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Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

At least 163 records · Page 9Linked to original sources

[Recurrent Crohn disease--definition and diagnosis].

Recurrence in Crohn's disease is a frequently encountered problem in the history of this chronic incurable disease. A number of studies have shown different recurrence and reoperation rates, which is partly due to different definitions and diagnostic strategies. 'Surgical relapse' as defined as reappearance of disease activity in operated patients, 'clinical relapse' after conservatively induced remission or 'endoscopical recurrence' with new pathological changes in the operated gut may be differentiated. The different definitions of recurrence are discussed and diagnostic procedures like endoscopical, laboratory or radiological methods are explained.

Colonoscopy↗

Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system.

Human intestinal 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. In addition, T cells in the effector compartment of the mucosa bear surface antigens that 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, other markers of memory T cells, as CD29, are 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 Chlamydia trachomatis that show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. These findings indicate a specific state of differentiation of lamina propria T cells that is adapted to the specific requirements in the gut. In inflammatory bowel disease (IBD) and in celiac disease, an increase in the number of CD25-positive activated T cells is found in involved mucosa. It has been shown that mucosal T-cell activation induces epithelial cell damage and mucosal transformation. Thus, a T cell-mediated damage may contribute to the pathogenesis of IBD. HIV-infected patients have a decreased number of CD4-positive T cells in the intestinal lamina propria. The number of CD25-positive activated T cells is also significantly decreased in the intestine compared to controls. Correlating with the presence of HIV-infected mononuclear cells in the mucosa, mucosal atrophy with hyporegeneration and enterocyte dysmaturation is observed. HIV might thus cause impairment and depletion of activated regulatory T cells in the intestinal lamina propria, which could lead not only to a breakdown of the mucosal immune barrier, resulting in a variety of opportunistic infections, but also to malabsorption, due to mucosal atrophy or enterocyte dysfunction. These findings indicate a close relationship between mucosal T cells and enterocyte proliferation and maturation.

Animals↗

Serum carotene deficiency in HIV-infected patients. Berlin Diarrhoea/Wasting Syndrome Study Group.

OBJECTIVE: To assess total serum carotene concentration in HIV-infected patients as an indicator of fat malabsorption in correlation with diarrhoea, secondary enteric infections, and blood lymphocyte subsets. DESIGN: Prospective study. SETTING: Two referral-based tertiary care centres in Berlin, Germany. PATIENTS: A total of 33 controls and 116 HIV-infected patients who had complete microbiological evaluation of stools and biopsies obtained at upper endoscopy because of diarrhoea (n = 54), or other symptoms (n = 62), were studied. MAIN OUTCOME MEASURES: Total serum carotene concentration was determined spectrophotometrically. RESULTS: Total serum carotene concentration was abnormal (< 0.88 mumol/l) in 77% of HIV-infected patients and significantly decreased compared with controls [0.47 mumol/l (range, 0.06-1.69 mumol/l) versus 1.37 mumol/l (range, 0.88-2.92 mumol/l); P < 0.0001]. Total serum carotene concentration did not differ between AIDS patients and patients at earlier disease stages, between patients with or without secondary enteric infections, or between patients with or without fever. In patients at earlier disease stages, but not in AIDS patients, total serum carotene concentration was lower for patients with than without diarrhoea. The percentage of CD4 lymphocytes (r = 0.364; P < 0.001), CD4 count (r = 0.28; P = 0.0013), and CD4/CD8 ratio (r = 0.38; P < 0.001) in the peripheral blood correlated with total serum carotene levels in HIV-infected patients. CONCLUSION: HIV-infected patients frequently have abnormal total serum carotene concentrations indicating fat malabsorption which may contribute to diarrhoea. Furthermore, total serum carotene concentrations correlate with immunologic abnormalities in HIV infection.

CD4-Positive T-Lymphocytes↗

Abnormalities in subset distribution, activation, and differentiation of T cells isolated from large intestine biopsies in HIV infection. The Berlin Diarrhoea/Wasting Syndrome Study Group.

Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.

Acquired Immunodeficiency Syndrome↗

[Gastrointestinal manifestations of HIV infection].

