RESUMO
BACKGROUND: Although there is evidence that exposure to tobacco smoke is harmful to children's respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)-mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting. METHODS: Children aged 5-18 years (N = 1315) were assessed using serum cotinine measurement and microarray-based multiplexed detection of specific IgE against 40 allergens. RESULTS: Serum cotinine levels were positively associated with sensitization to foods (adjusted odds ratio [AOR] = 4.95; 95% CI: 1.59-15.34), cockroaches (AOR = 3.77; 95% CI: 1.49-9.51), and pollen (AOR = 2.84; 95% CI: 1.20-6.73) while the association was borderline significant for animals (AOR = 2.53; 95% CI: 0.92-6.93). No associations were found for sensitization against mites, mold, and latex. When considering the degree of allergic sensitization, serum cotinine levels were positively correlated to the number of sensitization to cockroaches (P = 0.004), pollen (P = 0.006), and foods (P < 0.001), with statistically significant positive dose-response relationships (all P < 0.01). Similar results were observed when summing up specific IgE concentrations for the aforementioned allergen categories. CONCLUSIONS: The association between tobacco smoke exposure and IgE sensitization to environmental allergens varies for different allergens among children. This study demonstrates that elevated serum cotinine levels are significantly associated with IgE sensitization to cockroaches, grass pollen, and certain foods, with potential dose-dependent relationships.
Assuntos
Exposição Ambiental/efeitos adversos , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Imunoglobulina E/imunologia , Nicotiana/efeitos adversos , Fumaça/efeitos adversos , Adolescente , Alérgenos/imunologia , Animais , Criança , Pré-Escolar , Cotinina/sangue , Feminino , Humanos , Imunização , Imunoglobulina E/sangue , Masculino , Razão de Chances , Vigilância da População , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Septic shock is a major cause of morbidity and mortality in intensive care units, but there is still no effective therapy for the patients. We evaluated the effects of rhodostomin (Rn), an Arg-Gly-Asp-containing snake venom disintegrin, on lipopolysaccharide (LPS)-activated phagocytes in vitro and LPS-induced endotoxemia in vivo. METHODS AND RESULTS: Rn inhibited adhesion, migration, cytokine production and mitogen-activated protein kinase (MAPK) activation of macrophage induced by LPS. Flow cytometric analysis revealed that Rn specifically blocked anti-αv mAb binding to RAW264.7. Besides inhibiting MAPK activation of THP-1, Rn bound to LPS-activated THP-1 and specifically blocked anti-αvß3 mAb binding to THP-1. Binding assays proved that integrin αvß3 was the binding site for rhodostomin on phagocytes. Rn reversed the enhancement of fibronectin and vitronectin on LPS-induced monocyte adhesion and cytokine release. Transfection of integrin αv siRNA also inhibited LPS-induced activation of monocyte, and Rn exerted no further inhibitory effect. Furthermore, Rn significantly decreased the production of tumor necrosis factor-α (TNF-a), interleukin (IL)-6, -1ß and -10 and attenuated cardiovascular dysfunction, including blood pressure and heart pulse, and thrombocytopenia in LPS-induced endotoxemic mice. Rn also protected against tissue inflammation as evidenced by histological examination. CONCLUSIONS: Rn may interact with αvß3 integrin of monocytes/macrophages leading to interfere with the activation of phagocytes triggered by LPS. These results suggest that the protective function of Rn in LPS-induced endotoxemia may be attributed to its anti-inflammation activities in vivo.
