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Biomedical subjects

A Stallmach

Publications and source records attributed to A Stallmach.

At least 55 records · Page 3Linked to original sources

Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice.

BACKGROUND & AIMS: We have shown in previous studies that an interleukin 2 (IL-2)-IgG2b fusion protein suppresses both humoral and cellular immune reactions in a murine model of DTH reaction. We now analyze the effects of IL-2-IgG2b in a model of intestinal inflammation in mice induced by the hapten reagent 2,4, 6-trinitrobenzene sulfonic acid (TNBS) that mimics immunologic characteristics of human Crohn's disease. METHODS: In TNBS-induced colitis, colonic and splenic T-cell subsets were characterized by immunohistochemistry and flow cytometry. Cytokine synthesis was studied by semiquantitative reverse-transcription polymerase chain reaction and intracellular cytokine staining in CD4(+) T cells. RESULTS: When mice were treated with IL-2-IgG2b, improvement in both wasting disease and histopathologic signs of colonic inflammation was observed. An increase in the number of colonic CD4(+)/CD25(+) T cells and increased synthesis of the immunosuppressive cytokine IL-10 also occurred. The protective role of IL-10 was demonstrated by the finding that neutralization of IL-10 in vivo using IL-10-specific antibodies inhibited the IL-2-IgG2b effects in TNBS-induced colitis. CONCLUSIONS: These studies show for the first time that the IL-2-IgG2b fusion protein can abrogate experimental colitis by local induction of IL-10-secreting T cells.

Animals↗

32/67-kD laminin receptor expression in human colonic neoplasia: elevated transcript levels correlate with the degree of epithelial dysplasia.

OBJECTIVE: The 32/67-kD laminin receptor is thought to be involved in tumor cell migration and metastasis formation, and enhanced expression was observed in human colorectal carcinoma. Our objective was to investigate further the expression of the 32/67-kD laminin receptor RNA in human colonic carcinogenesis. METHODS: We obtained sections of human colonic tissues in various stages of malignant transformation and analyzed them by in situ hybridization. RESULTS: Normal colonic mucosa displayed a gradient between crypt base and surface epithelium with lowest receptor RNA levels in superficial epithelial cells. Increased laminin receptor RNA expression was observed in epithelial cells of adenomas with positive correlation between transcript levels and the degree of epithelial dysplasia. At variance with published results, we did not observe significant differences in 32/67-kD laminin receptor transcripts between adenomas with high-grade dysplasia and invasive adenocarcinoma. However, adenocarcinoma metastases displayed significantly higher laminin receptor RNA levels than high-grade adenomas and primary carcinomas. CONCLUSIONS: We propose a two-step mechanism which controls first, upregulation of laminin receptor RNA before the acquisition of an invasive phenotype in dysplastic epithelial cells, and second, a further upregulation in metastatic cells during the adenoma-carcinoma sequence of the colon.

Adenocarcinoma↗

Palliative transhepatic biliary drainage and enteral nutrition.

Simultaneous intestinal and biliary obstruction is a rare but agonizing complication of metastatic abdominal cancer. Although endoscopic procedures exist that relieve jaundice or restore enteral nutrition, they can be impossible to perform for technical or anatomical reasons. We propose a palliative approach for these patients that includes transcutaneous common bile duct drainage, progressive dilation of the transhepatic channel over 1 wk, and, finally, insertion of a permanent silicon catheter that drains bile into the duodenum and is combined with an enteral feeding line. We report three patients whose metastatic abdominal tumors had led to simultaneous jaundice and gastric outlet obstruction, neither of which could be treated endoscopically. In all patients, the transcutaneous bile drainage catheter combined with the enteral feeding line was inserted and tumor symptoms resolved rapidly. As a result, the patients chose to return to home care with enteral nutrition and pain medication. The creation of a transhepatic access for simultaneous enteral bile drainage and nutrition is a technically simple procedure that causes little discomfort to a terminally ill patient. It relieves the symptoms of tumor obstruction, and the option of enteral nutrition and medication can obviate the need for intravenous infusions.

Aged↗

[The intestine as an immunological organ].

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.

Bacterial Translocation↗

Endoscopic sclerotherapy with fibrin glue as compared with polidocanol to prevent early esophageal variceal rebleeding.

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.

Aged↗

Decreased expression of CD44 splicing variants in advanced colorectal carcinomas.

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.

Adenoma↗

Esophageal involvement in cicatricial pemphigoid.

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.

Adolescent↗

Soluble CD44 and CD44v6 serum levels in patients with colorectal cancer are independent of tumor stage and tissue expression of CD44v6.

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.

Adenocarcinoma↗

Increased state of activation of CD4 positive T cells and elevated interferon gamma production in pouchitis.

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.

Adult↗

[Necessary diagnosis before and reliable examinations after surgical interventions in chronic inflammatory bowel diseases].

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.

Colitis, Ulcerative↗

[Diclofenac-associated acute cholestatis hepatitis].

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.

Anti-Inflammatory Agents, Non-Steroidal↗