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1.
Eur J Intern Med ; 98: 77-82, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35177308

RESUMO

BACKGROUND: COVID-19 pandemic has generated a million deaths worldwide. The efficiency of the immune system can modulate individual vulnerability with variable outcomes. However, the relationships between disease severity and the titer of antibodies produced against SARS-CoV-2 in non-vaccinated, recently infected subjects need to be fully elucidated. METHODS: A total of 99 patients admitted to a COVID-unit underwent clinical assessment and measurement of serum levels of anti-spike protein (S1) IgM, and anti-nucleocapsid protein IgG. Patients were stratified according to the clinical outcome (i.e., discharged at home or in-hospital death). RESULTS: Following hospitalization, 18 died during the hospital stay. They were older, had lymphopenia, a higher co-morbidity rate, and longer hospital stay than 81 patients who were discharged after healing. Patients in this latter group had, at hospital admittance, 7.9-fold higher serum concentration of IgM, and 2.4-fold higher IgG levels. Multivariate Cox regression models indicated age and anti-nucleocapsid protein IgG concentration at admission as independently associated with the risk of in-hospital death. CONCLUSIONS: An efficient immunological response during the early phase of COVID-19 protects from mortality, irrespective of age. Advanced age is a critical risk factor for poor outcome in infected subjects. Further studies must explore potential therapeutic strategies able to restore a valid functional humoral immunity in elderly patients with poor antibody response during the early stage of COVID-19 infection.


Assuntos
COVID-19 , Idoso , Anticorpos Antivirais , Mortalidade Hospitalar , Humanos , Imunoglobulina G , Imunoglobulina M , Pandemias , SARS-CoV-2
2.
JHEP Rep ; 3(1): 100203, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33490935

RESUMO

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. METHODS: We used orally administered (13C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. RESULTS: NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. CONCLUSIONS: The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases. LAY SUMMARY: Obesity is progressively increasing worldwide and is paralleled by fat accumulation in the liver (non-alcoholic fatty liver disease [NAFLD]), the most common chronic liver disease worldwide. NAFLD can alter liver structure and function, with a variety of consequences ranging from asymptomatic and subclinical alterations to cirrhosis and cancer. (13C)-Methacetin breath test, a non-invasive diagnostic tool, can reveal early subclinical alterations of liver dynamic function in individuals with obesity and in patients with NAFLD.

3.
Eur J Cancer ; 138: 109-112, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871524
5.
Clin Rheumatol ; 39(2): 585-594, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31401792

RESUMO

An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting 2-3 days. He never suffered from abdominal or chest pain, rash, or arthralgia. Major causes of fever were excluded (pulmonary, urinary, abdomen, skin infections, neoplasms, and major rheumatologic disorders). The patient was native of Altamura with a family history of familial Mediterranean fever (FMF). The genetic testing confirmed the presence of MEFV gene variants c.442G>C (E148Q) on exon 2 and c.2282G>A (R761H) on exon 10, all in heterozygosity. Mildly elevated serum transaminases suggested an ongoing form of FMF hepatitis on nonalcoholic liver steatosis. The patient started colchicine 1 mg/day that induced symptom control and normalization of inflammatory markers, hyperbilirubinemia, and markers of cholestasis. Symptoms of FMF can appear at any age in life and our patient represents a very late-onset clinical case. The Apulian region has a consistent clustering of MEFV variants and FMF families with affected individuals in multiple consecutive generations. Families show unique clinical features and rare signs of secondary amyloidosis without kidney damage. Genetic and environmental bases of this phenotypic variant are under scrutiny. Colchicine lifetime remains the mainstay of treatment in FMF patients. KEY POINTS: • Familial Mediterranean fever (FMF) is the most frequent hereditary monogenic recurrent fever syndrome, and symptoms can appear at any age in life. • Late-onset FMF approaches 30% in late adulthood, but in general, onset of FMF after the age of 40 (late onset FMF) is rare, usually associated with M694V heterozygosity. • In a local cluster of FMF families (Altamura, Puglia, Southern Italy), we report a very late-onset FMF (variants E148Q, R761H) in an 86-year-old patient with a positive family history of FMF in two generations of descendants. • While lifetime colchicine remains the mainstay of treatment in FMF patients, prospective studies need to identify the characteristics of several phenotypic variants accounting for (very)-late onset FMF.


