RESUMO
Massive hernias of the abdominal wall present a major challenge to the general surgeon. In some extreme cases of patients with severe cardio-respiratory disease, the repair of such hernias may be impracticable. In these cases, we believe the volume transposition technique is appropriate. In this approach, the hernia volume is calculated and the wall repaired with mesh to accommodate the estimated volume of the hernia sac, thus avoiding any increase in intra-abdominal pressure. We believe this technique is simple, reproducible and useful in cases that are inoperable due to cardio-respiratory problems that make any loss of lung volume unacceptable.
Assuntos
Hérnia Ventral/diagnóstico por imagem , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Cavidade Peritoneal/diagnóstico por imagem , Implantação de Prótese/métodos , Tamanho Corporal , Feminino , Cardiopatias/complicações , Hérnia Ventral/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Respiratórias/complicações , Telas Cirúrgicas , Tomografia Computadorizada por Raios XRESUMO
The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, GSK2315698, Ro 63-8695), which depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specific recognition by subsequently administered therapeutic anti-SAP antibodies. Herein, we report a mechanistic model that predicts, with clinically acceptable precision, the exposure-response relationship for CPHPC, both in healthy individuals and in patients with systemic amyloidosis. The model covariates are gender, renal function, total amyloid load, and presence of hepatic amyloid, all of which are known at baseline. The model is being used to predict individualized dosing regimens in an ongoing, first-in-human study with anti-SAP antibodies.
RESUMO
Swimming is beneficial for persons with haemophilia (PWH) providing good maintenance of the cardiovascular and musculoskeletal system and improving many psychological characteristics. In the Desafío del Caribe Project, young PWH from Venezuela and Mexico took part in an open water competition in the Gulf of Mexico under a multidisciplinary team supervision. Eight severe haemophilia A, two moderate haemophilia A, one severe haemophilia B and two moderate haemophilia B subjects were included. Haematological, musculoskeletal and psychological evaluations were carried out before and during training for the competition. Training program included physical exercise routines and swimming practices that alternated between pools and open water. Swimmers had coverage with factor concentrates before pool and open water trainings. In physiatric evaluations, the Hemophilia Joint Health Score (HJHS) was used. The objective of the psychology area was to analyse self-esteem, precompetition anxiety, coping mechanisms and relaxation levels. The need of factor prophylaxis before intense trainings was confirmed. In the musculoskeletal system a decrease of elbow pain as well as an increase of muscle strength in the ankles were observed. In the psychological area significant differences between the first and second test in self-esteem levels, cognitive anxiety and group cohesion were found. PWH must be provided with orientation and encouragement to practice swimming regularly. High competition exercise must be supervised by a multidisciplinary team which must evaluate the pros and cons of the activity to make relevant recommendations.
Assuntos
Hemofilia A/fisiopatologia , Hemofilia A/psicologia , Hemofilia B/fisiopatologia , Hemofilia B/psicologia , Natação , Adolescente , Testes Hematológicos , Hemofilia A/sangue , Hemofilia B/sangue , Humanos , Exame Físico , Autoimagem , Adulto JovemRESUMO
The biological activity of mainstream smoke from experimental kretek cigarettes with and without three mixes of ingredients was assessed in a 90-day rat inhalation study and in a 4-day in vivo micronucleus assay. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes, were applied at a low and a high target level to test cigarettes with a typical Indonesian blend of tobaccos and cloves. In the 90-day inhalation study, effects commonly seen in rat inhalation studies with mainstream smoke were observed. In general, no ingredients-related histopathological changes were found in the respiratory tract. In the 4-day micronucleus assay exposure of male rats to mainstream smoke from the test cigarettes containing any of the three mixes did not increase the proportions of micronucleated cells in peripheral blood and bone marrow over the proportion of micronucleated cells in the control group. Based on the results of these studies, it can be concluded that the addition of ingredients commonly used in the manufacture of kretek cigarettes did not change the overall in vivo toxicity profile of the mainstream smoke.
