Coronary stenting and use of abciximab.
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Biomedical subjects
Publications and source records attributed to M Zeitz.
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The intestinal mucosa is in close contact with a large number of foreign antigens and mitogenic substances in the gut lumen. To protect the host against invasion of potential pathogens or an inappropriate immune response to the enormous number of antigens, a highly specialized immune system in the intestinal mucosa has developed, the so-called gut-associated lymphoid tissue (GALT). The passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa is called bacterial translocation. Bacterial translocation in critically ill patients may lead to a significant incidence of systemic sepsis. This has attracted much clinical interest, as it has been shown that disturbances of the GALT and malnutrition itself, impair various aspects of barrier function. Enteral nutrition seems to be superior to parenteral nutrition in maintaining the functional barrier of the gut. Defined dietary variable (fibre, glutamine) influence bacterial translocation. Future therapeutic strategies should therefore concentrate on early enteral feeding in traumatised patients to reduce the incidence of bacterial translocation and septic complications.
OBJECTIVE: To investigate differences in viral and proviral load between the peripheral blood and the intestinal mucosal immune system in HIV-infected patients. DESIGN: HIV-1 p24 and HIV DNA content were compared in blood samples and intestinal biopsies from HIV-infected patients. METHODS: Intestinal biopsies and peripheral blood were simultaneously obtained from 27 HIV-infected patients undergoing diagnostic endoscopy. The p24 concentrations were measured in serum and homogenized intestinal biopsies by enzyme-linked immunosorbent assay after acid-dissociation of immune complexes. Proviral load was determined in blood and intestinal biopsies by a quantitative competitive polymerase chain reaction amplifying the HIV-1 nef gene from genomic DNA. RESULTS: No significant differences were found in proviral load comparing HIV copies per 1.5 x 10(5) cell equivalents in blood [2650 (600-44000)] and intestinal biopsies [4200 (1325-19 625)]. Paired analysis revealed a strong positive correlation between serum and mucosal proviral load. In contrast, HIV core protein p24 was detected in intestinal biopsies from 18 patients in much higher concentrations than in serum [858 (262-4111) pg/g versus 34 (9-242) pg/g; P < 0.005]. The p24 concentrations in serum and intestinal biopsies did not correlate and no significant correlation was observed in serum or intestinal biopsies between proviral load and p24 concentrations. No clear correlations were observed between clinical parameters and HIV DNA or HIV p24 levels in blood or biopsies. CONCLUSIONS: Our findings demonstrate a homogenous distribution of HIV proviral load in the peripheral blood and the intestinal mucosal immune system. The high viral antigen load in the intestine therefore indicates that mucosal HIV production is upregulated at the transcriptional and/or translational level. The intestinal mucosa is a major reservoir for HIV in HIV-infected patients.
BACKGROUND/AIMS: Endoscopic sclerotherapy is of proven benefit for patients after esophageal variceal bleeding, but is associated with substantial local and systemic complications. Since fibrin glue is a promising agent for endoscopic sclerotherapy of esophageal varices, we compared its safety and efficacy in patients after esophageal variceal bleeding. PATIENTS AND METHODS: In a randomized, controlled trial, 36 patients with an acute episode of variceal bleeding were endoscopically treated with either polidocanol (18 patients) or fibrin glue (18 patients) by intravariceal injections within 12 h of admission. Tissue compatibility, incidence of various complications, episodes of rebleeding and overall survival rates were investigated. RESULTS: Rebleeding, especially from enrollment to day 28, was less common in the fibrin group (p=0.046), and all patients treated with fibrin glue survived for more than 28 days, whereas five patients treated with polidocanol died within this period. The incidence of sclerotherapy-induced ulcers was significantly lower in the fibrin group than in the polidocanol group (p=0.001), and major complications such as perforation or ulcer bleeding were observed only in the polidocanol group. There were no complications in any group due to activation of systemic coagulation, fibrinolysis or clinically relevant pulmonary embolization. CONCLUSIONS: We conclude that fibrin glue is an efficient and safe agent for endoscopic sclerotherapy of bleeding esophageal varices, especially in the immediate posthemorrhagic period.
