Donatello Salvatore - Academia.edu (original) (raw)

Papers by Donatello Salvatore

Research paper thumbnail of Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: Implications in screening for the disease and phenotype characterization for patients with homozygote mutations

Clinical Chemistry

The search for the eight most frequent mutations (i.e., ⌬F508, G542X, W1282X, N1303K, 1717-1G3 A,... more The search for the eight most frequent mutations (i.e., ⌬F508, G542X, W1282X, N1303K, 1717-1G3 A, R553X, 2183AA3 G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles. Methods: We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations. Results: The screening revealed five mutations, R1158X, 711؉1G3 T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3-1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested negative by molec-ular analysis. We therefore designed a second allelespecific oligonucleotide set to analyze the five mutations. Among the patients analyzed, one patient homozygous for the L1065P mutation expressed a mild pulmonary and intestinal form of the disease with pancreatic insufficiency. Two other patients, homozygous for mutations R1158X and 4016insT, both expressed a severe cystic fibrosis phenotype. Conclusions: Five cystic fibrosis mutations are peculiar to patients from Southern Italy. The method described for their analysis is efficient, inexpensive, and can be semi-automated by use of a robotic workstation. The results obtained in patients from Southern Italy may have an impact on laboratories in other countries, given the large migrations of populations from Southern Italy to other countries in the last two centuries.

Research paper thumbnail of A noval nonsense mutation (Y849X) in the CFTR gene of a CF patient from southern Italy Communicated by: Garry R. Cutting Online Citation: Human Mutation, Mutation and Polymorphism Report #69 (1999) Online http://journals.wiley.com/1059-7794/pdf/mutation/mpr69.pdf Acknowledgments: Grants from MURS...

Research paper thumbnail of The delta F508 mutation in cystic fibrosis patients of southern Italy

Human Genetics

Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Souther... more Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Southern Italy (Campania) have been analyzed for KM19 and XV2c haplotypes and the delta F508 mutation: 54% of the total CF chromosomes show the delta F508 mutation. No significative correlations were obtained when clinical score, radiological score, Pseudomonas colonization, or clinical symptoms at presentation were matched with the presence or absence of the delta F508 mutation.

Research paper thumbnail of p.Leu636Pro mutation is associated with cystic fibrosis transmembrane conductance regulator-related disorders (congenital bilateral absence of vas deferens)

International Journal of Urology, 2015

Research paper thumbnail of Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: implications in screening for the disease and phenotype characterization for patients with homozygote mutations

Clinical chemistry, 1999

The search for the eight most frequent mutations (i.e., DeltaF508, G542X, W1282X, N1303K, 1717-1G... more The search for the eight most frequent mutations (i.e., DeltaF508, G542X, W1282X, N1303K, 1717-1G-->A, R553X, 2183AA-->G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles. We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations. The screening revealed five mutations, R1158X, 711+1G-->T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3-1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested neg...

Research paper thumbnail of Biosynthesis of alpha-N-acetylglucosaminidase in cultured human kidney carcinoma cells

Enzyme, 1985

The biosynthesis of alpha-N-acetylglucosaminidase was studied in cultured human kidney carcinoma ... more The biosynthesis of alpha-N-acetylglucosaminidase was studied in cultured human kidney carcinoma cells by labeling cells with 35S-methionine, isolation of the enzyme by immunoprecipitation and analysis on gel electrophoresis of the denatured polypeptide(s) and analysis of the native enzyme on linear sucrose gradient centrifugation. The enzyme is synthesized as precursor forms of apparent molecular weight 82,000-86,000. Processing of these precursors yields a polypeptide of apparent molecular weight of 80,000. The precursor-product relationship was indicated by pulse-chase as well as endocytosis experiments. Sucrose gradient centrifugation of the native enzyme shows that, extracellularly, the molecule is present with a molecular weight of 80,000; intracellularly, 80-90% of the enzyme is present with an apparent molecular weight of 240,000. We suggest that this is a polymeric form and that polymerization of alpha-N-acetylglucosaminidase is a late event of the maturation process.

