RESUMO
The use of needle-knife sphincterotomy has become an established technique for precut sphincterotomy to achieve am otherwise inaccessible bile duct. The present case report describes an accidental cannulation of the proper hepatic artery following needle-knife sphincterotomy. The endoscopic retrograde cholangiopancreaticography (ERCP) was performed for diagnosis and treatment of a pancreatitis presumably caused by cholelithiasis. After guide-wire placement and angiography of the artery through the papilla, there were no further complications. The distance between the catheter and the hepatic hilus was seen under X-ray control.
Assuntos
Cateterismo/instrumentação , Cateterismo/métodos , Artéria Hepática/diagnóstico por imagem , Erros Médicos/prevenção & controle , Esfincterotomia Transduodenal/métodos , Humanos , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
BACKGROUND: With an increasing role of the patient as a partner in making a combined decision in care plan goals, it is important to identify the patient's perspective of the experience of removal of catheter (ROC). METHODS: A non-consecutive prospective randomized study was performed in 84 patients who underwent a transurethral resection of the prostate to determine the impact of midnight versus early-morning ROC on sleep deprivation, over all discomfort to the patient. RESULTS: There was no difference in the patient experience in both groups. We found a reduced frequency during the first 6 h of ROC at midnight. However, there was an increased incidence of sleep disturbances in this group. This may in part be due to an anxiety of urge incontinence and may be allayed by appropriate counselling. There was no delay in discharge of the patients in both groups. CONCLUSION: The patients must, therefore, be given the choice of ROC either at midnight or early morning, as the advantages of a reduced frequency must be correlated with an increased incidence of sleep disturbances.
Assuntos
Agendamento de Consultas , Remoção de Dispositivo , Cuidados Pós-Operatórios , Prostatectomia/enfermagem , Idoso , Humanos , Masculino , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/enfermagem , Estudos Prospectivos , Prostatectomia/efeitos adversos , Doenças Prostáticas/cirurgia , Cateterismo Urinário/instrumentação , Cateterismo Urinário/enfermagem , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Micção/fisiologiaAssuntos
Injúria Renal Aguda/etiologia , Aneurisma da Aorta Torácica/complicações , Dissecção Aórtica/complicações , Dor Lombar/etiologia , Oligúria/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/cirurgia , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular , Diagnóstico Diferencial , Humanos , Dor Lombar/diagnóstico , Dor Lombar/cirurgia , Masculino , Pessoa de Meia-Idade , Oligúria/diagnóstico , Oligúria/cirurgia , Tomografia Computadorizada por Raios XRESUMO
The internalizing anti-Le(y) monoclonal antibody (MAb) BR64 was conjugated to the anticancer drug doxorubicin (DOX) using an acid-labile hydrazone bond to the DOX and either a disulfide or thioether bond to the MAb. The resulting disulfide (BR64-SS-DOX) and thioether (BR64-S-DOX) conjugates were evaluated for stability, potency, and antigen-specific activity in both in vitro and in vivo model systems. The BR64-SS-DOX conjugates demonstrated antigen-specific activity both in vitro and when evaluated against antigen-expressing, DOX-sensitive human carcinoma xenografts. However, the stability and potency of disulfide conjugates were poor, and in vivo activity superior to unconjugated DOX was seen only at doses approaching the maximum tolerated dose. Furthermore, BR64-SS-DOX conjugates were not active against antigen-expressing, DOX-insensitive colon tumor xenografts. In contrast, the BR64-S-DOX conjugates demonstrated good stability both in vitro and in vivo. The increased stability of the BR64-S-DOX conjugates resulted in the delivery of more biologically active DOX to tumors with a concomitant increase in potency and efficacy over that which could be achieved with either unconjugated DOX or BR64-SS-DOX conjugates. Delivery of DOX by BR64-SS-DOX conjugates resulted in complete regressions and cures of both DOX-sensitive lung xenografts and DOX-intensitive colon tumor xenografts. These results demonstrate the importance of linker stability when delivering drugs such as DOX to carcinomas via internalizing antibodies and are likely to have direct relevance to the clinical utility of MAb-directed delivery.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Anticorpos Monoclonais/farmacologia , Antígenos de Neoplasias/imunologia , Doxorrubicina/farmacologia , Imunoconjugados/farmacologia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacocinética , Ensaios de Seleção de Medicamentos Antitumorais , Epitopos/imunologia , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
A new cytotoxic N-hydroxypyridone, fusaricide (1), was isolated from a Fusarium sp. Its structure was solved by X-ray diffraction and spectroscopic analyses.
