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Biomedical subjects

M Zappa

Publications and source records attributed to M Zappa.

At least 55 records · Page 3Linked to original sources
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

Overdiagnosis of prostate carcinoma by screening: an estimate based on the results of the Florence Screening Pilot Study.

OBJECTIVES: To estimate overdiagnosis (detection of latent carcinomas) as a consequence of screening for prostate cancer. DESIGN: Based on actual screen (first or repeat) detected and interval prostate cancer rates observed in the Florence screening pilot study, a scenario was simulated where males aged 60 years (or 65) had six biennal screens and were followed up for four years. Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence. SETTING: City of Florence, Italy, from 1992 through 1995. POPULATION: 2,740 resident males, aged 60 to 74 years. RESULTS: Overdiagnosis was estimated to be 51% (95% confidence limits: 44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250%. CONCLUSIONS: Screening for prostate cancer is associated with a relevant risk of overdioagnosis. As latent carcinomas can not be presently identified, this would lead to overtreatment in most overdiagnosed cases. The negative consequences of overdiagnosis (knowledge of having a cancer) and of overtreatment (impotence, incontinence, perioperatory death) may be extremely serious. In absence of any scientific evidence of screening benefits (if any) screening should not be recommended as a current practice, but should be limited to prospective controlled studies designed to assess its cost-effectiveness.

Aged↗
PubMed1998

A cross-sectional audit of benzodiazepine use among general practice patients.

In order to assess how many general practice patients take benzodiazepines for long periods, a cross-sectional audit of clinical practice was conducted. During a 3-day census period, 26 general practitioners in the area of Bergamo, Italy, entered into the study every patient who was taking benzodiazepines. The prevalence of use of this class of drugs was 14.0% (CI 12.5-15.7), while the prevalence of daily use for 12 months or more was 4.7% (CI 3.8-5.8). Finally, the prevalence of very long-term use of benzodiazepines, i.e. those taking these drugs for more than 10 years, was 0.65% (CI 0.34-1.14). Compared to non-long-term users, long-term users were older (OR 2.38, CI 1.39-4.08) and had a lower level of education (OR 2.40, CI 1.04-5.54). In addition, insomnia was associated with long-term use of this class of drugs (OR 1.82, CI 1.02-3.24). These findings provide evidence that the long-term use of benzodiazepines is an important issue in everyday general practice and that this calls for precise management tactics.

Adolescent↗
PubMed1997

Effect of faecal occult blood testing on colorectal mortality: results of a population-based case-control study in the district of Florence, Italy.

The aim of our case-control study was to estimate the effect on mortality from colorectal cancer (CRC) of a population-based screening with a faecal occult blood test started in 1982 in a rural area of the district of Florence. We examined the relationship between mortality and the interval since the most recent screening. The cases in the study were 206 individuals who had died from CRC after the age of 41 years. Five controls were selected randomly from the list of individuals alive at the time of diagnosis of the corresponding case and were matched by sex, age and place and length of residence. After adjustment for potentially confounding factors, the odds ratio (OR) for death from CRC for screened persons vs. those not screened was 0.60 [95% confidence interval (CI), 0.4-0.9]. The OR was lowest in the first 3 years after the most recent test (OR = 0.54; 95% CI, 0.3-0.9) and increased towards unity subsequently. Our results suggest that screening for CRC by biennial faecal occult blood testing can reduce mortality from the disease.

Aged↗
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

Risk of breast cancer subsequent to histological or clinical diagnosis of fibroadenoma--retrospective longitudinal study of 3938 cases.

BACKGROUND: The widespread belief that fibroadenoma is associated with an increased risk of subsequent breast cancer is based on studies of histologically-confirmed fibroadenomas. In current practice only a minority of fibroadenomas are excised; most of them are diagnosed on the basis of palpation and imaging, and are not surgically removed. The decision for surgical excision may be influenced by the presence of individual risk factors, and this can act as a confounder and bias studies that are based only on surgically excised fibroadenomas. PATIENTS AND METHODS: To investigate this hypothesis we linked data from a consecutive series of 3938 fibroadenomas diagnosed histologically (n = 1335) or clinically (n = 2603) in women aged 30 to 69 years to the Tuscany Cancer Registry database. After exclusion of concurrent breast cancers or cancers occurring within six months after the diagnosis of fibroadenoma, the observed and expected incidence of subsequent breast cancer were compared. RESULTS: The overall Standardized Incidence Ratio (SIR) for excised and non-excised fibroadenomas was 1.38 (95% CI = 1.1-1.7). The SIR for histologically-confirmed fibroadenomas was 2.0 (95% CI 1.4-2.7) whereas there was no apparent risk for non-excised fibroadenomas (SIR = 0.97, 95% CI = 0.7-1.4). CONCLUSION: This study suggests that assessment of breast cancer risk subsequent to a diagnosis of fibroadenoma may be biased if the analysis is limited to surgically-excised fibroadenomas.