The intestinal (in particular rectal) mucosa is the main portal of entry for HIV in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4-positive T cells, macrophages and follicular-dendritic cells in the intestinal mucosa. HIV may be transported through M-cells directly to mucosal lymph follicles. Alternatively HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4-independent receptor. By successive budding on the basolateral side of the enterocytes HIV may be released into the lamina propria. The loss and functional impairment of activated CD4-positive lamina propria T-cells could be responsible for both the decreased immune defense and altered structure and function of the mucosa. The common intestinal symptoms in HIV-infected patients may be caused by a variety of mechanisms. The high number of secondary opportunistic or non-opportunistic infections and secondary malignancies of the gut may be responsible for the observed symptoms. However, the pathogenic relevance of some of these pathogens is questionable since there is often no correlation between symptoms and presence of the pathogen. In addition, there is a considerable percentage of symptomatic patients without identifiable microorganisms. Yet unidentified pathogens, small intestinal bacterial overgrowth, damage of intestinal nerve fibres, or secretory diarrhea may contribute to the pathogenesis of gastrointestinal symptoms. The findings of a pathogen-negative diarrhea, of HIV-infected mononuclear cells in the gut, and of epithelial hypoproliferation and enterocyte dysmaturation is in agreement with the hypothesis that there is an enteropathy caused by HIV itself.

AIDS-Related Opportunistic Infections↗

Bacillary angiomatosis in a German patient with AIDS.

A 52-year old male homosexual patient with acquired immunodeficiency syndrome (AIDS) presented in our clinic with multiple nodular papules (more than 100) spread over the whole body which had developed within 3 months. Bacillary angiomatosis was suspected, which is a bacterial infectious disease recognized recently mainly in patients with AIDS. Histological and immunohistochemical examinations of extirpated skin lesions were in agreement with the diagnosis, and the detection of rod-shaped bacteria in the lesions by Warthin-Starry silver stain confirmed it. The patient was treated with 2 x 100 mg doxycycline per day. The fever disappeared, and the cutaneous lesions showed a slight tendency to improve. However, after 5 days of therapy the patient showed increasing weakness, with muscle and bone pain. The patient died 10 days after the doxycycline therapy had been started. The cutaneous lesions in bacillary angiomatosis may resemble Kaposi's sarcoma and may therefore be misdiagnosed. The disease may be fatal, but timely antibiotic treatment is usually effective; therefore, the diagnosis of bacillary angiomatosis is important. Although many cases have been reported from the United States, only one case is known from Europe. Our finding of bacillary angiomatosis in a German AIDS patient supports the concept of a worldwide distribution of this bacterial agent.

AIDS-Related Opportunistic Infections↗

Comparison of computed tomography, endosonography, and intraoperative assessment in TN staging of gastric carcinoma.

From 1986 to 1990 a prospective comparative study was undertaken to compare the relative accuracy of computed tomography, endogastric ultrasonography, and intraoperative surgical assessment in evaluating the depth of invasion (T category) and involvement of lymph nodes (N category) of patients with gastric carcinoma. One hundred and eight consecutive patients, who were treated by total gastrectomy and previously evaluated with computed tomography, endogastric ultrasonography, and intraoperative surgical assessment, entered the study. Results (T and N category) were compared with those of histopathological staging (pT and pN category). T categories were correctly staged in 43% of cases with computed tomography, 86% with endogastric ultrasonography, and 56% with intraoperative surgical assessment. Computed tomography scanning correctly staged 51% of all N1 and N2 lymph nodes compared with 74% for endogastric ultrasonography and 54% for intraoperative surgical assessment. In general, computed tomography was more accurate for advanced stages of cancer and showed a tendency to overstage the T category and understage N category of gastric tumours. By contrast, endogastric ultrasonography was equally accurate for all T categories and showed an understaging for N categories. Intraoperative surgical assessment overstaged early T stages, understaged T4 tumours, and was equally accurate for all grades of N categories. Computed tomography scanning and intraoperative surgical assessment of T and N categories were of little value in staging of gastric carcinoma. Endogastric ultrasonography is more accurate than computed tomography scanning and intraoperative surgical assessment. Therefore endogastric ultrasonography should be introduced in the preoperative assessment of patients with gastric carcinoma.

Adult↗

T cell differentiation antigens on lymphocytes in the human intestinal lamina propria.

