RESUMO
OBJECTIVES: To correlate hepatic and splenic CT perfusion parameters with hepatic venous pressure gradient (HVPG) measurements in patients with cirrhosis. METHODS: Twenty-one patients with cirrhosis (males, 17; females, 4; mean ± SD age, 57 ± 7 years) underwent hepatic and splenic perfusion CT on a 320-detector row volume scanner as well as invasive measurement of HVPG. Different CT perfusion algorithms (maximum slope analysis and Patlak plot) were used to measure hepatic arterial flow (HAF), portal venous flow (PVF), hepatic perfusion index (HPI), splenic arterial flow (SAF), splenic blood volume (SBV) and splenic clearance (SCL). Hepatic and splenic perfusion parameters were correlated with HVPG, and sensitivity and specificity for detection of severe portal hypertension (≥12 mmHg) were calculated. RESULTS: The Spearman correlation coefficient was -0.53 (p < 0.05) between SAF and HVPG, and -0.68 (p < 0.01) between HVPG and SCL. Using a cut-off value of 125 ml/min/100 ml for SCL, sensitivity for detection of a HVPG of ≥12 mmHg was 94%, and specificity 100%. There was no significant correlation between hepatic perfusion parameters and HVPG. CONCLUSION: CT perfusion in patients with cirrhosis showed a strong correlation between SCL and HVPG and may be used for detection of severe portal hypertension. KEY POINTS: ⢠SAF and SCL are statistically significantly correlated with HVPG ⢠SCL showed stronger correlation with HVPG than SAF ⢠125 ml/min/100 ml SCL-cut-off yielded 94 % sensitivity, 100 % specificity for severe PH ⢠HAF, PVF and HPI showed no statistically significant correlation with HVPG.
Assuntos
Hipertensão Portal/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Veia Porta/diagnóstico por imagem , Baço/diagnóstico por imagem , Algoritmos , Feminino , Veias Hepáticas , Humanos , Fígado/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão , Pressão na Veia Porta , Sensibilidade e Especificidade , Baço/irrigação sanguínea , Tomografia Computadorizada por Raios XRESUMO
There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.
Assuntos
Hepacivirus/fisiologia , Hepatite Viral Humana/terapia , Transplante de Fígado , Fígado/efeitos dos fármacos , Sirolimo/administração & dosagem , Estudos de Coortes , Seguimentos , Hepatite Viral Humana/imunologia , Hepatite Viral Humana/mortalidade , Hepatite Viral Humana/patologia , Hepatite Viral Humana/fisiopatologia , Humanos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Transaminases/genética , Transaminases/metabolismo , Carga Viral/efeitos dos fármacos , Ativação Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Listas de EsperaAssuntos
Fístula Biliar/etiologia , Colangite Esclerosante/etiologia , Colestase Intra-Hepática/etiologia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Fístula Biliar/patologia , Fístula Biliar/cirurgia , Colangiografia , Colangite Esclerosante/patologia , Colangite Esclerosante/cirurgia , Colestase Intra-Hepática/patologia , Colestase Intra-Hepática/cirurgia , Drenagem , Humanos , Imunossupressores/uso terapêutico , Transplante de Fígado , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , ReoperaçãoRESUMO
From the synthetic point of view the fast developing fields of medicine and biology offer new opportunities for the design of very effective drugs with high selectivity. Especially in the field of anticancer therapy many efforts have been made to deliver drugs to specific tissues. Sugar substituted porphyrin compounds, bile acid conjugates, and pH-sensitive immunoliposomes are only some examples. Although there are many different approaches to exploit biomolecules as shuttles only a start has been made. Since the targeting of a drug is a very complex process, a successful design of a new compound has to consider chemical as well as biological aspects and requires a multidisciplinary cooperation with physicians and biologists. Three interesting concepts are evaluated exemplarily: antibodies, molecules with binding affinity to hormone receptors, and bile acids. The main issues are: selection of the drug and the carrier, ways of linking the pharmacological active compound to the biomolecule, the optimal way of linking the drug to the spacer, and cytotoxicity, apoptosis, and drug resistance.
Assuntos
Antineoplásicos/química , Metais Pesados/química , Compostos Organometálicos/química , Animais , Anticorpos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Ácidos e Sais Biliares/química , Ligação Competitiva , Sequência de Carboidratos , Desenho de Fármacos , Humanos , Dados de Sequência Molecular , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/uso terapêuticoRESUMO
This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue.