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2.
Obes Rev ; 14(5): 417-31, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23387384

RESUMO

Obstructive sleep apnoea syndrome (OSAS) and non-alcoholic fatty liver disease (NAFLD) are common in clinical practice. NAFLD encompasses simple steatosis and non-alcoholic steatohepatitis (NASH): both confer an increased risk of cardiovascular disease and diabetes; NASH increases also liver-related risk. Growing experimental evidence connects chronic intermittent hypoxia of OSAS to NAFLD. We reviewed English and non-English articles and international meeting abstracts through December 2012. Observational studies were included if they assessed OSAS by polysomnography and NAFLD by histological, radiological or biochemical criteria. Two reviewers evaluated retrieved articles by appropriate quality scores. Main outcomes were pooled using random- or fixed-effects models. The effect of age, sex and body mass index (BMI) on effect estimates was assessed by meta-regression. Eighteen cross-sectional studies (2,183 participants) were included. Pooled odds ratios (ORs) of OSAS for the presence of NAFLD, as defined by histology, radiology, and AST or ALT elevation, were 2.01(95% CI: 1.36-2.97), 2.99(1.79-4.99), 2.36(1.46-3.82) and 2.60(1.88-3.61), respectively. Pooled ORs of OSAS for NASH, fibrosis-any stage, or advanced fibrosis in biopsy-proven NAFLD patients were 2.37(1.59-3.51), 2.16(1.45-3.20) and 2.30(1.21-4.38). The magnitude and direction of effects were unaffected by age, sex and BMI. In conclusion, OSAS is associated with an increased risk of NAFLD, NASH and fibrosis. OSAS patients should be screened for the presence and severity of NAFLD.


Assuntos
Fígado Gorduroso/epidemiologia , Obesidade/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Índice de Massa Corporal , Comorbidade , Fígado Gorduroso/patologia , Humanos , Hepatopatia Gordurosa não Alcoólica
3.
Diabetologia ; 55(4): 885-904, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22278337

RESUMO

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD. METHODS: Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated. RESULTS: Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50% patients. Statins and polyunsaturated fatty acids improved steatosis, but their effects on liver histology are unknown. Thiazolidinediones improved histological disease activity, glucose, lipid and inflammatory variables and delayed fibrosis progression. Pioglitazone also improved blood pressure. Weight gain (up to 4.8%) was common. Antioxidants yielded mixed histological results: vitamin E improved histological disease activity when administered for 2 years, but increased insulin resistance and plasma triacylglycerols. CONCLUSIONS/INTERPRETATION: Weight loss is safe, and improves liver histology and cardio-metabolic profile. For patients not responding to lifestyle intervention, pioglitazone improves histological disease activity, slows fibrosis progression and extensively ameliorates cardio-metabolic endpoints. Further randomised controlled trials (RCTs) of adequate size and duration will assess long-term safety and efficacy of proposed treatments on clinical outcomes.


Assuntos
Doenças Cardiovasculares/metabolismo , Fígado Gorduroso/tratamento farmacológico , Glucose/metabolismo , Fígado Gorduroso/metabolismo , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco
4.
Eur J Intern Med ; 23(1): 65-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22153534

RESUMO

BACKGROUND: Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity. AIMS: To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population. PATIENTS AND METHODS: 1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F=197/144, mean age=65.17±11.16 years), colorectal adenoma (385 pts., M/F=247/138, mean age=62.49±13.01 years), healthy controls (311 pts., M/F=150/161, mean age=57.31±13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR. RESULTS: The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR=1.106; CI 95%=0.788-1.550; p=0.561) or colorectal adenomas (OR=0.830; CI 95%=0.602-1.144; p=0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI. CONCLUSION: The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Obesidade/genética , Proteínas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Minerva Gastroenterol Dietol ; 56(1): 27-34, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20190722

