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Biomedical subjects

G Sirchia

Publications and source records attributed to G Sirchia.

At least 55 records · Page 3Linked to original sources
PubMed1999

Placental/umbilical cord blood transplantation.

In this article we summarize the clinical outcome of unrelated placental/umbilical cord blood (CB) transplantation, discuss the biological characteristics of CB hematopoietic progenitor/stem cells (HPC) and balance the relative advantages and disadvantages of this therapy as compared with transplantation of other HPC sources. Moreover, we discuss CB banking programs at local, national and international levels. The data reported by the investigators of the New York Placental/Umbilical Cord Blood Program and of the Eurocord group indicate that the clinical outcome of allogeneic unrelated CB transplantation is significantly related to cell dose, being more effective in children than in adults, and is highly dependent on disease stage at transplantation. Furthermore, both studies show lower graft-versus-host disease (GvHD) frequency and severity and prolonged time intervals for platelet engraftment as compared to those of bone marrow and mobilized peripheral blood recipients. Although the data from the New York Placental/Umbilical Cord Blood Program seem to support a negative effect of HLA differences, the latter were not significantly associated with survival in the Eurocord series. Additional observations are therefore necessary to collect conclusive evidence in this regard. Currently available data show that CB contains a higher proportion of primitive HPC and that CB-HPC possess higher proliferation and expansion potentials as compared to adult bone marrow. Furthermore, there is some evidence indicating that CB-HPC are more adequate than HPC from other sources for genetic manipulation and gene therapy. Despite the significant advances in the knowledge of the biology and in the clinical use of CB, a number of problems remain unsolved, including the standardization of banking procedures and unit quality and the development of suitable protocols for transplantation of adult patients.

Adult↗
PubMed1998

A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia.

Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent beta-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti-hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV- by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4. 27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values >/=3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P < .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.

Adolescent↗
PubMed1998

The current risk of retroviral infections transmitted by transfusion in patients who have undergone multiple transfusions. Cooleycare Cooperative Group.

BACKGROUND: To conduct a multicenter, prospective survey within the program of the Cooleycare Cooperative Group to evaluate the rate of transfusion-transmitted infections with human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV) in a cohort of patients who were homozygous for beta thalassemia and underwent multiple transfusions during the 6-year follow-up. PATIENTS AND METHODS: One thousand three hundred eighty-four patients with beta thalassemia from 36 centers were enrolled from December 1989 to March 1990. Serum samples were tested at regular intervals during the period from December 1989 to March 1996 for anti-HIV and anti-HTLV antibodies in 1 laboratory. Samples from 1073 and 1001 of the 1384 patients were available for evaluation also during the periods from December 1992 to March 1993 and December 1995 to March 1996, respectively. The risk of acquiring infection was calculated by the ratio between the number of patients who experienced seroconversion and the number of red blood cell units administered to the patients during the study period. RESULTS: The prevalence of HIV infection found in the period from December 1989 to March 1990 was 2.9% (40 of 1384 patients). During follow-up, 1 of 1001 patients showed anti-HIV seroconversion. The incidence of HIV infection was 1.7 per 10,000 person-years (upper boundary of the 95% confidence interval, 5 per 10,000). The risk of HIV infection was 1 in 190,000 U (upper boundary of the 95% confidence interval, 1 in 67,000). At baseline, 4 patients were infected with HTLV (3 with HTLV-1 and 1 with HTLV-2). No seroconversions were observed during follow-up; the risk of HTLV infection was less than 1 in 190,000 U. CONCLUSION: The application of reliable screening procedures for donor selection reduced the transmission of transfusion-associated HIV infection in 1989-1995 to fewer than 2 cases in 10,000 person-years or 1 case per 190,000 units of red blood cells.

Adolescent↗
PubMed1998

The incidence and natural course of transfusion-associated GB virus C/hepatitis G virus infection in a cohort of thalassemic patients. The Cooleycare Cooperative Group.

