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L Ridolfi

Publications and source records attributed to L Ridolfi.

At least 19 recordsLinked to original sources
PubMed2005

Potential of real-time PCR assessment of granzyme B and perforin up-regulation for rejection monitoring in intestinal transplant recipients.

Granzyme B (GrB) and perforin are promising markers to predict acute rejection episodes of transplanted organs. Having recently reported that immunohistochemical expression of GrB/perforin correlates with histologically assessed acute cellular rejection (ACR) episodes in intestinal transplantation recipients, herein we have additionally explored the potential of real-time polymerase chain reaction (PCR) assessment of GrB/perforin gene up-regulation in peripheral blood mononuclear cells. Both immunohistochemical evaluation of GrB/perforin expression and real-time PCR assessment of up-regulation, which was defined as a 2-fold increase with respect to "basal" levels during maintenance immunosuppressive protocols, were performed among a population of 23 intestinal transplant recipients under routine surveillance, in addition to histological analysis of ACR. The ACR scores showed direct relationships both with GrB/perforin immunohistochemistry (IHC) scores (P < .001) and with gene up-regulation by real-time PCR (P = .004). Furthermore, real-time PCR upregulation was associated with the IHC score (P < .001). A preliminary analysis of diagnostic accuracy-performed to gain information to plan future studies-indicated that when using histological assessment as the reference technique, our current definition of PCR up-regulation provided good specificity (84%) but insufficient sensitivity (44%) for a noninvasive prediction of ACR. The results of this pilot study suggested that real-time PCR analysis of GrB/perforin upregulation may help therapeutic decision making, and have the potential for detection of presymptomatic rejection. More extensive studies must investigate strategies to improve the sensitivity of the analyses of GrB/perforin up-regulation.

Adolescent↗
PubMed2004

Utilization of suboptimal kidney donors.

In recent years over 30% of cadaver donors utilized in the Emilia Romagna (ER) region are over 60 years of age often with some additional risk factors. The organs of these Suboptimal Kidney Donors (SOKD) had been seldomly accepted from 1996 to 1999 (Group 1). From 2000, marking the beginning of use of double transplantation for marginal kidneys, a routine biopsy was performed for SOKD using the Score System proposed by Remuzzi. (Group 2) The 40% of marginal kidneys harvested were utilize in 76% of cases. The few biopsies available for Group 1 patients testify that good kidneys had been discarded, but even in Group 2, when we followed the biopsy Score, strictly several mistakes were suspected: kidneys discarded for an unbelievable difference of 2 points between two kidneys of the same size, cases with an high score based on only a few glomeruli, double kidney transplants that become single and still had fair functions. In the future the utilization of SOKD should probably be improved: (1) with scores only based on a biopsy specimen with more than 25 glomeruli, (2) a score system for incorporating clinical data, and (3) continuous perfusion preservation of kidneys whose characteristics provide some more information that may mitigate some of the damage of marginal donor kidneys.

Aged↗
PubMed2004

Molecular monitoring of organ recipients from cancer-affected donors by detection of circulating tumor cells.

We have initiated regular molecular monitoring based on nested RT-PCR detection of circulating tumor cells for monitoring recipients of organs from cancer-affected donors in Italy (in the context of a "Donation Safety and Donated Organ Quality" project organized by the Centro Nazionale Trapianti). Five patients are being monitored. For two patients who each received a kidney from a single donor with prostate adenocarcinoma, RT-PCR was performed using PSA mRNA. For three recipients of organs (two livers and one kidney) from donors with renal cell carcinoma, RT-PCR was performed using cytokeratine 18 and 19 mRNA. Blood samples from five healthy subjects were used as negative controls. After a median monitoring time of 26 months (range 8 to 32), none of the regular 3-month assays has tested positive. This pilot study suggests that detection of circulating tumor cells by nested RT-PCR may provide a feasible molecular monitoring, which might assist decision making regarding other forms of clinical surveillance.

