Endothelial adhesion molecules in human liver grafts: overview on the differential expression of leukocyte ligand molecules.
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Biomedical subjects
Publications and source records attributed to M Behrend.
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The expression of leucocyte adhesion facilitating molecules on endothelia is a major stimulus for tissue inflammation and cell infiltration. Recently, specific receptor ligands have been identified that mediate cellular adhesion of lymphocytes or monocytes. In the present study, sequential changes in the expression of immune adhesion receptors (LFA-1, CD2) and their ligand molecules (ICAM-1, LFA-3) were studied in heart allografts during rejection. Consecutive endomyocardial biopsies (n = 157; d.3-1013) of 16 heart transplanted patients were studied using monoclonal antibodies and standard immunohistology. In biopsies that showed no rejection, immune adhesion molecules (ICAM-1) were weakly expressed on a few endothelial cells. ICAM-1 was induced on blood vessel and capillary endothelia during rejection. After treatment, expression declined, as did the clearance of infiltrates. Occasionally, ICAM-1 persisted on capillaries compared with class II MHC expression. Weak LFA-3 induction on endothelia was observed in acute rejection, similar to ICAM-1, however LFA-3 expression was more restricted. Infiltrating lymphocytes expressed the adhesion receptor molecules LFA-1 and/or CD2. The variability of expression of ICAM-1 and FA-3 ligand molecules was related to the inflammatory changes in the graft during acute rejection. It is likely that the induction of adhesion ligand molecules in tissue is regulated by systemic and local release of cytokines, and is an initiating step in graft infiltration. The demonstration of immune adhesion-molecule induction in heart graft rejection may also be applicable to inflammatory heart disease in viral myocarditis.
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The regulation of expression of adhesion molecules in human liver grafts in the course of rejection and inflammatory reactions was studied. The tissue distribution of adhesion receptor molecules and ligand molecules in graft biopsies taken during complications was compared to that in normal liver and reference biopsies taken at the time of transplantation.
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A total of 232 patients with rheumatoid arthritis were treated with DPA. Withdrawal from treatment was mainly due to adverse events in the first year of treatment, while in the subsequent years it was mainly due to loss of efficacy. Of the patients treated, 68 were included in the present study, as they fulfilled the criteria of continuous long-term observation regularly performed. The effects of therapy were graded after 1 year of treatment, at the last examination in the outpatient department or before withdrawal, respectively. It could be seen that a long duration of the disease did not exclude positive effects of therapy; however, early use of DPA led to more favourable results with respect to the number of successfully treated patients and to the extent of the grading of efficacy. In patients who did not respond to DPA therapy, not only was the duration of the disease longer, but also previous therapy with other slow acting antirheumatic agents had been stopped because of inefficacy. This group of patients seems to cover therapy-resistant cases. After 1 year of treatment, improvement was measured in 54 patients. During further treatment, a tendency to return to initial values of clinical and laboratory parameters was noted. In about half the patients with only moderate improvement after 1 year, subsequent treatment was terminated (because of inefficacy) quite soon in most cases, i.e. within 5 years. Optimal improvement after 1 year, however, seems to indicate a long-term positive response to DPA therapy. In cases with no obvious effect of DPA after 1 year a response is not to be expected with ongoing treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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We report on a 39-year-old woman suffering from deep venous thrombosis due to a heterozygous factor-V-Leiden mutation with resistance to activated protein C. Four months after beginning oral anticoagulation, generalized jaundice appeared. Subsequently, subacute liver failure developed necessitating an orthotopic liver transplantation. Histopathology showed features of extensive liver cell necrosis without evidence of a substantial inflammatory infiltrate. Based on histopathology and exclusion of other liver diseases, phenprocoumon-induced liver failure was diagnosed. Five months after transplantation the patient is well with normal liver function tests. Because of the widespread use of oral anticoagulants, not only bleeding complications but also hepatotoxicity should be considered in therapy supervision.
