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2.
Rev Sci Instrum ; 93(2): 023504, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232154

RESUMO

India is responsible for the supply of diagnostic neutral beam systems for ITER to diagnose its helium ash during the deuterium-tritium plasma phase using the charge exchange recombination spectroscopy technique. Considering the many first of its kind in terms of technologies and beam development aspects, ITER Indian domestic agency has adopted a strategy of developing the technology and beam experimentation in parallel. On the beam development front three test beds, namely, the ROBIN (Rf Operated Beam source in India for Negative ion research), the TWIN (TWo rf driver-based Indigenously built Negative ion source), and the INTF (INdian Test Facility) are presently in their various phases of operation, optimization, and setting up at IPR, respectively. Experiments related to plasma production, beam production, and acceleration up to 30 keV in volume and surface mode have been performed on ROBIN. The maximum negative hydrogen ion current density to a tune of 27 mA/cm2 is obtained in the surface mode with Cs injection. Optimal source performance requires optimal surface conditions, minimum impurities, careful characterization of the plasma, cesium feed and its redistribution, and optimal wall temperatures of the surfaces of the plasma box and the plasma grid. A combination of probe, optical, vacuum, laser based, electrical, and calorimetric diagnostic measurements enables such a control. At ROBIN, the above diagnostics are being used regularly. The operational and diagnostic experiences on ROBIN shall provide the desired experience and database for operations of TWIN and INTF in the coming years. A large number of conventional and advanced diagnostic techniques are used for plasma and beam characterization. These diagnostics are suitable not only to detect and understand the plasma but also for studies related to impurity evolution. The temporal evolution of impurities significantly impacts the plasma and beam properties. The studies help in establishing correlations between physical parameters and operational parameters to optimize the source performance ensuring adequate safety and investment protection. This paper will present a brief overview of various diagnostics implemented, lessons learned, and the results obtained from ROBIN. In addition, an outline of the diagnostics planned for INTF based on the experience and understandings developed during the present experiments on ROBIN and TWIN and considering the requirements of large systems shall be discussed.

3.
Hepatol Int ; 16(5): 1094-1104, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35657479

RESUMO

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Colangite Esclerosante , Austrália/epidemiologia , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/complicações , Colangite Esclerosante/complicações , Colangite Esclerosante/epidemiologia , Estudos de Coortes , Humanos , Cirrose Hepática/complicações , Estudos Retrospectivos
4.
Br J Cancer ; 105(6): 796-806, 2011 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-21847123

RESUMO

BACKGROUND: We reported that Notch-1, a potent breast oncogene, is activated in response to trastuzumab and contributes to trastuzumab resistance in vitro. We sought to determine the preclinical benefit of combining a Notch inhibitor (γ-secretase inhibitor (GSI)) and trastuzumab in both trastuzumab-sensitive and trastuzumab-resistant, ErbB-2-positive, BT474 breast tumours in vivo. We also studied if the combination therapy of lapatinib plus GSI can induce tumour regression of ErbB-2-positive breast cancer. METHODS: We generated orthotopic breast tumour xenografts from trastuzumab- or lapatinib-sensitive and trastuzumab-resistant BT474 cells. We investigated the antitumour activities of two distinct GSIs, LY 411 575 and MRK-003, in vivo. RESULTS: Our findings showed that combining trastuzumab plus a GSI completely prevented (MRK-003 GSI) or significantly reduced (LY 411 575 GSI) breast tumour recurrence post-trastuzumab treatment in sensitive tumours. Moreover, combining lapatinib plus MRK-003 GSI showed significant reduction of tumour growth. Furthermore, a GSI partially reversed trastuzumab resistance in resistant tumours. CONCLUSION: Our data suggest that a combined inhibition of Notch and ErbB-2 signalling pathways could decrease recurrence rates for ErbB-2-positive breast tumours and may be beneficial in the treatment of recurrent trastuzumab-resistant disease.