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↗
PubMed1997

Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.

OBJECTIVE: To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-). METHODS: Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests. RESULTS: 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased. CONCLUSIONS: Our data confirm that screening by RPHA is more cost effective than by Hemoccult.

Adult↗
PubMed1996

Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia.

We have studied four unrelated Italian patients with chronic hemolytic anemia associated with glucose phosphate isomerase (GPI) deficiency. Using intronic primers, we were able to detect the gene alterations on the genomic DNA of the patients. Five different mutations were identified among the eight mutated alleles found: three missense mutations (301A,584T,1028G), one nonsense mutation (286T), and a four nucleotides deletion [Del 1473-IVS16(+2)]. All of these were new except for mutation 1028G, which was previously identified in a Japanese variant (GPI Narita). Two patients were homozygotes (301A/301A and 1028G/1028G), whereas the other two were compound heterozygotes sharing a common mutation [286T/584T and Del 1473-IVS16(+2)/584T]. The missense mutations were found to involve highly conserved amino acids, suggesting that these residues are crucial for the maintenance of the enzyme function. The mutation 286T results in a truncated protein of 95 amino acids in comparison with the 558 of the normal one. The four nucleotides deletion located at the junction of exon/intron 16(5'-TTGGTCGgtgagt-3') is the first GPI mutation affecting a splice site. Moreover one difference from the published sequence (473T-->G) was found in exon five in all of the eight alleles studied and in 30 normal subjects. Correlation was made between mutations, biochemical characteristics of the enzyme, and clinical course of the disease.

Adult↗
PubMed1996

Antenatal diagnosis of short-limb dwarfism: sonographic approach.

Based on the findings in 12 patients with skeletal dysplasia diagnosed antenatally, the authors propose a tailored approach to the evaluation of foetuses with shortened long bones, depending on the time of discovery, the degree of shortening and the associated findings. During the second trimester, a very short femur [2 standard deviations (SD) - 5 mm and less] most probably corresponds to a bone dysplasia, although the differential diagnosis is mainly early intra-uterine growth retardation, and the foetal skeleton should be surveyed completely in order to find supplementary features suggestive of dwarfism. Anomalies of long bones in their shape, thickness or contour, or spinal ossification disorders or undermineralisation (best evaluated at the level of calvarial bones) are most helpful in determining the type of dysplasia. A short femur (between 2 SD and 2 SD - 4 mm) may indicate growth retardation, a chromosomal anomaly or dwarfism. Follow-up examinations are mandatory in order to differentiate between them. During the third trimester a very short femur may indicate a bone dysplasia and the work-up should be the same as in the second trimester. A short femur may correspond to dwarfism of late development, a growth-retarded foetus or constitutional shortness. Various ratios, especially that of the femur/foot, are helpful in differentiating between them. In case of previous family history, a short or very short femur usually indicates recurrence of the dwarfism. In all cases of antenatal diagnosis, confirmation of the sonographic findings should be obtained either by foetal or neonatal radiographs. The approach proposed by the authors should provide sufficient information to counsel the family not only for the ongoing pregnancy but also for subsequent ones.

Bone and Bones↗
PubMed1996

Immunochemical vs guaiac faecal occult blood tests in a population-based screening programme for colorectal cancer.

Two faecal occult blood tests (FOBTs), Hemoccult II (guaiac based) and Hemeselect (immunochemical) were compared in a population screening for colorectal cancer on 24 282 subjects aged 40-70. Hemeselect was interpreted according to a lower (+ and +/-) and a higher (+) positivity threshold. A total of 8008 compliers were enrolled in the study. Positivity rates: Hemoccult = 6.0%, Hemeselect (+ and +/) = 8.2%, Hemeselect (+) = 3.1%. Among FOBT-positive subject complying with the diagnostic work-up, 22 had colorectal cancer (17 Hemeselect-positive (+), four Hemeselect-borderline (+/-), 15 Hemoccult-positive) and 166 subjects had adenomas (62 Hemeselect(+), 56 Hemeselect-borderline (+/-), 79 Hemoccult-positive) were detected. The positive predictive values (PPVs) for cancer were as follows: Hemoccult = 3.7%, Hemeselect (+ and +/-) = 3.8%, Hemeselect (+) = 8.4%. The PPVs for adenoma(s) were: Hemoccult = 19.7%, Hemeselect (+ and +/-) = 21.4%, Hemeselect (+) = 30.5%. The specificity for cancer was: Hemoccult = 94.1%, Hemeselect (+ +/-) = 92%, Hemeselect (+) = 97.1%. Ratios between detection rates of each test and expected incidence of colorectal cancer suggest that Hemoccult anticipates cancer diagnosis by approximately 2 years on average whereas the mean diagnostic anticipation of Hemeselect ranges between 2.5 and 3.2 years. Hemeselect is superior to Hemoccult as it is at least as effective but more efficient and acceptable than guaiac testing. Further evaluation of Hemeselect cost-effectiveness and sensitivity is needed in order to assess the optimal threshold of positivity and screening frequency.