Assuntos
Sistema Respiratório/efeitos dos fármacos , Fumaça/efeitos adversos , Syzygium , Produtos do Tabaco/toxicidade , Administração por Inalação , Animais , Carboxihemoglobina/análise , Feminino , Masculino , Testes para Micronúcleos , Nicotina/metabolismo , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Sistema Respiratório/patologia , Testes de Toxicidade SubcrônicaRESUMO
The biological effects of mainstream smoke (MS) from Indonesian-blended cigarettes with and without added cloves, cloves extracted with hot ethanol, and extracted cloves replenished with eugenol or clove oil were assessed in a 90-day inhalation study in rats. A separate 35-day inhalation study in rats was performed with MS from American-blended cigarettes with 0%, 2.5%, 5% or 10% added eugenol. Effects commonly seen in inhalation studies with MS were observed. These included histopathological changes indicative of irritation in the entire respiratory tract and inflammatory responses in the lung. Adding cloves to American- or Indonesian-blended cigarettes reduced the inflammatory response in the lung but with no difference between the two blend types. When the clove oil was extracted (â¼ 75% reduction of eugenol achieved) from cloves, the inflammatory response in the lung was still reduced similarly to whole cloves but the severity of histopathological changes in the upper respiratory tract was less reduced. Add back of clove oil or pure eugenol reduced this response to a level similar to what was seen with whole cloves. When eugenol was added to American-blended cigarettes, similar findings of reduced lung inflammation and severity of histopathological changes in respiratory the tract was confirmed. These studies demonstrate a clear effect of cloves, and in particular eugenol, in explaining these findings.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Óleo de Cravo/toxicidade , Eugenol/toxicidade , Fumaça/efeitos adversos , Produtos do Tabaco/toxicidade , Administração por Inalação , Animais , Carboxihemoglobina/análise , Contagem de Células , Citocinas/metabolismo , Feminino , Masculino , Nicotina/metabolismo , Pneumonia/patologia , Pneumonia/fisiopatologia , Ratos Sprague-Dawley , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/patologia , Sistema Respiratório/fisiopatologia , SyzygiumRESUMO
BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between the plasma concentration (PK) of the novel histamine H3 receptor antagonist, GSK239512, and the brain occupancy of H(3) receptors (RO) in healthy human volunteers. EXPERIMENTAL APPROACH: PET scans were obtained after i.v. administration of the H(3) -specific radioligand [(11) C]GSK189254. Each subject was scanned before and after single oral doses of GSK239512, at 4 and 24 h after dose. PET data were analysed by compartmental analysis, and regional RO estimates were obtained by graphical analysis of changes in the total volumes of distribution of the radioligand, followed by a correction for occupancy by the high affinity radioligand. The PK/RO relationship was analysed by a population-modelling approach, using the average PK of GSK239512 during each scan. KEY RESULTS: Following administration of GSK239512, there was a reduction in the brain uptake of [(11) C]GSK189254 in all regions, including cerebellum. RO at 4 h was higher than at 24 h, and the PK/RO model estimated a PK associated with 50% of RO of 0.0068 ng·mL(-1) . This corresponds to a free concentration of 4.50 × 10(-12 ) M (pK = 11.3). CONCLUSIONS AND IMPLICATIONS: The affinity of GSK239512 for brain H3 receptors in humans in vivo is much higher than that expected from studies in vitro, and higher than that observed in PET studies in pigs. The study illustrates the utility of carrying out PET studies in humans early in drug development, providing accurate quantification of GSK239512 ROâ in vivo as a function of time and dose.
Assuntos
Benzazepinas/farmacocinética , Encéfalo/metabolismo , Antagonistas dos Receptores Histamínicos/farmacocinética , Niacinamida/análogos & derivados , Receptores Histamínicos H3/metabolismo , Adulto , Benzazepinas/sangue , Encéfalo/diagnóstico por imagem , Antagonistas dos Receptores Histamínicos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/sangue , Niacinamida/farmacocinética , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. For a long time, it has been said that VWD was absent in some countries due to ethnical differences. Information about the prevalence of VWD in Mexico remains unclear, owing largely to poor awareness and diagnosis of the disease. The aim of this study was to objectively diagnose VWD in a cohort of highly selected Mexican patients with a chronic history of bleeding. Mexican Mestizos were recruited between July 2010 and August 2011. Included were 133 adult and paediatric patients with a high suspicion of VWD. Fifty-three were diagnosed with VWD: 47 (88.7%) with type 1 VWD, four (7.5%) with type 2a VWD and two (3.8%) with type 3 VWD. Mean age for female patients was 19.5 years (range 3-44 years) and 18.5 years (range 4-63 years) for male patients. Mean age at start of bleeding symptoms was 8.8 years (range 1-61). The most frequent clinical symptoms were epistaxis (84.9%), ecchymosis (79.2%), haematomas (71.7%), gum bleeds (62.3%) and petechia (50.9%). Severe transoperative or postoperative bleeding was found in 17 patients (32.1%). Twenty-six women at childbearing age had a history of abnormal gynaecological bleeding. Our results clearly demonstrate the presence of VWD in Mexican and underscore the importance of a more detailed description of VWD. Efforts to increase the awareness and diagnosis of VWD could help in better identification of patients with bleeding disorders and lead to early, appropriate management with safe and efficacious therapies such as desmopressin and plasma concentrates.
