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BACKGROUND: Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life-threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1-INH) isolated from human plasma. OBJECTIVES: This open-label extension to a European, Israeli and Argentinean randomized study (NCT00262301) aimed to investigate the efficacy and safety of recombinant human C1 inhibitor (rhC1-INH) as a first-line treatment following an HAE attack, together with its effect on subsequent attacks. METHODS: An HAE-specific visual analogue scale (VAS) 0-100 mm was used by patients to assess the severity of attack at four anatomical locations. Patients were treated with one, single-vial, fixed-dose of rhC1-INH (2100 U), followed by up to two further vials at the investigators discretion. The primary end-point was the time from first rhC1-INH injection to first onset of relief of symptoms (≥ 20 mm decrease on VAS). Response to treatment was defined as the onset of relief within 4 h. RESULTS: A total of 57 patients were treated for 194 HAE attacks. Overall, sustained relief of symptoms was achieved in 87% of rhC1-INH-treated patients within 4 h of treatment, with 57% of attacks requiring only one vial of rhC1-INH. When categorized by successive attacks experienced by individual patients, the response rate to rhC1-INH treatment was 96%, 83%, 87%, 80% and 80% for attacks 1-5 respectively. Treatment with rhC1-INH was well tolerated, with no discontinuations owing to treatment-emergent adverse events and no adverse events relating to immunogenicity. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with rhC1-INH provides fast-onset relief for an HAE attack, with a high rate of therapeutic response maintained throughout subsequent attacks.
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Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Inativadores do Complemento/uso terapêutico , Adolescente , Adulto , Idoso , Proteína Inibidora do Complemento C1/administração & dosagem , Proteína Inibidora do Complemento C1/efeitos adversos , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Differential diagnosis of dyspnea is vital for the management of respiratory failure, where routine parameters can now be integrated with thoracic ultrasound data. The objective of this study was to evaluate the validity and accuracy of this approach in a department of internal medicine. MATERIALS AND METHODS: We enrolled 152 patients consecutively hospitalized with a diagnosis of dyspnea. After clinical evaluation, chest radiography, biochemical assays (NT-proBNP), and emergency treatment, patients underwent ultrasound examination of the lungs. Results were considered positive if the total number of lines B was higher than 8. The ultrasound examination and NT-proBNP assay were repeated after 48 h. The gold standard was the clinical diagnosis of heart failure made by medical experts in accordance with AHA guidelines. RESULTS: The group of patients with positive ultrasound findings had a higher frequency of heart failure diagnoses (X(2) 92.5, p < 0.005) and significantly higher values of NT-proBNP (10,384 ng/l vs 3889 ng/l, p < 0.05). Moreover, the decrease in the number of B lines at 48 h was significantly greater (p < 0.005) among patients treated for heart failure. There were no significant changes in the values of NT-proBNP (p = 0.37). DISCUSSION: In conclusion we have shown that even in a department of internal medicine, lung ultrasonography is a useful tool for diagnosing respiratory insufficiency and monitoring its response to therapy.
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INTRODUCTION: US (US) examination of the abdomen has acquired a growing role in the investigation of abdominal pain; however its role in the diagnosis of some important causes of abdominal pain is still under investigation. The aim of this study was to evaluate the role of US of the abdomen in the diagnosis of abdominal pain in patients referred to a department of internal medicine. MATERIALS AND METHODS: A retrospective analysis was carried out on 248 US examinations performed in our department due to abdominal pain. For each examination the data written on the request form were registered as well as US findings which could be correlated with abdominal pain. RESULTS: In 105 patients (42%), US examination of the abdomen resulted in a relevant clinical finding and was thus considered positive. A high percentage of patients were elderly (>65 years; 52%) and very elderly (>80 years; 24%); these patients showed a significantly higher percentage of positive US scans. The proportion of positive scans was not significantly different between localized and non-localized pain. Specific pain location was associated with US findings such as hepatic masses, ovarian masses and renal stones, whereas non-localized pain was associated with abdominal free fluid and fluid-distended bowel loops. DISCUSSION: A high percentage of US examinations identified conditions that could possibly cause abdominal pain. Diagnostic yield of abdominal US was higher in elderly and very elderly patients. When a US examination is requested, it should always be evaluated within the clinical context. The physician should be aware of the great value of abdominal US in the diagnosis of the various causes of abdominal pain, but also of its possible limitations.