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CD44v6 expression appears to be associated with adverse prognosis and propensity for metastasis in patients with colorectal cancer. However, expression of CD44 variants in different tumour stages has been poorly characterised. CD44 variant expression was investigated in normal colonic mucosa (n = 36), colorectal adenomas (n = 15), carcinomas (n = 62) and metastases (n = 6) by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting with exon-specific probes. High frequencies of CD44 standard (CD44s) and CD44 epithelial (CD44e) were observed in normal and neoplastic tissue. CD44v2 was seen predominantly in adenomas (27%) and UICCI carcinomas (29%). CD44v5 expression was low in normal mucosa (3%), higher in adenomas and carcinomas (29-33%), independent of tumour stage. CD44v6 expression was low in normal mucosa (6%) and higher in adenomas (47%) and carcinomas (42%). Surprisingly, a significant decrease of CD44v6 was observed in metastatic primary tumours (8%) and metastases (17%) (UICCIV) (P < or = 0.05). Therefore, the concept of CD44v6 conferring metastatic potential to malignant cells cannot be supported by our data.
We report on a 17-year-old male patient with dysphagia, cachexia, and physical underdevelopment. Despite a known esophageal stenosis, the patient received several months of psychiatric treatment, which failed to improve the clinical picture. After systematic diagnostic procedures, including repeated biopsies of the esophageal stenosis, a cicatricial pemphigoid was diagnosed and adequate therapy could be initiated.
BACKGROUND: Our aim was to study the influence of psychotherapy in addition to a standardized corticosteroid treatment on the somatic and psychosocial course of Crohn's disease. METHODS: In a prospective, randomized multicenter study 108 of 488 patients received either drug treatment or, in the intervention group, additionally psychotherapy in the first half of the 2-year follow-up period. RESULTS: Eighty-four patients (77.8%) completed the somatic and 81 (75%) the psychosocial follow-up. Twenty-three per cent of the control group and 30% of the psychotherapy group showed episode-free courses; 29% and 17%, respectively, underwent surgery due to failure of drug treatment. The main analysis, which was based on subranking by number, duration, and severity of relapses, failed to show significant differences between the two groups (P = 0.125). The same result was obtained for the psychosocial status after 1 year in the main target criteria depression, anxiety, psychosocio-communicative status, and quality of life. CONCLUSIONS: The confirmatory analysis did not prove significantly better courses after additional psychotherapy. There was a tendency towards fewer operations.
A patient with short bowel syndrome as a consequence of multiple intestinal resections for Crohn's disease, had a port system implanted to improve her nutritional status. One year later she presented with fever, weakness and nighttime sweating. Metschnikowia pulcherrima Pitt et Miller was grown in blood cultures from the port system. After antifungal chemotherapy using fluconazole and removal of the implant, the patient's condition improved markedly and her fever and sweating disappeared. We conclude that Metschnikowia pulcherrima can turn into a human pathogen in patients with indwelling catheters for parenteral nutrition. Chemotherapy with fluconazole and, whenever possible, removal of the implant, appear to be adequate treatment.
OBJECTIVES: Tissue overexpression of CD44 variants, especially CD44v6, and elevated serum concentrations of soluble CD44 variants (sCD44) have been demonstrated in patients with colorectal cancer and several other tumors. Our aim was to evaluate the clinical value of their measurement in colorectal cancer. METHODS: To examine the suitability of sCD44 and sCD44v6 as tumor markers in colorectal cancer these parameters were analyzed in serum of patients with colorectal cancer, inflammatory bowel disease, chronic renal failure, and controls. Tissue expression of CD44v6 in colorectal carcinomas was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: sCD44 and sCD44v6 levels were significantly elevated in most of the patient groups (medians, sCD44: 330-709 ng/ml; sCD44v6: 125-160 ng/ml) compared to controls (sCD44: 346 ng/ml; sCD44v6: 106.5 ng/ml). No difference was seen between colorectal cancer patients of different UICC (Union Internationale Contre le Cancer) stages and between patients with CD44v6-positive or -negative primary tumors. CONCLUSIONS: sCD44 and sCD44v6 concentrations showed no correlation to tumor burden or CD44v6 tissue expression. Sensitivity and specificity were low, compared to CEA. Therefore, in our view sCD44 and sCD44v6 measurement in screening or follow-up of patients with colorectal cancer is of very little clinical value.
