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Biomedical subjects

A Zanella

Publications and source records attributed to A Zanella.

At least 37 records · Page 2Linked to original sources
PubMed2000

Red cell pyruvate kinase deficiency: from genetics to clinical manifestations.

Pyruvate kinase deficiency is the most frequent enzyme abnormality of the Embden-Meyerhof pathway causing hereditary non-spherocytic haemolytic anaemia. The degree of haemolysis varies widely, ranging from very mild or fully compensated forms, to life-threatening neonatal anaemia and jaundice necessitating exchange transfusions. Splenectomy should be reserved for young patients who require regular blood transfusions. The gene encoding for pyruvate kinase (PK-LR) has been localized to the long arm of chromosome I; the cDNA of R-type is 2060 bp long and codes for 574 amino acids. More than 130 different mutations, mostly missense, have so far been described in association with PK deficiency, 1529A and 1456T being considered to be the most common mutations in Caucasians. Analysis of the three-dimensional structure of the enzyme may help in predicting the severity of the molecular defect. Further data on clinical features of homozygous patients are needed, at least for some mutations, to allow a more precise genotype/phenotype correlation.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed2000

A simulation study for the design of a control system for the blood concentration process in autotransfusion.

Autotransfusion is the process in which a patient serves as his or her own blood donor; its most important application is the intraoperative blood salvage, in which the blood collected during a surgical operation is filtered, concentrated, washed, and then reinfused. In an automatic autotransfusion device, such as the DIDECO Compact Advanced, red blood cells (RBCs) are separated from the other unwanted components and concentrated by using a rotating bowl and the effect of centrifugal force. An important characteristic of concentrated RBCs is their hematocrit (Hct), i.e., percent RBC volume divided by total blood volume. The aim of this study is to assess the feasibility of a controller, based on the artificial neural network approach, which is able to provide a closed loop control of the hematocrit of the blood in the bowl at the end of the concentration phase. A simulation approach was adopted both for training the network and for assessing its performances. The results obtained are quite satisfactory, since the target Hct was typically reached within a 3% error, and always within 6% in highly challenging situations.

Biomedical Engineering↗
PubMed2000

[Autoimmune hemolytic anemia].

Autoimmune hemolytic anemias (AIHAs) are the most ancient and well known example of clinical autoimmunity. They may be still distinguished in two main groups, that is with "warm" or "cold" antibodies, according to the optimal temperature at which they react with the erythrocyte antigens in vivo and in vitro. There is also a subgroup where both kinds of autoantibodies coexist. AIHAs may be idiopathic or secondary. The immunologic techniques for the demonstration of the antibodies are well established, but one must remember that there are infrequent cases with negative DAT (Coombs) test when performed with conventional procedures. The fundamental concepts of therapy are discussed, and the detailed review of the principal procedures is performed, including blood transfusions (when and how), plasma exchanges, high-dose immunoglobulins, glycocorticosteroids, splenectomy, cytotoxic agents and stem cell transplantation, autologous and allogeneic.

Anemia, Hemolytic, Autoimmune↗
PubMed1999

A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia.

A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.

Adolescent↗
PubMed1999

Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Aged↗
PubMed1999

A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia.

Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA --> TGA, Arg --> Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.

Adenylate Kinase↗
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 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

Erythrocyte engineering for drug delivery and targeting.

A new procedure for the encapsulation of non-diffusible drugs into human erythrocytes was developed. With as little as 50 ml of blood and by using a new apparatus, it was possible to encapsulate a variety of biologically active compounds into erythrocytes in 2 h at room temperature and under blood-banking conditions. The process, which is based on two sequential hypotonic dilutions of washed red cells followed by concentration with a haemofilter and resealing of red cells, allows a 35-50% cell recovery and approx. 30% encapsulation of added drugs. The resulting processed erythrocytes have a normal survival in vivo and can be modified further, with the same apparatus, to increase their recognition by tissue macrophages to perform as a drug-targeting system. The new equipment designed and built for this procedure was named 'Red Cell Loader'.

Cell Membrane Permeability↗
PubMed1998

High prevalence but low pathogenicity of hepatitis G virus infection in Italian patients with genetic haemochromatosis.