Research paper thumbnail of Phenotypic Heterogeneity in a Cystic Fibrosis Family and the “Pseudomonas Dilemma”

Pediatric Allergy, Immunology, and Pulmonology, 2014

ABSTRACT doi: 10.1089/ped.2014.0347 We describe an unusual family in which 2 adult siblings and t... more ABSTRACT doi: 10.1089/ped.2014.0347 We describe an unusual family in which 2 adult siblings and the son of 1 are all affected by cystic fibrosis with rare mutations and different phenotypes. We discuss the dilemma surrounding the treatment of Pseudomonas aeruginosa colonization in the asymptomatic father, while minimizing disruption to the father–son relationship.

Research paper thumbnail of Clinical expression of patients with the D1152H CFTR mutation

Journal of Cystic Fibrosis, 2015

Background: Discordant results were reported on the clinical expression of subjects bearing the D... more Background: Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. Methods: A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. Results: 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary

Research paper thumbnail of Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study

Journal of Medical Case Reports, 2014

Introduction: Cystic fibrosis is the most common autosomal recessive genetic disease in the Cauca... more Introduction: Cystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing.

Research paper thumbnail of Effects of salmeterol on arterial oxyhemoglobin saturations in patients with cystic fibrosis

Pediatric Pulmonology, 2002

Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus ... more Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus we studied the effects of inhaled Salmeterol xinafoate, a long-acting beta-2 agonist, on transcutaneous oxyhemoglobin saturation in sleeping, stable CF patients. Patients with stable CF (n = 23) were divided into responders and nonresponders to beta-2 agonists, based on an albuterol challenge during daytime testing, and then they received salmeterol before sleep, in a double-blind crossover design. Overnight oxyhemoglobin saturation measurements and spirometry on awakening were performed. Salmeterol administration before sleep resulted in statistically significant increases in mean arterial oxyhemoglobin saturation and in FEV(1) and FEF(25-75) on awakening compared to placebo values, but only in patients responding to daytime albuterol inhalation by showing improvement in lung function. We conclude that salmeterol inhalation at bedtime could prevent or reduce nocturnal hypoxemia in daytime albuterol-responsive CF patients, thus improving the long-term clinical outcome of CF lung disease.

Research paper thumbnail of Cisapride and Cystic Fibrosis

Journal of Pediatric Gastroenterology and Nutrition, 1989

Research paper thumbnail of Phenotype/Genotype Correlation and Cystic Fibrosis Related Diabetes Mellitus (Italian Multicenter Study)

Journal of Pediatric Endocrinology and Metabolism, 2000

A genotype/phenotype correlation between early onset cystic fibrosis related diabetes (CFRD) and ... more A genotype/phenotype correlation between early onset cystic fibrosis related diabetes (CFRD) and the N1303K mutation of the CF gene was previously identified in a small series of 28 CFRD patients, out of 313 CF patients. In order to confirm the observation, data of 141 CFRD patients out of 1,229 CF patients attending 14 Italian CF centers were collected. All patients were older than 10 years and had been genotyped. DeltaF508 was the most frequent mutation (147/282 alleles: 52%) and N1303K the second most frequent mutation (18/282 alleles: 6.3%) in CFRD patients, without significant difference as compared with CF patients without DM (52% vs 48.6% and 6.3% vs 5.1%, respectively). W1282X was the third most frequent mutation in CFRD patients, more frequent than in CF patients without DM (5.3% vs 2%; p<0.001). Unlike the previous study, we did not find a higher frequency of the N1303K mutation in CFRD patients; moreover, data from this large CF series showed a significant correlation between the W1282X mutation and CFRD.