Resection and end-to-end anastomosis of the trachea represent the preferred treatment for various benign and malignant diseases involving the trachea. Various studies have reported conflicting results with alternative techniques and suture materials for tracheal anastomosis. Our objective was to evaluate three frequently used techniques concerning stenosis rate and histological reaction in a large-animal species. Tracheal resection of 3 cm and end-to-end anastomosis were performed in 15 sheep with the use of three different techniques. In the first group, an interrupted suture with polyglactin, in the second group an interrupted suture with polydioxanone, and in the last group a continuous suture with polypropylene were used. The animals were killed 1, 2, 4, 8, and 24 weeks postoperatively. The luminal stenosis was determined by means of computerized planimetry. All three techniques appeared to be appropriate for tracheal anastomosis. The luminal stenosis developed within the first 8 weeks after surgery. A cross-sectional area of approximately 40-70% was finally achieved. Differences dependent on the suture material are less important than the technical details of the operation.
Tracheal anastomoses are, even more so than other sutures, often only possible to prepare under tension and thus in danger of breakage. No information is available regarding native tracheae and freshly sutured tracheae. For this reason, our objective was to examine the tensile strength of native tracheae and compare it with freshly sutured specimens. Fresh tracheae were collected from the local slaughterhouse within 30 min of slaughter. With the help of a suitable holding device, 24 fresh tracheae were mounted on a material testing machine and stretched to breaking point, during which the force and distance required were recorded. The same study was carried out on each 10 freshly anastomosed tracheae using three different suturing techniques. The mean value of the maximum force required for native tracheae was 198 N. With continuous suturing (polypropylene), a mean value of 171 N was attained, and with single interrupted suturing (polydioxanone and polyglactin 910), 123 N, respectively, 108 N. Differences between the groups proved to be highly significant. With respect to the mechanical strain from traction, the continuous suture proved to be statistically identical to native tracheae, whereas single interrupted sutures revealed a considerably lower stability under burden. Therefore, the continuous suture is of advantage in respect of the mechanical strain from traction and the suture protection of tracheal anastomoses. Further studies with differing survival times in vivo with this method provide insight into the stability of tracheal anastomoses during the healing process.
BACKGROUND: This case report describes a patient with symptomatic anaemia due to a bleeding duodenal metastasis from metastasising differentiated thyroid cancer (DTC), which was treated by partial duodenopancreatectomy (DP). CASE REPORT: A 71-year old male was sent to hospital with severe anaemia. This patient had suffered multiple cervical recurrences of differentiated papillary thyroid cancer, which had been treated by several resections and irradiation, and an adrenal gland metastasis, via adrenalectomy. Abdominal computed tomography showed an enlarged pancreatic head, an upper gastrointestinal endoscopy revealed a bleeding ulcer in the duodenum, and a biopsy revealed metastasis from DTC. Due to the symptomatic metastasis, a partial DP was performed; the postoperative course was uneventful. Histopathological examination revealed metastasis of the DTC next to the papilla lying in the head of the pancreas, with growth into the muscularis propria of the duodenum. The patient survived for another 41/2 years before dying from progressive metastatic disease elsewhere. CONCLUSION: DP for metastatic disease should be considered in selected patients for alleviation of the symptoms and prolongation of survival, as long as this operation is performed by experienced surgeons who can achieve minimal morbidity and mortality.
The early diagnosis and effective treatment of cytomegalovirus (CMV) pneumonia remains a keystone for patient survival after lung transplantation. At present, the use of DHPG (ganciclovir sodium) opens the possibility of a potent antiviral therapy. The use of monoclonal antibodies directed to immediate early CMV antigens offers a fast method to detect the early phase of systemic or local viral replication. Five single lung and heart-lung transplant patients at high risk for CMV infection (donor, CMV-positive; recipient, CMV-negative) were monitored by cellular immunohistology for immediate early antigens. Specimens from bronchoalveolar lavage (n = 39) and bronchial biopsies (n = 17), and peripheral blood leukocytes (n = 57) were examined. In peripheral blood leukocytes and bronchial biopsy specimens no CMV-positive cells were detected. The bronchoalveolar lavage analysis of two patients showed immediate early antigen-positive cells after 1 to 3 months. At the same time the patients had clinical symptoms that could also be related to lung rejection. Serologic conversion (CMV-IgM) occurred only 6 days later in one patient with informative follow-up analysis; CMV culture (available 4 to 6 weeks later) confirmed the diagnosis retrospectively. DHPG treatment was started immediately and resulted in CMV antigen negativity in bronchoalveolar lavage fluid after one or two courses (10 mg/kg/day; 14 days). Direct antigen detection offers a fast and specific monitoring of early CMV infection. The implications to the clinical management of lung transplant patients are discussed.