Assuntos
Febre Familiar do Mediterrâneo/genética , Pirina/genética , Idade de Início , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Linhagem
6.
Ann Hepatol ; 16(Suppl. 1: s3-105.): s87-s105, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29080344

RESUMO

Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.


Assuntos
Ácidos e Sais Biliares/metabolismo , Transformação Celular Neoplásica/metabolismo , Poluentes Ambientais/efeitos adversos , Estilo de Vida , Neoplasias/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Animais , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Dieta/efeitos adversos , Metabolismo Energético , Exposição Ambiental/efeitos adversos , Epigênese Genética , Microbioma Gastrointestinal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/patologia , Estresse Oxidativo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Risco , Transdução de Sinais , Fumar/efeitos adversos , Fumar/epidemiologia
7.
Eur J Case Rep Intern Med ; 4(2): 000495, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30755918

RESUMO

Inflammatory pseudotumor (IPT) of the liver is a rare, benign lesion of unclear etiology, which may be misdiagnosed as hepatocellular carcinoma, cholangiocarcinoma, secondary tumor or abscess, because of its non-specific clinical, biochemical and radiologic findings. We present the case of a 48-old-year male in whom diagnosis of liver IPT was suspected by contrast enhanced ultrasound (CEUS) and confirmed by fine-needle liver biopsy. The diagnosis is in contrast to most of the literature reports in which the diagnosis was made only based on a surgical specimen. LEARNING POINTS: The inflammatory pseudotumor (IPT) of the liver is a rare benign disease that may be misdiagnosed as a malignant primary or secondary tumor.The diagnosis of IPT may be improved by the use of contrast enhanced ultrasound (CEUS) and the fine-needle liver biopsy without surgical intervention.The therapy of IPT may be monitored by ultrasonography (US) and CEUS.

8.
Am J Physiol Gastrointest Liver Physiol ; 309(10): G826-40, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26336926

RESUMO

The p66Shc protein mediates oxidative stress-related injury in multiple tissues. Steatohepatitis is characterized by enhanced oxidative stress-mediated cell damage. The role of p66Shc in redox signaling was investigated in human liver cells and alcoholic steatohepatitis. HepG2 cells with overexpression of wild-type or mutant p66Shc, with Ser36 replacement by Ala, were obtained through infection with recombinant adenoviruses. Reactive oxygen species and oxidation-dependent DNA damage were assessed by measuring dihydroethidium oxidation and 8-hydroxy-2'-deoxyguanosine accumulation into DNA, respectively. mRNA and protein levels of signaling intermediates were evaluated in HepG2 cells and liver biopsies from control and alcoholic steatohepatitis subjects. Exposure to H2O2 increased reactive oxygen species and phosphorylation of p66Shc on Ser36 in HepG2 cells. Overexpression of p66Shc promoted reactive oxygen species synthesis and oxidation-dependent DNA damage, which were further enhanced by H2O2. p66Shc activation also resulted in increased Erk-1/2, Akt, and FoxO3a phosphorylation. Blocking of Erk-1/2 activation inhibited p66Shc phosphorylation on Ser36. Increased p66Shc expression was associated with reduced mRNA levels of antioxidant molecules, such as NF-E2-related factor 2 and its target genes. In contrast, overexpression of the phosphorylation defective p66Shc Ala36 mutant inhibited p66Shc signaling, enhanced antioxidant genes, and suppressed reactive oxygen species and oxidation-dependent DNA damage. Increased p66Shc protein levels and Akt phosphorylation were observed in liver biopsies from alcoholic steatohepatitis compared with control subjects. In human alcoholic steatohepatitis, increased hepatocyte p66Shc protein levels may enhance susceptibility to DNA damage by oxidative stress by promoting reactive oxygen species synthesis and repressing antioxidant pathways.