To evaluate the risk of transmitting blood-borne GB virus C/hepatitis G virus (GBV-C/HGV) and to define the natural course of infection, we performed a prospective study in a cohort of multitransfused beta-thalassemics during a 6-year follow-up period. We analyzed serum samples of 150 patients collected at 3-year intervals from 1990 to 1996. GBV-C/HGV RNA was determined by reverse transcriptase-polymerase chain reaction and antibodies to E2-protein by an enzyme immunoassay. At baseline, 14.5% of patients had viremia and 18.5% anti-E2. None of the patients with anti-E2 in 1990 subsequently became viremic. Of the 100 GBV-C/HGV RNA-, anti-E2- patients, 10 acquired infection during follow-up, as indicated by positivity of GBV-C/HGV RNA (n = 2), anti-E2 (n = 7), or both markers (n = 1) in 1996. The incidence was 1.7 per 100 person-years (95% confidence interval [CI], 0.8 to 3). Since approximately 19,000 blood units were transfused to these patients during follow-up, the risk of infection was 5.3 in 10,000 units (95% CI, 2 to 8.5). Six of 22 viremic patients cleared the virus during follow-up; 4 of them became anti-E2+. Twelve of 28 patients lost anti-E2 reactivity during follow-up. In conclusion, more than 25% of infections resolve within 6 years; the presence of anti-E2 seems to be protective against infection. Anti-E2 reactivity may decrease with time.

Adolescent↗
PubMed1998

A retrospective evaluation of HLA-A, B and -DRB1 matching in liver transplantation.

Studies on the influence of histocompatibility in liver transplantation have not produced clearcut results. We retrospectively studied the influence of HLA-A, B and -DRB1 matching on the survival of 517 liver-transplanted patients using univariate analysis. The following parameters were also considered in relation to transplant outcome: donor and recipient age, original disease, transplant center, and pretransplant blood transfusions. Twenty-four-month graft survival according to the number of HLA-A, B, DRB1 mismatches (MM) was 70.9% (n = 28) for zero to two MM, 76.6% (n = 248) for three to four MM, and 73.1% (n = 241) for five to six MM (P = 0.7). We obtained similar results when considering HLA-A, B MM alone. Survival rates according to HLA-DRB1 MM were 71.7% (n = 36) for zero MM, 73.7% (n = 236) for one MM, and 76.4% (n = 245) for two MM (P = 0.6). The same analyses, performed on cirrhotic patients alone, gave identical results. In conclusion, this study suggests, on a large series of patients, that HLA compatibility has no influence on liver transplant survival. On the contrary, an influence on transplant outcome was found for donor age, transplant center, and original disease.

Adolescent↗
PubMed1998

Organizational aspects of donor procurement activity in the North Italy Transplant programme (NITp).

In Italy, organ procurement is insufficient to meet patient need. The aim of this study was to estimate the potential donor pool, quantify nonused donors, identify causes of nonretrieval, and evaluate the impact of some hospital organizational problems on organ procurement. In 1995 a questionnaire was sent to 103 intensive care units (ICUs) in 92 hospitals of the NITp area. Out of 432 potential donors identified, 239 (55.3%) were used. Causes of nonretrieval included family refusal (51.7%), clinical reasons (43.9%) and organizational problems (4.4%). In comparison with 1990 and 1993 data, a higher percentage of donors were used and the donors lost for organizational reasons had decreased significantly, while no significant differences were observed in the number of donors lost for family refusal and for clinical reasons. The marked improvement in donor procurement in NITp from 1990 to 1995 was probably as result of measures aimed at motivating ICU personnel and solving their organizational difficulties.

Humans↗
PubMed1998

Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines.

