month history of diarrhea and weight loss, since infected cells showed signs of degeneration, and no other pathogens were ever detected in stool or biopsy. Our finding of Enterocytozoon bieneusi infection in a German AIDS patient supports the concept of a worldwide distribution of this parasite; further studies are needed to define its exact prevalence in HIV-infected patients and its pathogenic relevance.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Phenotype and function of lamina propria T lymphocytes.

Lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells (table 2). In addition, T cells in the effector compartment of the mucosa bear surface antigens which are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors and IL-2 receptor alpha chain mRNA, and are able to synthesize high amounts of IL-2. However, another marker of memory T cells, CD29, is not expressed in high density in the lamina propria indicating that lamina propria T cells differ from 'classical' memory T cells. This is supported by functional studies in nonhuman primates infected rectally with C. trachomatis which show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis (table 2). The intestinal lamina propria therefore contains highly specialized T cells which have a distinctive phenotype and are activated. Functionally these T cells can be characterized as differentiated effector lymphocytes which respond to triggering the antigen-specific T cell receptor by secreting helper factors for B cells. This concept is supported by recent studies showing that the pattern of lymphokines produced by lamina propria T cells and the responsiveness to certain lymphokines differ from those of other lymphocyte populations [25]. Lamina propria T cells thus represent a subset of memory T cells with a unique maturational state.

Animals↗
PubMed1991

Role of lymphokines in immunoregulatory function of mucosal T cells in humans and nonhuman primates.

The findings presented above and in other studies provide substantial evidence that lymphocytes in the intestinal lamina propria differ from lymphocyte populations in the circulation or in other tissue sites in a number of ways. First, lamina propria lymphocytes are phenotypically distinct and have evidence of activation. Lymphocytes in the intestinal lamina propria are different in their potential for expression of lymphokine gene products, since activated cells from the lamina propria have high expression of mRNA for IL-2, IL-4, IL-5 and IFN-gamma in comparison to circulating lymphocytes. Mesenteric lymph node T cells also differ from circulating lymphocytes in their high expression of IL-4 and IL-5 mRNA. A further difference between mesenteric lymph node and lamina propria T cells is that the former are capable of proliferating in response to IL-4, whereas the latter are not. These phenotypic and mRNA differences of lamina propria lymphocytes also correlate well with their high helper activity in vitro for immunoglobulin synthesis in the pokeweed mitogen system. Finally, lamina propria T cells at a site of inflammation are able to provide high helper activity in response to specific antigens. These observations are all consistent with the conclusion that T cells in the lamina propria are pleomorphic, but are highly enriched for subpopulations of activated memory cells that are geared for effector functions. These functions are likely to be critical in maintaining normal host defense in the mucosal environment.

Animals↗
PubMed1991

Comparison of enteral nutrition and drug treatment in active Crohn's disease. Results of the European Cooperative Crohn's Disease Study. IV.

This study compared the effect of enteral nutrition as the sole therapy of active Crohn's disease with drug treatment. Patients with active Crohn's disease (Crohn's Disease Activity Index greater than 200) were randomized to receive either enteral nutrition with a liquid oligopeptide diet (n = 55) or a combination of 6-methylprednisolone, 48 mg daily, subsequently tapered, and sulfasalazine, 3 g daily (n = 52). The two groups were not different with respect to age, sex, body weight, location of disease, or treatment before the study. The severity of disease was similar at the beginning of the study in both groups [Crohn's Disease Activity Index (mean +/- SEM), 323 +/- 12 vs. 316 +/- 11]. Remission was defined as a decrease of the initial Crohn's Disease Activity Index by 40% or at least 100 points. Twenty-nine patients in the diet group and 41 patients in the drug group reached remission within 6 weeks of therapy (chi 2 test, P less than 0.01). The median elapsed time to remission was 30.7 days in the diet group compared with 8.2 days in the drug group (Mantel Cox, P less than 0.01). To determine whether one of these treatments was more beneficial for a subgroup of patients, the effectiveness of both treatments was analyzed separately in patients with very severe disease (initial Crohn's Disease Activity Index greater than 300) and less severe disease (initial Crohn's Disease Activity Index less than 300), and in patients with different disease location. However, no influence of initial disease activity or disease location on the effect of either treatment could be shown. These data show that enteral nutrition is less effective than a combination of 6-methylprednisolone and sulfasalazine in treating active Crohn's disease.

Adult↗
PubMed1991

Evaluation of endosonography in sclerotherapy of esophageal varices.

During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow-up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy.

Esophageal and Gastric Varices↗
PubMed1991

Evaluation of endosonography in TN staging of oesophageal cancer.

Strategies for the treatment of cancer of the oesophagus depend on the tumour stage at the time of diagnosis. Resection, the only curative treatment, is confined to early tumour stages. Tumours with local infiltration are usually unresectable and require palliative treatment. Computed tomography has been widely used for preoperative staging but often fails to define this correctly. Endoscopic ultrasound allows direct visualisation of the parietal wall and may be useful in staging gastrointestinal tumours. In a comparative prospective study, 52 patients with tumours of the oesophagus were investigated preoperatively both by endoscopic ultrasound and computed tomography to determine the stage of tumour infiltration and local lymph node involvement. Thirty seven of these patients underwent operation, resection, or dissection and entered the study. The intraoperative findings or the histopathological assessment, or both, were taken as a reference. For all TN stages of oesophageal tumours, correct preoperative staging was accomplished by endoscopic ultrasound in 89% for T stage and 69% for N stage compared with 51% and 51% respectively by computed tomography (highly significant using Fisher's exact test). This study shows that endoscopic ultrasound is useful in preoperative TN staging of tumours of the oesophagus.

Adult↗
PubMed1990

The HML-1 antigen of intestinal lymphocytes is an activation antigen.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.

Antibodies, Monoclonal↗
PubMed1990

Preoperative staging of gastrointestinal tumors by endosonography.

Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date.

Endoscopy, Gastrointestinal↗