Research paper thumbnail of Clinical features of cystic fibrosis patients with rare genotypes

Journal of Medical Genetics, 1996

We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear ... more We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear rare genotypes: (1) a patient homozygous for the 2183 AA-8G mutation who was affected by a very early pulmonary form of cystic fibrosis, and five patients who were compound heterozygotes either for the 2183 AA-+G mutation or for the I148T mutation, in both instances with the AF508 mutation; and (2) a patient homozygous for the early nonsense R553X mutation who showed only a moderately severe form of cystic fibrosis. Our results confirm that environmental or genetic factors unrelated to the CF disease contribute significandy to the development of the phenotype. (JMed Genet 1996;33:73-76) 1996 33: 73-76 J Med Genet G Castaldo, E Rippa, V Raia, et al. with rare genotypes. Clinical features of cystic fibrosis patients http://jmg.bmj.com/content/33/1/73

Research paper thumbnail of Isolation measures for prevention of infection with respiratory pathogens in cystic fibrosis: a systematic review

Journal of Hospital Infection, 2006

Respiratory infections are the most important cause of morbidity and mortality in patients with c... more Respiratory infections are the most important cause of morbidity and mortality in patients with cystic fibrosis (CF). These infections are typically caused by a limited number of respiratory pathogens, particularly Burkholderia cepacia complex (BCC) and Pseudomonas aeruginosa (PA). Since the 1980s, several outbreaks of unique strains of PA and BCC among CF patients attending the same CF care centres have been described, leading to a sharp decline in the patients' health. One of the measures adopted in CF centres to interrupt ongoing outbreaks is the separation of patients with a respiratory tract culture that is positive for PA or BCC from patients who are not infected. This type of measure has been implemented routinely in many CF centres to prevent cross-transmission of PA and BCC. The aim of this review was to determine what evidence is available to support the efficacy of isolation (or segregation) practices in preventing, delaying or reducing the risk for CF patients of acquiring PA and BCC. A systematic review of scientific literature from 1980 to 31 December 2004 was performed. Existing guidelines regarding infection control in CF were also analysed. In total, 398 relevant papers were retrieved. Only 10 well-designed studies were found that evaluated the efficacy of isolation practices in preventing the transmission of respiratory pathogens in CF care centres (one prospective controlled study, one retrospective cohort study, five 'before-after' studies and three cross-sectional studies. No systematic reviews or randomized controlled trials exist on this subject. In the absence of studies with an experimental, controlled design, the efficacy of isolation practices in preventing the transmission of respiratory pathogens in CF remains unproven. However, notwithstanding the considerable limits represented by the study designs, which were mainly retrospective, the observational studies reviewed seem to support the implementation of isolation (or segregation) measures to reduce the risk of transmission of BCC and PA in CF patients.

Research paper thumbnail of Validation of a predictive survival model in Italian patients with cystic fibrosis

Journal of Cystic Fibrosis, 2012

In 2001 Liou published a 5-year survival model using CFF Registry data. To evaluate its validity ... more In 2001 Liou published a 5-year survival model using CFF Registry data. To evaluate its validity in predicting survival in Italian CF patients. In a retrospective study on 945 patients, the 9 variables selected by Liou were analyzed, vital status on December 2008 recorded and observed and expected deaths compared. To develop a new model, patients were randomly divided into a derivation (n=475) and a validation sample (n=470). A significant difference was found between observed and expected deaths based on Liou's model (62 vs 94), with a 34% reduction in mortality (p<0.05). A new model (based on FEV1, Staphylococcus aureus and Burkholderia cepacia complex infection, number of pulmonary exacerbations/year) was generated, that correctly predicted survival in the validation sample (31 observed vs 29 expected deaths, p=0.660). The Liou model did not adequately predict 5-year survival in our CF population that, compared to the one in which it was originally tested, could benefit from 10 years of improvement in treatments and practice patterns. A new generated model, based on only four variables, was more accurate in predicting 5-year survival in Italian CF patients.