The continuous infusion of the opioid peptide beta-endorphin prolongs skin allograft survival in mice, while the opiate receptor antagonist naloxone, administered together with the opioid at the time of transplantation, abolishes the effect of the opioid. Consistently, naloxone, when given alone at the time of transplantation, but not later, accelerates graft rejection and increases splenocyte IL-2 and interferon-gamma (IFN-gamma) production. Splenocyte beta-endorphin concentrations are lower in transplanted animals. The effects of exogenous beta-endorphin and naloxone suggest that the endogenous opioid peptide beta-endorphin exerts a tonic inhibitory effect over early events of T cell-mediated immune responses in vivo. The effects of beta-endorphin and naloxone are consistent with the previously shown role of the opioid system in the modulation of the Th1/Th2 cytokine pattern.

Animals↗
PubMed1998

Evaluation of a new automated instrument for pretransfusion testing.

BACKGROUND: A number of automated devices for pretransfusion testing have recently become available. This study evaluated a fully automated device based on column agglutination technology (AutoVue System, Ortho, Raritan, NJ). STUDY DESIGN AND METHODS: Some 6747 tests including forward and reverse ABO group, Rh type and phenotype, antibody screen, autocontrol, and crossmatch were performed on random samples from 1069 blood donors, 2063 patients, and 98 newborns and cord blood. Also tested were samples from 168 immunized patients and 53 donors expressing weak or variant A and D antigens. Test results and technician times required for their performance were compared with those obtained by standard methods (manual column agglutination technology, slide, semiautomatic handler). RESULTS: No erroneous conclusions were found in regard to the 5028 ABO group and Rh type or phenotype determinations carried out with the device. The device rejected 1.53 percent of tests for sample inadequacy. Of the remaining 18 tests with discrepant results found with the device and not confirmed with the standard methods, 6 gave such results because of mixed-field reactions, 10 gave negative results with A2 RBCs in reverse ABO grouping, and 2 gave very weak positive reactions in antibody screening and crossmatching. In the samples from immunized patients, the device missed one weak anti-K, whereas standard methods missed five weak antibodies. In addition, 48, 34, and 31 of the 53 weak or variant antigens were detected by the device, the slide method, and the semiautomated handler, respectively. Technician time with the standard methods was 1.6 to 7 times higher than that with the device. CONCLUSION: The technical performance of the device compared favorably with that of standard methods, with a number of advantages, including in particular the saving of technician time. Sample inadequacy was the most common cause of discrepancy, which suggests that standardization of sample collection can further improve the performance of the device.

ABO Blood-Group System↗
PubMed1998

Implementation of a quality system (ISO 9000 series) for placental blood banking.

Although placental blood has recently become a new source of hematopoietic progenitors for marrow replacement, limited attention has been given to systems suitable to ensure the short-term and long-term quality of placental blood units used for transplantation. In this article, we describe a quality system for placental blood banking developed in accord with ISO 9002 norms at Milano Cord Blood Bank. The quality system is the organizational structure, procedures, processes, and resources needed to implement quality management. ISO 9002 is a model for quality assurance in production, installation, and servicing, which includes a number of clauses providing guidance for the implementation of the quality system. The quality system was started by the bank medical director with step 1: the general quality plan, which included (a) the written description of mission, objectives, technical and organizational policies, and staff organization chart of the placental blood bank, (b) the definition and acquisition of adequate financial, human, and structural resources, (c) the appointment of a quality system head independent from the production laboratory and reporting directly to the medical director. Tasks of the quality system head were (a) to identify the placental blood banking process together with the placental blood bank personnel, (b) to implement a documentation plan finalized at the production and maintenance of (i) the quality manual, which provides a summary on how the bank operates with a quality system in compliance with the ISO 9002 clauses, (ii) the general procedures (or quality system procedures), which provide more detail on selected clauses, including at least those prescribed by the ISO 9002 standard, (iii) the operative procedures (or process procedures), which describe in detail the process of placental blood banking and how technical activities must be performed, (iv) the work instructions, which provide stepwise descriptions of individual activities, (v) records/forms for data collection and storage, (c) to identify quality indicators, (d) to start a regular internal audit, (e) to report audit results to the medical director for review. This was followed by step 2: the job descriptions, staff training, and qualification; step 3: the documentation plan; step 4: the internal audit plan; step 5: the launch of the quality system, and step 6: the assessment by an external team from an accredited third-party organization and final certification for compliance to ISO 9002. The quality system, which must be maintained and undergo external audit at regular intervals so that certification is confirmed, ensures the high probability that placental blood units provided to clinicians conform regularly to predefined levels of quality.