Assuntos
Endotoxemia/tratamento farmacológico , Endotoxemia/fisiopatologia , Integrina alfaVbeta3/fisiologia , Peptídeos/farmacologia , Animais , Sítios de Ligação , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Citocinas/biossíntese , Desintegrinas/farmacologia , Humanos , Integrina alfaVbeta3/antagonistas & inibidores , Integrina alfaVbeta3/genética , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fagócitos/efeitos dos fármacos , Fagócitos/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , Trombocitopenia/sangue , Trombocitopenia/tratamento farmacológicoRESUMO
The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31%) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias do Timo/metabolismo , Adolescente , Adulto , Idoso , Envelhecimento/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/etiologia , Miastenia Gravis/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Timoma/complicações , Timoma/metabolismo , Timoma/patologia , Timo/crescimento & desenvolvimento , Timo/metabolismo , Neoplasias do Timo/complicações , Neoplasias do Timo/patologia , Regulação para CimaRESUMO
The adult spleen is a source of early hematopoietic stem cells (HSC). We therefore studied whether culturing spleen or bone marrow (BM) HSC in medium containing 5-azacytidine could induce a cardiac phenotype. c-kit enrichment and depletion of adult pig spleen and BM mononuclear cells were obtained by magnetic bead separation using biotinylated pig stem cell factor (c-kit ligand). Cells were incubated with 5-azacytidine for 24 h and refreshed with 5-azacytidine-free medium every 48 h. Western blot was used to detect cardiac troponin and myosin heavy chains. Although 5-azacytidine treatment led to the formation of ball-like cell clusters in both c-kit-enriched populations, these clusters showed no rhythmic contractions (beating), as observed by others. Furthermore, neither cardiac troponin nor myosin was detected in cells derived from either source. Our methodology and treatment with 5-azacytidine did not induce cardiac gene expression in porcine HSC derived from either pig spleen or BM.
Assuntos
Azacitidina/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Miocárdio/citologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Animais , Western Blotting , Células da Medula Óssea/citologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Hematopoese , Separação Imunomagnética , Miosinas/deficiência , Proteínas Proto-Oncogênicas c-kit/genética , Baço/citologia , Suínos , Troponina I/deficiênciaAssuntos
Transplante de Coração/efeitos adversos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/cirurgia , Papio , Suínos , Animais , Antitrombinas/metabolismo , Ligante de CD40/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Transplante Heterólogo , Troponina T/sangueRESUMO
Other than from the thalamus and sensory cortex, episodic pain is an extremely rare neurological manifestation in the central compartment. This study reports a middle-aged man who experienced an acute onset of episodic oscillatory burning pain restricted to the cheiro-oral region, who was found to have a singular infarct at the left tegmental pons. A close relationship between his pain attack and an elevation of arterial blood pressure was clearly observed. Blood adenohypophyseal hormones and electroencephalogram did not reveal an abnormality in the ictus. Neuroimaging and clinical studies did not support involvement of the thalamus, periaqueductal gray matter, hypothalamus or regional structure. Therefore, episodic pain may be an isolated manifestation with a pontine lesion. A relapsing expansion of focal cerebral oedema with fluid retention may have corresponded to the oscillation of his sensory deficit. This accumulating, devastating calamity by a repetitive and paroxysmal offense after a blood-brain barrier breakdown should be cautiously reviewed.
Assuntos
Infartos do Tronco Encefálico/complicações , Mãos/inervação , Boca/inervação , Dor/etiologia , Doença Aguda , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Periodicidade , Ponte , SíndromeRESUMO
BACKGROUND: The aim of this study was to investigate the hypothesis that outcome following concomitant airway resection is superior to that after shaving of the tumour in patients with airway invasion of thyroid carcinoma. METHODS: The records of 34 patients with thyroid cancer with airway invasion were reviewed retrospectively. In addition to total thyroidectomy, airway resection was performed in 18 patients (group 1), whereas the tumour was shaved away from the airway in the other 16 patients (group 2). 131I was used as postoperative adjuvant therapy in all patients. Metastasis and recurrence of the primary lesion were determined by 131I whole-body scans, serum thyroglobulin levels, and computed tomography or ultrasonography of the neck. RESULTS: In group 1, two anastomotic dehiscences resulted in one death. Patients in group 2 had a higher rate of local recurrence (relative risk 8.0, P = 0.013) and earlier recurrence (mean(s.e.m.) 2.6(0.8) versus 7.0(1.1) years; P = 0.026) than those in group 1. Median survival was 5.8 and 4.3 years in the 18 patients of group 1 and 16 patients of group 2 (P = 0.259), and the respective 5-year survival rates were 88 and 84 per cent (P = 0.783). CONCLUSION: Aggressive airway resection can minimize local recurrence of thyroid carcinoma with airway invasion.
Assuntos
Neoplasias Brônquicas/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Brônquicas/mortalidade , Neoplasias Brônquicas/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/prevenção & controle , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for alpha1,3-galactosyltransferase gene-knockout (GalT-KO). METHODS: Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. RESULTS: A mean of 11 x 10(8) BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days 1, 2 and 4, respectively, were 641/microl (9.5%), 132/microl (3.4%), 242/microl (3.9%), and 156/microl (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (<1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. CONCLUSIONS: By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved.