Research paper thumbnail of Influenza A/H1N1 in patients with cystic fibrosis in Italy: a multicenter survey of the Italian CF Society

Journal of Cystic Fibrosis, 2010

Research paper thumbnail of Cystic fibrosis presenting as metabolic alkalosis in a boy with the rare D579G mutation

Journal of Cystic Fibrosis, 2004

We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test wa... more We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test was borderline and genetic analysis was negative for common mutations. Analysis of the whole coding regions of the CFTR gene revealed the rare mutation D579G in homozygosity. D

Research paper thumbnail of A noval nonsense mutation (Y849X) in the CFTR gene of a CF patient from southern Italy

Research paper thumbnail of Lung involvement, the ΔF508 mutation and DNA haplotype analysis in cystic fibrosis

Human Genetics, 1992

... colonized Pseudomonas ° 60 29.7 (P = 0.011) % colonized Staphylococcus ~ 51 27 (P = 0.04) HI ... more ... colonized Pseudomonas ° 60 29.7 (P = 0.011) % colonized Staphylococcus ~ 51 27 (P = 0.04) HI NI HI NI IgG ° 33 12 11 26 (P < 0.0005) ... colonized Staphylococcus c 60.0 48.1 44.4 NS HI NI HI NI HI NI IgG c 10 6 29 23 5 9 NS IgA ° 12 4 32 20 5 9 NS ...

Research paper thumbnail of The ΔF508 mutation in cystic fibrosis patients of Southern Italy

Human Genetics, 1990

... mutation. Introduction and methods Preliminary data reveal significative differences of cysti... more ... mutation. Introduction and methods Preliminary data reveal significative differences of cystic fibrosis (CF) haplotypes frequencies between popula-tions from the North, Center and South of Italy (Gaspa-rini et al. 1990). These ...

Research paper thumbnail of Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: Implications in screening for the disease and phenotype characterization for patients with homozygote mutations

Clinical Chemistry

The search for the eight most frequent mutations (i.e., ⌬F508, G542X, W1282X, N1303K, 1717-1G3 A,... more The search for the eight most frequent mutations (i.e., ⌬F508, G542X, W1282X, N1303K, 1717-1G3 A, R553X, 2183AA3 G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles. Methods: We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations. Results: The screening revealed five mutations, R1158X, 711؉1G3 T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3-1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested negative by molec-ular analysis. We therefore designed a second allelespecific oligonucleotide set to analyze the five mutations. Among the patients analyzed, one patient homozygous for the L1065P mutation expressed a mild pulmonary and intestinal form of the disease with pancreatic insufficiency. Two other patients, homozygous for mutations R1158X and 4016insT, both expressed a severe cystic fibrosis phenotype. Conclusions: Five cystic fibrosis mutations are peculiar to patients from Southern Italy. The method described for their analysis is efficient, inexpensive, and can be semi-automated by use of a robotic workstation. The results obtained in patients from Southern Italy may have an impact on laboratories in other countries, given the large migrations of populations from Southern Italy to other countries in the last two centuries.

Research paper thumbnail of A noval nonsense mutation (Y849X) in the CFTR gene of a CF patient from southern Italy Communicated by: Garry R. Cutting Online Citation: Human Mutation, Mutation and Polymorphism Report #69 (1999) Online http://journals.wiley.com/1059-7794/pdf/mutation/mpr69.pdf Acknowledgments: Grants from MURS...

Research paper thumbnail of The delta F508 mutation in cystic fibrosis patients of southern Italy

Human Genetics

Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Souther... more Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Southern Italy (Campania) have been analyzed for KM19 and XV2c haplotypes and the delta F508 mutation: 54% of the total CF chromosomes show the delta F508 mutation. No significative correlations were obtained when clinical score, radiological score, Pseudomonas colonization, or clinical symptoms at presentation were matched with the presence or absence of the delta F508 mutation.