Base Sequence↗
PubMed2001

Mean first passage times of processes driven by white shot noise.

We consider mean first passage times in systems driven by white shot noise with exponentially distributed jump heights. Simple interpretable results are obtained and the linkage between those results and the steady-state probability density function of the process is presented. The virtual waiting-time or Takács process (constant losses) and the shot noise process with linear losses are analyzed in depth, along with a more complex process with useful implications for the modeling of the soil moisture dynamics in hydrology.

Journal Article↗
PubMed2001

Hospital attitude survey on organ donation in the Emilia-Romagna region, Italy.

UNLABELLED: The role of hospital staff in the organ procurement process is crucial. Nevertheless, there is little literature about their attitudes toward donation. The Donor Action Hospital Attitude Survey (HAS) comprises a series of questions to assess hospital staff's attitudes, beliefs, and knowledge on organ donation and transplantation. Further analysis of the data will help identify any weak areas in the staff viewpoint and information, highlight potential needs for more education on specific issues, and establish a baseline to monitor future improvements. We used the Donor Action HAS in the Emilia-Romagna region, Italy. The aim of this paper is to assess and better understand the personnel's viewpoint in the 12 main hospitals of the region. The survey was carried out among hospital staff involved in organ donation. 1576 responses were collected (52 % of distributed questionnaires), of which 1024 came from nurses, 475 from physicians, and 77 from other backgrounds. Questions were subdivided into categories, and for every point an overall mark (maximum 3/3) was calculated. RESULTS: 1. Involvement in donation process during the past year: 1.24 /3, 2. Attitudes to organ donation (OD): 2.51 /3, 3. Skills / Self-confidence in donation practices: 1.36 /3, 4. Satisfaction with local transplant coordinator (TC) services: 2.31 /3. The attitude towards organ donation was positive, 1386 respondents support organ donation. A high percentage (93.6 % of respondents) is of the opinion that transplantation helps save other people's lives. Most uncertainty arises on the question whether donation helps families with grief. It is remarkable that only 53 % of those prepared to donate organs have informed the family of their wish. Many respondents do not feel comfortable performing key tasks close to donation. Major difficulties were observed in explaining to a family the concept of brain death (0.98 /3). Knowledge on the concept of brain-death was one of the most requested subjects for improvement. Emilia-Romagna is the region with one of the highest donation rates in Italy (29.9 pmp in 2000). Nevertheless, more profound knowledge of the local situation could help further improve donation.

Adult↗
PubMed2001

A revised consideration on the use of very aged donors for liver transplantation.

The upper age limit for organ donation for liver transplantation has increased over the past few years. A retrospective case control study was carried out to evaluate the outcome of 36 liver transplants (group A) performed with grafts procured from donors over 70 years old in the period 1996 to April 2000, matched with 36 transplants (group B) chronologically performed thereafter with organs procured from donors below the age of 40 yr. The groups were comparable as regards main clinical characteristics. Mean follow-up was 14.5 months. Clinical and laboratory parameters of the donors, cold ischemia period, intraoperative blood transfusions, 30-d mortality, incidence of primary graft nonfunction, acute rejection episodes, arterial complications and long-term survival of recipients were considered. The main postoperative biochemical parameters were also collected and compared. A liver biopsy was obtained in 20/36 old donors, revealing less than 25% of steatosis in all but one, which showed steatosis involving 70% of the hepatocytes. There were two postoperative deaths (5.6%) in group A and one (2.8%) in group B (p = NS). Seven postoperative arterial complications (19.4%) occurred in group A, leading to the patient's death because of rupture of the hepatic artery in one case, to successful surgical revascularization in three cases and to retransplantation in three cases. Only one patient in group B (2.8%) experienced hepatic artery thrombosis (p = 0.055). One-year patient survival rates were 77.4% for group A and 88.8% for group B (p = NS); 1-yr graft survival rates were 73.3% for group A and 85.7% for group B (p = NS). In conclusion, donors over 70 should not be excluded a priori for liver transplantation in elective settings. Great attention should be paid to the pathological conditions of arterial vessels caused by atherosclerosis, i.e. the presence of calcified plaques on the hepatic artery, which might represent the source of severe complications.

