Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
1.
Ital J Pediatr ; 47(1): 112, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990208

RESUMO

BACKGROUND: The sweat chloride test (ST) is the gold standard for cystic fibrosis (CF) diagnosis in symptomatic patients, within the newborn screening and in the follow-up of CF patients during molecular therapies. However, false positives have been reported in patients with different diseases. We describe and discuss 4 cases due to different clinical conditions in which we recorded false positive ST, and the test remained altered for a period of varying length. CASES PRESENTATION: Case 1: Eight months old female child suffering from constipation, recurrent vomiting and failure to thrive, family history of recurrent pancreatitis without mutations in the PRSS1 and SPINK1 genes. Both ST and fecal elastase were altered although no CFTR gene mutations were found. Due to rapid clinical deterioration, celiac disease was suspected and diagnosed by laboratory tests and intestinal biopsy. After 2 weeks of gluten-free diet ST and fecal elastase normalized. Case 2: 14 months old male suffering from bilateral renal dysplasia, episodes of metabolic alkalosis, recurrent respiratory infections and recurrent vomiting. The child had more ST positives, but no CFTR mutations were found. During follow-up, he developed sensorineural hearing loss and an atrial septic defect was found. Finally, a diagnosis of Klinefelter was made, but the ST normalized several years later. Case 3 and 4: Two boys with stubborn constipation and fecal occlusion treated with Poly Ethylene Glycol (PEG) with salts showed pathological ST. The test returned normal a few days after stopping treatment. CONCLUSIONS: We hypotesized the possible causes of ST alteration in these conditions: in celiac disease it could be due to a transient dysregulation of the aquaporins, rapidly reversed by the diet; in Klinefelter, it may be due to stable pubertal hypoandrogenism; while, the PEG formulation itself contains salts that can temporarily alter ST.


Assuntos
Cloretos/análise , Fibrose Cística/diagnóstico , Suor/química , Doença Celíaca/diagnóstico , Constipação Intestinal/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Síndrome de Klinefelter/diagnóstico , Masculino
2.
Clin Ter ; 172(2): 129-133, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33763680

RESUMO

CONCLUSION: High suspicion of scar endometriosis are painful no-dule in the abdominal scar. Wide surgical excision is the treatment of choice. INTRODUCTION: Endometriosis has been described as the presence of endometrial tissue outside uterine cavity. Scar endometriosis (SE) is a rare disease reported in 0.03-1.08% of women following gynaecologic surgery. In our retrospective observational cohort study we studied anamnesis, symptoms, surgical procedures and outcomes linked to scar endometriosis in our medical experience from 2004 to 2018. METHODS: We reviewed the medical records of 46 patients with a histopathological diagnosis of SE. All patients had a history of at least one previous caesarean section (n=46, 100%). Forty-two patients (91,3%) complained gradually growing nodular abdominal mass near or adjacent to caesarean incision scar, while only 4 patients (8,6%) complained aspecific abdominal pain. Ultrasound scan was performed in all patients (n=46, 100%) and mean size of the nodules at US was 26,8 ± 13,8 mm. RESULTS: All patients underwent surgery. Seven patients (15,2%) needed mesh implantation, while 39 patients (84,8%) underwent local resection with reconstruction of muscle fascia. Mean follow-up was 31,6 ± 14 months and no patients reported local recurrence of disease.


Assuntos
Cicatriz/patologia , Endometriose/patologia , Parede Abdominal/patologia , Parede Abdominal/cirurgia , Adulto , Cesárea/efeitos adversos , Endometriose/diagnóstico , Endometriose/cirurgia , Feminino , Humanos , Estudos Retrospectivos
3.
Clin Ter ; 171(1): e16-e22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33346321

RESUMO

BACKGROUND: Esophagogastroduodenoscopy (EGDS) is the gold standard exam for upper gastrointestinal diseases. EGDS is very important in Early Gastric Cancer diagnosis and treatment but it is an operator-dependent exam and there are lots of factors that reduce its visibility (mucus, bubbles and foam). AIM: The aim of our study is to evaluate if the use of Lumevis™ improves mucosa visualization during EGDS without increasing the examination time and complications' rate and comparing the differences in patients prepared with water or no intervention. MATERIALS AND METHODS: we recruited 50 patients from 01/08/2020 to 31/08/2020 who came to our observation for epigastric pain, dyspepsia and gastroesophageal reflux (GERD). For each patient we evaluate the satisfaction of the procedure, vision quality, EGDS duration and the presence of bubbles following the administration of: nothing (group 1); 50 ml of water alone (W) (group 2); W + simethicone (S) 150 mg+N-acetylcysteine (NAC) 250 mg+10% acetic acid 2.5 ml (group 3); W+S 100 mg + NAC 300 mg + 10% acetic acid 2 ml (group 4); W + S 100 mg + NAC 200 mg + 10% acetic acid 1.5 ml (group 5). RESULTS: Our results suggest that the lesion detection rate improves with the use of simethicone, acetylcysteine and acetic acid prior to EGDS, although this needs to be studied prospectively. CONCLUSIONS: Lumevis™ is proposed as a new product in the routine preparation of all patients who have to undergo an EGDS, raising the level in the quality of the exam.