Assuntos
Transplante de Medula Óssea , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Deleção de Genes , Papio , Suínos , Animais , Animais Geneticamente Modificados , Anticorpos/imunologia , Medula Óssea/imunologia , Transplante de Medula Óssea/imunologia , Quimerismo , Galactosiltransferases/imunologia , Leucócitos/imunologia , Teste de Cultura Mista de Linfócitos , Papio/imunologia , Reação em Cadeia da Polimerase , Suínos/genética , Condicionamento Pré-Transplante , Transplante HeterólogoRESUMO
Theoretically, the jejunum, fasciocutaneous or myocutaneous flap is recommended as an esophageal substitute in redoing reconstruction of the esophagus after a second incidence of corrosive injury. However, other esophageal substitutes should also be considered. We present a case of a 42-year-old woman who underwent esophageal reconstruction using an ileocolon graft for corrosive esophageal stricture ten years before. The patient ingested caustic drain cleaner again and underwent resection of the ileocolon graft secondary to corrosive necrosis. Two and a half months after the second incidence of corrosive injury, reconstruction of the esophagus was again performed using a graft of remnant ileo-left colon aided by microvascular anastomosis. The patient was able to swallow a regular diet after the procedure. Remnant ileo-left colon is a good alternative esophageal substitute in cases of repeated corrosive injury.
Assuntos
Anastomose Cirúrgica/métodos , Queimaduras Químicas/cirurgia , Colo/transplante , Estenose Esofágica/induzido quimicamente , Esofagectomia/métodos , Íleo/transplante , Microcirurgia/métodos , Complicações Pós-Operatórias/cirurgia , Adulto , Cáusticos , Estenose Esofágica/cirurgia , Feminino , Humanos , Necrose , Tentativa de SuicídioRESUMO
BACKGROUND: Compared with free drug, sterically stabilized liposomal drug has prolonged circulation time and, thereby, higher tumor selectivity and antitumor activity. The stability in plasma is an important consideration in the formulation of clinically useful liposomal drug. A Phase I study of a stable liposomal doxorubicin with polyethylene glycol (PEG) coating and phospholipid component of distearoyl phosphatidylcholine (DSPC) was performed to characterize its pharmacokinetic properties, toxicity profile, and maximal tolerated dose. METHODS: The starting dose was 30 mg/m(2) every 3 weeks with an increment of 10 mg/m(2) for each level. A cohort of at least three patients was entered for each level. Dose escalation stopped when more than one-third of patients had dose limiting toxicity (DLT), which was equal to or more than Grade 3 nonhematologic toxicity. Blood was sampled immediately before and at 5 minutes, 2 hours, 4 hours, 10 hours, 24 hours, 48 hours, 72 hours, and 168 hours after the completion of PEGylated liposomal doxorubicin (PLD) infusion. Plasma level of doxorubicin was determined with fluorometry, and the pharmacokinetic properties were analyzed. RESULTS: Twenty-six patients were entered, and 101 courses were studied. This DSPC PLD had a steady-state distribution volume (Vss) of 2.4 +/- 0.9 liters (mean +/- standard deviation), a clearance of 0.027 +/- 0.010 liters per hour, and a beta half-life of 65.0 +/- 17.8 per hour. These characteristics were dose independent, and the Vss and clearance were smaller than those of a well characterized PLD comprised of hydrogenated soybean phosphatidylcholine (HSPC). At the dose level of 50 mg/m(2), its plasma area under the concentration time curve was approximately twice that of HSPC PLD. Attenuation of acute toxicity, such as nausea, emesis, and alopecia, was noted in all dose levels. However, stomatitis was common from the dose level of 30 mg/m(2), and its incidence and severity increased with dosage and became dose limiting at 50 mg/m(2). A dose of 45 mg/m(2) every 3 weeks was then given in eight patients, and the side effects were acceptable. This dose was recommended for Phase II clinical trials. Fourteen of 17 patients with a dose level > or = 40 mg/m(2) were evaluable for response, but none achieved partial remission. CONCLUSIONS: This DSPC PLD had the characteristics of second-generation liposomal drug pharmacokinetically and toxicologically. The incidence of severe stomatitis was higher than that of HSPC PLD, corresponding to the difference in pharmacokinetics. Only limited antitumor activity was observed, although defining its therapeutic application will need further Phase II studies. Further prolongation of plasma stability of PLD may not be clinically beneficial considering the increased stomatitis and the reduced achievable dose intensity.