Assuntos
Doenças de von Willebrand/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Adulto Jovem , Doenças de von Willebrand/epidemiologiaRESUMO
This study assesses the proportion of patients presenting with nonvisceral chronic abdominal pain who have thoracic disk herniation as a possible cause. We designed a descriptive transversal study of patients attending our offices between February 2009 and October 2010, with a complaint of chronic abdominal pain of suspected abdominal wall source (positive Carnett sign). Nuclear magnetic resonance (NMR) of the spinal column was performed on all patients. When the NMR showed thoracic disk herniation the patients were treated according to their etiology. We also evaluated the symptoms in patients with thoracic disk herniation and their response to the applied treatment. Twenty-seven patients with chronic abdominal pain were evaluated. The NMR results in 18 of these 27 patients (66.66%) showed evidence of disk herniation. We report on the results of these 18 patients, emphasizing that the symptoms are florid and varied. Many patients had been previously diagnosed with irritable bowel syndrome. Thoracic disk herniation may account for chronic abdominal pain in many patients who remain undiagnosed or are diagnosed with irritable bowel syndrome. Thus, this possibility needs to be taken into account to achieve a correct diagnosis and a suitable mode of treatment.
Assuntos
Dor Abdominal/etiologia , Dor Crônica/etiologia , Deslocamento do Disco Intervertebral/diagnóstico , Imageamento por Ressonância Magnética , Vértebras Torácicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/epidemiologia , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , PrevalênciaAssuntos
Doenças Cardiovasculares/prevenção & controle , Comportamentos Relacionados com a Saúde , Educação em Saúde/métodos , Neoplasias/prevenção & controle , Serviços de Saúde Escolar , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Criança , França/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Inquéritos e QuestionáriosRESUMO
AIMS: Major bleeding complications with low-molecular-weight heparin (LMWH) treatment have been reported both in clinical studies and during postmarketing surveillance. Monitoring of antifactor Xa (anti-Xa) activities is therefore recommended in special populations often predisposed to renal impairment. The PROPHRE.75 study was conducted to estimate the distribution parameters of anti-Xa activity in the elderly. METHODS: PROPHRE.75 was a prospective study of a cohort of consecutive patients aged >75 years and treated with 4000 IU of enoxaparin once daily for venous thromboembolism prophylaxis. Dosing history and measurements of anti-Xa activity in sparse samples were recorded throughout treatment. The covariates included weight, gender, age, renal function, medical history and concomitant medication. Population parameters and interindividual variability were estimated using NONMEM V software. RESULTS: Anti-Xa activity was studied in 189 patients (mean age 82 +/- 5 years, 22% weighing <50 kg, 50% presenting renal impairment according to the Cockcroft and Gault formula). A first-order input two-compartment model best fitted the data. Clearance was significantly related to body weight and creatinine clearance based on the simplified Modification of Diet in Renal Disease formula, central volume being related to body weight. According to individual Bayesian estimations, 4% of patients presented with a peak anti-Xa activity >1.0 IU ml(-1), but this group did not include the sole patient experiencing a major bleed (0.53%). CONCLUSIONS: Systematic monitoring of anti-Xa activity in elderly patients treated with enoxaparin at prophylactic doses does not seem to be necessary to prevent the occurrence of major bleeding.