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AIM: The clinical evaluation of patients with chronic diarrhea and/or abdominal pain requires a complex work-up. The aim of the study was to evaluate whether routine duodenal biopsy sampling of macroscopically normal mucosa of patients with irritable bowel syndrome-like symptoms undergoing upper endoscopy assists in diagnosis and management. METHODS: Consecutive adults scheduled for upper endoscopy for evaluation of uninvestigated dyspepsia and abdominal pain and/or chronic diarrhea based upon the history, were enrolled. Gastric biopsies and 3 duodenal biopsies were taken for histological evaluation. RESULTS: A total of 786 sets of biopsies from 262 consecutive patients (200 females and 62 males, mean age 46 years; range: 15-82), were analyzed. Microscopic damage was observed in 212 of 262 patients (81%) with normal mucosa. Mild to moderate and severe duodenitis or villi atrophy was histologically confirmed in 65%, 26% and 8% of 212 patients respectively. The negative predictive value of a normal appearing duodenal mucosa was 19%. Additional tests confirmed celiac disease in 12 patients. Lactose malabsorption was present in 42%, bacterial overgrowth in 14%, and H. pylori infection in 28%. Colonoscopy performed in 92 patients revealed non specific colitis (25%), microscopic colitis (28%), Crohn's disease (1%), and diverticulosis (15%). CONCLUSION: Duodenal biopsies revealed abnormalities in the majority of adults with chronic diarrhea and/or abdominal pain despite macroscopically normal gross findings. These results suggest that duodenal biopsies could be helpful in patients with chronic diarrhea and/or abdominal pain for the following work up.
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Biópsia/métodos , Duodenite/patologia , Duodeno/patologia , Síndrome do Intestino Irritável/patologia , Estômago/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/diagnóstico , Colonoscopia , Feminino , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/patologia , Intolerância à Lactose/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer. AIM: Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells. MATERIAL AND METHODS: We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis. RESULTS: Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression. CONCLUSION: Zol may affect cancer cells also by targeting the gene expression of STEAP.
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Antígenos de Neoplasias/metabolismo , Conservadores da Densidade Óssea/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Difosfonatos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Oxirredutases/metabolismo , Neoplasias da Próstata/fisiopatologia , RNA Mensageiro/metabolismo , Antígenos de Neoplasias/genética , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Oxirredutases/genética , RNA Mensageiro/genética , Ácido ZoledrônicoRESUMO
Primary hyperparathyroidism (PHPT) is a common endocrine disease. High levels of PTH cause demineralization of bone and increased risk of fracture. On the other hand, the effect of PHPT on bone structure is more ambiguous. The aim of this study was to evaluate the effect of PHPT on cancellous bone volume, structure, and microarchitecture. Thirteen transiliac biopsy specimens taken in untreated post-menopausal women aged 65+/-5 yr with primary hyperparathyroidism were compared with 13 biopsies taken in normal women aged 66+/-6 yr. None of the patients presented any other disorder affecting bone metabolism. In these samples we evaluated the direct and indirect histomorphometric parameters of bone microarchitecture using an image analysis system consisting of an epifluorescent microscope (Leica DMR) connected to an analogic 3 CCD camera (Sony DXC 390P) and a computer equipped with specific software for histomorphometric analyses. No significant differences between PHPT patients and controls in cancellous bone volume, trabecular thickness, and number were found. Two-dimensional parameters showed a preserved microarchitecture in PHPT patients. On the other hand, indirect parameters of microarchitecture [Marrow Star Volume (MSV) and Trabecular Bone Pattern Factor (TBPf)] showed a significant compromising of microarchitecture in these patients. PHPT patients have similar structural parameters to normal subjects. Concerning microarchitecture, indirect approach by MSV and TBPf shows a significant compromising of connectivity. These results can explain trabecular fragility observed in clinical studies on PHPT.