BACKGROUND: Various environmental factors have been shown to hasten cirrhosis and hepatocellular carcinoma in patients with genetic haemochromatosis. AIM: To assess the prevalence and the role of the recently identified hepatitis G virus in 70 patients with genetic haemochromatosis in comparison with 40 patients with cryptogenic chronic hepatitis and 200 regular blood donors. PATIENTS: Six patients with genetic haemochromatosis (9%) had serum hepatitis B surface antigen, 14 (20%) had serum hepatitis C virus RNA. A liver biopsy was available in 66 patients with genetic haemochromatosis (43 with cirrhosis) and 40 with cryptogenic hepatitis (4 with cirrhosis). METHODS: Serum HGV-RNA was detected by a reverse transcriptase polymerase chain reaction using primers derived from the 5'-non-coding and non-structural-5A regions of the viral genome. Serum IgG antibodies against HGV were detected by enzyme-linked immunosorbent assay using a recombinant E2 protein of the virus envelope. RESULTS: The prevalence of serum HGV-RNA was higher in patients with cryptogenic hepatitis (n = 6, 15%) and genetic haemochromatosis (n = 6, 9%) than in donors (n = 3, 1.5%) (p = 0.0008 and p = 0.01, respectively). The corresponding figures for serum anti-HGV were 4 (10%), 16 (23%) and 10 (5%). The six haemochromatotic patients with serum HGV-RNA more often had parenteral exposure to blood (50% vs 5%, p < 0.001), and persistently elevated serum aminotransferases (100% vs 31%, p < 0.001) than the 64 non-viraemic patients. The six HGV-RNA seropositive patients with cryptogenic hepatitis were older than the 34 non-viraemic patients (56 vs 34 years, p < 0.05). CONCLUSIONS: The prevalence of serum markers of HGV infection in patients with genetic haemochromatosis is higher than in blood donors, but similar to that of patients with cryptogenic chronic hepatitis. However, HGV is not a cofactor of morbidity in patients with genetic haemochromatosis.

Adult↗
PubMed1997

High rates of hepatitis G virus infection in multitransfused patients with hemophilia.

The parallel measurement of serum antibodies to the hepatitis G virus (anti-HGV) and of viremia (HGV-RNA) should improve our understanding of HGV transmission by coagulation factor concentrates. The aim of this study was to assess the relationship between HGV, the type of concentrate infused, and liver disease in multitransfused hemophiliacs. To this end, anti-HGV and HGV-RNA were evaluated by an enzyme-linked immunosorbent assay and a nested-polymerase chain reaction assay in patients treated lifelong with nonvirus-inactivated plasma-derived concentrates (n = 128), virus-inactivated concentrates (n = 33), or recombinant factors (n = 7), and in 200 regular blood donors. The prevalence of serum HGV-RNA and anti-HGV was higher in the recipients of nonvirus-inactivated factors than in blood donors (HGV-RNA: 9% v 1.5%, P = .002; anti-HGV: 32% v 5%, P < .0001). In the recipients of virus-inactivated concentrates the prevalences of these markers were similar to those in blood donors (HGV-RNA: 3% v 1.5%; anti-HGV: 15% v 5%). The prevalence of either marker in the recipients of nonvirus-inactivated concentrates was higher than in the recipients of virus-inactivated factors (39% v 18%, P = .04). The former group had serum hepatitis C virus (HCV) RNA or anti-HCV more frequently than the latter group (HCV-RNA: 86% v 15%, P < .0001; anti-HCV: 96% v 18%, P < .0001). Serum alanine aminotransferase was persistently high in 83 (81%) patients with HCV-RNA alone, in 8 (89%) with HCV/HGV coinfection, and in none of the three patients with HGV-RNA only. Thus, HGV infection in hemophiliacs is more common than previous studies of HGV-RNA prevalence have suggested, but it resolved in most cases and caused chronic viremia only in a small number of patients, without biochemical evidence of persistent liver damage.

Adolescent↗
PubMed1997

Molecular characterization of PK-LR gene in pyruvate kinase-deficient Italian patients.

We studied the PK-LR gene in 15 unrelated Italian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency. Fourteen different mutations were detected among 26 mutated alleles identified: a five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(-2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and 1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231, 1269C, IVS3(-2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new polymorphic site was detected in the 3' untranslated region of the mRNA (C/T, nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77, probably resulting in an unstable gene product. Mutations 1269C and IVS3(-2)c lead to an alteration of the 5' and 3' splice-site consensus sequence, respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting that these mutations generate an unstable mRNA that is rapidly degraded. Of the five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although found in less conserved regions, affect the balance of the electric charges of the protein. Mutation 787T (Gly263-Trp) is likely to determine strong modifications in the local structure of the molecule. The most frequent mutation in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of 30) and 994A (three of 30). A correlation was found between mutations, biochemical characteristics of the enzyme, and clinical course of the disease.