Assuntos
Endoscopia do Sistema Digestório/métodos , Gastroenteropatias/diagnóstico por imagem , Pré-Medicação/métodos , Ácido Acético/química , Acetilcisteína/química , Adulto , Dispepsia/diagnóstico por imagem , Feminino , Refluxo Gastroesofágico/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Simeticone/química , Neoplasias Gástricas/diagnóstico por imagem
5.
Acta Otorhinolaryngol Ital ; 37(3): 207-213, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27897275

RESUMO

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicentre studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%.


Assuntos
Fibrose Cística/tratamento farmacológico , Células Cultivadas , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/análise , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Mutação , Mucosa Nasal/citologia
6.
Cell Death Differ ; 23(8): 1380-93, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27035618

RESUMO

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.


Assuntos
Catequina/análogos & derivados , Cisteamina/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/tratamento farmacológico , Adolescente , Animais , Autofagia/efeitos dos fármacos , Biomarcadores/análise , Biomarcadores/metabolismo , Catequina/farmacocinética , Catequina/uso terapêutico , Catequina/toxicidade , Criança , Cisteamina/farmacocinética , Cisteamina/toxicidade , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Modelos Animais de Doenças , Quimioterapia Combinada , Homozigoto , Humanos , Interleucina-8/análise , Interleucina-8/genética , Interleucina-8/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Knockout , Mutação , Escarro/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
7.
Acta Diabetol ; 52(4): 633-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25863781

RESUMO

Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF), occurring in a variable number of children and adolescents. Glucose metabolism derangements (GMDs) are responsible for a negative impact on the general health status of CF patients. Screening of GMDs is important since the youngest age and should be performed by means of OGTT, including its intermediate times, that could detect other non-traditional GMDs. Insulin treatment, administered before overt diabetes, could be beneficial in reducing the number of pulmonary infections, in improving both pulmonary function and nutritional status. Early screening of GMDs in pediatric age can exert an important preventing role regarding all aspects of health status of patients with CF.


Assuntos
Fibrose Cística/metabolismo , Intolerância à Glucose/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Comorbidade , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Intolerância à Glucose/sangue , Intolerância à Glucose/epidemiologia , Teste de Tolerância a Glucose , Humanos
8.
J Cyst Fibros ; 14(2): 203-10, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25458463

RESUMO

BACKGROUND: In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. METHODS: 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. RESULTS: Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. CONCLUSIONS: Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.


Assuntos
Transporte Biológico/efeitos dos fármacos , Fibrose Cística , Glutationa , Pulmão , Administração por Inalação , Adolescente , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Criança , Fibrose Cística/tratamento farmacológico , Fibrose Cística/metabolismo , Monitoramento de Medicamentos/métodos , Teste de Esforço/efeitos dos fármacos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Glutationa/administração & dosagem , Glutationa/farmacocinética , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento
9.
J Cyst Fibros ; 13(5): 579-84, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24525081

RESUMO

BACKGROUND: Currently no tools to predict risk of acute (AP) and recurrent pancreatitis (ARP) in children with cystic fibrosis (CF) are available. We assessed the prevalence of AP/ARP and tested the potential role of Pancreatic Insufficiency Prevalence (PIP) score in a cohort of children with CF. METHODS: We identified two groups of children, on the basis of presence/absence of AP/ARP, who were compared for age at diagnosis, clinical features, genotypes and sweat chloride level. PIP score was calculated for each patient. RESULTS: 10/167 (5.9%) experienced at least one episode of AP during follow up; 10/10 were pancreatic sufficient (PS). Patients with AP/ARP showed a PIP score ≤0.25 more frequently (6/10) than patients without AP/ARP. The odds ratio (95% CI) of developing pancreatitis was 4.54 (1.22-16.92) for patients with PIP <0.25 when compared with those who have a PIP score >0.25 (p 0.0151). PIP score was correlated with sweat chloride test (p < 0.01). CONCLUSION: PIP score, PS status and normal/borderline sweat chloride levels could be applied to predict pancreatitis development in children with CF. ARP could lead to pancreatic insufficiency.


