Prolongation of heart xenograft survival in the rat: effectiveness of cyclosporine in preventing early xenoantibody rebound after membrane plasmapheresis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Filipponi.
Explore the source record for details and available documents.
The results of 56 consecutive orthotopic liver transplants in the pig were reviewed to determine the incidence of primary biliary tract complications. There were 8 biliary tract complications in 56 grafts (14.2%) directly responsible for death. End-to-end choledochocholedochostomy (ee-CC) was the most frequently used technique (40 cases) with 4 technical failures (10.0%). Choledochojejunostomy with a Roux-en-Y jejunal loop (RYCJ) was used in 9 cases with 2 technical failures (22.2%). Side-to-side choledochocholedochostomy (ss-CC) was used in 7 cases with 2 technical failures (28.5%). Biliary leak and stenosis were the most common complications. End-to-end choledochocholedocostomy appears to be the most suitable and easy biliary reconstruction in the pig but possible gross disparity in the sizes of the donor and recipient ducts may represent and adverse factor.
The need for liver grafts is critical in countries where brain death is not accepted as a legal criterion for organ retrieval. This experimental study was conducted with nonhuman primates in order to evaluate the feasibility of liver transplantation using a living donor. An original technique was employed to remove the left part of the liver from the donor: transection of the parenchyma was done while the blood flow was kept to the left part of the liver. In the recipients, the graft was placed heterotopically. No blood transfusions were administered to donors or recipients. In spite of a few failures, due to consequences of intraoperative bleeding, several donor operations using this original technique were successful, in the immediate postoperative period as well as several months later. Among the recipients, the large number of early failures suggests that the heterotopic position is probably not the appropriate one and that orthotopic transplantation should be preferred.
This study was conducted to evaluate various methods to reduce the mortality rate following acute portal vein occlusion in rat: systemic heparinization, intravenous saline infusion, enteral antibiotics and simultaneous clamping of the superior mesenteric artery were tested alone or in combination. Each of these treatments improved the survival rate after 45 or 60 min occlusion of the portal vein; combination of all treatments provided better results than each treatment alone. These results indicate that, following acute portal vein occlusion in the rat, several factors cooperate to cause death. The decrease in mean arterial blood pressure during occlusion of the portal vein was correlated with the mortality rate; this correlation was significant in the animals with 45 min occlusion of the portal vein. It appeared in this study that, when used in association, simple therapeutic methods are highly effective in improving the survival rate following acute portal vein occlusion in the rat.
A technique is described for orthotopic liver transplantation in the rat using polyethylene cuffs to re-establish subhepatic cava and portal vascular anastomoses. This procedure reduces the time of portal clamping, an important factor of survival. This technique was found to be reliable with a 72.9% long-term survival (more than 60 days) in an experimental group of 59 iso- and allografts. The method was employed in 212 animals during studies on iso-, allo- and xenografts to evaluate the tolerance and rejection mechanisms in rats of pure strain.
Natural antidonor antibodies are known to play a prominent role in hyperacute xenograft rejection. The aim of this work was to devise an experimental protocol to prolong the survival time of guinea pig heart xenografts transplanted into rats. A technique of continuous plasma exchange adapted to small animals was used to remove the natural cytotoxic antibodies from the recipient prior to the transplantation. In some experiments, cyclosporine (CsA), cyclophosphamide (CY), or splenectomy were associated with the plasma exchange. In this highly discordant xenogenic donor-recipient combination, the mean graft survival time in nontreated rats was 16 min. When an exchange of 1.5 plasma volume was performed 24 hr before the transplantation, no prolongation of the graft survival time was observed. When CsA, CY, or splenectomy were associated with the plasma exchange, the graft survival time was significantly increased by more than 2500% (up to 418 min with CsA). When used isolately, none of these 3 immunosuppressive methods was able to prolong the graft survival time. Natural cytotoxic antibodies were monitored by a complement-mediated cytotoxicity assay. After a plasma exchange, the titers decreased from 1:16-1:32 to 1:1-1:2. When no immunosuppressive method was associated with the plasma exchange, the antibodies returned to their initial level within the 24 hr that preceded the transplantation, and the graft was rejected as in nontreated animals. When an immunosuppressive method was associated with the plasma exchange, and particularly in the case of CsA, the titers remained low, and the hyperacute rejection was delayed. Therefore, it can be concluded that plasma exchanges, associated with CsA, are an efficient experimental protocol in the rat to increase the survival time of guinea pig heart xenografts. The effect of the treatment is correlated with the decrease in natural cytotoxic antidonor antibodies.
The mitotic index (M.I.) of the colonic mucosa was evaluated in 67 biopsies and divided into 6 groups. The M.I. was evaluated by one author twice at magnification X 1000 and by the other author once at magnification X 1000 and once at X 400, in order to assess the degree of intra- and interobserver agreement and the most suitable magnification for the evaluation of the M.I. of human colonic mucosa. The results indicate that the mean M.I. of a group of biopsies was similar between the two authors and may therefore be proposed as a valuable estimate of the mitotic activity of a group of patients during scientific investigations, provided that it is evaluated at sufficiently high magnification (X 1000, to our experience). On the contrary, there was only partial agreement (though highly significant) on the M.I. of each individual biopsy between the two authors and between different counts of the same author as well, thus indicating that the M.I. cannot be proposed as an accurate estimate of the mitotic activity of individual patients.