RESUMO

AIM: This was a retrospective survey of 88 inflammatory bowel disease patients (43 with ulcerative colitis, 38 with Crohn's disease, 7 with indeterminate colitis) who were visited between January 2008 and June 2009 at a newly established out-patient service at a primary care hospital in Turin. METHODS: Treatments included corticosteroids (48 courses), mesalamines (79 courses), thiopurines (46 courses), and biological drugs (three treatments). With more extra-intestinal manifestations, more steroid needs, more visits and more surgeries, Crohn's proved more fastidious than ulcerative colitis. All of the drugs used gave side-effects that required skillful action for control: switch to mercaptopurine was advantageously used to react to azathioprine intolerance. RESULTS: Percentages of steroid needs, of stable remission, and resort to surgery were 30, 50, <20 and 40, 27, 30, respectively in ulcerative colitis and Crohn's. Thiopurines played a crucial role in the maintenance of remission of ulcerative colitis: the patients maintaining remission in the absence of azathioprine had either been resected or had left-sided disease only; left-sided disease proved also fairly responsive to beclomethasone. The unusual conduction of this service by a single doctor caused an increased trust-in-physician, but also more bias and placebo effects as drawbacks. CONCLUSIONS: The results suggest that in the last 30 years management of inflammatory bowel disease has still improved mainly due to refinement of the use of traditional drugs.


Assuntos
Assistência Ambulatorial , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adulto , Feminino , Humanos , Itália , Masculino , Encaminhamento e Consulta
6.
J Physiol Pharmacol ; 60(4): 111-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20065504

RESUMO

Increased extracellular fluid volume (ECF) characterizes compensated cirrhosis. To identify the mechanisms of fluid retention in cirrhosis through clearance methods, 10 control and 10 preascitic rats with CCl(4)-induced cirrhosis were studied following i.v. loading with 1 ml 5% glucose solution. Glomerular filtration rate and renal plasma flow were evaluated through inulin and para-aminohippurate clearances; water and electrolyte handling was assessed measuring urine and plasma osmolarity, electrolyte excretions, and tubular solute-free water reabsorption (TFWR = osmolar clearance minus urinary output); ECF was assessed through hormonal status determination. After water loading, cirrhotic rats had increased ECF (lower plasma renin activity and aldosterone and higher atrial natriuretic peptide levels, all P<0.03), solute-free water retention (increased TFWR and decreased plasma osmolarity, all P<0.05), reduced absolute and fractional sodium excretions (P<0.05). Cirrhotic rats showed sodium retention in the medullary thick ascending limb of Henle's loop (i.e. increased values of TFWR for any given value of osmolar clearance). Trans-tubular potassium gradient in medullary collecting duct was similar in the two groups (P=0.55), ruling out aldosterone-dependent sodium retention and potassium hyper-secretion. In experimental preascitic cirrhosis NaCl retention in the ascending limb of Henle's loop increases medullary interstitial tonicity leading to vasopressin-independent water back-diffusion in thin descending limb of Henle's loop and collecting duct.


Assuntos
Cirrose Hepática/fisiopatologia , Alça do Néfron/fisiopatologia , Desequilíbrio Hidroeletrolítico/fisiopatologia , Aldosterona/sangue , Animais , Fator Natriurético Atrial/sangue , Líquido Extracelular/fisiologia , Taxa de Filtração Glomerular , Rim/irrigação sanguínea , Túbulos Renais Distais/metabolismo , Cirrose Hepática/induzido quimicamente , Masculino , Concentração Osmolar , Potássio/sangue , Potássio/urina , Ratos , Ratos Wistar , Renina/sangue , Sódio/administração & dosagem , Sódio/sangue , Sódio/urina , Vasopressinas/sangue , Água/administração & dosagem
7.
Am J Physiol Renal Physiol ; 290(6): F1337-43, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16449355

RESUMO

Neutral endopeptidase degrades atrial natriuretic peptide (ANP) and bradykinin and may generate endothelin-1 from big-endothelin. In advanced cirrhosis, sodium retention is accompanied by elevated plasma ANP levels, and infusion of ANP causes hypotension, but in normal humans increasing the concentration of ANP through the inhibition of neutral endopeptidase, localized in renal proximal tubule cells, causes natriuresis without any arterial pressure drop. The purpose of this study was the assessment of kidney neutral endopeptidase expression and responses to candoxatrilat (a specific inhibitor of this enzyme) in rats with CCl4-induced cirrhosis. Two groups of control rats (n = 5) were injected with vehicle or 3 mg/kg candoxatrilat. Three groups of cirrhotic rats with ascites (n = 10) received vehicle alone or 3 or 10 mg/kg candoxatrilat. In cirrhotic rats, Western blot analysis revealed a 170% increase in renal neutral endopeptidase protein content (P < 0.03), mainly in the proximal nephron and macula densa, and both candoxatrilat dosages increased plasma ANP levels, urinary volume, and urinary excretion of sodium, ANP, and cGMP compared with vehicle alone (all P < 0.03). Candoxatrilat (10 mg/kg) also reduced tubular solute-free water reabsorption (P < 0.03) in cirrhotic rats, but renal blood flow, arterial pressure, and plasma renin activity were unaffected. Neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of this enzyme in renal cortex.


