Biomedical subjects
Publications and source records attributed to D Alfani.
Biliary complications following liver transplantation continue to present major difficulties. Damage to the biliary tract has been reported after preservation of the liver before transplantation. Studies in the rabbit are reported that confirm the extensive biliary autolysis during preservation. This damage is directly related to the presence of bile in the biliary tract and can be reduced by the washout of bile and biliary perfusion.
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The presence of alloantibodies may play a role in accelerated or acute humoral rejection. Different therapeutic strategies based on a removal of anti donor antibodies and prevention of their resynthesis have been used in the management of transplant rejection episodes. Immunoadsorption with staphylococcal protein A, a method to selectively remove immunoglobulin G, may represent a new treatment to reverse humoral rejection in kidney transplantation. From 1991 to January 1996, such a method was used in 23 patients in whom an acute humoral rejection developed over a mean period of 14.1 +/- 9.5 days after operation. Twenty-two patients had been transplanted from living donors and one from a cadaveric donor. The ages ranged from 23 to 58 years (mean, 34 +/- 10 years). All transplants were performed according to a negative direct crossmatch. Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). Rejection was diagnosed on the basis of hematochemical tests, Doppler ultrasonography, and kidney biopsy. Only steroid and monoclonal and polyclonal antibody resistant rejections with > 165% positive direct crossmatches against the donor were treated with Protein A immunoabsorption. The procedure used is based on the treatment of 2-3 plasma volumes for the first 2 days and then every other day until a negative crossmatch is obtained, together with improvement in clinical status (mean treatments, 7.3 +/- 4.5 [range, 4-23]; mean duration of treatment, 12.3 +/- 10.2 days [range, 3-44]). From the start of treatment, azathioprine is replaced by cyclophosphamide at a dose of 1-2 mg/kg/day. During treatment, a remarkable fall in immunoglobulin G levels is achieved on the first day, whereas immunoglobulin M titers remain constant, with a slight decrease in serum albumin. Immediately after treatment, a negative crossmatch was found in 22 (95.6%) of 23 patients. In six patients (26%), graft function did not recover, and one patient (4.3%) died. Preliminary results show that immunoabsorption with staphylococcal protein A may be an effective support in the treatment of humoral acute rejection, particularly when it is performed as soon as an early diagnosis of humoral rejection is made. In fact, such treatment has a highly selective adsorption, allows treatment of large volumes of plasma, and can achieve a rapid decrease in the titer of circulating immunoglobulins.
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Single lung transplantation was performed in 22 pigs. The first 10 experiments were devoted to settle the surgical technique: in these cases we employed small animals (8-12 kg); technical difficulties and the high incidence of perioperative complications induced us to utilize bigger animals (greater than 20 kg) in the subsequent experiments. In the recipient, after left pneumonectomy we prepared the right pulmonary artery and encircled it with an inflatable silicon cuff connected to a reservoir positioned outside the chest cavity of the animal. The inflation of the cuff allows the complete occlusion of the right pulmonary artery and thus the functional evaluation of the isolated transplanted lung. Perioperative functional evaluation has been performed at different times till the third postoperative day, documenting the good status of the transplanted lung. This study confirms the possibility to employ pigs for experimental single lung transplantation to settle the surgical technique with economic and organizing advantages. Furthermore, it confirms the good results achieved in the dog, in which the occlusion of the contralateral pulmonary artery by means of an inflatable silicon cuff allows to evaluate the isolated transplanted lung function.
Kidney transplantation was first introduced in Italy in 1966 by the II Surgical Pathology of the University of Rome giving a great contribution to the development of the transplant surgery in this country. The authors report their 25-year experience analyzing the results obtained in more than 700 kidney allografts. A progressive refinement in the surgical transplant technique both from cadaver and live as well as clinical trials on new immunosuppressive protocols characterized their work.
It is well known that highly sensitized patients and/or high responders, even under CsA therapy, constitute a risk category for transplantation. Based on this evidence, in 1982, our group initiates a pilot study using total lymphoid irradiation (TLI) as a pre-transplant modulator of patient's immuno-response. TLI has been employed in 30 uremic, non diabetic, patients. During this experience the first protocol, characterized by pre-transplant TLI greater than 2,000 rads (13 pts.) and post-transplant conventional therapy, was abandoned because of the severe TLI side effects. In the second protocol TLI dose never exceeded 2,000 rads and CsA was given, at initial dose of 7-12 mg/Kg/day according to CsA blood through levels. The immunological monitoring was performed during TLI treatment and in the postoperative clinical course by cell markers profile determination and functional assays. The data obtained have demonstrated that TLI treatment causes a prolonged depression in CD4 positive cells, a predominant recovery of T suppressor population, a pronounced impairment of T functions and a development of specific unresponsiveness to donor antigens. Furthermore the TLI plus CsA protocol, showing an additive effect which steadily decreases patient immunoreactivity, a lack of side effects and a stable long term graft function seems to be a more useful method for transplantation in high-risk or in strongly immunoreactive patients.
Infection by hepatitis B (HBV) and/or delta virus (HDV), is the most frequent acquired pathology in patients affected by end-stage hepatic disease, candidates for liver transplant. To reduce the risk of virus reactivation after surgery, we used alpha Interferon (IFN) therapy in patients who were HBV-DNA and/or HDV-RNA positives before transplant. Our protocol included alpha IFN at low dosage associated to a thymic hormone that seems to have a synergistic activity with IFN. We have evaluated in four patients, affected by post hepatitic end-stage liver disease, the outcome of HBV and HDV markers in relation to immunological response during treatment. Our interest has been focused on monocyte and natural killer cytotoxic activity. The data show that all patients, before starting therapy, had evidence of active phase viral replication. They also displayed low values of the immunological parameters tested. The study of viral markers showed decrease of HBV and HDV in all patients. The relation between viral markers and natural killer and monocyte cytotoxicity was very interesting; during the treatment we observed a marked increase of both activities. At the same time no relevant modifications in the other immunological parameters tested were found.
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