Assuntos
Fibrose Cística/fisiopatologia , Pancreatite/etiologia , Doença Aguda , Adolescente , Criança , Fibrose Cística/complicações , Feminino , Previsões , Humanos , Masculino , Razão de Chances , Recidiva , Risco
10.
Minerva Pediatr ; 65(6): 669-72, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24217635

RESUMO

We report a case of a 2,5 years old female, referred to our center for pancreatitis. Medical investigation revealed history of acute recurrent pancreatitis (ARP) since 1 year of age. Family history was negative for pancreatitis. Abdominal ultrasonography and magnetic resonance excluded both biliary tract stenosis and anatomic abnormalities. Calcium metabolic disorders, viral and bacterial infections were ruled out. Molecular sequencing of CFTR revealed heterozygosis for the mutation S1235R, a CFTR-related disorders associated mutation. Fecal elastase-1 (E1) was 529 µg/gr feces (normal value 200-500 µg/gr feces). No mutation of PRSS1 gene was detected but heterozygosity for p.Lys41Asn (c.123G>C), a new mutation of SPINK1 gene, was revealed. We speculate that the association of both SPINK1 and CFTR gene mutations may be responsible of ARP in our patient. Further studies need to better elucidate the role of genetic factors in ARP, as well as the influence of environmental factors.


Assuntos
Proteínas de Transporte/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Pancreatite/genética , Doença Aguda , Pré-Escolar , Feminino , Humanos , Recidiva , Inibidor da Tripsina Pancreática de Kazal
11.
Cell Death Differ ; 20(8): 1101-15, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23686137

RESUMO

Mismanaged protein trafficking by the proteostasis network contributes to several conformational diseases, including cystic fibrosis, the most frequent lethal inherited disease in Caucasians. Proteostasis regulators, as cystamine, enable the beneficial action of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators in ΔF508-CFTR airways beyond drug washout. Here we tested the hypothesis that functional CFTR protein can sustain its own plasma membrane (PM) stability. Depletion or inhibition of wild-type CFTR present in bronchial epithelial cells reduced the availability of the small GTPase Rab5 by causing Rab5 sequestration within the detergent-insoluble protein fraction together with its accumulation in aggresomes. CFTR depletion decreased the recruitment of the Rab5 effector early endosome antigen 1 to endosomes, thus reducing the local generation of phosphatidylinositol-3-phosphate. This diverts recycling of surface proteins, including transferrin receptor and CFTR itself. Inhibiting CFTR function also resulted in its ubiquitination and interaction with SQSTM1/p62 at the PM, favoring its disposal. Addition of cystamine prevented the recycling defect of CFTR by enhancing BECN1 expression and reducing SQSTM1 accumulation. Our results unravel an unexpected link between CFTR protein and function, the latter regulating the levels of CFTR surface expression in a positive feed-forward loop, and highlight CFTR as a pivot of proteostasis in bronchial epithelial cells.


Assuntos
Brônquios/fisiopatologia , Membrana Celular/fisiologia , Regulador de Condutância Transmembrana em Fibrose Cística/fisiologia , Fibrose Cística/fisiopatologia , Células Epiteliais/fisiologia , Deficiências na Proteostase/fisiopatologia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Reguladoras de Apoptose/fisiologia , Proteína Beclina-1 , Brônquios/patologia , Linhagem Celular , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/patologia , Humanos , Proteínas de Membrana/fisiologia , Mutação/genética , Monoéster Fosfórico Hidrolases/fisiologia , Receptores da Transferrina/fisiologia , Proteína Sequestossoma-1 , Proteínas rab5 de Ligação ao GTP/fisiologia
12.
J Endocrinol Invest ; 35(3): 246-53, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21483232

RESUMO

AIM: To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD). SUBJECTS AND METHODS: One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic ß-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR). RESULTS: The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes. CONCLUSIONS: IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, ß-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.