Assuntos
Rim/enzimologia , Rim/fisiopatologia , Cirrose Hepática/enzimologia , Neprilisina/análise , Animais , Western Blotting , Tetracloreto de Carbono , Ácidos Cicloexanocarboxílicos/farmacologia , Diurese , Inibidores Enzimáticos/farmacologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/fisiopatologia , Masculino , Natriurese , Neprilisina/antagonistas & inibidores , Concentração Osmolar , Ratos , Ratos Wistar
8.
Dig Liver Dis ; 37(3): 170-5, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15888281

RESUMO

BACKGROUND AND AIMS: Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human-environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm. PATIENTS AND METHODS: Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66+/-11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65+/-11 years); Healthy controls (238 patients, M/F 117/121, mean age 63+/-10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion. RESULTS: No statistically significant differences in the genotype distribution among Control and Adenoma groups (p=0.93), Control and Carcinoma groups (p=0.52), and Adenoma and Carcinoma groups (p=0.53) were observed. CONCLUSION: There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.


Assuntos
Adenoma/genética , Antígenos de Diferenciação/genética , Neoplasias Colorretais/genética , Idoso , Antígenos CD , Antígeno CTLA-4 , Progressão da Doença , Regulação para Baixo/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Medição de Risco
9.
J Intern Med ; 257(4): 358-66, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15788006

RESUMO

BACKGROUND AND AIM: In preascitic cirrhosis increased sodium retention occurs in kidney distal tubule in spite of normal aldosterone plasma levels. No clearance technique can dissect the respective contribution to sodium retention exerted by Henle's loop, distal convoluted tubule and collecting duct, so we evaluated proximal and distal tubular sodium handling in preascites during two manoeuvres that temporarily increase aldosterone secretion. METHODS: Ten patients with compensated cirrhosis and nine controls were studied in recumbency, during standing and after dopamine receptor blockade with metoclopramide through: 4 h renal clearances of sodium, potassium, lithium and creatinine; plasma levels of active renin and aldosterone. RESULTS: Whilst comparable in recumbency, aldosterone levels significantly rose during standing and after metoclopramide in both groups. In patients, dopaminergic blockade caused a fall of distal sodium delivery (P < 0.01) but urinary sodium excretion was unchanged because the reabsorbed fraction of distal sodium delivery also fell (P < 0.03). Cirrhotic patients showed the same findings in the passage from recumbency to standing. CONCLUSIONS: In preascitic cirrhosis, the distal tubular segments of the nephron are able to cope with decreases in tubular flow by reducing reabsorption at an aldosterone-independent site (possibly the loop of Henle).


Assuntos
Aldosterona/fisiologia , Túbulos Renais Distais/metabolismo , Cirrose Hepática/metabolismo , Sódio/metabolismo , Adulto , Idoso , Aldosterona/sangue , Antagonistas de Dopamina/farmacologia , Feminino , Humanos , Rim/fisiopatologia , Túbulos Renais Distais/efeitos dos fármacos , Lítio/metabolismo , Cirrose Hepática/fisiopatologia , Masculino , Metoclopramida/farmacologia , Pessoa de Meia-Idade , Natriurese/efeitos dos fármacos , Postura , Renina/sangue , Decúbito Dorsal
10.
J Viral Hepat ; 12(1): 2-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15655042