Adult↗
PubMed2001

Intralesional granulocyte-monocyte colony-stimulating factor followed by subcutaneous interleukin-2 in metastatic melanoma: a pilot study in elderly patients.

AIM AND BACKGROUND: Recent data in the literature indicate that antigen-presenting cells (APC) are inactive in tumour tissue because of local immunosuppression. Tumour-infiltrating lymphocyte (TIL) signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF) may lead to APC recovery and interleukin (IL)-2 may restore local TIL activation. Moreover, IL-2 increases the systemic lymphocyte population, an event that seems to correlate with a better prognosis. STUDY DESIGN: The present phase I-II study was carried out to examine whether intralesional injection of GM-CSF followed by subcutaneous IL-2 would induce a clinical response in advanced, pretreated elderly melanoma patients. METHODS: Sixteen patients over 60 years of age received intralesional GM-CSF (150 ng per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous IL-2 (3,000,000 IU) for 5 days (days 3-7 inclusive) every 3 weeks. RESULTS: Four clinical responses [two partial (PR) and two minimal (MR)] (25%), which also involved lesions that had not been directly treated, and nine cases of stable disease were observed. The response duration for PR and MR was 9, 4, 4 and 2.5 + months, respectively. Stable disease (56%) recorded in the nine patients was short-term (3-6 months). Three patients rapidly progressed after two, two and one therapy cycles, respectively. The patient who reached the best PR had a fairly high absolute lymphocyte count (1600-2400/mm3). The second one, who reached complete remission after subsequent locoregional chemotherapy and hyperthermia, however, had a low absolute lymphocyte count that had doubled by the end of treatment. Blood lymphocyte values in the other patients were too varied to allow any correlation with clinical response. Therapy was well tolerated and only mild fever was observed, with the exception of one patient who had grade 3 fever, with muscle pain and arthralgia. CONCLUSIONS: Considering the very low toxicity observed, this treatment might be indicated in elderly patients for whom systemic therapy is no longer a viable option. Improved scheduling and timing could result from further studies.

Aged↗
PubMed2000

Efficiency of organ procurement and transplantation programs.

The number of donations per million population (pmp) per year and the number of transplants pmp/year enables one to compare donation or transplant programs made in different years in the same area or made the same year in different areas. These pmp indexes may be integrated with an evaluation system by which each organ is evaluated separately in terms of the efficiency of its procurement and transplant systems using the procurement index (percentage in terms of number of organs utilized/number of organs procurable from donors utilized in a single area during 1 year) and the transplant index (percentage in terms of number of transplants performed/number of organs harvested in a single area during 1 year). We have called them Caldes I (procurement) and Caldes II (transplant) indexes. The harvest index evaluates the efficiency of utilization of organs retrieved from suitable donors. It usually ranges between 80-90% for the kidney, 70-95% for the liver, 40-50% for the heart, and 5-15% for the lungs. The transplant index evaluates for each organ the transplant team capacity to use available organs which can be harvested locally or in different areas. It usually ranges between 60-120%. Index determination did not require information different from the standard data available. Both the harvest and transplant indexes could be used to compare the efficiency of donation and transplant programs and policies in the same area during different years or at the same time in different areas. They can be critical in evaluating: (a) marginal donor utilization, (b) marginal organ utilization, and (c) dishomogeneity of organ retrieval and organ transplantation in different regions belonging to the same area. They also enable to evaluate if organs considered not available in a single area are offered to other areas or are not retrieved at all from available donors.

Efficiency, Organizational↗
PubMed2000

Organ donation and transplantation as health programs in Italy.