Adult↗
PubMed1996

Erythropoietin production and erythropoiesis in compensated and anaemic states of hereditary spherocytosis.

A compensated haemolytic state is defined by decreased red cell life-span without anaemia, i.e. by increased erythropoiesis in the absence of the physiological stimulus for erythropoietin (Epo) production. We evaluated s-Epo levels and the expansion of erythropoiesis (as measured by circulating transferrin receptor, s-TfR) in 32 patients with hereditary spherocytosis (HS) with the aim of verifying whether the enhanced erythropoiesis of compensated haemolysis was Epo-dependent. 20 of the patients (62.5%) had normal Hb values (> 12 g/dl in females and > 13 g/dl in males). Their compensated haemolytic state was the result of up to 8.2 times normal s-Epo and up to 3.9 times normal s-TfR levels, which were maintained by physiological regulation of erythropoiesis, as documented by the inverse dependence of Hb on s-Epo levels. Considering that patients with iron-deficiency anaemia represented the predicted physiological Epo response to anaemia, the observed/predicted in s-Epo ratio (O/P ratio) was calculated in HS patients with anaemia and was used as an index of the adequateness of Epo production. All the anaemic HS patients had an O/P ratio > 1, documenting inappropriately high s-Epo levels. This work demonstrates that the compensated haemolytic state of HS patients is produced by an inappropriately high s-Epo level, and that the pattern of Epo overproduction is a biological characteristic of the disease.

Adolescent↗
PubMed1996

Colorectal cancer survival--population-based rates in the province of Florence.

This study aimed to evaluate survival in 2,339 colorectal cancer patients diagnosed in 1985-87 in the province of Florence, where the Tuscany Tumour Registry is active. The effect of sex, site (colon, rectum), sub-site, disease diffusion (localized, regional, distant, unspecified), year of diagnosis, place of residence (municipalities involved in the screening programme, Florence, others) and source of diagnosis (Center for the Study and Prevention of Cancer-CSPO, others) were evaluated. Five-year observed and relative survivals were 37.9 and 48.1% respectively. Five-year prognosis was worse in men, in older age groups, in advanced stages and in patients not diagnosed at the CSPO. No differences were shown in residents of municipalities involved in the screening programme. Relative 5-year survival in Florence was among the highest in Europe for cancers of both the colon and the rectum. Sex, age, disease diffusion and source of diagnosis showed an independent prognostic effect. The effect of screening was not evident, probably due to the low compliance during the period under study and to the use of a low sensitivity test.

Adult↗
PubMed1996

Does the classification system fit disease progression in perinatal human immunodeficiency virus infection?

The objective was to test the applicability of the new classification for paediatric human immonodeficiency virus infection. The person-time of each state, transition probabilities and survival (+/- standard errors) at 5 years, and median sojourn-time were calculated on 39 perinatally infected children followed up from the first month of life for a median of 64.5 (1.2-120.1) months. The person-times of the N2, N3, B1, C1, and C2 states were low. The transition probabilities and sojourn-times were similar for A (48.1 +/- 10.8%; 63.5 months), B (50.5 +/- 15.5%; 44.9 months) and C (74.6 +/- 15.1%; 43.1 months) clinical categories, which differed (p < 0.025) from the N category (87.9 +/- 5.5%; 12.05 months). The survival probabilities after 5 years of entering the A, B and C categories were 84.8 +/- 10.7%, 60.5 +/- 19.8% and 14.8 +/- 13.5%, respectively (p < 0.001). Immunological category 3 had lower transition probabilities and longer sojourn-times (58.8 +/- 16.6%; 53.3 months) than categories 1 (71.3 +/- 8.1%; 33.2 months) and 2 (75.6 +/- 10.5%; 19.8 months) (p < 0.01). The transition probabilities to C3 for states N3, A3 or B3 were 52.5 +/- 13.5%. In conclusion, the classification fits the clinical history better than the immunological history.

Age Factors↗