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Hiperparatireoidismo Primário/patologia , Ílio/anatomia & histologia , Idoso , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Feminino , Humanos , Hiperparatireoidismo Primário/fisiopatologia , Ílio/fisiologia , Pessoa de Meia-Idade , Pós-Menopausa/fisiologiaRESUMO
UNLABELLED: Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1. CONTROL: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 mug/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 microg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31+/-1 vs 35+/-1%, p<0.05; Tb.Th: 43+/-2 vs 50+/-3 microm, p<0.01; Ac.f: 1.8+/-0.2 vs 1.6+/-0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.
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Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/patologia , Ácido Etidrônico/análogos & derivados , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Modelos Animais de Doenças , Ácido Etidrônico/farmacologia , Ácido Etidrônico/uso terapêutico , Feminino , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osteoporose/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ácido RisedrônicoRESUMO
Regenerative Medicine is a rapidly evolving field of therapy integrating different scientific and technological areas, including cell biology, biomedical and computer engineering, and clinical medicine, thus creating an interdisciplinary exchange network of skill, ideas, materials and efforts between basic and clinical research. Even if significant achievements have been obtained particularly in Plastic Surgery, Ophthalmology and Orthopedics, the field is still experimental and so far has failed to meet the expectations. The present article reviews the major hurdles that are still hampering the translational "bench to bedside" process and limiting the availability of these innovative therapeutic tools.
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Órgãos Artificiais , Transplante de Células , Regeneração , Engenharia Tecidual , HumanosRESUMO
BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.
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Transplante de Medula Óssea/métodos , Hiperbilirrubinemia Hereditária/terapia , Regeneração Hepática , Condicionamento Pré-Transplante/métodos , Animais , Bilirrubina/metabolismo , Diferenciação Celular , Modelos Animais de Doenças , Sobrevivência de Enxerto , Hepatócitos/patologia , Hiperbilirrubinemia Hereditária/metabolismo , Hiperbilirrubinemia Hereditária/patologia , Circulação Hepática , Ratos , Ratos Gunn , Traumatismo por Reperfusão/patologia , Resultado do TratamentoRESUMO
AIM: Diabetic patients should understand their disease correctly and be sure of what they know, but certainty is rarely considered by educators. Furthermore little is known about how certainty changes with time after an educational intervention. To clarify this, in 38 patients with type 1 diabetes (0.3-36 years duration) we analysed the effect of a course on insulin use by administering a questionnaire before the course, after the course and 1 and 3 years later. METHODS: Answers, accompanied by a subjective estimate of the degree of certainty, were assigned to mastered knowledge (certainty>or=90%, correctness>or=90%), hazardous knowledge (certainty>or=90%, correctness
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/reabilitação , Conhecimentos, Atitudes e Prática em Saúde , Insulina/uso terapêutico , Educação de Pacientes como Assunto , Avaliação Educacional , Humanos , Ensino/métodosRESUMO
The increasing use of densitometric devices for assessing bone fragility has progressively strengthened the assumption that mass is the most important property determining bone mechanical competence. Nevertheless, structure and microarchitecture are relevant aspects of bone strength. The study of microarchitecture is based on the measure of width, number, and separation of trabeculae as well as on their spatial organization. There are several methods to assess bone architecture, particularly at the trabecular level. In particular, histomorphometry, based on the use of optical microscopy and on the principles of quantitative histology and stereology, evaluates microarchitecture two-dimensionally, even if these measures appear well correlated to the three-dimensional structure and properties of bone. In addition, new computerized methods allow the acquisition of more sophisticated measurements by means of a digitizer have been introduced to integrate the use of the microscope. These methods supply information on trabecular width as well as on its distribution and on the organization of the trabeculae in the marrow space. Microarchitecture seems to be a determinant of bone fragility independent of bone density and it is important for understanding the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) can provide an additional interpretation for the anti-fracture effect of such drugs. For instance, bisphosphonates and parathyroid hormone seem to preserve or even improve microarchitecture. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods used today.