Assuntos
Secretases da Proteína Precursora do Amiloide/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptores Notch/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Linhagem Celular Tumoral , Óxidos S-Cíclicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Marcação de Genes , Genes erbB , Genes erbB-2 , Humanos , Lapatinib , Camundongos , Camundongos Nus , Transplante de Neoplasias , Quinazolinas/administração & dosagem , Receptores Notch/genética , Recidiva , Tiadiazóis/farmacologia , Trastuzumab
5.
Public Health Action ; 7(1): 46-54, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28775943

RESUMO

Setting: Four selected antiretroviral therapy (ART) centres of Gujarat State, India, which accounts for 8% of the human immunodeficiency virus (HIV) burden in India. Objectives: 1) To assess the proportion of people living with HIV (PLHIV) whose partners were not tested for HIV; 2) to assess sociodemographic and clinical characteristics of index cases associated with partner testing; and 3) to understand perceived facilitators and barriers to partner testing and make suggestions on how to improve testing from the perspective of the health-care provider. Design: A mixed-method design with a quantitative phase that involved reviewing the programme records of married PLHIV enrolled during 2011-2015, followed by a qualitative phase of key informant interviews. Results: Of 3884 married PLHIV, 1279 (33%) did not have their partners tested for HIV. Factors including index cases being male, illiterate, aged >25 years, belonging to key populations, substance use and being in advanced clinical stages were more likely to be associated with partner non-testing. Non-disclosure of HIV status (due to fear of marital discord) and lack of awareness and risk perception were the key barriers to testing. Conclusion: One third of PLHIV did not have their partners tested for HIV. Several factors were identified as being associated with the non-testing of partners, and solutions were explored that need to be implemented urgently if we are to achieve the 90-90-90 targets and end HIV.


Contexte : Quatre centres du traitement antirétroviral (TAR) sélectionnés de l'état de Gujarat, qui compte pour 8% du poids du virus de l'immunodéficience humaine (VIH) en Inde.Objective : Nous avons voulu 1) évaluer la proportion de personnes vivant avec le VIH (PVVIH) dont les partenaires n'ont pas été testés pour le VIH ; 2) évaluer les caractéristiques sociodémographiques et cliniques du cas index associées au test du partenaire ; et 3) comprendre les facilitateurs et les contraintes perçus au test du partenaire et faire des suggestions pour améliorer les tests du point de vue des prestataires de soins de santé.Schéma à plusieurs methods: La phase quantitative a impliqué de retrouver dans les archives du programme les PVVIH mariés enrôlés entre 2011 et 2015 ; la phase qualitative a ensuite consisté en entretiens avec des informateurs clés.Résultats: Sur 3884 PVVIH mariés, 1279 (33%) n'ont pas fait tester leurs partenaires pour le VIH. Les facteurs comme le fait que le cas index soit un homme, illettré, d'âge >25 ans, appartenant à des populations clés, utilisant des drogues, étant à un stade avancé de la maladie, ont été plus susceptibles d'être associés à l'absence de test du partenaire. Le non divulgation du statut VIH (due à la peur d'une discorde maritale) et le manque de connaissances et de perception des risques ont été les obstacles majeurs au test.Conclusion : Un tiers des PVVIH n'ont pas fait tester leurs partenaires pour le VIH. Plusieurs facteurs associés à l'absence de test des partenaires ont été identifiés et des solutions ont été recherchées. Elles doivent être mises en œuvre d'urgence si nous voulons atteindre les cibles de 90­90­90 et mettre fin au VIH.