Research paper thumbnail of p.Leu636Pro mutation is associated with cystic fibrosis transmembrane conductance regulator-related disorders (congenital bilateral absence of vas deferens)

International Journal of Urology, 2015

Research paper thumbnail of Detection of five rare cystic fibrosis mutations peculiar to Southern Italy: implications in screening for the disease and phenotype characterization for patients with homozygote mutations

Clinical chemistry, 1999

The search for the eight most frequent mutations (i.e., DeltaF508, G542X, W1282X, N1303K, 1717-1G... more The search for the eight most frequent mutations (i.e., DeltaF508, G542X, W1282X, N1303K, 1717-1G-->A, R553X, 2183AA-->G, and I148T) by allele-specific oligonucleotide dot-blot analysis revealed 78% of 396 cystic fibrosis alleles in Southern Italy. The observation of frequent haplotypes on the unidentified cystic fibrosis alleles suggested that a few mutations could account for a large number of unidentified alleles. We screened most of the coding sequence of the cystic fibrosis transmembrane regulator gene by denaturing gradient gel electrophoresis to determine the spectrum of these mutations in 68 unrelated cystic fibrosis patients bearing one or both unidentified mutations. The screening revealed five mutations, R1158X, 711+1G-->T, 4016insT, L1065P, and G1244E, each of which had a frequency of 1.3-1.8% (7% collectively). The 7% increase in the detection rate (85% vs 78%) reduces by >50% the residual risk of being cystic fibrosis carriers for couples who had tested neg...

Research paper thumbnail of Biosynthesis of alpha-N-acetylglucosaminidase in cultured human kidney carcinoma cells

Enzyme, 1985

The biosynthesis of alpha-N-acetylglucosaminidase was studied in cultured human kidney carcinoma ... more The biosynthesis of alpha-N-acetylglucosaminidase was studied in cultured human kidney carcinoma cells by labeling cells with 35S-methionine, isolation of the enzyme by immunoprecipitation and analysis on gel electrophoresis of the denatured polypeptide(s) and analysis of the native enzyme on linear sucrose gradient centrifugation. The enzyme is synthesized as precursor forms of apparent molecular weight 82,000-86,000. Processing of these precursors yields a polypeptide of apparent molecular weight of 80,000. The precursor-product relationship was indicated by pulse-chase as well as endocytosis experiments. Sucrose gradient centrifugation of the native enzyme shows that, extracellularly, the molecule is present with a molecular weight of 80,000; intracellularly, 80-90% of the enzyme is present with an apparent molecular weight of 240,000. We suggest that this is a polymeric form and that polymerization of alpha-N-acetylglucosaminidase is a late event of the maturation process.

Research paper thumbnail of Phenotypic Heterogeneity in a Cystic Fibrosis Family and the “Pseudomonas Dilemma”

Pediatric Allergy, Immunology, and Pulmonology, 2014

ABSTRACT doi: 10.1089/ped.2014.0347 We describe an unusual family in which 2 adult siblings and t... more ABSTRACT doi: 10.1089/ped.2014.0347 We describe an unusual family in which 2 adult siblings and the son of 1 are all affected by cystic fibrosis with rare mutations and different phenotypes. We discuss the dilemma surrounding the treatment of Pseudomonas aeruginosa colonization in the asymptomatic father, while minimizing disruption to the father–son relationship.

Research paper thumbnail of Clinical expression of patients with the D1152H CFTR mutation

Journal of Cystic Fibrosis, 2015

Background: Discordant results were reported on the clinical expression of subjects bearing the D... more Background: Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. Methods: A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. Results: 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary

Research paper thumbnail of Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study

Journal of Medical Case Reports, 2014

Introduction: Cystic fibrosis is the most common autosomal recessive genetic disease in the Cauca... more Introduction: Cystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing.