Assuntos
Anticoagulantes/uso terapêutico , Inibidores dos Fatores de Coagulação Sanguínea/metabolismo , Enoxaparina/uso terapêutico , Fator Xa/metabolismo , Taxa de Filtração Glomerular/efeitos dos fármacos , Tromboembolia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacocinética , Peso Corporal/fisiologia , Monitoramento de Medicamentos , Enoxaparina/farmacocinética , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
A model was developed to assess the lifetime costs and outcomes associated with haemophilia in Mexico. A retrospective chart review of 182 type A haemophiliacs was conducted for patients aged 0-34 years receiving one of three treatments: (i) cryoprecipitate at clinic; (ii) concentrate at home; or (iii) concentrate at clinic. Patients treated at home experienced 30% less joint damage, used 13-54% less factor VIII, had four times fewer clinic visits, and utilized half as many hospital days than those treated at a clinic. For cryoprecipitate at clinic patients, the annual incidence rates of HCV and HIV were calculated to be 3.6% and 1.4% respectively. The life expectancy for patients receiving cryoprecipitate and those receiving concentrate was estimated to be 49 years and 69 years respectively, with 58% of cryoprecipitate patients predicted to die of AIDS before age 69. Across the lifespan, the average annual cost of care was US$11,677 (MN$110,464) for cryoprecipitate at clinic patients, US$10,104 (M$95,580) for concentrate at home patients and US$18,819 (MN$178,027) for concentrate at clinic patients. Using a 5% discount rate, the incremental lifetime cost per year of life added for treatment with concentrate at home compared with cryoprecipitate at a clinic was US$738 (MN$6981). Rank order stability analysis demonstrated that the model was most sensitive to the cost of fVIII. These results indicate that treatment with concentrate at home compared with cryoprecipitate at a clinic substantially improves clinical outcomes at reduced annual cost levels.
Assuntos
Hemofilia A/economia , Adolescente , Adulto , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Custos e Análise de Custo , Pessoas com Deficiência , Fator VIII/economia , Fibrinogênio/economia , Recursos em Saúde/economia , Humanos , Lactente , Recém-Nascido , Expectativa de Vida , México , Modelos Econômicos , Análise de Regressão , Características de Residência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Anticardiolipin antibodies (ACA) frequently appear in patients with autoimmune disorders such as systemic lupus erythematosus, and have also been detected in infections, neoplasia, the primary antiphospholipid syndrome, in association with certain medications and also in subjects without apparent disease. Recently, anticardiolipin antibodies have been described in the acquired immunodeficiency syndrome. Eighty-four human immunodeficiency virus (HIV)-infected patients were studied to assess the influence of risk factors for HIV infection and of the stage of HIV-1 infection on the prevalence of IgG-ACA in HIV-seropositive patients. Patients were divided in two groups, one composed of 38 asymptomatic HIV-infected individuals and the other of 46 AIDS patients. A control group of 42 healthy HIV-negative blood donors was also studied. All subjects of the control group were IgG-ACA-negative. Of the 84 HIV-positive patients, 50 were IgG-ACA positive (59.5%) and 34 IgG-ACA negative (40.5%). None of the HIV-positive patients presented any thromboembolic phenomena. No significant differences were found with respect to sex, risk factors and stage of disease when the presence of IgG-ACA in HIV-positive patients was considered. ACA does not appear to be a pronostic marker in HIV-1-infected subjects. The presence of IgG-ACA is probably related to HIV-1-infection itself, and is indicative of impaired humoral immunity in these patients.
PIP: Anticardiolipin antibodies (ACA) frequently appear in patients with autoimmune disorders such as systemic lupus erythematosus, and have also been detected in infections, neoplasia, the primary antiphospholipid syndrome, in association with certain medications and also in those patients without apparent disease. Recently, anticardiolipin antibodies were described in connection with acquired immunodeficiency syndrome (AIDS). 84 human immunodeficiency virus (HIV)-infected patients were examined in order to assess the influence of risk factors for HIV infection and of the stage of HIV-1 infection on the prevalence of IgG-ACA in HIV-seropositive patients. 2 groups were created -- 1 composed of 38 asymptomatic HIV-infected individuals and the other of 46 AIDS patients. A control group of 42 healthy HIV-negative blood donors was also studied. All those in the control group were IgG-ACA-negative. Of the 84 HIV-positive patients, 50 were IgG-ACA positive (59.5%) and 34 IgG-ACA-negative (40.5%). None of the HIV-positive individuals presented any thromboembolic phenomena. There were no significant differences with respect to sex, risk factors, and stage of disease when the presence of IgG-ACA in HIV-positive patients was ascertained. ACA does not appear to be a prognostic marker in HIV-1 infected patients; the presence of IgG-ACA is probably related to HIV-1 infection itself and is indicative of impaired humoral immunity in this group. (author's modified)