BACKGROUND: Secretory immunity is a major defence mechanism against infections at mucosal surfaces which are common in HIV infected patients. AIMS: To analyse intestinal immunoglobulin production in HIV infection in comparison with that in saliva and serum. PATIENTS AND METHODS: Immunoglobulin G (IgG), A (IgA), and M (IgM) concentrations were determined in supernatants of short term cultured duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28) and controls (n = 14) by radial immunodiffusion. RESULTS: IgG was increased in the supernatants of short term cultured biopsy samples and saliva from HIV infected patients compared with controls (p < 0.01), but IgA and IgM levels were normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV infected patients than in controls (p < 0.002). No correlation was found between IgA produced by duodenal biopsy specimens and serum IgA. CONCLUSION: Abnormalities in mucosal immunoglobulin production in HIV infection were surprisingly small, indicating that specific secretory immunity rather than quantitative immunoglobulin production may be impaired. However, increased production of IgG could contribute to mucosal inflammation by complement activation. Our findings of normal mucosal IgA production and the lack of correlation between serum and mucosal IgA argues against an intestinal origin for the increased serum IgA levels in HIV infected patients.
BACKGROUND: Immunoregulatory abnormalities of T cells might be of importance in the pathogenesis of pouchitis after ileoanal pouch anastomosis (IAP). AIMS: To characterise T cell subsets, their state of activation, and production of cytokines in inflamed and non-inflamed pouches in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The influence of T cell activation on mucosal transformation was also studied. PATIENTS: Mucosal biopsy specimens were taken from 42 patients with IAP (33 with UC and nine with FAP). METHODS: Mononuclear cells were isolated by standard techniques and characterised by three colour flow cytometry. Interferon gamma (IFN-gamma) production was studied using the ELISPOT technique. RESULTS: In patients with UC with pouchitis there was a significant increase in the CD4:CD8 ratio, expression of activation markers on CD3+ cells, and number of IFNgamma producing mononuclear cells compared with patients with UC without pouchitis (CD4:CD8 ratio 1.3 (range 0.7-2.7) versus 0.6 (0. 1-1.0), p=0.012). In addition, a positive correlation between increased crypt depth and the number of CD4+ cells (r=0.57) was shown. CONCLUSION: The observed increase in activated mucosal CD4+ T cells and IFN-gamma production might lead to mucosal destruction and crypt hyperplasia as seen in pouchitis.
Secretory IgA plays a crucial role in the defense of pathogens at mucosal surfaces. As CD4+ T cells are lost early in the mucosa of human immunodeficiency virus (HIV)-infected patients and as CD4+ T cells play an essential role in the regulation of specific IgA responses to pathogenic agents at mucosal sides, it could be expected that this first line of defense is impaired in HIV-infected patients. Therefore, several studies were undertaken to characterize the humoral immune response at mucosal surfaces. However, the results obtained so far are in part contradictory. For intestinal IgA, reduced, increased and no changes compared to controls were described. The different results may be due to different methods applied. In most studies an abnormal predominance of HIV-specific IgG over IgA response was found in the intestine of HIV-infected patients. Studies on cytomegalovirus-specific intestinal antibodies indicate a complete lack of a specific intestinal IgA response. However, in cryptosporidiosis of HIV-infected patients, diarrhea persists despite a secretory IgA response indicating that other factors are also important for the clearance of this pathogen.