Research paper thumbnail of Effects of salmeterol on arterial oxyhemoglobin saturations in patients with cystic fibrosis

Pediatric Pulmonology, 2002

Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus ... more Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus we studied the effects of inhaled Salmeterol xinafoate, a long-acting beta-2 agonist, on transcutaneous oxyhemoglobin saturation in sleeping, stable CF patients. Patients with stable CF (n = 23) were divided into responders and nonresponders to beta-2 agonists, based on an albuterol challenge during daytime testing, and then they received salmeterol before sleep, in a double-blind crossover design. Overnight oxyhemoglobin saturation measurements and spirometry on awakening were performed. Salmeterol administration before sleep resulted in statistically significant increases in mean arterial oxyhemoglobin saturation and in FEV(1) and FEF(25-75) on awakening compared to placebo values, but only in patients responding to daytime albuterol inhalation by showing improvement in lung function. We conclude that salmeterol inhalation at bedtime could prevent or reduce nocturnal hypoxemia in daytime albuterol-responsive CF patients, thus improving the long-term clinical outcome of CF lung disease.

Research paper thumbnail of Cisapride and Cystic Fibrosis

Journal of Pediatric Gastroenterology and Nutrition, 1989

Research paper thumbnail of Phenotype/Genotype Correlation and Cystic Fibrosis Related Diabetes Mellitus (Italian Multicenter Study)

Journal of Pediatric Endocrinology and Metabolism, 2000

A genotype/phenotype correlation between early onset cystic fibrosis related diabetes (CFRD) and ... more A genotype/phenotype correlation between early onset cystic fibrosis related diabetes (CFRD) and the N1303K mutation of the CF gene was previously identified in a small series of 28 CFRD patients, out of 313 CF patients. In order to confirm the observation, data of 141 CFRD patients out of 1,229 CF patients attending 14 Italian CF centers were collected. All patients were older than 10 years and had been genotyped. DeltaF508 was the most frequent mutation (147/282 alleles: 52%) and N1303K the second most frequent mutation (18/282 alleles: 6.3%) in CFRD patients, without significant difference as compared with CF patients without DM (52% vs 48.6% and 6.3% vs 5.1%, respectively). W1282X was the third most frequent mutation in CFRD patients, more frequent than in CF patients without DM (5.3% vs 2%; p<0.001). Unlike the previous study, we did not find a higher frequency of the N1303K mutation in CFRD patients; moreover, data from this large CF series showed a significant correlation between the W1282X mutation and CFRD.

Research paper thumbnail of Clinical features of cystic fibrosis patients with rare genotypes

Journal of Medical Genetics, 1996

We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear ... more We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear rare genotypes: (1) a patient homozygous for the 2183 AA-8G mutation who was affected by a very early pulmonary form of cystic fibrosis, and five patients who were compound heterozygotes either for the 2183 AA-+G mutation or for the I148T mutation, in both instances with the AF508 mutation; and (2) a patient homozygous for the early nonsense R553X mutation who showed only a moderately severe form of cystic fibrosis. Our results confirm that environmental or genetic factors unrelated to the CF disease contribute significandy to the development of the phenotype. (JMed Genet 1996;33:73-76) 1996 33: 73-76 J Med Genet G Castaldo, E Rippa, V Raia, et al. with rare genotypes. Clinical features of cystic fibrosis patients http://jmg.bmj.com/content/33/1/73

Research paper thumbnail of Isolation measures for prevention of infection with respiratory pathogens in cystic fibrosis: a systematic review

