[Kidney tolerance of imipenem and cilastatin].
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Biomedical subjects
Publications and source records attributed to C Hammer.
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During organ graft rejection, soluble mediators of inflammation are released into the polymorphs (PMNs) and monocytes recruited from the blood. One functional capacity of polymorphs and monocytes/macrophages is the production of cytotoxic activated oxygen species upon stimulation, which may contribute to the rejection process. Nothing is known about the influence of allograft rejection on this inflammatory cell property. Chemiluminescence (CL) allows measurement of respiratory burst capacity in small cell samples. Zymosan-induced and luminol-amplified CL of diluted whole blood, separated PMNs, and mononuclear cells from peripheral venous blood, as well as of intragraft phagocytes was measured after allogeneic and autologous kidney transplantation in untreated dogs. CL of separated PMNs, mononuclear cells, and intragraft phagocytes was significantly elevated during allograft rejection. In autologous kidneys transplanted to recipients of allografts, CL was also increased in the autologous grafts during rejection of the allogeneic ones, indicating a systemic alteration in phagocyte function.
A method of hetero-orthotopic heart-lung transplantation is described in the dog. The model was developed to study patterns of rejection in the transplanted heart and lung, since the dog will not survive bilateral pneumonectomy and loss of the Hering-Breuer reflex. After removal of the recipient's left lung the donor heart and left lung are explanted en bloc. End-to-end connection is made of both left main bronchi, and the donor aorta is joined end-to-side with the recipient's descending aorta. An atrio-atrial anastomosis is performed between the recipient's left and the donor's right atrium. Four experiments were done to develop the surgical technique and 10 long-term studies were performed to investigate rejection patterns. The average survival rate of these animals was 28.5 +/- 8.3 days, ranging from 5 to 53 days. Causes of death were not due to operative complications. Heterotopic heart-lung transplantation is an uncomplicated surgical method which does not require cardiopulmonary bypass or anticoagulation and allows the investigator to study heart and lung grafts in dogs for long-term periods after surgery. Bronchoscopy, bronchoalveolar lavage, and heart and lung biopsies of both donor and recipient organs can be performed.
During its differentiation in the insect vector to a stage infective for the mammalian host, Trypanosoma cruzi becomes resistant to lysis by the alternative pathway of complement. To elucidate the mechanism of complement evasion, we studied control of complement activation on the surface of the noninfective epimastigote and the infective culture-derived metacyclic trypomastigote stages (CMT) of T. cruzi. It was found that the predominant form of complement component C3 on epimastigotes is C3b, whereas the majority of C3 on CMT is in the form of the hemolytically inactive fragment iC3b, which cannot participate in C5 convertase formation or lead to deposition of the lytic C5b-9 complex. Our results also showed that C3 binds by a covalent ester linkage to surface molecules of different molecular weight in the epimastigote stage and CMT. Binding studies with purified complement components indicated that CMT do not support efficient formation of an alternative pathway C3 convertase. C3b on the parasite surface fails to bind the amplification component, factor B, rather than showing enhanced binding of the control component, factor H. These results identify the biochemical basis for evasion of complement-mediated killing in T. cruzi and reveal a mechanism for developmental regulation of complement activation.
During the past 4 years, 36 orthotopic heart transplantations and two heart-lung transplantations were performed at Munich University Hospital. Immunosuppressive regimen consisted of cyclosporine A and low dose prednisone. The rejection diagnosis was based on daily cyto-immunological monitoring (CIM) and high frequency electrocardiography. In addition, viral, bacterial, and fungal infections were examined by CIM. The CIM is based on an evaluation of activated lymphocytes, lymphoblasts, and lymphocyte subsets in the mononuclear concentrate isolated from the peripheral blood by Ficoll Hypaque separation. Of the 38 patients, 24 are currently alive from 1 month to 4 years later (including one heart-lung recipient 1.5 years postoperatively). Altogether, 40 rejection episodes occurred among the patients. The diagnosis was based on CIM (sensitivity = 95%) and on endomyocardial biopsies (sensitivity = 95%). Control of rejection therapy was also done by using these methods. When the biopsies showed ongoing acute rejection, additional antithymocyte globulin or antilymphocyte globulin therapy was administered, relative to the CIM results. When using the endomyocardial biopsies for rejection control only, results showed a very low rate of two to three biopsies per patient in the first 3 months postoperatively. In addition, 16 infection periods were detected: five viral, six bacterial, four fungal, and one case of toxoplasmosis. The CIM showed typical hints of these inflammations in 12 cases (sensitivity = 75%) before clinical signs were visible. This immediately led to further diagnostic examinations and specific anti-infectious therapies, which were initiated early.
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The status of lymphocyte subpopulations in splenectomized (Sx) stomach cancer patients (SCa-patients), assessed by monoclonal antibodies, has not been evaluated so far. Therefore subsets of peripheral white blood cells were monitored prior to and following surgical treatment in gastrectomized (Gx) and Sx (n = 64) as well as in non-Sx patients (n = 39). Postoperative surgical complications were more frequent in the Sx group. However, the 2-year survival rate of this group was higher than in non-Sx patients. Lymphocytes were significantly decreased in both groups of patients during the early postoperative period. Monocytes and polymorphonuclear cells (PMN) increased correspondingly. A significant loss of lymphocytes and their subsets in Sx patients was observed during the 1st-3rd postoperative days as compared to the Gx only patients. The OKT4/OKT8 ratios did not differ in either group of patients, whereas the OKT3+anti-B-Ly2 ratio was significantly increased in Sx patients 1 to 3 days postoperatively.