RESUMO

Delta virus related chronic hepatitis is difficult to treat. The response to alpha-interferon (IFN), which still represents the only therapy for chronic hepatitis D, varies widely and occurs at different times from the beginning of treatment. The rate of response is proportional to the dose of IFN, with 9 million units (MU) three times a week being more effective than 3 MU thrice weekly. Sustained responses are unusual and are accompanied by the clearance of serum hepatitis B virus surface antigen (HBsAg), seroconversion to anti-HBs and improvement of liver histology. Although disease of a short-standing may respond better to therapy, clear predictors of response are still unidentified. Besides IFN, other therapeutic approaches such as immunosuppressive drugs, acyclovir, ribavirin and thymosin, have been unhelpful. Available evidence does not support the use of deoxynucleotide analogues. Famciclovir has no effect on disease activity and hepatitis D virus (HDV)-RNA levels. Twelve- or 24-month lamivudine treatment does not significantly affect biochemical, virological or histological parameters. Pegylated-IFN could represent a reasonable therapeutic option in the long-term treatment required for chronic hepatitis D. Antisense oligonucleotides and prenylation inhibitors hold promise as therapeutic agents of the future. Liver transplantation provides a valid option for end-stage HDV liver disease; the risk of re-infection is lower for HDV than for HBV under long-term administration of hyperimmune serum against HBsAg. Molecularly tailored drugs capable of interfering with crucial viral replicative processes of HDV appear to be the best prospect in the treatment of hepatitis D.


Assuntos
Hepatite D/terapia , Ensaios Clínicos como Assunto , Humanos , Interferons/efeitos adversos , Interferons/farmacologia , Interferons/uso terapêutico , Transplante de Fígado
11.
Cephalalgia ; 24(6): 503-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15154861

RESUMO

The purpose of this study was to evaluate whether a particular genotype of the dopamine D2 receptor (DRD2) gene would affect the clinical features of migraine. In a group of 118 migraineurs (55 migraine with aura and 63 migraine without aura patients), we tested the association of the biallelic C/T NcoI DRD2 polymorphism with several characteristics of the disease. Genotype and allele frequencies resulted similarly distributed in migraine with aura and migraine without aura patients (chi2 = 1.58, P = 0.45 and chi2 = 0.09, P = 0.77, respectively). The different DRD2 genotypes (C/C, C/T and T/T) had no significant effects on age at onset of migraine, presence of premonitory phenomena, frequency of headache attacks, associated symptoms, psychological features and quality of life of our migraine patients. The results of our study do not support a role for the DRD2 gene in modifying the clinical features of migraine.


Assuntos
Transtornos de Enxaqueca/genética , Polimorfismo Genético/genética , Receptores de Dopamina D2/genética , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/psicologia
12.
Dig Liver Dis ; 35(10): 732-4, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14620624

RESUMO

We report the magnetic resonance imaging of a severe, but fully reversible, vertebral osteopenia, due to bone marrow hyperplasia, occurring in a patient with chronic hepatitis C treated with the interferon-alpha/ribavirin combination.


Assuntos
Antivirais/uso terapêutico , Doenças Ósseas Metabólicas/etiologia , Medula Óssea/patologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Humanos , Hiperplasia , Interferon alfa-2 , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
13.
Dig Liver Dis ; 35(8): 571-6, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14567462

RESUMO

AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.


Assuntos
Colangite Esclerosante/genética , Antígenos HLA-B/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Adulto , Estudos de Casos e Controles , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Homozigoto , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética
14.
Dig Liver Dis ; 35(5): 325-31, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12846404

RESUMO

BACKGROUND: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. RESULTS: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). CONCLUSIONS: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.


Assuntos
Colagogos e Coleréticos/administração & dosagem , Colangite Esclerosante/tratamento farmacológico , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Itália , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Dig Liver Dis ; 35(5): 339-46, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12846406

RESUMO

BACKGROUND: Osteoporosis is a recognized complication of primary biliary cirrhosis but it has been suggested that its prevalence may overlap that observed among postmenopausal women. AIM: To evaluate prevalence and risk factors of osteoporosis in primary biliary cirrhosis. PATIENTS: A total of 133 female patients (age 53+/-10 years, menopausal status 70%, histological stage I-II 61%, portal hypertension 28%, Mayo Risk Score 4.11+/-0.59) were enrolled. METHODS: Dual X-ray absorptiometry of the lumbar spine. RESULTS: Mean bone mineral density, T and Z score were 0.861+/-0.160 g/cm2, -1.87+/-1.45 and -0.78+/-2.63, respectively. At multivariate analysis, bone mineral density was inversely correlated with age (p<0.05). Osteoporosis was present in 39/92 (41%) postmenopausal and 8/41 (20%) premenopausal patients. In the premenopausal group, osteoporosis was significantly correlated with serum albumin (p<0.05) and Mayo Risk score (p<0.005). No significant correlation was present in the postmenopausal group. CONCLUSIONS: Despite the accepted wisdom that osteoporosis is a common complication of primary biliary cirrhosis, its frequency in post-menopausal patients overlaps that observed in the general population, but is much more frequent in premenopausal patients, where it appears to be related to severity of liver disease and cholestasis.