Marco de referencia: Cuatro centros de tratamiento antirretrovírico (TAR) en el estado de Guyarat, que representa el 8% de la carga de morbilidad por el virus de la inmunodeficiencia humana (VIH) de la India.Objetivos: 1) Examinar la proporción de personas positivas frente al VIH cuyas parejas no cuentan con la prueba diagnóstica del VIH; 2) analizar las características socioeconómicas y clínicas del caso inicial que se relacionan con la práctica de la prueba diagnóstica en la pareja; y 3) comprender los elementos facilitadores y los obstáculos percibidos a la prueba del VIH en las parejas y las propuestas encaminadas a mejorar su utilización, desde el punto de vista de los profesionales de salud.Métodos: Se aplicó un modelo de métodos mixtos con una etapa inicial cuantitativa, que comportó el examen de los registros del programa de las personas positivas frente al VIH casadas inscritas del 2011 al 2015, seguida por una etapa cualitativa durante la cual se realizaron entrevistas a informantes clave.Resultados: De las 3884 personas positivas frente al VIH casadas, 1279 parejas no contaban con la prueba del VIH (33%). Las características del caso inicial que se asociaron con mayor frecuencia a la falta de prueba diagnóstica de la pareja fueron el sexo masculino, el analfabetismo, la edad más de 25 años, el hecho de pertenecer a una población clave, el consumo de sustancias psicoactivas y un estadio clínico avanzado de la enfermedad. Los principales obstáculos a la práctica de las pruebas fueron la negativa a divulgar su situación frente al VIH (por temor a una discordia conyugal) y la falta de sensibilización y percepción de los riesgos.Conclusión: En un tercio de las personas positivas frente al VIH, no se había practicado a su pareja la prueba diagnóstica de la infección. Se reconocieron diversos factores vinculados con esta situación y se analizaron las soluciones. La aplicación de estas medidas es urgente con el fin de cumplir con las metas 90­90­90 y eliminar la infección por el VIH.

6.
Poult Sci ; 85(11): 2009-11, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17032837

RESUMO

Bismuth compounds have been used since the 18th century to treat gastrointestinal ailments in man. Colloidal bismuth subcitrate (De-Nol) is currently used in combination with antibiotics to reduce enteric Helicobacter pylori colonization as a treatment of stomach ulcers. We investigated whether bismuth citrate or its parent compound, colloidal bismuth subcitrate, would reduce colonization of the closely related foodborne pathogen, Campylobacter jejuni in chickens. In 2 studies, birds were either fed 0, 50, or 200 ppm bismuth citrate or bismuth subcitrate (De-Nol) for 10 or 21 d and were orally challenged with 7 combined strains of C. jejuni (n = 6 birds/treatment). For both treatment groups, cecal Campylobacter colonization was reduced when birds were fed 200 ppm for 10 d but not 21 d. For the 50 ppm treatment group, only birds dosed with bismuth citrate for 21 d demonstrated any reduction in cecal Campylobacter concentrations when compared with controls. These data suggest that bismuth citrate and colloidal bismuth subcitrate may reduce cecal colonization by Campylobacter in broilers, but these effects are inconsistent.


Assuntos
Antiácidos/farmacologia , Bismuto/farmacologia , Infecções por Campylobacter/veterinária , Campylobacter jejuni/efeitos dos fármacos , Galinhas , Doenças das Aves Domésticas/prevenção & controle , Administração Oral , Animais , Infecções por Campylobacter/prevenção & controle , Campylobacter jejuni/crescimento & desenvolvimento , Contagem de Colônia Microbiana/veterinária , Qualidade de Produtos para o Consumidor , Relação Dose-Resposta a Droga , Contaminação de Alimentos/prevenção & controle , Distribuição Aleatória
7.
Biochim Biophys Acta ; 992(1): 23-9, 1989 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-2752035

RESUMO

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt.) for 3 days produced leucopenia, lymphocytopenia and significantly decreased body wt. (P less than 0.001) and organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Low molecular weight (LMW) bleomycin detectable iron content was accumulated in bone marrow, whereas hepatic LMW iron was not detectable after benzene intoxication to rats. Prior administration of single dose (250 micrograms/100 g body wt.) of Poly IC, an interferon inducer with immunomodulating potential was found to be ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content (bone marrow) were normalised. Pretreatment of animals with Poly IC was able to enhance the SRBC antibody titre in benzene-treated animals. This study suggests that the beneficial effects of Poly IC in the amelioration of the acute toxicity of benzene has clinical significance.