The gastrointestinal tract is not only a major site of clinical manifestations of the acquired immune deficiency syndrome but also an important compartment for HIV infection at all stages of the disease. In intestinal biopsies HIV has been detected so far mainly in mononuclear cells of the lamina propria but also in epithelial cells. Primary and permanent epithelial cell lines can be productively infected by HIV in vitro and epithelial cell monolayers can rapidly transport HIV by transcytosis. Both phenomena are most effective for cell-associated virus and do not require CD4 expression but seem to involve the interaction of gp120 with galactosyl ceramide. In vivo, productive HIV infection of epithelial cells appears to be rare if it occurs at all. Mucosal HIV infection is highly active at all stages of HIV infection and the gastrointestinal tract is probably a major source of HIV in the body. Highest mucosal HIV production is found rather early in HIV disease and is associated with histological abnormalities and gastrointestinal symptoms. The excessive production of HIV in the intestine appears to be due to transcriptional or translational upregulation and local variations in HIV production correlate with local cytokine levels.
The gastrointestinal tract is one of the major target organs for secondary infections and malignancies in HIV infection in humans indicating disturbed local immunologic defense mechanisms. Immunohistology and flow cytometric studies have demonstrated a more pronounced loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood in humans infected with HIV. In parallel, activated CD8+ T cells in the lamina propria are increased in this compartment. In SIV-infected nonhuman primates a very early loss of CD4+ T cells in the intestinal mucosa compared to the peripheral blood occurs already at 2 weeks after infection. Depletion and functional impairment of mucosal CD4+ T lymphocytes with consecutive altered cytokine secretion in HIV/SIV infection may explain the breakdown of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, due to the interrelation between the mucosal immune system and epithelium, these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients.
The primary diagnosis of chronic inflammatory bowel disease (Crohn's disease, ulcerative colitis) is performed by standardized procedures in specialized Gastroenterology Departments or Ambulances. For the assessment of disease activity the clinical presentation of the patient is most important. This is also true for the indication for surgical interventions. In certain instances laboratory markers, endoscopic and histologic examinations, ultrasound, X-ray, and cross-sectional imaging like computed tomography (CT) or magnetic resonance imaging (MRI) give important additional informations. Depending on the clinical situation surgeons and gastroenterologists decide on the most useful technical examinations for planning the operative strategy. After surgery, diagnostic procedures focus on disease progression and complications. Disturbances of intestinal function as consequence of the operation have also to be considered in the routine diagnostic program.
Diclofenac is an anti-inflammatory analgesic which is widely used in the therapy of inflammatory joint pain. Diclofenac hepatotoxicity ranges from asymptomatic elevation of transaminase activity to significant liver disease. 31 cases of diclofenac-induced hepatitis with five associated deaths have been already reported in the English, French and Spanish literature. We report the case of a 64-year-old patient who was admitted to the hospital with an icteric hepatitis of sudden onset. The only drug that was taken before admission was diclofenac in a daily dose of 150-200 mg because of a spondylodiscitis. Work-up of the patient included ERCP, laparoscopy and liver biopsy and excluded other reasons of a cholestatic hepatitis. Discontinuation of diclofenac resulted in normalization of transaminase activity and bilirubin concentration within four months. The frequent use of diclofenac and the possibility of fatal liver damage highlights the need that diclofenac-toxicity should be considered in the differential diagnosis of acute cholestatic hepatitis.
There are indications that pouchitis after ileal pouch-anal anastomosis is a remanifestation of the underlying disease--ulcerative colitis--under different conditions. A small group (approximately 5-10% of the patients) develops chronic severe pouchitis with total villus atrophy. It has recently been shown that even high-grade dysplastic epithelial changes and DNA aneuploidy occur in chronic pouchitis. Thus, surveillance programs might be necessary for these patients. Pouchitis is a clinical model to study the pathogenesis of chronic destructive mucosal inflammation systematically.