Assuntos
Dano ao DNA , Fígado Gorduroso Alcoólico/metabolismo , Hepatócitos/metabolismo , Oxirredução , Estresse Oxidativo , Proteínas Adaptadoras da Sinalização Shc , Técnicas de Cultura de Células , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Proteína Oncogênica v-akt/metabolismo , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras da Sinalização Shc/genética , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Transdução de Sinais , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src
9.
Radiol Med ; 120(7): 627-33, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25599661

RESUMO

PURPOSE: The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver exclude any role of contrast-enhanced ultrasound (CEUS) in the diagnosis of hepatocellular carcinoma (HCC) while the Italian Association for the Study of the Liver suggests its use for larger HCC. This study evaluated the accuracy of CEUS in comparison with computed tomography (CT) in the diagnosis of HCC and of residual of HCC after treatment. MATERIALS AND METHODS: We retrospectively evaluated 124 patients with 148 HCC nodules: 34 small (≤20 mm) and 114 large nodules (>20 mm). Ninety-three patients underwent treatment [one resection, 23 transcatheter arterial chemoembolisation (TACE), 37 radiofrequency ablation (RFA), 32 TACE/RFA combined with sorafenib]. The diagnosis of HCC on CEUS was confirmed by the typical pattern of arterial enhancement and portal and/or venous phase washout. RESULTS: We performed 90 CEUS for the initial diagnosis of HCC in 85 patients and 107 CEUS for the diagnosis of residual HCC after 1-month treatment in 92 patients. Sensitivity, specificity, positive predictive value, negative predictive value of CEUS and CT in the initial diagnosis of HCC were: 63 vs 92, 100 vs 100, 100 vs 100, 9 vs 25 for small HCC; 77 vs 92, 100 vs 100, 100 vs 100, 13 vs 22 for large HCC. In the diagnosis of residual of HCC, CEUS had a sensitivity of 70 % for small nodules and 76 % for large nodules, with an overall specificity of 100 %. CONCLUSION: CEUS is useful in the initial diagnosis and in the assessment of necrosis after RFA and TACE of HCC nodules.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia
10.
Int Clin Psychopharmacol ; 30(2): 103-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25514607

RESUMO

The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders.


Assuntos
Prolactina/sangue , Prolactina/química , Risperidona/efeitos adversos , Adolescente , Antipsicóticos/efeitos adversos , Criança , Saúde da Família , Feminino , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/complicações , Masculino , Estudos Prospectivos , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
11.
Clin Exp Med ; 15(1): 65-72, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24323278

RESUMO

In some tumors, psychosocial interventions may enhance health-related quality of life (HRQOL) of patients. The effects of psychological variables on HRQOL in hepatocellular carcinoma (HCC) patients have been rarely assessed. The aim of this work is to evaluate the psychopathological profile of HCC and cirrhotic patients and its effect on HRQOL. Twenty-four HCC patients (median age 71, Child A 21, Child B 3), 22 cirrhotic patients (median age 68, Child A 20, Child B 2) and 20 control subjects were included in this study. Each subject completes four questionnaires: medical outcomes study short form-36 (SF-36, HRQOL evaluation); Hamilton-D (quantitative evaluation of depression; positive ≥8); symptom check list 90-revised (SCL 90-R, general psychopathological profile; nine domains, each positive >1); Toronto alexithymia scale (TAS 20) (positive ≥60). SCL 90-R: cirrhotic patients differ from HCC subjects for somatization (SOM) (M ± SD 1.09 ± 0.6 vs 0.65 ± 0.6; p = 0.01) and anxiety (M ± SD 0.85 ± 0.46 vs 0.58 ± 0.38; p = 0.01) items. TAS 20: positive in 50% of HCC patients, in 54% of cirrhotic patients (p = n.s.) and in none of controls. Hamilton-D: higher scores in cirrhotic patients than in the HCC group (86 vs 46%; p = 0.005). SF-36: each item, except bodily pain, is lower in both group of patients in comparison with controls. Pearson correlation analysis shows negative correlations on HRQOL of depression, SOM and anxiety both in cirrhotic and HCC subjects, also of obsessive-compulsive and hostility items in HCC. This is the first report on the psychopathological profile of HCC patients: the results open questions on the role of psychological interventions that may improve HRQOL of patients before treatment and in the follow-up.