Assuntos
Benzeno/antagonistas & inibidores , Indutores de Interferon , Poli I-C/farmacologia , Animais , Benzeno/toxicidade , Medula Óssea/enzimologia , Medula Óssea/metabolismo , Feminino , Hemaglutininas/análise , Ferro/metabolismo , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo
8.
Biochim Biophys Acta ; 1076(3): 439-47, 1991 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-2001393

RESUMO

The room temperature Cu K-edge EXAFS (extended X-ray absorption fine structure) spectrum of reduced and oxidized amicyanin, the blue copper protein from Thiobacillus versutus, was measured at low and high pH. The data interpretation was partly based on independent NMR evidence for the occurrence of a ligand histidine protonation at low pH (pKa = 6.9) in the reduced protein. In the oxidized protein two nitrogen-donors (from two histidines; Cu-N distances 1.95-2.01 A and 1.86-1.89 A) and a sulfur-donor (from a cysteine; Cu-S distance 2.11-2.13 A) were identified and the coordination appears independent of pH. Upon reduction at high pH the Cu-S bond and one of the Cu-N bonds lengthen slightly (from 2.11 to 2.19 A and from 2.01 to 2.18 A, respectively). Upon lowering of the pH one of the N-donors of the Cu in reduced amicyanin disappears from the Cu EXAFS and a second S-donor (from a methionine) becomes visible at 2.41 A from the Cu. The Debye-Waller factors are compatible with a Cu-N vibrational stretch frequency in the range of 150-250 cm-1 and one greater than 285 cm-1, and a Cu-S vibrational stretch frequency of about 150 cm-1 (Cu-Smet; reduced amicyanin at low pH) and one in the range of 230-800 cm-1 (Cu-Scys).


Assuntos
Proteínas de Bactérias/metabolismo , Thiobacillus/metabolismo , Proteínas de Bactérias/isolamento & purificação , Cisteína , Microanálise por Sonda Eletrônica/métodos , Análise de Fourier , Histidina , Concentração de Íons de Hidrogênio , Oxirredução , Conformação Proteica
9.
J Clin Oncol ; 12(9): 1796-805, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8083703

RESUMO

PURPOSE: We studied oncologists' attitudes and behavior with regard to their participation in randomized clinical trials. METHODS: We surveyed the 1,737 physician members of the Eastern Cooperative Oncology Group (ECOG) using the Physician Orientation Profile (POP), a self-administered mailed questionnaire. A response rate of 86% was achieved (1,485 of 1,737); each physician's actual patient accrual was recorded. RESULTS: All respondents indicated that they had a systematic pattern of patient preselection for entry onto trials beyond the formal inclusion/exclusion trial criteria. Eighty-nine percent stated that improving patient quality of life rather than prolonging survival was more personally satisfying. Sixty-two percent did not enter a single patient during the 12-month period following the survey, while 10% entered 80% of all patients during that time. Physicians overestimated their accrual rate by a factor of 6. Eighty-three percent defined randomization and adherence to trial protocol as a serious challenge to their ability to make individualized treatment decisions. CONCLUSION: This study raises questions regarding the following: (1) the perceived generalizability of trial findings, (2) the role of end points other than survival for clinical trials, (3) the consequences of physician overestimation of patient accrual, and (4) the impact of randomized trials on the behavior of clinicians. Further investigation into these critical issues will provide meaningful recommendations to enhance the future design, implementation, and conduct of randomized clinical trials in cancer.


Assuntos
Oncologia , Estudos Multicêntricos como Assunto , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Atitude do Pessoal de Saúde , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos
10.
J Clin Oncol ; 16(5): 1669-76, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9586877

RESUMO

PURPOSE: To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). PATIENTS AND METHODS: One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. RESULTS: Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models. CONCLUSION: There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/secundário , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoximesterona/administração & dosagem , Fluoximesterona/efeitos adversos , Humanos , Neoplasias Hepáticas/secundário , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Indução de Remissão , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
11.
J Clin Oncol ; 18(10): 2059-69, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10811671