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Densidade Óssea , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/patologia , Doenças Ósseas/fisiopatologia , Osso e Ossos/efeitos dos fármacos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/ultraestrutura , Difosfonatos/farmacologia , Fraturas Ósseas/patologia , Fraturas Ósseas/fisiopatologia , Ósteon/citologia , Ósteon/patologia , Histocitoquímica , Humanos , Processamento de Imagem Assistida por Computador , Osteoporose/patologia , Osteoporose/fisiopatologia , Hormônio Paratireóideo/farmacologia , RatosRESUMO
UNLABELLED: Helicobacterpylori (Hp) resistance to clarithromycin, one of the antibiotics most used to eradicate infection, is connected with the presence of a point mutation on the level of adenine at position 2143 or 2144 of 23S rRNA. AIM: The aim of the study is to evaluate of the presence of these mutation vs control clarithromycin resistant Hp strains present in North Sardinia; to verify the real association between the type of mutation and the resistance-level; to use easier molecular biology methods to quickly locate the resistance-associated mutations beginning with the bioptic material. The clarithromycin susceptibility of Hp isolates was tested by the E-test method (antibiotic assay). Genomic DNA of Hp strains was amplified using specific primers for the domain V. of ribosomic 23S rRNA and sequenced after the reaction with a primer within the fragment 23S. At the same time PCR-RFLP reliability was examined underlining the presence of these mutations with BsaI, BbsI, MboII restriction enzymes. Two mutations in 2143 (A- - G) and 2144 (A- - G) were found by domain V sequencing. The strains with mutation 2143 are characterized by a greater resistance level (MIC>64 g/ml) than those with mutation 2144 (MIC <64 g/ml). Restriction endonucleases BbsI and MboII recognise the site containing the mutation 2143 (A- - G), while BsaI recognise the mutation 2144 (A- - G). These methods might enable us to identify the presence of Hp directly from bioptic material and possible clarithromycin resistance and plan a suitable therapeutic strategy and consequently a better control of the infection.
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Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Helicobacter pylori/genética , Antibacterianos/farmacologia , Sequência de Bases , DNA Bacteriano/análise , Genótipo , Helicobacter pylori/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 23S/genéticaRESUMO
OBJECTIVE: Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population. METHODS: This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4-6 wk after therapy. Eradication was defined as no positive test. RESULTS: We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients. CONCLUSIONS: Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.
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Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Estudos Prospectivos , Tetraciclina/administração & dosagem , Tetraciclina/uso terapêuticoRESUMO
Chronic hepatitis may progress to cirrhosis and hepatocellular carcinoma (HCC). Progressive accumulation of mutations and genomic instability in chronic viral hepatitis might flag an increased risk of HCC development. Genomic instability at dinucleotide microsatellite loci in chromosomes 2, 13, and 17 and at 2 mononucleotide repeat loci was examined in liver tissues from 41 patients, including 30 without HCC (18 patients with chronic hepatitis and 12 with cirrhosis) and 11 with HCC. Genomic instability was detected in 51% of the 41 cases. Allelic imbalance at informative dinucleotide loci occurred in 37% of the cases. In 14 cases (34%), allelic imbalance was detected in chronic hepatitis or cirrhosis without HCC. Allelic imbalance at the chromosome 13 locus was detected in 50% of the cases of chronic hepatitis C. Allelic imbalance at the TP53 chromosome locus and/or at the chromosome 13 locus was significantly more frequent than alterations at the chromosome 2 locus (P =.026). Low-level microsatellite instability was found in 20% of all cases examined and high-level microsatellite instability in 3 patients (7.5%), including 2 cases of chronic hepatitis and 1 case of cirrhosis. Our results show that allelic imbalance occurs frequently in hepatitis-related HCC as well as in chronic hepatitis in patients without HCC. Allelic imbalance at the D13S170 chromosome 13 locus (13q31.2) occurs frequently in chronic hepatitis, suggesting that genomic alterations affecting the long arm of chromosome 13 might be used to monitor the natural progression of chronic hepatitis-associated liver carcinogenesis.