Organ and tissue donation and transplantation have a role in public health programs as organizational projects designed by public health departments to increase the quality and number of donations and transplantations. These programs serve as communication projects to inform public opinion on cerebral death, organ and tissue shortages, procurement and allocation rules, and the quality of life of transplanted patients. The health department of Emilia-Romagna created a regional law and a multimedia communication program for these purposes, resulting in a 95% increase of cadaver donor in 4 years. In 1995, regional activity reached the European mean level and afterwards surpassed it. In 1997, the bone bank was activated, followed in 1998 by the heart valve and vascular segment bank. The regional health department now considers transplant activities a primary goal; human and professional relations between intensive care units and the transplant reference center are considered crucial; cooperation among health departments, medical teams involved in organ procurement and transplant activities has been fostered, and the local coordination network has been active and efficient. The public information campaign has proven important in providing information both to professionals and citizens.

Health Care Rationing↗
PubMed2000

Reliability of ultrasound screening of liver and kidney donors: a retrospective study.

The reliability of abdominal ultrasound in screening liver and kidney donors was assessed by correlating ultrasound findings with the suitability of organs for transplantation as determined by direct examination of the organs. We evaluated 100 multiorgan donors (100 livers, 200 kidneys) during a 15-month period. Abdominal ultrasound showed the following results for liver and kidney, respectively: specificity, 95.6% and 98.9%; sensitivity, 62.5% and 66.6%; and accuracy, 93% and 97%. These results show that abdominal ultrasound is a valuable tool for determining suitability of organs for transplantation when the ultrasound findings are normal. When ultrasound findings are abnormal, further studies are necessary to determine the suitability of the organs for transplantation.

Adolescent↗
PubMed2000

[The transplant coordinator].

Spain was the first European country adopting a strategy of organ procurement based on a specific health professional named transplant coordinator, who was first established in Catalunya in the middle eighties. In principle, the transplant coordinator is a doctor with hospital experience who is involved full time in organ procurement. The transplant coordination activity is available without interruption, due to a team work. Transplant coordination is based on four main functions: clinical, research, training and communication, management. The principles of transplant coordination according to the Spanish model are reported in the recently approved Italian law on transplantation (law 91/1999), indicating the coordinator's specific functions: a) communication to the regional reference centre of the data concerning the possible organ donors, b) preparation of the documents needed, c) relationship with the donors' family, d) information and education of the population on transplantation issues.

Humans↗
PubMed1999

A comparison of pediatric and adult kidney donors for adult recipients.

The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia-Romagna and Piemonte) over an 11-year period. A group of pediatric donors (< 15 years old, n = 30) was compared with an adult donor group (n = 67). All recipients were adults who received cyclosporin as immunosuppression. Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96% and 96% for pediatric donors versus 98% and 92% for adult donors at 1 and 5 years post-transplantation; graft survival 76% and 68% for pediatric donors versus 88% and 74% for adult donors 1 and 5 y post-transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.

Adolescent↗
PubMed1999

Antithrombin replacement in patients with sepsis and septic shock.

Sepsis is a frequent complication of critically ill patients and its incidence is increasing. Currently, septic shock is the most common cause of death in non-coronary intensive care units. Over the last 10 to 15 years, new antibiotics and increasingly sophisticated critical care have had little impact on the mortality rate of septic shock. The Italian SEPSIS Study, carried out in 99 intensive care units in 1994, reported mortality rates of 52% and 82% for severe sepsis and septic shock respectively. New therapeutic approaches aimed at neutralizing microbial toxins and modulating host mediators have shown some efficacy in large clinical trials and/or in animal models, but to date, no therapy of sepsis aimed at reversing the effects of bacterial toxins or of harmful endogenous mediators of inflammation has gained widespread clinical acceptance. Because of the strong association of severe sepsis with a state of activation of blood coagulation and of the potential role of capillary thrombosis in the development of the multiple organ dysfunction syndrome, anticoagulant agents have been tested in the setting of septic shock. However, neither administration of heparin nor of active site-blocked factor Xa or of anti-tissue factor antibodies have proven effective in preventing deaths due to septic shock in animal models. In contrast, infusion of antithrombin, protein C, or tissue factor pathway inhibitor all resulted in a significant survival advantage in animals receiving lethal doses of E. Coli. Antithrombin concentrates have been used in a significant number of critically ill patients. A double-blind, placebo controlled study carried out in 3 italian intensive care units has recently shown that the administration of antithrombin aimed to normalize plasma antithrombin activity had a net beneficial effect on 30-day survival of patients requiring respiratory and/or hemodynamic support because of severe sepsis and/or post-surgery complications.