Assuntos
Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Neoplasias/metabolismo , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Leucopenia/etiologia , Lipossomos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to evaluate the surgical management results of lung abscess in immunocompetent and immunocompromised children. METHODS: Surgery was performed on 30 children with lung abscess or necrotizing pneumonia refractory to medical treatment in a 12-year period. Of them, 23 were immunocompetent, and 7 were immunocompromised. Pulmonary resection was performed including unilateral lung in 28, bilateral in 2, and 2 lobes in 6. Concomitant decortication was performed in 18 (78.2%) immunocompetent patients. RESULTS: Increased incidence of surgery for lung abscess was caused mainly by drug-resistant and fungal infection. Surgery was performed commonly for bacterial lung abscess on patients less than 5 years old and fungal lung abscess on adolescence. A multiple small abscess was the predominant type of abscess in immunocompetent patients, whereas 2-lobe involvement tended to occur in immunocompromised patients. Fungal lung abscess tended to occur on left lung and in female patients. Left lower lobe was involved most commonly in both groups of patients in which majority need lobectomy. Immunocompromised patients required a more extensive pulmonary resection. There were 3 postoperative complications (morbidity of 10.2%) with no postoperative mortality. Length of postoperative hospital stay ranged from 6 to 85 days with average of 18.4 days. CONCLUSIONS: The incidence and pattern of lung abscess that required surgery between immunocompetent and immunocompromised children were different. A more aggressive, extensive surgical procedure is preferable for immunocompromised patients, and the surgical results were comparatively excellent to immunocompetent patients. However, the prognosis of immunocompromised children depends on their underlying disease process.
Assuntos
Imunocompetência , Hospedeiro Imunocomprometido , Abscesso Pulmonar/cirurgia , Pneumonectomia/métodos , Pneumonia/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Abscesso Pulmonar/etiologia , Abscesso Pulmonar/imunologia , Abscesso Pulmonar/mortalidade , Masculino , Complicações Pós-Operatórias , Taiwan/epidemiologiaRESUMO
BACKGROUND: To elucidate the relationship between the expression of epidermal growth factor receptor family members (ErbB-1, neu/ErbB-2, ErbB-3, and ErbB-4) and tumor recurrence. METHODS: We used immunohistochemistry to examine the expression of four epidermal growth factor receptor family members in 73 patients with stage I non-small cell lung cancer. RESULTS: Using Cox univariate analysis, we determined that angiolymphatic tumor emboli and non-well-differentiated tumor cells were two significant conventional pathologic predictors of tumor recurrence, and that ErbB-1 and ErbB-3 were also significant predictors. Co-expression of ErbB-1+, -3+, or expression of three or more epidermal growth factor receptor family members had a significant effect on lung cancer recurrence. A stepwise multivariate Cox proportional hazards regression analysis provided a predictive model for tumor recurrence. CONCLUSIONS: The present study shows that in patients with a non-well-differentiated tumor, overexpression of ErbB-3 is a useful marker for predicting tumor recurrence. The present study also confirmed that ErbB-1 expression increased in proportion to the loss of tumor differentiation. The correlation between ErbB-3 and distant metastasis was good.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/análise , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptor ErbB-2/análise , Receptor ErbB-3/análise , Receptor ErbB-4RESUMO
BACKGROUND AND OBJECTIVE: Conventionally, pulmonary resection with thoracoplasty is used to treat fibrocavernous complication of pulmonary tuberculosis. This operation is usually bloody, time-consuming with complicated postoperative course. To prevent massive blood loss and preserved pulmonary function, a more simplified operative procedure, cavernostomy combined intrathoracic muscle flap transposition was used and the outcome was evaluated in this study. DESIGN: Retrospective review. METHODOLOGY: Between December 1989 and June 1996, a total of ten patients with fibrocavernous pulmonary tuberculosis were managed using cavernostomy combined with intrathoracic muscle flap transposition. Five of them had concomitant aspergilloma within the cavity while three had multiple drug resistant pulmonary tuberculosis. The muscle flap was used to plombage the cavity and reinforce the closure of bronchopleural fistula after cavernostomy. RESULTS: Six postoperative complications occurred in five patients, including reformation of cavity (2), bronchopleurocutaneous fistulae (3), and postoperative bleeding (1). The success or failure of intrathoracic muscle flap transposition on patients with fibrocavernous tuberculosis was significantly correlated with the size of the cavity (194.0+/-11.2 vs. 283.0+/-44.6 cm(3), P=0.016) and the number of bronchopleural fistulae (1.6+/-0.4 vs. 4.0+/-0.4, P=0.008). There was no operative death and in long term follow-up, there was no recurrence of hemoptysis or deterioration of pulmonary function in the successful group of patients. CONCLUSIONS: Cavernostomy combined with intrathoracic muscle flap transposition can be used to treat well-selected fibrocavernous pulmonary tuberculosis patients, except on patients with large size cavity, multiple bronchopleural fistulae or multiple drug resistance tuberculosis.