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Carcinoma Hepatocelular/genética , Hepatite B Crônica/genética , Hepatite C Crônica/genética , Neoplasias Hepáticas/genética , Perda de Heterozigosidade , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , DNA de Neoplasias/análise , Repetições de Dinucleotídeos , Feminino , Marcadores Genéticos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
The aim of this study was to evaluate the distribution and clinical significance of hepatitis C virus (HCV) genotypes in European patients with compensated cirrhosis due to hepatitis C (Child class A) seen at tertiary referral centres. HCV genotypes were determined by genotype-specific primer PCR in 255 stored serum samples obtained from cirrhotics followed for a median period of 7 years. Inclusion criteria were biopsy-proven cirrhosis, absence of complications of cirrhosis and exclusion of all other potential causes of chronic liver disease. The proportion of patients with types 1b, 2, 3a, 1a, 4 and 5 were 69%, 19%, 6%, 5%, 0.5% and 0.5%, respectively. Kaplan-Meier 5-year risk of hepatocellular carcinoma (HCC) was 6% and 4% for patients infected by type 1b and non-1b, respectively (P=0.8); the corresponding figures for decompensation were 18% and 7% (P=0.0009) and for event-free survival were 79% and 89% (P=0.09), respectively. After adjustment for baseline clinical and serological features, HCV type 1b did not increase the risk for HCC [adjusted relative risk=1.0 (95% confidence interval=0.47-2.34)], whereas it increased the risk for decompensation by a factor of 3 (1.2-7.4) and decreased event-free survival by a factor of 1.7 (0.9-3.10). In conclusion, type 1b and, to a lesser extent, type 2, are the most common HCV genotypes in European patients with cirrhosis. HCV type 1b is not associated with a greater risk for HCC, but increases the risk for decompensation by threefold in patients with cirrhosis.
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Hepacivirus/genética , Hepatite C/epidemiologia , Cirrose Hepática/virologia , Adulto , Fatores Etários , Idoso , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Intervalo Livre de Doença , Europa (Continente)/epidemiologia , Feminino , Hepacivirus/química , Hepacivirus/classificação , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , RNA Viral/genética , Fatores Sexuais , Estatísticas não Paramétricas , Reação Transfusional , Resultado do TratamentoRESUMO
OBJECTIVES: When and how Helicobacter pylori (H. pylori) originally entered the human population as well as how the infection is transmitted in different communities is unknown. We previously showed that Sardinian shepherds had almost a 100% prevalence of H. pylori and that the prevalence was higher than that of their same-household siblings. AIM: To examine whether H. pylori infection might be transmitted from sheep. METHODS: Milk and gastric tissue were cultured and analyzed by PCR amplification using three sets of primers Helicobacter genus-specific 16S rRNA and two sets of primers specific for H. pylori vacA gene. RESULTS: Helicobacter DNA was demonstrated in 60% (38/63) of milk samples and in 30% (6/20) of sheep tissue samples. H. pylori vacA gene was amplified in five of 38 milk samples, and in two of six sheep tissue samples respectively. H. pylori were cultured from sheep milk and tissue samples and confirmed as H. pylori on the basis of colony morphology, positive biochemical reactions, and negative Gram stain. Sequence analysis of 16S rRNA PCR products from these isolates demonstrated 99% identity with H. pylori. CONCLUSIONS: Together, the presence of H. pylori in sheep stomach in the absence of associated gastritis and recovery of H. pylori from sheep milk and gastric tissue suggest that sheep may be a natural host for H. pylori.