Assuntos
Cirrose Hepática Biliar/complicações , Osteoporose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas Metabólicas/epidemiologia , Feminino , Humanos , Hipertensão Portal/epidemiologia , Cirrose Hepática Biliar/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/diagnóstico por imagem , Osteoporose Pós-Menopausa/epidemiologia , Radiografia
16.
Minerva Gastroenterol Dietol ; 49(3): 167-72, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16484953

RESUMO

AIM: Achalasia is a disease of unknown etiology resulting from degeneration of the esophageal Auerbach submucous plexus. This degeneration makes normal relaxation of the cardia during swallowing impossible leading to dysphagia, chest pain and regurgitation of varying degree. Until 15 years ago the main conservative treatment for achalasia was dilatation of the cardia with the Starck apparatus. Such approach to achalasia was usually reported as fairly effective, but complicated by an exceedingly high rate of perforation. This led most centers to replace the Starck procedure with pneumatic or hydrostatic balloon dilators. The aim of our study was to evaluate safety, early and late results of the Starck procedure. METHODS: Our report is based on the retrospective analysis of 21 patients [male/female: 12/9, mean age 46 years (range-65)] who underwent 52 Starck procedures for esophageal achalasia. The effectiveness of the Starck procedure was assessed according to the scale of Vantrappen and Hellemans. RESULTS: After the scheduled 2 Starck sessions, an excellent result was seen in 10 patients (50%), a good result in 8 (40%); 2 patients (10%) showed a poor result. One month after the last Stark procedure 1 patient (5%) experienced gastroesofageal reflux easily managed with protein pump inhibitors. During or after dilations no major complications were observed. CONCLUSIONS: The Starck procedure, now replaced by the new Rigiflex pneumatic dilator, resulted effective and safe in experienced hands.

17.
Scand J Gastroenterol ; 37(10): 1205-11, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12408527

RESUMO

BACKGROUND: Primary sclerosing cholangitis (PSC) confers a high risk of cholangiocarcinoma (CC) development. Since patients at risk of CC may be selected for early liver transplantation, it is a challenge to identify any predisposing factors. We compared the presentation and natural history of a large number of PSC patients with and without later CC development to identify features associated with risk of CC. METHODS: Clinical and laboratory data from presentation and follow-up were collected from 394 PSC patients from five European countries. The cohort included 48 (12.2%) patients with CC. RESULTS: CC was diagnosed within the first year after diagnosis of PSC in 24 (50%) cases and in 13 (27%) patients at intended liver transplantation. Jaundice, pruritus, abdominal pain and fatigue were significantly more frequent at diagnosis of PSC in the group that developed CC, but not after exclusion of cases diagnosed within the first year. Inflammatory bowel disease was diagnosed at least 1 year before PSC more often among patients with CC development than among those without (90% and 65%, respectively: P = 0.001). The duration of inflammatory bowel disease before diagnosis of PSC was significantly longer in patients who developed CC than in the remaining group (17.4 years and 9.0 years, respectively: P=0.009 in multivariate analysis). CONCLUSIONS: A high proportion of CC cases is diagnosed within the first year after diagnosis of PSC. A long history of inflammatory bowel disease is a risk factor for CC development.


