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Biomedical subjects

A Buscaroli

Publications and source records attributed to A Buscaroli.

At least 19 recordsLinked to original sources

Combined liver-kidney transplantation with preformed anti-HLA antibodies: a case report.

A pretransplant positive cross-match is a contraindication for kidney transplantation, unlike in liver transplantation (OLT). In combined liver kidney transplantation (LKT) it is hypothesized that liver can protect kidney from rejection. We report the case of a 35-year-old woman on renal replacement therapy with gastrointestinal tract compression due to a hematoma following spontaneous liver rupture (May 2004). She was affected by amyloidosis, treated with a bone marrow autotransplantation (2001). The liver rupture was surgically untreatable, so an LKT was proposed. Panel-reactive antibody was 80% to 100% (complement dependent cytotoxicity) with specific anti-HLA antibodies (enzyme-linked immunosorbent assay). A compatible donor was found (July 2004). The cross-match before LKT was positive for B and T cells (score 8): an emergency OLT was performed. Immediately after liver reperfusion the cross-match result was less positive (6) for T cells. After 6 hours it was negative for T and slightly positive for B cells (4): the kidney was transplanted. The immunosuppressive therapy was: alemtuzumab, steroids, and tacrolimus. Renal function immediately recovered. On day 7 a rejection episode was successfully treated by increasing steroids (intravenous bolus). At discharge hepatic and renal function were normal (creatinine 1 mg/dL). They are stable after 1 year. This case showed LKT efficacy even in complex immunological situations. Many immunological mechanisms, still not defined, are hypothesized about the protective role of the liver. This case confirmed experimental data that highlighted that in vivo in humans a cross-match can change from positive to negative after OLT giving highly sensitized patients the possibility for LKT.

Adult↗

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).

Adult↗

Application of Prastat ELISA in the determination of anti-HLA specificity for immunized patients awaiting kidney transplant: five years' experience.

Three hundred sixty-five patients who underwent cadaver donor kidney transplantation between 1993 and 1998 were divided into four groups: 40 immunized patients with at least one peak panel-reactive antibody (PRA) value more than 50%, 11 hyperimmunized patients with more than three peak PRA values over 50%, 10 retransplanted patients and 304 control patients. Before transplantation, we ascertained the antibody specificities against individual HLA antigens (Prastat Sangstat ELISA method for HLA typing of first donor, husbands of multiparous women and potential donors against whom candidates gave positive cross-matches); thus, patients underwent transplantation excluding the presence of the HLA antigens previously detected and looking for high HLA (class I and II) compatibility. Actuarial graft survival after 12 months was satisfactory in all groups: 87% immunized, 81% hyperimmunized and 80% retransplanted vs 92% controls. Renal function at the end of the first year was similar and the number of rejection episodes in the first 3 months did not significantly differ.

Actuarial Analysis↗

Immune response following fresh arterial homograft replacement for aortoiliac graft infection.

INTRODUCTION: this prospective study defines the immune response to fresh arterial homograft replacement for graft infection. MATERIALS AND METHODS: ten patients who underwent ABO-compatible homograft transplantation were studied for anti-HLA antibody production, and CD3-CD4-CD8-positive lymphocytes subset. Immunological studies were performed preoperatively, and at early (1, 3, 7 days) and late (1, 3, 6, 12, 18, 24 months) follow-up. All patients received immunosuppressive treatment with cyclosporine (1-3 mg/kg/day). Abdominal CT scans were performed postoperatively at the 1, 6, 12, 18, 24 months follow-up. RESULTS: preoperatively, antibodies could not be detected. Postoperatively, as from 1st month post-transplant, a progressive increase in % PRA was observed in all patients, up to the 12th month of follow-up. Subsequently, at 18 and 36 months, a progressive decrease in % PRA was detected. Data showed that the recipient antibodies were directed against donor-specific antigens. During the immediate postoperative period (1, 3, 7 days) CD3- and CD4-positive T lymphocytes slightly increased, whereas CD8 simultaneously decreased. Later, CD3 and CD4 progressively decreased and CD8 increased. Clinically, all patients were cured of infection at late follow-up. CT scans showed thickening of the aortic wall (range: 2.5-4.5 mm), with no signs of aneurysmal degeneration. CONCLUSIONS: fresh arterial homografts are immunogenic. Implanted homografts induce a strong anti-HLA antibody response, similar to chronic rejection, in spite of immunosuppressive treatment.

ABO Blood-Group System↗

Ureteral stenosis after kidney transplantation. A study on 869 consecutive transplants.

Ureteral obstruction with impaired urine flow is the most common urological complication following renal transplantation. From December 1976 to December 1997, 869 kidney grafts were performed by our kidney transplantation group, 96 from living related donors and 773 from cadaver donors (736 first grafts and 37 regrafts). A stricture of the ureter (SU) was observed in 27 cases with a follow-up ranging from 18 months to 18 years after the graft and 11 months to 11 years after the treatment of the SU. In six patients, SU was immediately apparent and limited to the anastomosis: they were obviously technical flaws. In all the other patients, there was a free interval ranging from 2 months to 11 years after surgery; the SU usually involved the entire ureter, suggesting multiple etiologies. Repeated urinary infections could be a cause but immunological problems might be more determinant. In our series, acute rejection was more common than chronic so that the correction of SU was followed in many cases by a good and long lasting result (up to 11 years). In our experience, SU was not a dangerous complication even in patients in whom for different reasons (mainly refusal of treatment) the therapy was delayed - even if anuria occurred, no case of graft loss or serious damage were observed. At the beginning of our experience, the diagnosis of SU was based on urography, and therapy has always been re-operation. For 15 years, the diagnosis of SU has been based on routine echographic surveillance, which was intensified after each rejection, and the first treatment of SU in the last 8 years was re-operation in early technical SU and interventional radiology (balloon dilatation with or without temporary stent) in other cases. When it failed or in case of recurrence, surgical correction was performed utilizing the native ipsilateral or contralateral ureter for a uretero-ureterostomy.