RESUMO

PURPOSE: The identification of a subset of patients with axillary lymph node-positive breast cancer with an improved prognosis would be clinically useful. We report the prognostic importance of histologic grading and proliferative activity in a cohort of patients with axillary lymph node-positive breast cancer and compare these parameters with other established prognostic factors. PATIENTS AND METHODS: This Eastern Cooperative Oncology Group laboratory companion study (E4189) centered on 560 axillary lymph node-positive patients registered onto one of six eligible clinical protocols. Flow cytometric (ploidy and S-phase fraction [SPF]) and histopathologic analyses (Nottingham Combined Histologic Grade and mitotic index) were performed on paraffin-embedded tissue from 368 patients. RESULTS: Disease recurred in 208 patients; in 161 (77%), within the first 5 years. Mitotic index and grade were associated with both ploidy and SPF (P

Assuntos
Neoplasias da Mama/patologia , Adulto , Idoso , Axila , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Funções Verossimilhança , Metástase Linfática , Pessoa de Meia-Idade , Mitose , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
12.
J Clin Oncol ; 11(8): 1529-35, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8336191

RESUMO

PURPOSE: To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS: A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS: For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION: GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Gosserrelina/uso terapêutico , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Humanos , Menopausa , Pessoa de Meia-Idade , Metástase Neoplásica , Receptores de Estrogênio/metabolismo , Análise de Sobrevida , Resultado do Tratamento
13.
J Clin Oncol ; 16(7): 2382-91, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9667255

RESUMO

PURPOSE: The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU. PATIENTS AND METHODS: A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance. RESULTS: At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference. CONCLUSION: The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento
14.
Arch Intern Med ; 149(9): 2115-6, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2774787

RESUMO

Four patients with long-term ventilator dependency and severe hypothyroidism discovered in a single year are described. Correction of hypothyroidism was helpful in weaning three patients from the ventilator. The fourth patient died of other medical problems. None of these patients had goiter or clinical evidence of hypothyroidism. Hypothyroidism was discovered during workup for neurologic or cardiologic problems. Although hypothyroidism is not a common cause of ventilator dependency, it might be more common than we think.


Assuntos
Hipotireoidismo/complicações , Respiração Artificial , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Desmame do Respirador
15.
Biochem Pharmacol ; 31(2): 201-3, 1982 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-7059361

RESUMO

Studies on alkaline phosphatase were conducted in albino rats exposed to n-octane or n-nonane for 2 and 7 days; there was an increase in alkaline phosphatase activity of liver, spleen and bone marrow. Increase in spleen alkaline phosphatase activity persisted up to 42 days after single dose of n-octane or n-nonane. Pretreatment with protein synthesis inhibitors, cycloheximide or ethionine removed this observed increase of alkaline phosphatase activity in liver and spleen.


Assuntos
Fosfatase Alcalina/metabolismo , Alcanos/farmacologia , Octanos/farmacologia , Animais , Cicloeximida/farmacologia , Etionina/farmacologia , Feminino , Fígado/enzimologia , Proteínas/metabolismo , Ratos , Baço/enzimologia , Fatores de Tempo , Distribuição Tecidual
16.
Biochem Pharmacol ; 33(13): 2009-12, 1984 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-6331455

RESUMO

The 59Fe distribution after a single i.v. injection of 59Fe citrate in rats exposed to benzene was studied in circulating erythrocytes and organs up to period of 1 hr to 14 days. The iron content was significantly higher in bone marrow and liver compared to a control group of animals. A few cells with hemosiderin granules were observed in the benzene-administered group. Benzene increased lipid peroxidation in the liver and bone marrow and iron accelerated it further. Superoxide dismutase activities measured in terms of epinephrine auto-oxidation, an indirect measure of superoxide anion generation was enhanced in the benzene-treated groups. The data suggest the involvement of oxygen activation in benzene toxicity.


Assuntos
Benzeno/toxicidade , Ferro/fisiologia , Animais , Medula Óssea/efeitos dos fármacos , Feminino , Radicais Livres , Ferro/sangue , Peróxidos Lipídicos/metabolismo , Ratos , Ratos Endogâmicos , Superóxidos/metabolismo
17.
Biochem Pharmacol ; 46(3): 517-24, 1993 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-8347175

RESUMO

Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P < 0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene.