Antithrombins↗
PubMed1998

Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study.

BACKGROUND: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study. METHODS: 120 patients admitted to the ICU with an ATIII concentration < 70% were randomized to receive ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had septic shock. RESULTS: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97-102%). The Kaplan-Meier analysis showed no difference in overall survival between the two groups: 50 and 46% for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1% increase in the ATIII plasma concentration at baseline. CONCLUSIONS: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.

APACHE↗
PubMed1998

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↗
PubMed1998

Adjuvant adoptive immunotherapy with tumour-infiltrating lymphocytes and modulated doses of interleukin-2 in 22 patients with melanoma, colorectal and renal cancer, after radical metastasectomy, and in 12 advanced patients.

Adoptive tumour infiltrating lymphocytes (TIL) in combination with a modulated dosage of interleukin-2 (IL-2) can be used with acceptable toxicity in the treatment of immunogenic tumours. Following an experience of reinfusion in advanced melanoma, colorectal and renal cancer patients, treatment was given to disease-free patients after metastasectomy. The high risk of relapse and favourable ratio between reinfused TIL and possible microscopic residual disease determined this choice of adjuvant treatment. A group of 12 patients with advanced disease (7 melanoma, 4 colorectal carcinoma, 1 kidney carcinoma) were treated with TIL (median 5.8 x 10(10) cells) and IL-2 (West's schedule) modulated towards a lower dosage (from 12 to 6 MIU/day) in order to maintain an acceptable level of toxicity. As treatment was well tolerated, it was offered to another 22 patients in an adjuvant setting after metastasectomy (11 melanoma, 10 colorectal carcinoma, 1 renal cancer), the median dose of TIL reinfused being 4.95 x 10(10) cells. No objective response was observed in advanced patients: all patients progressed after a median of 1.5 months (0-8 months) and median survival was 8 months (3-22+ months). Thirteen patients from the second group are still disease-free after a median of 23+ months (9+ - 47+ months). The remaining 9 patients relapsed after a median of 5 months (3-18 months). Toxicity was moderate as clinical and hepatic/renal function parameters were used to assess the need for dose reductions. Consequently, there was great diversity in IL-2 dosages administered. In particular, there seemed to be a difference in IL-2 doses administered between disease-free cases and those who progressed (17.5 MIU/day versus 7 MIU/day in melanoma patients; 11.2 MIU/day versus 7.1 MIU/day in colorectal cancer patients). By contrast, no differences were observed between number of TIL reinfused and clinical response. Phenotypical characteristics of reinfused TIL were similar to those reported in the literature: 97% were CD3 and 92% were CD8. Aspecific cytolytic activity was evaluated on 12 cases whereas, in 2 melanoma cases, autologous tumour tissue was available for the specific cytotoxicity test. Perforin levels in TIL measured at the end of culture were generally high or very high. Cytokine levels were measured on the supernatant at the end of culture, with an estreme variability in results. Finally, delta chain and p56lck were histologically assessed on the resected tissue from which TIL were cultivated. There were virtually none of the former and a complete absence of the latter, which concurs with data reported in the literature. The same immunocytochemical analysis was carried out on TIL at the end of culture. This time an almost complete restoration of both functions was seen, especially in melanoma patients, who are still free from disease. The study is on-going and it has been decided to focus on disease-free patients after metastasectomy in order to increase the number and possibility of clinical and histological correlations.

Adolescent↗