HLA-DR Antigens↗

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.

Antibodies↗

Beta2-microglobulin and low-flux synthetic dialyzers.

The aim of this study was to compare the effect on beta2-microglobulin (beta2-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of beta2-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma beta2-M level while the beta2-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in beta2-M removal was able to significantly lower the predialysis plasma beta2-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different beta2-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of beta2-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.

Aged↗

The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies.

Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.

Cytotoxicity, Immunologic↗

A comparison of dialysers with low-flux membranes: significant differences in spite of many similarities.

The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.

Adult↗

ELISA anti-HLA antibody screening identifies non-complement-fixing antibodies responsible for acute graft rejection. A case report.

We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.

Adult↗

Effect of different dialysis membranes on platelet function. A tool for biocompatibility evaluation.

Intradialytic coagulative and platelet activation, one of the main consequences of blood-membrane contact, was studied in a group of 5 RDT patients with a comparative evaluation of 3 different dialytic membranes: Cuprophan (CU), Polysulfone (PS) and Cellulose Triacetate (CT). Each patient underwent 5 consecutive dialysis sessions with the above mentioned membranes. Intradialytic platelet activation was studied through a morpho-functional evaluation between the mean platelet volume (MPV) and Serotonin (S), beta-Thromboglobulin (beta-TG) and Platelet Factor 4 (PF4) serum levels. These determinations were made before HD (time 0) and after 30', 120', and 240'. We also checked the intradialytic status of thrombogenesis and fibrinolysis determining aPTT, thrombin time, fibrinogen, antithrombin III (AT III), alpha-2 antiplasmin and plasminogen, at the same time intervals. All membranes tested (CU, PS, CT) caused appreciable intradialytic platelet activation, above all after 15' and at the end of dialysis sessions, more marked for CU than PS or CT. In particular MPV showed a decrease throughout the session (-5% at 30' and -9% at 240') while S, beta TG and PF4 peripheral blood levels showed a significant increase at the same intervals with CU membrane. Lastly coagulative and fibrinolytic parameters showed no significant differences among any of the membranes tested.

Adult↗

Is Ace inhibitor treatment a possible cause of better cardiovascular remodelling in well functioning kidney transplant?

Diseases of the cardiovascular system are a common cause of death in renal transplanted patients. In this study we assessed the echocardiographic morphological and functional findings after renal transplantation of two homogenous groups of transplanted patients with normal renal function. The first (A) with spontaneously normotensive patients, the second (B) with moderate hypertension treated mainly with Ace inhibitors. Analysis of these data highlights two noteworthy results: the similar left ventricle hypertrophy found in both groups and the existence of better diastolic compliance among the hypertensive transplanted patients. If this is confirmed by studies currently in progress, the importance of Ace-inhibitors treatment in remodelling cardiac dysfunction after long term dialysis treatment might be seriously considered.

Adult↗

[High-resolution computed tomography study (HRCT) in so-called emphysema B. The correlations between the radiogram, the anatomical findings yielded by high-resolution computed tomography and the clinico-functional assessment].

The results are reported of a prospective study on 28 emphysematous patients with clinical, functional and radiologic correlations. Thirteen of 28 patients had type-B, the clinical "blue and bloater", emphysema. The grade of emphysema was investigated on conventional chest films and on HRCT scans, with a visual scoring system. Hyperinflation was assessed on conventional chest films and correlated with the extent of emphysema on HRCT images and with functional impairment. In our series, the extent of emphysema in B-type patients was markedly lower than in other patients of the same age, with the same smoking habits, dyspnea and functional impairment. Moreover, the incidence of centrilobular involvement was higher, though not statistically significant. The B-type exhibited more severe dilatation of subsegmental pulmonary arteries (76.9% vs. 20% p < 0.001) and a striking incidence of small airway disease (84.6% vs. 26.6%, p < 0.002). This findings may explain the radiographic pattern of "increased vascularity" seen on chest films. Bronchiolectasis and small airway wall thickening are much more frequent in type-B emphysema, together with patchy areas of ground-glass opacity and small peripheral nodules. A close correlation was observed between signs of small airway disease on HRCT images and functional clinical impairment. Thus, the small airway disease might eventually prove to be a more critical factor in causing functional and hemodynamic impairment in B-type emphysema than the actual extent of centrilobular emphysema.

Adult↗

Value of panel reactive antibodies (PRA) as a guide to the treatment of hyperimmunized patients in renal transplantation.

Patient presensitization represents a considerable problem in candidacy for renal transplantation. While it is well known that hyperimmunized patients--panel reactive antibody (PRA) higher than 60%--create difficulties in donor matching and have a worse outcome than non-hyperimmunized patients, less information is available on patients with an intermediate degree of sensitization (30-60%). In order to evaluate how graft outcome relates to such degrees of sensitization, 241 consecutive transplanted patients were divided into two groups on the basis of their previous year's PRA peak: group A, PRA 0-29%; group B, PRA 30-60%. Group A showed a significantly better survival both in the first year (90% vs 79%, P < 0.05) and in the third year (82% vs 64%, P < 0.01). However, detailed analysis of group B demonstrated that some parameters may significantly influence graft outcome: (1) better compatibility on locus DR; (2) a primary kidney transplant; (3) a dialysis duration of less than 6 months; and (4) the prophylactic use of antilymphocyte globulin (ALG).

Adolescent↗