Assuntos
Ansiedade/psicologia , Carcinoma Hepatocelular/psicologia , Depressão/psicologia , Cirrose Hepática/psicologia , Neoplasias Hepáticas/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Ansiedade/patologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Depressão/complicações , Depressão/patologia , Feminino , Hepatite B/complicações , Hepatite B/patologia , Hepatite B/psicologia , Hepatite C/complicações , Hepatite C/patologia , Hepatite C/psicologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Dor/complicações , Dor/patologia , Dor/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários
12.
Int Clin Psychopharmacol ; 28(4): 177-83, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23689836

RESUMO

The aim of this prospective observational study was to verify the tolerability and safety profile of risperidone in a sample of antipsychotic-naive children/adolescent patients having a different psychiatric diagnosis. Twenty-two (mean age of 12±3.2) antipsychotic-naive patients who started therapy with risperidone were recruited. The assessment involved anthropometric data (weight, height, BMI, BMI z-score and BMI percentile), cardiovascular parameters (blood pressure and QTc interval) and blood tests (levels of glucose, triglycerides, total cholesterol, glutamic oxaloacetic and pyruvic transaminases, γ-glutamyl transferase, prolactin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroglobulin, antithyroid peroxidase and antithyroglobulin). After an average follow-up of 6 months of risperidone therapy, a statistically significant increase in weight and body composition was observed. Furthermore, an increase in serum levels of prolactin was observed in 50% of patients. No other significant changes in metabolic and cardiovascular parameters were found. Although an increase in these parameters was detected, it remained in the normal range. This study suggests the use of specific protocols for monitoring children/adolescents treated with second-generation antipsychotics to manage the metabolic long-term complications and progression to more severe disease states.


Assuntos
Antipsicóticos/efeitos adversos , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtornos Globais do Desenvolvimento Infantil/tratamento farmacológico , Antagonistas de Dopamina/efeitos adversos , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Antagonistas do Receptor 5-HT2 de Serotonina/efeitos adversos , Adolescente , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/uso terapêutico , Monitoramento de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Prolactina/sangue , Risperidona/administração & dosagem , Risperidona/uso terapêutico , Antagonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Transtornos de Tique/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos
13.
Eur J Clin Invest ; 43(1): 41-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23134583

RESUMO

AIMS: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, has been implicated in the pathogenesis of atherosclerosis. We therefore evaluated the genotyping of OLR1 gene in a sample of 55 patients with Metabolic Syndrome, a clinical condition characterized by a high cardiovascular risk. METHODS AND PATIENTS: The genotyping of the LOX-1 was performed by polymerase chain reaction (PCR) analysis of the IVS4-14 A>G OLR1 polymorphism embedded within the OLR1 Linkage Disequilibrium block. Patients were assessed for routine serum parameters, microalbuminuria, insulin resistance (HOMA) and oxidative stress (thiobarbituric acid reactive substances, TBARs and thioredoxin). RESULTS: The allele or genotype distribution of the OLR1 IVS4-14 A>G was not statistically different between MS and controls subjects. A positive association was found between IVS4-14 GG genotype, microalbuminuria and fasting glycaemia as well as a higher frequency of type 2 diabetes, elevated microalbuminuria, fasting serum glucose and HOMA index in the same subjects. Thioredoxin values were higher in patients with MS but did not differ in relation to OLR1 IVS4-14 A>G genotype. The TBARs/Cholesterol ratio was higher in MS both in IVS4-14 GG and in IVS4-14 AG. CONCLUSION: IVS4-14 GG genotype seems to be related to glucose metabolism disturbance, elevated insulin level and lipid peroxidation in patients with MS.