Journal of Hospital Infection, 2006

Respiratory infections are the most important cause of morbidity and mortality in patients with c... more Respiratory infections are the most important cause of morbidity and mortality in patients with cystic fibrosis (CF). These infections are typically caused by a limited number of respiratory pathogens, particularly Burkholderia cepacia complex (BCC) and Pseudomonas aeruginosa (PA). Since the 1980s, several outbreaks of unique strains of PA and BCC among CF patients attending the same CF care centres have been described, leading to a sharp decline in the patients' health. One of the measures adopted in CF centres to interrupt ongoing outbreaks is the separation of patients with a respiratory tract culture that is positive for PA or BCC from patients who are not infected. This type of measure has been implemented routinely in many CF centres to prevent cross-transmission of PA and BCC. The aim of this review was to determine what evidence is available to support the efficacy of isolation (or segregation) practices in preventing, delaying or reducing the risk for CF patients of acquiring PA and BCC. A systematic review of scientific literature from 1980 to 31 December 2004 was performed. Existing guidelines regarding infection control in CF were also analysed. In total, 398 relevant papers were retrieved. Only 10 well-designed studies were found that evaluated the efficacy of isolation practices in preventing the transmission of respiratory pathogens in CF care centres (one prospective controlled study, one retrospective cohort study, five 'before-after' studies and three cross-sectional studies. No systematic reviews or randomized controlled trials exist on this subject. In the absence of studies with an experimental, controlled design, the efficacy of isolation practices in preventing the transmission of respiratory pathogens in CF remains unproven. However, notwithstanding the considerable limits represented by the study designs, which were mainly retrospective, the observational studies reviewed seem to support the implementation of isolation (or segregation) measures to reduce the risk of transmission of BCC and PA in CF patients.

Research paper thumbnail of Validation of a predictive survival model in Italian patients with cystic fibrosis

Journal of Cystic Fibrosis, 2012

In 2001 Liou published a 5-year survival model using CFF Registry data. To evaluate its validity ... more In 2001 Liou published a 5-year survival model using CFF Registry data. To evaluate its validity in predicting survival in Italian CF patients. In a retrospective study on 945 patients, the 9 variables selected by Liou were analyzed, vital status on December 2008 recorded and observed and expected deaths compared. To develop a new model, patients were randomly divided into a derivation (n=475) and a validation sample (n=470). A significant difference was found between observed and expected deaths based on Liou's model (62 vs 94), with a 34% reduction in mortality (p<0.05). A new model (based on FEV1, Staphylococcus aureus and Burkholderia cepacia complex infection, number of pulmonary exacerbations/year) was generated, that correctly predicted survival in the validation sample (31 observed vs 29 expected deaths, p=0.660). The Liou model did not adequately predict 5-year survival in our CF population that, compared to the one in which it was originally tested, could benefit from 10 years of improvement in treatments and practice patterns. A new generated model, based on only four variables, was more accurate in predicting 5-year survival in Italian CF patients.

Research paper thumbnail of Influenza A/H1N1 in patients with cystic fibrosis in Italy: a multicenter survey of the Italian CF Society

Journal of Cystic Fibrosis, 2010

Research paper thumbnail of Cystic fibrosis presenting as metabolic alkalosis in a boy with the rare D579G mutation

Journal of Cystic Fibrosis, 2004

We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test wa... more We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test was borderline and genetic analysis was negative for common mutations. Analysis of the whole coding regions of the CFTR gene revealed the rare mutation D579G in homozygosity. D

Research paper thumbnail of A noval nonsense mutation (Y849X) in the CFTR gene of a CF patient from southern Italy

Research paper thumbnail of Lung involvement, the ΔF508 mutation and DNA haplotype analysis in cystic fibrosis

Human Genetics, 1992

... colonized Pseudomonas ° 60 29.7 (P = 0.011) % colonized Staphylococcus ~ 51 27 (P = 0.04) HI ... more ... colonized Pseudomonas ° 60 29.7 (P = 0.011) % colonized Staphylococcus ~ 51 27 (P = 0.04) HI NI HI NI IgG ° 33 12 11 26 (P < 0.0005) ... colonized Staphylococcus c 60.0 48.1 44.4 NS HI NI HI NI HI NI IgG c 10 6 29 23 5 9 NS IgA ° 12 4 32 20 5 9 NS ...

Research paper thumbnail of The ΔF508 mutation in cystic fibrosis patients of Southern Italy

Human Genetics, 1990

... mutation. Introduction and methods Preliminary data reveal significative differences of cysti... more ... mutation. Introduction and methods Preliminary data reveal significative differences of cystic fibrosis (CF) haplotypes frequencies between popula-tions from the North, Center and South of Italy (Gaspa-rini et al. 1990). These ...