Recently, T cell subpopulations presumably representing memory T lymphocytes have been described in vitro. Intestinal lamina propria T cells (LP-T) have characteristics resembling those of memory cells. We therefore investigated the expression of surface Ag associated with memory phenotype in vitro on lamina propria lymphocytes (LPL) and PBL and on the T cell subpopulations defined by the bright expression of CD45R0 by flow cytometric analysis of isolated cell populations. LPL had significantly increased percentages of CD45R0 and CD58 positive cells compared with PBL. Whereas PBL showed bimodal expression profiles of CD45R0, CD58, and CD2, the vast majority of LPL was bright for these Ag. Expression of CD45RA was significantly reduced in both frequency and intensity in LPL, and LPL had significantly reduced percentages of CD11a/CD18 and CD29 positive cells compared with PBL. The CD45R0 bright T cell subpopulations of both PBL and LPL were characterized by a lack of CD45RA. CD45R0 bright T cells from the peripheral blood (PB-T) were predominantly bright for CD2, CD58, CD29, and CD11a/CD18 whereas CD45R0 dim PB-T had bimodal expression profiles and CD45R0 negative PB-T were dim or even negative for these Ag. CD45R0 bright LP-T were also bright for CD2 and CD58 but had significantly reduced surface densities of CD11a/CD18 and CD29 compared with CD45R0 bright PB-T. The surface density of CD29 on CD45R0 bright LP-T corresponded to that of CD45R0 negative PB-T, and a significant proportion of CD45R0 bright LP-T was even negative for CD11a/CD18 and CD29. Additionally, CD45R0 bright LP-T in contrast to PB-T were characterized by a lack of 1-selectin and the expression of CDw49a and the mucosa-specific T cell Ag HML-1 on high percentages of cells. Our results show that the phenotype of CD45R0 bright T cells from the lamina propria clearly deviates from that of memory T cells in vitro and of CD45R0 bright T cells in the peripheral blood. We conclude that memory T cell populations in vivo undergo specific differentiation depending on their tissue localization, leading to unique phenotypic and presumably functional features.

Adult↗

Development of ulcerative colitis under the immunosuppressive effect of cyclosporine.

In recent studies, cyclosporine has been used for the treatment of both ulcerative colitis and Crohn's disease. The results of these studies were variable. We report on a patient who was treated for 6 years with cyclosporine after kidney transplantation. He developed chronic distal colitis with all the features of ulcerative colitis. An infectious etiology of the colitis was carefully excluded. High-dose treatment with methylprednisolone was required to induce remission. This report shows that immunosuppressive therapy with cyclosporine did not prevent the development of ulcerative colitis in this patient.

Colitis, Ulcerative↗

Ion transport in the experimental short bowel syndrome of the rat.

The adaptational changes of epithelial ion transport in the short bowel syndrome were studied. Ileal remnants of rats were investigated 8 weeks after 70% proximal small intestinal resection. Pure epithelial resistance measured by impedance analysis decreased from 27 +/- 1 to 21 +/- 1 omega.cm2, and polyethylene glycol 4000 fluxes increased from 2.5 +/- 0.3 to 3.6 +/- 0.3 nmol.h-1.cm-2, indicating increased permeability of the short bowel. Unidirectional flux measurements in control ileum showed absorptive net fluxes of Na+ and Cl- that were assigned to electroneutral NaCl absorption and a short-circuit current that was accounted for by the residual flux (HCO3- secretion). Neither NaCl absorption nor HCO3- secretion were altered in the short bowel. Also, electrogenic Cl- secretion, defined after maximal stimulation by theophylline and prostaglandin E1 was not changed in the short bowel. In contrast, electrogenic Na+/glucose cotransport increased in Vmax from 2.0 +/- 0.3 in controls to 5.0 +/- 1.0 mumol.h-1.cm-2 in the short bowel. Tight junction structure was studied by freeze-fracture electron microscopy. The number of horizontal strands was unchanged, whereas tight junction depth was slightly increased in the short bowel. Microvillus area of short bowels was increased by 20% in villus regions. Under the light microscope, villus height was increased by 30%. In conclusion, the short bowel mucosa undergoes adaptive responses to reduced overall absorptive area by increasing glucose-dependent electrogenic Na+ absorption to 250%, which is partly caused by increased villus and microvillus surface area. Electrogenic Cl- and HCO3- secretion and electroneutral NaCl absorption remained unchanged. The decreased epithelial resistance is caused by mucosal surface amplification.