Assuntos
Antineoplásicos/isolamento & purificação , Benzopiranos/isolamento & purificação , Fusarium/química , Piridonas/isolamento & purificação , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Cristalografia por Raios X , Fungos/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Piridonas/farmacologia , Células Tumorais Cultivadas , Vírion/efeitos dos fármacosRESUMO
During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol-methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0 microM and 7.6 microM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200 micrograms/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38 microM against the murine tumor cell line M-109.
Assuntos
Fármacos Anti-HIV/metabolismo , Benzopiranos/metabolismo , Butiratos/metabolismo , Produtos do Gene rev/metabolismo , Quinolizinas/metabolismo , Trichoderma/metabolismo , Fármacos Anti-HIV/química , Benzopiranos/química , Butiratos/química , Linhagem Celular , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Ligação Proteica , Quinolizinas/química , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
During the screening of natural products for their ability to inhibit the binding of HIV-REV protein to [33P]-labeled RRE RNA, one novel compound, niruriside (1), was isolated from the MeOH extract of the dried leaf of Phyllanthus niruri L. by bioassay-guided fractionation. The structure of niruriside was determined by spectroscopic methods. Niruriside showed specific inhibitory activity against the binding of REV protein to RRE RNA with an IC50 value of 3.3 microM; however, niruriside did not protect CEM-SS cells from acute HIV infection at concentrations up to 260 microM using an XTT dye reduction assay.
Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Cinamatos/isolamento & purificação , Cinamatos/farmacologia , Dissacarídeos/isolamento & purificação , Dissacarídeos/farmacologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Produtos do Gene rev/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Folhas de Planta/química , Plantas Medicinais/química , Antivirais/química , Ligação Competitiva , Cinamatos/química , Dissacarídeos/química , Produtos do Gene rev/genética , HIV-1/genética , Humanos , Índia , Leucemia de Células T , Extratos Vegetais/química , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , RNA Viral/efeitos dos fármacos , Células Tumorais Cultivadas , Produtos do Gene rev do Vírus da Imunodeficiência HumanaRESUMO
Granulocyte-macrophage (GM)-CSF is an important hematopoietic cytokine that regulates proliferation and differentiation of macrophages, neutrophils, and eosinophils. In this study, we generated mAb to five synthetic peptides that correspond to regions along the murine GM-CSF molecule. The ability of anti-peptide mAb to bind to and inhibit biologic activity of murine (m) GM-CSF was determined. mAb with the highest neutralization titers were derived from mice immunized with peptide II, which correspond to amino acids 27 to 38 of mGM-CSF. Immunochemical studies showed that peptide II specifically blocked binding of anti-peptide II mAb to GM-CSF. mAb to two other peptides in the N-terminal half corresponding to residues 7 to 17 and 47 to 58, respectively, of mGM-CSF also inhibited GM-CSF-dependent proliferation and differentiation of murine bone marrow precursors for macrophages and granulocytes. Anti-peptide mAb also inhibited growth of a murine hematopoietic cell line FDCP1 and a murine T cell line HT-2, which was shown to be dependent on GM-CSF for growth in vitro. Biologic activity of both natural and recombinant mGM-CSF was neutralized by anti-peptide mAb. These findings indicate that epitopes in the N-terminal region of mGM-CSF are important for biologic activity, and the epitope defined by peptide II (residues 27 to 38) lies within a particularly important functional domain of the mGM-CSF molecule.