Blood Banks↗
PubMed1998

Comparison of serological and molecular typing for HLA-A and -B on cord blood lymphocytes.

HLA class I typing by standard microcytotoxicity testing has been unsatisfactory for 14.5% of 1644 cord blood samples. In this study, we evaluated the capacity of PCR-SSP in solving problems in HLA-A,B typing with serological methods. With this aim we have compared serology with PCR-SSP in 100 cord blood samples with doubtful or unreliable HLA-A,B typing. PCR-SSP was successful in amplifying HLA-A,B alleles in all 100 cord blood samples. Forty-six typings gave discrepant results with the 2 methods (serology and PCR-SSP). Typings were considered discrepant also in the case of inability to define a split. For 19 specimens, no serological conclusion was drawn due to high mortality of the cell suspension, while PCR-SSP allowed the definition of a clear typing. In 6 cases it was necessary to infer information from serology to define the current typing. Finally, in 3 other cases it was impossible to exclude or attribute the antigen/allele B67 or B4802. PCR-SSP for HLA-A,B can improve the overall reliability of HLA-A,B typing requiring a small amount of blood although, with the set of sequence specific primers adopted, a number of alleles are still poorly defined.

Alleles↗
PubMed1998

Cadaver kidney allocation in the north Italy transplant program on the eve of the new millennium.

The identification of parameters impacting on cadaver kidney graft outcome is of paramount importance to ensure proper organ allocation, a process that must take into account ethical, biological, social and administrative factors. This is particularly critical in countries where organ procurement is largely insufficient. In the present chapter we report the results of studies carried out to determine the impact of 17 factors on graft survival and function at 4 years posttransplant in 2,917 recipients transplanted from January 1990-September 1997 in the North Italy Transplant program (NITp). Patient and graft survival rates at 4 years (+/- SEM) were 93.5 +/- 0.5% and 81.4 +/- 0.8%, respectively. Excellent graft function at 4 years was shown by 69.8% of recipients. Younger donor age, absence of pretransplant transfusions, patient dialysis center in the NITp area and level of HLA match showed a statistically significant positive association with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. These global outcomes were confirmed when the analysis was limited to the subset of the 2,617 adult recipients and to the subset of 1,211 cases for whom both donor and recipient HLA-DRB1 types were available before transplant. The results were used to develop a computer-assisted, refined version of the NITp adult kidney allocation algorithm that was named NITK3. A preliminary evaluation of 472 transplants allocated in 12 months with NITK3 compared with 459 transplants allocated in the preceding 12 months according to the previous algorithm (NITK2) showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.1% vs 21.1%). The use of NITK3 was also associated with a significantly increased ability to transplant alloimmunized patients (17.7% vs 9.5% with NITK2) and recipients with 0-1 HLA mismatches (21.2% vs 13.5% with NITK2). Differences in 6-month graft survival rates and in the percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with NITK3 versus NITK2. Survival rates were 96.9% and 92.4%, respectively. Percentages of patients with excellent renal function were 68.3% and 70.5%, respectively. These preliminary data suggest that NITK3 improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

Adolescent↗
PubMed1998

A quality system for placental blood banking.