Assuntos
Resistência à Insulina/genética , Peroxidação de Lipídeos/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Síndrome Metabólica/genética , Receptores Depuradores Classe E/genética , Adulto , Albuminúria/diagnóstico , Análise de Variância , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Resistência à Insulina/fisiologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Polimorfismo Genético , Receptores Depuradores Classe E/metabolismo , Tiobarbitúricos/sangue , Tiorredoxinas/sangue
14.
Acta Radiol ; 53(8): 885-92, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22919052

RESUMO

BACKGROUND: Recent reports indicate that numerical assessment of B-lines during transthoracic ultrasound may aid the differential diagnosis of acute diffuse pleuropulmonary disorders. PURPOSE: To determine whether B-lines are different in normal and diseased lungs and whether they can be used to discriminate between different types of pulmonary disorders in acutely ill patients. MATERIAL AND METHODS: In this multicenter study, transthoracic ultrasonography was performed on 193 patients with acute dyspnea, 193 healthy non-smokers, and 58 patients who had undergone pneumonectomy for lung cancer. Examinations were done with a low-medium frequency (3.5-5.0 MHz) convex probe and a high-frequency (8-12.5 MHz) linear probe. Video recordings were re-examined by a second set of examiners. In each participant, we measured the number of B-lines observed per scan. RESULTS: B-lines counts were higher in dyspnoic patients (means: 3.11 per scan per linear probe scan vs. 1.93 in healthy controls and 1.86 in pneumonectomized patients; P < 0.001 for all); all counts were higher when convex probes were used (5.4 in dyspnoic patients and 2 in healthy controls; P < 0.001 vs. the linear probe). Subgroups of dyspnoic patients defined by cause of dyspnea displayed no significant differences in the number of B-lines. CONCLUSION: Our results demonstrate that there are a significant higher number of B-lines in the lungs of patients with dyspnea compared to healthy subjects and to pneumonectomized patients. Nevertheless, the quantification of B-lines does not make any significant contribution to the differential diagnosis of dyspnea.


Assuntos
Artefatos , Dispneia/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Dispneia/etiologia , Feminino , Humanos , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Adulto Jovem
15.
Clin Biochem ; 44(17-18): 1400-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21963381

RESUMO

BACKGROUND AND AIMS: Cholestasis is associated with systemic and hepatic oxidative and nitrosative stress; in this scenario, the conjugated hydrophilic bile salt ursodeoxycholate (UDCA) might play a protective role. METHODS: Circulating oxidative and nitrosative stress markers were assessed in patients with primary biliary cirrhosis (PBC) before and during UDCA (15-20mg/kg/day) therapy. RESULTS: In patients with stage I-II PBC, UDCA improved ALT and alkaline phosphatase levels and near normalized serum thioredoxin (1.97 ± 0.37 vs 2.41 ± 0.39 nmol/L), nitrotyrosine (15 ± 4 vs 22 ± 7 nmol/L), nitrosothiols (144 ± 28 vs 205 ± 84 nmol/L) and K-18 levels (162 ± 21 vs 228 ± 33 U/L). Conversely, less marked changes were noted in patients with stages III-IV who showed lower thioredoxin (1.01 ± 0.31 nmol/L), higher nitrosothiols (605 ± 64 nmol/L), nitrotyrosine (62 ± 13 nmol/L) and K-18 levels (521 ± 57 U/L). Overall, thioredoxin was inversely related with nitrotyrosine (r=-0.838, P<0.001) and K-18 (r=-0.838, P<0.001) levels. Nitrosothiols and K-18 were linearly and significantly related with nitrotyrosine (r=0.862, P<0.001; r=0.894, P<0.001, respectively). CONCLUSIONS: Oxidative and nitrosative changes in patients with PBC are effectively counteracted by UDCA. The protective effect of UDCA, however, are limited to early disease stages and progressively diminishes with ongoing cholestasis.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/tratamento farmacológico , Estresse Oxidativo , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Colagogos e Coleréticos/farmacologia , Feminino , Humanos , Queratina-18/sangue , Masculino , Pessoa de Meia-Idade , Compostos Nitrosos/sangue , Oxirredução , Tiorredoxinas/sangue , Tirosina/análogos & derivados , Tirosina/sangue , Ácido Ursodesoxicólico/farmacologia
16.
Nat Genet ; 42(8): 658-60, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20639880