Assuntos
Anticorpos Monoclonais/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Fragmentos de Peptídeos/fisiologia , Sequência de Aminoácidos , Animais , Células da Medula Óssea , Linhagem Celular , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/química , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Hibridomas , Immunoblotting , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Ratos , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade , Linfócitos T/citologiaRESUMO
We have made antigen-specific cytotoxic reagents by conjugating the chimeric antibody BR96 (chiBR96) to Pseudomonas exotoxin A (PE), as either native PE or a truncated form (LysPE40) devoid of the cell-recognition region (domain I). PE kills cells by ADP-ribosylation of elongation factor 2, thereby inhibiting protein synthesis. Chimeric BR96 immunotoxins were constructed by chemical conjugation of the toxin to Fab', F(ab')2, and intact IgG and purified by anion-exchange and gel-filtration chromatography. Chimeric BR96 [IgG and F(ab')2] immunotoxins were cytotoxic against tumor cell lines displaying the BR96 antigen, with EC50 values ranging from 0.1 to 110 pM. Immunotoxins constructed with chiBR96 Fab' were 50-100-fold less cytotoxic. Competition analysis showed that the immunotoxins were specifically active through their BR96 antigen-binding ability. The binding of chiBR96-PE and chiBR96-LysPE40 to antigen was equivalent to that of BR96 itself and these immunotoxins were found to internalize very rapidly, displaying 90% of their cytotoxicity within 1 h. Binding assays determined that chiBR96 F(ab')2-LysPE40 bound as well as chiBR96-LysPE40; however, chiBR96 Fab'-LysPE40 bound 20-fold less efficiently. The chiBR96 Fab'-LysPE40 internalized similarly to the F(ab')2 or the IgG immunotoxins. Therefore, the chiBR96 Fab'-LysPE40 immunotoxin is less cytotoxic toward target cells because of reduced antigen binding. This is may be due to the monovalent nature of chiBR96 Fab'-LysPE40. This study shows that the monoclonal antibody chiBR96-Pseudomonas exotoxin A immunotoxins can be effective at inhibiting protein synthesis in target cells.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/química , Exotoxinas/toxicidade , Fragmentos Fab das Imunoglobulinas/imunologia , Imunoglobulina G/química , Imunotoxinas/toxicidade , Pseudomonas , Animais , Anticorpos Monoclonais/química , Especificidade de Anticorpos , Ligação Competitiva/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Exotoxinas/química , Humanos , Fragmentos Fab das Imunoglobulinas/química , Imunoglobulina G/imunologia , Imunotoxinas/química , Imunotoxinas/imunologia , Indicadores e Reagentes , Camundongos , Proteínas de Neoplasias/biossíntese , PlasmídeosRESUMO
Adriamycin hydrazone (ADM-Hzn) immunoconjugates have previously been shown to exhibit antibody-directed antitumor activity in vitro and in vivo. In this report, the biological and biochemical properties of the mAb and linker were investigated. Conjugates prepared with two antibodies 5E9 [anti-(transferrin receptor)] and G28.1 (anti-CD37), (which internalize from the surface of target cells following binding) were more cytotoxic in vitro and had greater antitumor activity against Daudi B lymphoma tumor xenografts than a non-internalizing immunoconjugate prepared with mAb 2H7 (anti-CD20). In addition, the 13-acylhydrazone bond linking the drug to the mAb was labile at pH 5 and released unmodified ADM at a rapid rate (t1/2 = 2.5 h). Immunoconjugates prepared with an oxime linkage at the C-13 position were stable to acid and were not cytotoxic. These findings suggest that internalization of ADM-Hzn immunoconjugates and release of free ADM from the mAb in acidic intracellular compartments were important steps in the mechanism of action of ADM-Hzn immunoconjugates.