Assuntos
Benzeno/toxicidade , Medula Óssea/efeitos dos fármacos , Fígado/efeitos dos fármacos , Proteína Estafilocócica A/farmacologia , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Glutationa/metabolismo , Testes de Hemaglutinação , Ferro/análise , Leucopenia/induzido quimicamente , Peroxidação de Lipídeos , Fígado/metabolismo , Fígado/patologia , Linfopenia/induzido quimicamente , Tamanho do Órgão , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
18.
Chest ; 103(2): 396-402, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8432126

RESUMO

Granulomatous involvement of skeletal muscle occurs in 50 to 80 percent of patients with sarcoidosis. How this may affect respiratory muscle function in sarcoidosis is not known. To attempt to answer this question, we compared respiratory function and muscle force generation, and control of ventilation in 12 untreated patients with 12 healthy, nonsmoking subjects. While seated, room air breathing, measurements included expiratory reserve volume (ERV), components of breathing pattern, and occlusion pressure at 1 s (P0.1). Three of nine patients who consented to muscle biopsy demonstrated granulomatous involvement on histologic examination, and Pmax values less than the group mean; however, some patients without muscle granulomas also demonstrated low Pmax values. Breathing pattern in the sarcoid patients was rapid and shallow, but not related to the degree of radiographic infiltration or respiratory elastance. Mean inspiratory flow (VT/TI), minute ventilation, and P0.1 were, in general, greater than in the control subjects, indicating an increase in central drive. There was a significant inverse correlation between FVC and P0.1, and a weak inverse relationship between ERV and P0.1. With no significant difference between group "effective impedances" (P0.1/(VT/TI)), findings indicate that in the sarcoidosis group, decreased muscle force generation was compensated for by an increase in central drive. Granulomatous infiltration may be one of many factors contributing to respiratory muscle weakness in sarcoidosis.


Assuntos
Músculos/patologia , Mecânica Respiratória , Músculos Respiratórios/fisiopatologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia , Adulto , Feminino , Granuloma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Health Psychol ; 11(4): 250-6, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1396493

RESUMO

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.


Assuntos
Terapia Comportamental , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Oncologia , Náusea/terapia , Neoplasias/tratamento farmacológico , Enfermagem Oncológica , Psicologia Clínica , Vômito/terapia , Seguimentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Toxicology ; 59(1): 59-65, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2573174

RESUMO

Cytotoxic effects of various quinone compounds are thought to be due to the formation of semiquinone free radicals. Hydroquinone and 1,2,4-benzenetriol in the presence of copper ions release from glutamate or DNA aldehydic products capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was greater in the presence of 1,2,4-benzenetriol in comparison with hydroquinone. Complete inhibition of formation of TBAR from glutamate by 1,2,4-benzenetriol and copper was observed in the presence of catalase, thiourea and mannitol. Albumin and superoxide dismutase offered substantial protection. Complete protection of formation of TBAR from DNA was observed in the presence of catalase and thiourea. Presence of albumin, mannitol and superoxide dismutase caused only partial inhibition. The formation of TBAR from glutamate or DNA is dependent on copper ion concentration. The present data indicate that hydroquinone and 1,2,4-benzenetriol in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release TBAR from glutamate or DNA.


Assuntos
Cobre/farmacologia , DNA/metabolismo , Glutamatos/metabolismo , Hidroquinonas/toxicidade , Tiobarbitúricos/metabolismo , Albuminas/farmacologia , Animais , Catalase/farmacologia , Bovinos , DNA/efeitos dos fármacos , Dano ao DNA , Sinergismo Farmacológico , Radicais Livres , Ácido Glutâmico , Técnicas In Vitro , Manitol/farmacologia , Superóxido Dismutase/farmacologia , Tiobarbitúricos/antagonistas & inibidores , Tioureia/farmacologia
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