RESUMO

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).


Assuntos
Alelos , População Branca/genética , Canadá , Genoma , Estudo de Associação Genômica Ampla , Humanos , Fatores Reguladores de Interferon , Cirrose Hepática Biliar , Metanálise como Assunto , Razão de Chances
18.
J Surg Res ; 157(2): 199-207, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19540521

RESUMO

BACKGROUND: Little is known on hepatic function in patients with hepatocellular carcinoma (HCC). Metabolic changes were explored in HCC patients before/after nonsurgical therapy. MATERIALS AND METHODS: HCV-related Child-Pugh A cirrhotic patients with (n = 37) or without HCC (n = 14) and healthy controls (n = 23) were enrolled. Subjects underwent breath testing with (13)C-methacetin or (13)C-ketoisocaproate for exploring microsomal and mitochondrial function, respectively. HCC patients repeated the tests 1-2, 30, and 180 d after radiofrequency ablation (n = 27, RFA) or transarterial chemoembolization (n = 10, TACE). RESULTS: At baseline, cirrhotic patients showed decreased methacetin demethylation capacity compared with controls (8.1 +/- 2.1 versus 13.7 +/- 1.3% cum. dose exhaled at 60 min, M +/- CI, P < 0.001) and minor changes in ketoisocaproate decarboxylation. HCC patients had methacetin demethylation comparable to cirrhotic subjects, but a significantly lower ketoisocaproate decarboxylation (8.5 +/- 1.0 versus 11.6 +/- 1.9% cum. dose exhaled at 60 min, P < 0.001). Methacetin metabolism was significantly decreased following TACE (-28%, P < 0.05) but not RFA. Ketoisocaproate decarboxylation was unaffected by TACE but decreased after RFA (-27%, P < 0.05). A recovery was noticed with ketoisocaproate as a probe after 1 and 6 mo (P < 0.003). HCC recurrence was associated with early decrease of ketoisocaproate decarboxylation. CONCLUSIONS: Liver mitochondrial function is decreased in cirrhotic patients with HCC suggesting a possible tumor-induced suppressant effect. RFA but not TACE appears to spare residual (microsomal) liver mass, but induces such a transient stunning effect on mitochondrial function. Improved mitochondrial function after 1 and 6 mo from RFA may represent an additional parameter of treatment efficacy. Breath test assessing liver function may have potential applications in HCC management.