Assuntos
Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Resistência à Insulina/fisiologia , Insulina/biossíntese , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Peptídeo C/sangue , Criança , Fibrose Cística/metabolismo , Feminino , Genótipo , Teste de Tolerância a Glucose , Homeostase/fisiologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Insulina/sangue , Células Secretoras de Insulina/fisiologia , Pulmão/fisiologia , Masculino , Adulto Jovem
13.
Eur J Clin Microbiol Infect Dis ; 30(8): 973-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21279730

RESUMO

The aims of this study were to evaluate the frequency of Achromobacter xylosoxidans infection in a cohort of cystic fibrosis patients, to investigate antimicrobial sensitivity, to establish possible clonal likeness among strains, and to address the clinical impact of this infection or colonization on the general outcome of these patients. The study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Center of the Naples University "Federico II". Sputum samples were checked for bacterial identification. For DNA fingerprinting, pulsed-field gel electrophoresis (PFGE) was carried out. Fifty-three patients (17.6%) had at least one positive culture for A. xylosoxidans; of these, 6/53 (11.3%) patients were defined as chronically infected and all were co-colonized by Pseudomonas aeruginosa. Of the patients, 18.8% persistently carried multidrug-resistant isolates. Macrorestriction analysis showed the presence of seven major clusters. DNA fingerprinting also showed a genetic relationship among strains isolated from the same patients at different times. The results of DNA fingerprinting indicate evidence of bacterial clonal likeness among the enrolled infected patients. We found no significant differences in the forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) when comparing the case group of A. xylosoxidans chronically infected patients with the control group of P. aeruginosa chronically infected patients.


Assuntos
Achromobacter denitrificans/isolamento & purificação , Fibrose Cística/complicações , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções Respiratórias/epidemiologia , Achromobacter denitrificans/classificação , Achromobacter denitrificans/genética , Adolescente , Adulto , Antibacterianos/farmacologia , Criança , Pré-Escolar , Análise por Conglomerados , Comorbidade , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais , Humanos , Lactente , Itália/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Prevalência , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/microbiologia , Adulto Jovem
15.
J Cyst Fibros ; 8(4): 229-37, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19419909

RESUMO

Patient registries are organized systems of data collection for scientific, clinical or health strategy purposes. Aims of our review were to document scientific literature based on data and information from cystic fibrosis (CF) registries; to understand which clinical problems have been addressed and for which of these the studies concerned have correctly answered the questions raised (i.e. a methodological critique) and to identify clinical issues in need of further investigation. The review included primary studies starting from a formally constituted CF registry of at least national level, using data from the registry to evaluate research hypotheses. This article is an overview of the research undertaken, focusing in detail on the issues of mortality and survival. The studies considered here focused mainly or secondarily on survival in CF, the aim being to ascertain an improving trend, identify any prognostic factors and, in some cases, attempt to provide a predictive model of survival.


Assuntos
Fibrose Cística/mortalidade , Sistema de Registros/estatística & dados numéricos , Humanos , Prognóstico
16.
Dig Liver Dis ; 41(11): 817-22, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19467940

RESUMO

BACKGROUND: Cystic fibrosis is the most common lethal recessive disorder among Caucasians. Over 1500 mutations have been identified in cystic fibrosis transmembrane conductance regulator disease-gene so far. A large variability of the clinical phenotype has been observed both in cystic fibrosis patients bearing the same genotype, and in affected sibpairs. Thus, genes inherited independently from cystic fibrosis transmembrane conductance regulator could modulate the clinical expression of cystic fibrosis. METHODS: We analysed some putative modifier genes of liver cystic fibrosis phenotype (serpin 1, hemochromatosis, transferrin receptor 2, ferroportin 1, mannose binding lectin and adenosine triphospate-binding cassette subfamily B member 4) in 108 unrelated cystic fibrosis patients with and without liver involvement. RESULTS: HYPD mannose binding lectin haplotype was significantly (p<0.05) more frequent in cystic fibrosis patients with liver disease versus those without liver disease. This haplotype already related to a more severe pulmonary cystic fibrosis phenotype, is associated to a reduced MBL immunological activity. The c.834-66G>T variant of adenosine triphospate-binding cassette subfamily B member 4 gene was significantly (p<0.05) less frequent in cystic fibrosis patients with liver disease as compared to those with no liver disease. CONCLUSIONS: The HYPD mannose binding lectin haplotype may predispose a subgroup of cystic fibrosis patients to a more severe liver involvement impairing the local defence mechanisms whereas the c.834-66G>T adenosine triphospate-binding cassette subfamily B member 4 variant may enhance the activity of the protein and thus exert a protective effect toward liver disease.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Fibrose Cística/genética , Hepatopatias/genética , Lectina de Ligação a Manose/genética , Adolescente , Adulto , Fibrose Cística/complicações , Feminino , Haplótipos , Humanos , Hepatopatias/complicações , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto Jovem
17.
J Cyst Fibros ; 7(5): 347-51, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18280224