Assuntos
Procedimentos Cirúrgicos Pulmonares/métodos , Retalhos Cirúrgicos , Tuberculose Pulmonar/cirurgia , Adulto , Idoso , Fístula Brônquica/cirurgia , Feminino , Seguimentos , Hemoptise/etiologia , Hemoptise/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios , Fístula do Sistema Respiratório/cirurgia , Estudos Retrospectivos , Estatísticas não Paramétricas , Retalhos Cirúrgicos/estatística & dados numéricos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/complicaçõesRESUMO
BACKGROUND: There is lack of effective and safe chemotherapy for advanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) has long circulation time and enhanced drug accumulation in the tumor tissues. It has significant activity in Kaposi's sarcoma, breast and ovarian cancers and the acute adverse effects of free drug are reduced. PATIENTS AND METHODS: A patient with advanced hepatocellular carcinoma was treated with PLD and a pharmacokinetic study was performed. Initial serum total and direct bilirubin were 3.6 and 6.8 folds of upper normal, respectively, and an indocyanine green clearance test at 15 minutes was 26.3% (normal < 15%). RESULTS: Compared to cases with normal liver function, increased volume of distribution of doxorubicin correlated with a large amount of ascites (P < 0.05). The clearance of drug was unexpectedly higher than in cases with normal liver function (P < 0.05). According to the pharmacokinetic studies, the disposition of PLD in this case has not been retarded even in the presence of severe liver dysfunction. Only minimal toxicities including grade 2 stomatitis and moderate leukopenia were observed. The tumor had a partial remission and the patient survived nine months after PLD treatment. CONCLUSION: PLD could serve as a safe and effective treatment for hepatocellular carcinoma even in the presence of impaired liver function. Its role in treating advanced hepatocellular carcinoma is worthy of further study.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacocinética , Portadores de Fármacos , Evolução Fatal , Humanos , Lipossomos , MasculinoRESUMO
Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Área Sob a Curva , Peso Corporal/efeitos dos fármacos , Doxorrubicina/farmacocinética , Portadores de Fármacos , Lipossomos , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidiletanolaminas , Polietilenoglicóis , Distribuição TecidualRESUMO
A liposome containing diverse synthetic lipid derivatives of polyethylene glycol (PEG) results in smaller distribution volume and longer circulation time in blood and, thus, may improve drug targeting. The characteristics and therapeutic efficacy of immunoliposomes with similar liposomal formulation have never been studied in lymphoma models. We have developed immunoliposomes conjugated with S5A8 monoclonal antibody, an anti-idiotype antibody to 38C13 murine B-cell lymphoma, and loaded them with doxorubicin using an ammonium sulfate gradient. Purified antibodies were covalently coupled to the termini of PEG on the surface of small unilamellar liposomes. Cell binding and internalization ability of these immunoliposomes were estimated by a fluorescence assay using a pH-sensitive fluorescent dye (HPTS). The in vitro cytotoxicity of doxorubicin encapsulated in immunoliposomes was greater for idiotype-positive 38C13 cells than for the idiotype-negative variant of this cell line. In syngeneic C3H/HeN mice, doxorubicin encapsulated in immunoliposomes exhibited a long circulation time and was more effective at prolonging survival of mice bearing 38C13 tumor than non-targeted liposomal doxorubicin or free doxorubicin plus empty immunoliposomes. Our results demonstrate the superiority of targeted therapy with these immunoliposomes and its potential in lymphoma treatment.