Assuntos
Testes Respiratórios/métodos , Carcinoma Hepatocelular/terapia , Testes de Função Hepática/métodos , Neoplasias Hepáticas/terapia , Fígado/fisiopatologia , Acetamidas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Isótopos de Carbono , Ablação por Cateter , Quimioembolização Terapêutica , Feminino , Humanos , Cetoácidos/metabolismo , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias Hepáticas/fisiologia , Resultado do Tratamento
19.
J Gastrointestin Liver Dis ; 17(4): 389-94, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19104698

RESUMO

BACKGROUND/AIMS: The epidemic diffusion of nonalcoholic fatty liver disease (NAFLD) represents an emerging problem in family medicine. General Practitioners (GPs) should pay attention to patients with fatty liver, look at associated conditions, identify causal factors and patients at risk of evolution. This study aimed to assess GPs' knowledge and practice and a training project impact about NAFLD: METHODS: 56 GPs filled a questionnaire before and after attending a tailored workshop on NAFLD, and performed a clinical survey in patients with persistent hypertransaminasemia including screening and liver biopsy when indicated. Four months after a training workshop, GPs were questioned again about their practice changes with NAFLD: RESULTS: At baseline, less than 30% of GPs considered NAFLD as a cause of persistent hypertransaminasemia; over two-thirds thought that NAFLD had a prevalence of 5-10% in the general population; about 50% considered hypertransaminasemia as the main indication for liver biopsy in NAFLD; their main approach included a low lipid-content diet. Comparison of pre/post workshop questionnaires showed significant improvements, despite knowledge on diet composition and steatogenic drugs remained poor. Among screened patients with hypertransaminasemia, NAFLD had a prevalence of 36% and was associated with the metabolic syndrome in more than 50%. Liver biopsy was obtained in 8% of NAFLD: Chronic viral hepatitis was better diagnosed than NAFLD (biopsy performed in 86% of cases). The training workshop resulted in practice changes concerning screening of risk patients, search for NASH and managing NAFLD in chronic viral hepatitis. CONCLUSIONS: GPs' knowledge about NAFLD appears barely adequate, thus targeted training is essential to improve their knowledge and practice.


Assuntos
Fígado Gorduroso/diagnóstico , Fígado Gorduroso/terapia , Conhecimentos, Atitudes e Prática em Saúde , Médicos de Família/educação , Padrões de Prática Médica , Atitude do Pessoal de Saúde , Competência Clínica , Educação Médica Continuada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
J Nutr Biochem ; 19(8): 491-504, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17855068

RESUMO

Although the biochemical steps linking insulin resistance with the metabolic syndrome have not been completely clarified, mounting experimental and clinical evidence indicate oxidative stress as an attractive candidate for a central pathogenic role since it potentially explains the appearance of all risk factors and supports the clinical manifestations. In fact, metabolic syndrome patients exhibit activation of biochemical pathways leading to increased delivery of reactive oxygen species, decreased antioxidant protection and increased lipid peroxidation. The described associations between increased abdominal fat storage, liver steatosis and systemic oxidative stress, the diminished concentration of nitric oxide derivatives and antioxidant vitamins and the endothelial oxidative damages observed in subjects with the metabolic syndrome definitively support oxidative stress as the common second-level event in a unifying pathogenic view. Moreover, it has been observed that oxidative stress regulates the expression of genes governing lipid and glucose metabolism through activation or inhibition of intracellular sensors. Diet constituents can modulate redox reactions and the oxidative stress extent, thus also acting on nuclear gene expression. As a consequence of the food-gene interaction, metabolic syndrome patients may express different disease features and extents according to the different pathways activated by oxidative stress-modulated effectors. This view could also explain family differences and interethnic variations in determining risk factor appearance. This review mechanistically focused on oxidative stress events leading to individual disease factor appearance in metabolic syndrome patients and their setting for a more helpful clinical approach.


Assuntos
Síndrome Metabólica/etiologia , Modelos Biológicos , Estresse Oxidativo , Animais , Diabetes Mellitus , Endotélio Vascular , Fígado Gorduroso , Predisposição Genética para Doença , Humanos , Hiperglicemia , Hipertensão , Resistência à Insulina , Gordura Intra-Abdominal , Metabolismo dos Lipídeos , Fenômenos Fisiológicos da Nutrição , Obesidade , Oxirredução , Fatores de Risco
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