RESUMO

BACKGROUND: Mutation epidemiology in each ethnic group is a crucial step of strategies for cystic fibrosis (CF) diagnosis and counselling. To date, the scanning of the whole coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene permits to identify about 90% of alleles from patients bearing CF and a lower percentage in patients bearing atypical CF. CFTR rearrangements in heterozygosis elude current techniques for molecular analysis, and some of them have been reported with a frequency up to 6% in various ethnic groups. METHODS: Using quantitative PCR analysis of all coding regions, we assessed the occurrence of CFTR rearrangements in 130 alleles from classic CF patients and in 198 alleles from atypical CF patients (all unrelated and from Italian descent) bearing unidentified mutations after the scanning of CFTR. RESULTS: Seven rearrangements (i.e., dele1, dele2, dele2_3, dele 14b_17b, dele17a_18, dele22_23, and dele22_24) were identified in 34/131 (26.0%) CF alleles bearing undetected mutations (which means about 2.5% of all CF alleles) and in none of the 198 alleles from atypical CF. The CFTR haplotype and the sequence analysis of the breakpoints confirmed the common origin of all the rearrangements. Thus, we set up a novel duplex PCR assay for the large-scale analysis of the seven rearrangements. The procedure was rapid (all PCR amplifications were obtained under the same conditions), costless and repeatable. CONCLUSIONS: It is useful to select the CFTR rearrangements more frequent in specific ethnic groups and to set up procedures for large-scale analysis. Their study can be performed in cases in which a high detection rate is required (i.e., partners of CF carriers/patients). On the contrary, the analysis of rearrangement is useless in atypical CF patients.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Rearranjo Gênico , Alelos , Fibrose Cística/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Mutação , Reação em Cadeia da Polimerase
19.
Thorax ; 60(9): 773-80, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15994249

RESUMO

BACKGROUND: Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. METHODS: A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from Pseudomonas aeruginosa (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. RESULTS: PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. CONCLUSION: These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.


Assuntos
Bronquite/enzimologia , Fibrose Cística/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Adolescente , Adulto , Western Blotting , Bronquite/prevenção & controle , Células Cultivadas , Ciclo-Oxigenase 2 , Fibrose Cística/patologia , Fibrose Cística/prevenção & controle , Feminino , Humanos , Interleucina-8/análise , Lipopolissacarídeos/farmacologia , Masculino , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/análise , Pseudomonas aeruginosa , RNA Mensageiro/análise , Mucosa Respiratória
20.
Ann Hum Genet ; 69(Pt 1): 15-24, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15638824

RESUMO

We screened the whole coding region of the cystic fibrosis transmembrane regulator (CFTR) gene in 371 unrelated cystic fibrosis (CF) patients from three regions of southern Italy. Forty-three mutations detected 91.5% of CF mutated chromosomes by denaturing gradient gel electrophoresis analysis, and three intragenic CFTR polymorphisms predicted a myriad of rare mutations in uncharacterized CF chromosomes. Twelve mutations are peculiar to CF chromosomes from southern Italy: R1158X, 4016insT, L1065P and 711 + 1G > T are present in 6.3% of CF chromosomes in Campania; G1244E and 852del22 are present in 9.6% of CF chromosomes in Basilicata and 4382delA, 1259insA, I502T, 852del22, 4016insT, D579G, R1158X, L1077P and G1349D are frequent in Puglia (19.6% of CF alleles). Several mutations frequently found in northern Italy (e.g., R1162X, 711 + 5G > T) and northern Europe (e.g., G551D, I507del and 621 + 1G > T) are absent from the studied population. The I148T-3195del6 complex allele was present in two CF chromosomes, whereas I148T was present in both alleles (as a single mutation) in another CF patient and in five CF carriers; this could result from crossover events. The haplotype analysis of three intragenic polymorphisms (IVS8CA, IVS17bTA and IVS17bCA) compared with data from other studies revealed that several mutations (3849 + 10kbC > T, 1717-1G > A, E585X, 3272-26G > A, L558S, 2184insA and R347P) originated from multiple events, whereas others (R1158X and S549R) could be associated with one or more intragenic recombinant events. Given the large population migration from southern Italy, knowledge of the CF molecular epidemiology in this area is an important contribution to diagnosis, counselling and interlaboratory quality control for molecular laboratories worldwide.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Haplótipos/genética , Mutação/genética , Polimorfismo Genético , Fibrose Cística/diagnóstico , Testes Genéticos , Homozigoto , Humanos , Itália/epidemiologia , Epidemiologia Molecular , Fenótipo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...