BACKGROUND AND METHODS: Intercellular reactions and cell-matrix interactions are mediated by a number of specific adhesion molecules. For the intravascular reactivity of leukocytes and thrombocytes the endothelial expression of adhesion ligand molecules is of main importance. This condition may be of special relevance for the organ-specific manifestation of immune reactions in heart and lung transplants. The question was investigated as to whether organ-specific differences exist on arterial, venous, and capillary endothelial lining cells in heart and lung transplants and whether this condition is modified during transplant rejection. Transplant biopsy specimens of 24 heart transplant recipients (n = 303) and lung transplant recipients who underwent retransplantation for rejection (n = 4), as well as normal heart (n = 7) and lung tissue (n = 4), were studied. Cell-cell adhesion molecules (intercellular adhesion molecule-1 (CD54) and -2; LFA-3; CD31; vascular cellular adhesion molecule-1; neural cellular adhesion molecule; E-/P-selectin; CD44) and cell-matrix adhesion molecules (very late antigen-1 through -6; CD51) were studied on cryostat sections by means of standard immunohistology. RESULTS: (1) Arterial, venous, and capilary endothelia in lung and heart tissue show a distinct pattern of cell-cell and cell-matrix adhesion molecules: capillary and venous endothelia are in contrast to arterioles negative for vascular cellular adhesion molecule-1 and P-selectin. Arterial endothelia of the lung, in contrast to veins and capillaries, express no receptors for laminin (very late antigen-2 and very late antigen-6). (2) With transplant rejection, an induction of a number of adhesion molecules was noted on all endothelial lining cells in heart and lung transplants (intercellular adhesion molecule-1[CD54], intercellular adhesion molecule-2, lymphocyte function antigen-3, very late antigen-2, and very late antigen-6). Capillaries of the lung, in contrast to heart capillaries, displayed no inducibility of vascular cellular adhesion molecule-1 and E-selectin. In heart transplants, differences between capillaries and arteriovenous endothelia were found for virus-like agent-2 and -3. CONCLUSIONS: These results show a distinct expression of a both cell-cell and cell-matrix adhesion molecules on arterial, venous, and capillary endothelia of heart and lung transplants. This expression may influence the local regulation of leukocyte and thrombocyte adhesion during transplant rejection. Especially lung capillaries show a lack of inducibility for vascular cellular adhesion molecule-1 and E- and P-selectin required for the induction phase of leukocyte adhesion. This lack was not found in heart transplants. This observation may explain differences in intravascular adhesion and infiltration between vessel compartments in hearts and lungs and could be of relevance for therapeutic interventions to modify leukocyte and thrombocyte adhesion, as during transplant rejection and reperfusion damage.
BACKGROUND: In case of distant metastases breast cancer is generally regarded as incurable. Therefore liver surgery is withheld from those patients, even in cases of isolated liver metastases. MATERIALS AND METHODS: Over 11 years we performed 35 liver resections in 34 patients with liver metastases of breast cancer. The median age was 47 years. The median interval between the primary operation and the liver resection was 27.3 months. 59% of the patients had a solitary metastasis. RESULTS: Curative (R0) resection was possible in 86%. Operative mortality was 3% (n = 1). Overall 5-year survival was 18.4% (median 27 months). Prognosis was significantly (p < 0.001) better following R0-resection (22%, median 41.5 months) than after R1/2-resection (maximum 20 months, median 5 months). Beside the radicality an unfavorable influence on the prognosis could be demonstrated only for a prior local recurrence of the primary tumor (p < 0.05). Other factors like stage of the primary tumor and number and size of the metastases were without prognostic significance. CONCLUSIONS: Patients with isolated liver metastases of breast cancer may have a long lasting benefit from liver resection. In individual cases cure may be possible.