A Quality System for Placental Blood Banking aimed at the transplantation of haematopoietic stem cells to related and unrelated allogeneic recipients is described. It includes the organizational structure, procedures, processes and resources needed to implement quality management. The Quality System described in this article is based on ISO 9002, a model for quality assurance in production, installation and servicing developed in 1987 and revised in 1994 by the International Organization for Standardization. ISO 9002 includes 20 clauses that provide guidance for the implementation of the Quality System. The development of the Quality System is started by the Placental Blood Bank Medical Director with the definition of a General Quality Plan including: (1) the written description of the Mission, Objectives, Technical and Organizational Policies, and Staff Organization Chart; (2) the definition and acquisition of adequate financial, human and structural resources; (3) the appointment of a Quality System Head, who must identify the Placental Blood Banking process together with the Placental Blood Bank personnel; implement a documentation plan; identify quality indicators; start regular internal audit; report audit results to the Medical Director for review. Following staff training and qualification, the Quality System is launched. The Placental Blood Bank can then undergo audit by an external inspector and be finally certified for compliance to ISO 9002. The Quality System must be maintained and subjected to external audit at regular intervals so that certification is confirmed.

Blood Banks↗
PubMed1997

The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

BACKGROUND: Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can be appropriate in patients in stable condition, but the safety of lower thresholds is uncertain. METHODS: We evaluated 255 adolescents and adults (age, 16 to 70 years) with newly diagnosed acute myeloid leukemia (but not acute promyelocytic leukemia), who were treated in 21 centers. One hundred thirty-five patients were randomly assigned to receive a transfusion when their platelet count fell below 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter in those with a temperature above 38 degrees C, with active bleeding, or a need for invasive procedures), and 120 patients were assigned to receive a transfusion when their platelet count was less than 20,000 per cubic millimeter. RESULTS: Patients in the group with a threshold of 10,000 platelets per cubic millimeter received 21.5 percent fewer platelet transfusions than the patients in the group with a threshold of 20,000 platelets per cubic millimeter (P=0.001). The numbers of red-cell units transfused were not significantly different between groups. Major bleeding (defined as any bleeding more than petechiae or mucosal or retinal bleeding) occurred in 21.5 and 20 percent of patients, respectively (P=0.41), and on 3.1 and 2.0 percent of the days of hospitalization. One episode of fatal cerebral hemorrhage occurred in the group with a threshold of 10,000 platelets per cubic millimeter; none occurred in the other group (P= 0.95). Actuarial estimates of survival during induction chemotherapy, actuarial estimates of the absence of major bleeding, and the length of hospital stay were not significantly different in the two groups. CONCLUSIONS: The risk of major bleeding during induction chemotherapy in adolescents and adults with acute myeloid leukemia (except acute promyelocytic leukemia, which we did not study) was similar with platelet-transfusion thresholds of 20,000 per cubic millimeter and 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter when body temperature exceeded 38 degrees C, there was active bleeding, or invasive procedures were needed). Use of the lower threshold reduced platelet use by 21.5 percent.

Adolescent↗
PubMed1997

Use of photografting technique for the immobilization of blood-grouping antibodies onto microtiter plates.

Commercial anti-A, anti-B, anti-A,B and anti-D monoclonal and polyclonal antisera were immobilized onto polystyrene microtiter plates using a photografting technique, to set up a new solid-phase assay (SPA) to be used for blood grouping. The reactivity and specificity of each grafted antisera were studied using red blood cells (RBCs) expressing normal and weak antigens. The stability of immobilized antisera was also studied. After dry storage of plates at +4 degrees C, room temperature, and +37 degrees C, SPA was performed using fresh and/or frozen RBCs. The same test was carried out after storing plates under protective conditions. Concordance of collected with expected results was obtained in all cases when the SPA was performed using monoclonal antisera and RBCs, with normal or weak expression of ABO and D antigens immediately after plate preparation or after dry storage at +4 degrees C. Plates stored dry at room temperature or at +37 degrees C gave inconsistent results, whereas a slight increase in reactivity was observed after storage under protective conditions. The specificity and the reactivity of tested antibodies were not modified by the immobilization procedure, not even after dry storage at +4 degrees C. Damage produced by water evaporation during dry storage in hard conditions could be reduced by adding a protective solution to microtiter wells at the beginning of storage.

ABO Blood-Group System↗