Adolescent↗
PubMed1997

The incidence and risk factors of community-acquired hepatitis C in a cohort of Italian blood donors.

To assess the incidence and source of community-acquired hepatitis C virus (HCV) infection among subjects at low risk for blood-borne diseases, we prospectively studied a cohort of 16,515 repeat blood donors over a mean follow-up time of 36 months. Second- and third-generation methods were used for hepatitis C virus antibody (anti-HCV) testing. HCV RNA was determined in the serum of anti-HCV-positive donors by reverse-transcription polymerase chain reaction. Liver biopsy was performed in the viremic subjects. Risk factors for HCV infection were identified by a psychosocial questionnaire in the whole cohort. During follow-up, 5 donors became infected with HCV. The incidence was 1 per 10,000 person-years (95% confidence interval, 0.3-2.4 per 10,000). During the 6 months before seroconversion, four subjects (80%) underwent medical or surgical percutaneous procedures, compared with 26.5% in the entire donor cohort (difference between frequencies, 53.5%; CI: 18.9-89.1). One seroconverting donor had sexual intercourse with an infected subject. Only 1 infected donor developed clinically evident acute hepatitis. HCV RNA remained detectable in 4 of 5 subjects for 8 to 36 months after seroconversion, and liver biopsy showed chronic hepatitis in all cases. Thus, new cases of hepatitis C occur among individuals without a history of known risk factors, some of which may be caused by nosocomial exposure.

Adult↗
PubMed1997

Resection of pulmonary metastases from colorectal carcinoma.

A retrospective study was made on 22 patients who underwent surgery (28 operations) for lung metastases of colorectal origin from 1986 to 1995 at the Department of Surgery II, Padova University. The overall 5-year survival (OS) following pulmonary resection was 62% and the 5-year disease-free interval after metastasectomy (DFIM) 45%. The median survival was 23.6 months and the median DFIM 15.3 months. Univariate (Mantel Cox) and multivariate (Cox's model) analyses were used to identify any prognostic factors significant for OS and DFIM. Site and stage of primary colorectal carcinoma, number of pulmonary metastases at presentation, disease-free intervals between treatment of primary tumour and diagnosis of lung metastases (DFIP) appeared to have no influence on OS and DFIM. However, patients who underwent radical resection for metastases had a significantly longer DFIM than those who underwent 'non-radical' resections (P = 0.02), but radical resection had no significant positive effect on OS. A short DFIP, multiple and/or bilateral lesions, lung metastases occurring after liver resection with a curative aim are not contraindications to surgery in patients with pulmonary metastases from colorectal cancer, the main criterion for selection of patients being the possibility of performing 'radical' resection.

Adult↗
PubMed1997

A variant of the EPB3 gene of the anti-Lepore type in hereditary spherocytosis.

The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations and band 3 deficiency. We report a large Italian family in which 10 of the 27 members investigated displayed an autosomal dominant HS. SDS-PAGE revealed a reduction in band 3 in the patients. Screening of the Pst I polymorphic site confirmed the linkage of HS with the EPB3 gene. Analysis of complementary and genomic DNA showed a large additional segment. Nucleotide sequencing disclosed an in-frame duplication of 69 nucleotides (nt) including a triplet of intronic origin and a genuine exonic duplication of 66 nt. Two CCTGC sequences occurred close to one another, one near the intron 12 acceptor splice site (nt -7 to -3), and the other within exon 13 (nt 1494-1498). We assumed that the abnormal allele arose from an unequal recombination event of the anti-Lepore type between the two CCTGC sequences. At the level of the mutated protein, termed band 3 Milano, the additional segment (Gln plus duplication of residues 478-499) corresponded to the last part of the third transmembrane domain (TM3), the entire second outer loop and part of TM4 as it is currently defined in hydropathy analysis. After deglycosylation of band 3, only the normal band was detected, supporting the view that band 3 Milano is probably not incorporated into the membrane.

Adolescent↗