Adaptation, Physiological↗

Effects of zidovudine treatment on the small intestinal mucosa in patients infected with the human immunodeficiency virus.

Zidovudine is associated with hematologic toxicity and may also impair the rapidly proliferating intestinal epithelium. However, patients with human immunodeficiency virus (HIV) infection receiving zidovudine gain body weight, indicating improved absorptive function. In the present study, 33 HIV-infected patients with gastrointestinal symptoms who were undergoing duodenoscopy and who had no detectable secondary intestinal pathogens were investigated; 12 of them received zidovudine. HIV antigen p24 was detected in duodenal biopsy specimens by immunohistology in 3 of 12 patients with zidovudine treatment and in 10 of 21 patients without zidovudine treatment. Morphometry of duodenal specimens showed reduced villus surface area (P less than 0.05) without crypt hyperplasia independent of zidovudine therapy and reduced numbers of crypt mitoses in patients with mucosal HIV infection (P less than 0.001) compared with controls. In the duodenal brush border, patients with mucosal HIV infection (P = 0.006) and patients without zidovudine treatment (P = 0.009) had absent lactase/beta-glucosidase activity more frequently than controls, and all HIV-infected patients (P less than 0.025) except zidovudine recipients had decreased alkaline phosphatase activity compared with controls. These findings show a hyporegenerative atrophy of the small intestine and enterocyte dysmaturation associated with mucosal HIV infection. Improved enterocyte maturation, indicated by increased brush border enzyme activity, may contribute to the clinical benefit of HIV-infected patients from zidovudine therapy.

Adult↗

Enteric immunologic abnormalities in human immunodeficiency virus infection.

The intestinal mucosa is an important portal of entry of HIV, and HIV-infected mononuclear cells are found in the intestinal lamina propria of 30 to 50% of HIV-infected patients even at early stages of the disease. HIV infection of epithelial cells has not consistently been detected and is still controversial. Intestinal T cells are phenotypically and functionally distinct from circulating T cells, especially in their state of activation and differentiation, which both affect the replication and cytopathicity of HIV. An increase in CD8+ cells and variable decreases in CD4+ cells have been found in the intestinal lamina propria by immunohistologic studies, resulting in a decreased CD4 to CD8 ratio; in addition, CD25 expression is reduced. Changes in intraepithelial lymphocytes are unclear. B-cell differentiation seems to be disturbed because IgA plasma cells and IgA2 secretion are reduced. Depletion or functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the breakdown of the mucosal immune barrier leading to opportunistic diseases; in addition, due to the interrelationship between mucosal immune system and epithelium, these changes might be responsible for the partial bowel atrophy and maturational defects in enterocytes of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Gastrointestinal symptoms in patients infected with human immunodeficiency virus: relevance of infective agents isolated from gastrointestinal tract.

The correlation of gastrointestinal symptoms and infections in 186 consecutive patients with human immunodeficiency virus (HIV) infection undergoing diagnostic endoscopy (oesophagogastroduodenoscopy, n = 124; colonoscopy, n = 37; both, n = 25) was investigated. Biopsy and stool samples were examined for infective agents. Only weight loss (p = 0.003) and dysphagia (p = 0.027) were more common in patients at stage CDC IV compared with earlier stages. In three of 27 patients at stage II/III and in 93 of 159 patients at stage IV an infective agent was identified in stool or gastrointestinal biopsy specimen (p < 0.001). Cytomegalovirus (n = 35), Candida sp (n = 28), M avium complex (n = 10), and Cryptosporidium (eight) were the most frequent agents detected. At stage IV, diarrhoea was more frequent in infected compared with non-infected patients (p = 0.006); however, an infective agent was also found in 39 of 82 patients at stage IV without diarrhoea. The frequency of gastrointestinal symptoms was not consistently increased in patients harbouring specific infective agents compared with non-infected patients. Our findings indicate that the pathogenic relevance of a gastrointestinal infection in HIV infected patients has to be verified and indirectly support the existence of an HIV associated enteropathy.

Adult↗