Assuntos
Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Animais , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais , Doxorrubicina/farmacocinética , Portadores de Fármacos , Endocitose , Feminino , Lipossomos , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C3H , Fosfatidiletanolaminas , PolietilenoglicóisRESUMO
Giant polyps of the esophagus are relatively rare. Without previous history, the diagnosis of the disease is difficult to be made by esophagography and esophagoscopy. A case of giant intraluminal fibrovascular polyp (13x4x3.5 cm) of the esophagus is presented. The polyp was retrieved from the esophagus by a Foley's catheter and resected via the oral route.
Assuntos
Neoplasias Esofágicas/cirurgia , Pólipos/cirurgia , Adulto , Cateterismo , Endoscopia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Esofagoscopia , Feminino , Humanos , Pólipos/diagnóstico , Pólipos/patologiaRESUMO
This study was carried out in order to evaluate the surgical results of benign tracheobronchial diseases. Between July 1988 and March 1996, tracheobronchial surgery was performed on 29 patients with a variety of benign diseases. The primary diseases were post intubation or post tracheostomy tracheal stenosis (n = 12), tuberculous stenosis (n = 7), congenital tracheal stenosis with or without vascular ring (n = 4), tracheobronchial tumour (n = 2), oesophageal tumour (n = 1), and miscellaneous conditions (n = 3). Thirty-one operative procedures included sleeve lobectomy (n = 7), sleeve resection of trachea (n = 17) and bronchus (n = 2), and plastic surgery of trachea (n = 4) and bronchus (n = 1). There was one operative death, which put the mortality rate at 3.4%. There were five postoperative complications in this series (17.2%), including anastomotic disruption of trachea (n = 1), bilateral vocal cord palsy (n = 1), prolonged endotracheal intubation (n = 1) and overgrowth of granulation (n = 2). The complication of anastomotic disruption of trachea was treated by insertion of a tracheal T-tube, and the granulation was treated by bronchoscopic excision. We suggest that tracheobronchoplasty is a safe procedure in carefully selected patients with benign diseases.
Assuntos
Broncopatias/cirurgia , Complicações Pós-Operatórias , Doenças da Traqueia/cirurgia , Adolescente , Adulto , Broncopatias/diagnóstico , Broncopatias/mortalidade , Neoplasias Brônquicas/diagnóstico , Neoplasias Brônquicas/mortalidade , Neoplasias Brônquicas/cirurgia , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios/métodos , Taxa de Sobrevida , Taiwan , Doenças da Traqueia/diagnóstico , Doenças da Traqueia/mortalidade , Neoplasias da Traqueia/diagnóstico , Neoplasias da Traqueia/mortalidade , Neoplasias da Traqueia/cirurgia , Resultado do TratamentoRESUMO
The objective of this study was to evaluate the surgical results of tracheobronchial injuries. Between July 1988 and March 1996, tracheobronchial surgery was performed on 23 injured patients. According to the aetiology, the injuries were categorized as blunt injury (n = 13), cutting or penetrating injury (n = 5), and corrosive injury (n = 5). Blunt injuries included three complete laryngotracheal disruptions, one tracheal laceration, and eight bronchial ruptures. Cutting or penetration injuries included four laryngotracheal ruptures and one tracheal cutting wound. Corrosive injuries included one tracheal necrosis, one tracheal stenosis and three esophagorespiratory fistulae. Operative procedures that were performed on the tracheobronchus included tracheoplasty (n = 12), bronchoplasty (n = 7), sleeve resection of the trachea (n = 2) and bronchus (n = 2). Two hospital deaths were encountered, with a mortality rate of 8.7%. One patient with caustic injury died of bronchopleural fistula and empyema. The other patient died with multiple injuries from multiple organ failure which was unrelated to the bronchoplasty. One postoperative complication was restenosis of the trachea in a caustic injured patient, which was treated by a T-tube insertion. In conclusion, tracheobronchoplasty is an effective life-saving emergency procedure for the patients with tracheobronchial injuries.