This study was undertaken to assess possible modifications of the proliferative activity of colonic mucosa, which could be related to a suggested cancer-promoting role of cholecystectomy. The mitotic index (number of mitoses per 1000 gland cells) was evaluated in the colonic mucosa of 14 healthy subjects, 11 patients with cholelithiasis, before and 6 months after surgery, and 10 patients who had undergone cholecystectomy 2 or more years previously. The mitotic index of cholecystectomized patients was significantly higher than controls. It rose significantly within 6 months of cholecystectomy. The mitotic index of patients with cholelithiasis before surgery was similar to controls. These data suggest that cholecystectomy is followed by an enhancement in the proliferative activity of the colonic mucosa, which could play a cancer-promoting role.
The authors have examined the survival rate of 111 patients with colorectal cancer (Dukes' A, B, and C stages) treated by potentially curative surgery. In particular, the survival has been evaluated with regard to the appearance of postoperative fever and/or septic complications. The preliminary results demonstrate that these factors do not significantly influence the long-term prognosis.
A histological study of colonic mucosa, including the measurement of the mitotic index, was performed in routinely processed specimens from control subjects and patients with multiple non-familial adenomatous polyps, to ascertain whether the onset of adenomatous polyps was accompanied by an increase in mucosal mitotic activity as compared with controls. The mitotic index of both the polyps and the mucosa 20 cm from the anal orifice of the same patients was significantly (P less than 0.01) higher than that of control 20 cm from the anal orifice and a shift of the mitotic activity from the lower two-thirds to the upper third of glands was observed in the polyps. These data suggest that an increase of mitotic activity in the superficial third of the glands as compared with controls plays a pathogenetic role in the onset of adenomatous polyps and that this phenomenon is accompanied by a diffuse increase of mitotic activity in the deeper two-thirds of the glands.
The authors show two cases of cystic lymphangioma, one located at the neck, the other in the inguinal region, both arising in aged patients. From the study of such cases, the Authors start for studying the etiopathogenetic and histologic aspects, dwell upon the clinics and diagnosis of such neoplasms, and indicate as the sole radical treatment the surgical extirpation.
It results cholelithiasis is very frequently associated to colorectal cancer. Clinical and autoptic studies thereabout result to be doubtful. In the present research, the Authors evaluated the proliferative activity of colonic mucous membrane, through the mitotic index, and the secretion of mucins, with histochemical methods, in control subjects and cholelithiasic patients. The results show no significant differences in both groups; the data obtained are discussed in the light of the importance of the biologic parameter considered in the evaluation of risk groups for colorectal neoplasms and, moreover, as morphologic support to the clinical question.
Some studies suggest cholecystectomy and the cholelithiasic disease are frequently associated to some neoplasms of the digestive tract. Cholecystectomy, through the physiopathologic alterations it causes, seems to assume the role of factor of risk for the development of a gastric neoplasm. The authors reviewed their casuistry by analysing the percentages of subjects in whom the gastric neoplasm was associated to a previous cholecystectomy or a concomitant cholelithiasis. The data obtained do not support the hypothesis that cholecystectomy or the "lithogenicity of the biliary ducts" may be a factor of risk for gastric cancer.
A histologic and histochemical study of the colonic mucosa, including a study of the mitotic index, was performed in routinely processed specimens from control and tumor-bearing patients. A significant increase in the mitotic index (number of mitosis X 1000 gland cells), without concomitant modifications in the distribution of mitotic figures along the crypt depth, in mucosal thickness, or in mucin secretion, was demonstrated in the colonic mucosa of patients with colonic or rectal cancer compared with controls. The results point to an accelerated cell renewal in the colonic mucosa of tumor-bearing patients compared with the controls, without concomitant dysplasia. Results are discussed in the light of the possibility that an increased cell proliferation may have preceded the onset of tumor and played a role in the second step of carcinogenesis, i.e., tumor promotion, independently of dysplasia.
We report herein on two male liver transplant (LT) recipients who presented with cyclosporine (CsA)-related gynecomastia 6 and 10 months after transplantation. The clinical workup showed increased luteinizing hormone (LH), associated with a slight reduction in testosterone blood levels in one patient and increased prolactin levels in the other. After excluding concomitant primary endocrine and/or malignant disease, conversion to tacrolimus (TAC) was performed resulting in clinical improvement of gynecomastia and return of hormone blood levels to normal range within 3 months. Our report confirms a putative role of CsA in post-LT gynecomastia, reversible however upon conversion to TAC.
In 1999, the Italian Parliament passed a law aimed at setting the standards of practice and quality in organ, tissue and cell donation, and transplantation. For the first time in the history of Italian transplantation, a coordinator-based model reproducing some of the basic principles of the Spanish system was officially enacted by the Parliament, bringing to an end years of lacking regulation. What differentiates those coordinator-based systems adopted in Southern Europe from Northern European national and multinational transplant organizations is the functional integration of donor and transplant care activities enacted by national governments. The Italian model of transplant health care consists of four levels of transplant coordination: local, regional, interregional, and national. The latter is represented by Centro Nazionale Trapianti (CNT; the Italian National Center for Transplantation). CNT objectives consist of ensuring equitable access to donation and transplant care for all citizens according to the principles of the Italian National Health System. In achieving these goals, CNT acts in cooperation with three interregional transplant agencies: the Nord Italia Transplant program, the Associazione InterRegionale Trapianti, and the Organizzazione Centro Sud Trapianti. Whereas local and interregional coordinators are at the front line of all donation and transplant activities, regional and national coordinators function to monitor, direct, and plan donation and transplant health care activities. Based on the increase in donation and transplant activities recently achieved in those countries that have adopted a governmental coordinator-based transplant care model, we believe that such a system is appropriate to serve patients' interests according to the principles of subsidiary and equity. However, it should further be improved by expansion of the governance model throughout Europe, through implementation of current standards of care, and by adopting the definition of common European objectives, health care strategies, and research integration.
Explore the source record for details and available documents.
Explore the source record for details and available documents.