Assuntos
Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/fisiopatologia , Ductos Biliares Intra-Hepáticos/fisiopatologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/fisiopatologia , Colangite Esclerosante/complicações , Colangite Esclerosante/fisiopatologia , Adulto , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangite Esclerosante/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
18.
Gut ; 51(5): 736-41, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12377816

RESUMO

BACKGROUND AND AIMS: Patients with preascitic liver cirrhosis display significant renal sodium retention in the upright posture and an exaggerated natriuresis during recumbency. To date, intrarenal sodium handling in these patients has not been studied using lithium clearance and fractional excretion techniques during recumbency and orthostatism. METHODS: Ten patients with preascitic (Child-Pugh A) liver cirrhosis and 10 healthy subjects underwent the following measurements during recumbency and then after four hours of standing: (a) active renin and aldosterone plasma levels; and (b) renal clearance of creatinine, sodium, potassium, and lithium (an index of fluid delivery to the loop of Henle). RESULTS: Unlike the control group, in the upright posture patients had significantly lower values of lithium clearance and fractional excretion compared with recumbency (21.6 (8.6) v 30.5 (10.2) ml/min (p<0.03) and 12.8 (4.4)% v 20.8 (4.9)% (p<0.01), respectively). Our patients showed maintenance of the glomerular-tubular balance-that is, the correlation between creatinine clearance and proximal tubular reabsorption of fluid-during both recumbency and in the upright posture (r=0.96, p<0.001; r=0.97, p<0.001, respectively). In contrast, patients displayed tubuloglomerular feedback only in the supine position. This was demonstrated by the observation of a negative correlation between lithium fractional excretion (a measure of the fractional delivery of sodium to the distal nephron) and filtered sodium load only in recumbency (r=-0.73; p< 0.03) and not during standing (r=0.22; p> 0.05). CONCLUSIONS: This study suggests that both the reduction in fluid and sodium delivery to the distal nephron and loss of tubuloglomerular feedback (the mechanism increasing glomerular filtration rate when the distal tubule is reached by a reduced sodium load) contribute towards the tendency to sodium retention in compensated cirrhosis during prolonged upright posture.


Assuntos
Rim/metabolismo , Lítio/farmacocinética , Cirrose Hepática/metabolismo , Postura , Adulto , Aldosterona/sangue , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Humanos , Glomérulos Renais/metabolismo , Túbulos Renais/metabolismo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Renina/sangue , Sódio/sangue , Estatísticas não Paramétricas
19.
Dig Liver Dis ; 34(4): 285-9, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12038813

RESUMO

BACKGROUND: Thymic humoral factor-gamma 2 is a thymus-derived synthetic octapeptide, shown to be effective in chronic hepatitis B virus infection; as the latter is needed to support hepatitis D virus, thymic humoral factor-gamma 2 may have a therapeutic role in hepatitis D. AIM: To evaluate tolerability and efficacy of thymic humoral factor-gamma 2 in chronic hepatitis D. METHODS: Intramuscular thymic humoral factor-gamma 2, 40 microg, was given for 15 consecutive days and twice weekly for 22 additional weeks to adult patients with chronic hepatitis D virus hepatitis. RESULTS: A total of 11 patients (male/female 9/2, mean age 45.9 years] completed the treatment period, 10 the 6-month follow-up. At baseline, hepatitis D virus-RNA was positive in 8/11 (73%) patients. During treatment, hepatitis D virus-RNA became undetectable in 3/8 (37%), decreased in 1/8 (13%), remained unchanged in 4/8 (50%) and persisted undetectable in 3 patients, negative at baseline. During follow-up hepatitis D-viraemia relapsed in all patients but 2, one already negative at baseline. No changes in hepatitis B virus markers occurred. Mean serum alanine aminotransferase levels did not change significantly None of the patients reached normal serum alanine aminotransferase levels. CONCLUSION: At the doses given, thymic humoral factor-gamma 2 has been of limited efficacy A possible role of thymic humoral factor-gamma 2 in the treatment of chronic hepatitis D requires further dose-finding studies and/or combination with other antivirals.


Assuntos
Hepatite D Crônica/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Alanina Transaminase/sangue , Feminino , Hepatite D/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Viral/análise , Resultado do Tratamento
20.
Scand J Gastroenterol ; 36(8): 886-90, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11495087

RESUMO

BACKGROUND: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. METHODS: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. RESULTS: The DRB1*03,DQA1*0501, DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). CONCLUSION: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.


Assuntos
Colangite Esclerosante/genética , Antígenos HLA-DQ/genética , Antígeno HLA-DR3/genética , Heterozigoto , Adolescente , Adulto , Idoso , Criança , Colangite Esclerosante/imunologia , Progressão da Doença , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
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