Subcutaneous (sc) transposition of the spleen followed by fine needle biopsies (FNB) from the organ allows the evaluation of relative numbers of splenic cells in Lewis lung tumor-bearing mice. Absolute cell numbers (N) can be calculated when the aspirated cells are weighed on a precision balance (m) and counted (c) after resuspension in a defined volume (v): N = C X V/m X M. The weight from the whole spleen (M) is derived from a calibration curve. Splenic nucleated cells and their subsets--as determined by the use of monoclonal antibodies--can thus probably be evaluated with a degree of accuracy which was not possible before. Shifts of splenic cells from and to the organ can be monitored.
Allogeneic nerve grafts of the sciatic nerve longer than 3 cm were transplanted between August- and Wistar rats. One group of animals were treated with 17 mg/kg body weight Cyclosporine A from day 1-28. Autologous nerves served as controls. At various postoperative days contact microangiography, stereoangiography, microdensitometry and histology were performed. Allogeneic untreated grafts were rejected at day 7. Undisturbed neovascularisation was only seen in autografts. In Cyclosporine A treated rats a gradually reduced revascularisation could be observed until day 90.
In this study, we examined the bacterial constituents associated with the complement C5b-9 complex in detergent extracts from serum-treated Neisseria gonorrhoeae (GC). 125I surface-labeled GC were incubated in 10% serum, were washed, and were solubilized in the zwitterionic sulfobetaine detergent SB12. Immunoprecipitation of 125I-GC from the extract with anti-C5 Sepharose was followed by 12.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography of immunoprecipitated material. Polyacrylamide gel analysis of surface-labeled 125I-GC showed prominent bands for proteins I and III for both serum-resistant GC strain 6305 and serum-sensitive GC strain 7189. These same bands were visible with similar intensity in the SB12 extracts from presensitized and non-presensitized 6305 and 7189 after serum incubation. For those organisms bearing bactericidal C5b-9 (6305 + IgG and 7189 +/- IgG), additional distinctive bands immunoprecipitated with antibody to C5 Sepharose. These components were of 93,000, 44,000 40,000, and 15,000 daltons for 6305 + IgG, and were of 90,000, 50,000, 44,000, and 19,000 daltons for 7189 +/- IgG. Nonbactericidal C5b-9 extracted from the surface of 6305 incubated in serum, but not sensitized with antibody, was not associated with these distinctive proteins. However, this nonbactericidal C5b-9 did have a different pattern of associated bacterial surface constituents from that observed in control samples incubated with antibody to human serum albumin, which were similar to those with nonserum-incubated organisms. These studies support our earlier experiments which demonstrated that C5b-9 is in a different molecular configuration on the surface of serum-resistant GC from that on the surface of serum-sensitive GC or resistant GC rendered sensitive with bactericidal antibody.
Allogeneic nerve specimens (sciatic nerve) were transplanted in rats. Cyclosporin A was used as an immunosuppressive agent. Under this treatment reinnervation occurred. Without treatment, nerve grafts were rejected. In order to monitor the acute cellular rejection, the nerve grafts were surrounded by a silicon tube. The perineural exudate and the mononuclear cells contained in it were aspirated at three day intervals by fine needle aspiration. Exact analysis of the mononuclear cells involved in the rejection mechanism and their degree of activation could in future provide a tool that allows control of nerve graft rejection and estimation of the effect of immunosuppressive treatment.
Five months after renal transplantation and an immunosuppressive trial with azathioprine and methylprednisolone, a black African female developed a cutaneo-nodular Kaposi's sarcoma that occurred symmetrically on the lower legs, thighs and forearms. Intensive search for visceral involvement was negative. Histologically, the nodes consisted of spindle cells; there were many new vessel formations with proliferation of atypical endothelial cells. After therapy with cytostatica and x-rays there was a time-limited disappearance of the Kaposi's sarcoma; 1 year later a relapse developed on the left lower leg. Field radiotherapy with accelerated electrons in a single dose of 8 Gy was successful. There is a greater incidence, in the literature, of Kaposi's sarcoma in immunosuppressed patients with organ transplants. Treatment with immunosuppressive substances is probably significant in the development of the Kaposi's sarcoma in those patients.
Fine needle aspiration cytology (FNAC) of the spleen was performed in 10 tumor bearing mice. The vascularized spleens were mobilized and re-located under the skin in order to facilitate fine needle biopsy (FNB). Samples of spleen cells thus obtained were studied and the lymphoid cells characterized and counted according to morphology. Owing to a relative decrease in numbers of lymphocytes during tumor growth a very marked intrasplenic increase in numbers of granulocytes was observed. The splenograms of a mouse rejecting the tumor were different from those of tumor bearing mice. FNAC of the spleen is a reliable method for monitoring immunocompetence in individual tumor bearing animals.