RESUMO
BACKGROUND: I.V. infusion of drag-reducing polymers (DRPs) has been shown to improve survival time in animals subjected to haemorrhagic shock. We hypothesized that DRPs might prolong survival time in rats following acute myocardial ischaemia (AMI). METHODS: Sixteen adult male rats were anaesthetized and mechanically ventilated. An i.v. infusion of either Dextran-40 2.5% (Control, n=8) or Dextran-40 2.5% containing 50 microg ml(-1) of an aloe vera-based DRP (DRP, n=8) was initiated at 3.5 ml h(-1). The left anterior descending coronary artery was ligated. Blood pressure, skin-tissue perfusion, and heart rate were monitored and arterial blood samples were analysed. RESULTS: The mortality at 60 min following coronary ligation was 0% in the DRP group vs 50% in the control group (P=0.025). DRP-treated animals maintained higher mean arterial pressure [60.9 (5.1) vs 47.5 (5.1) mm Hg, P=0.004] and tissue perfusion [4.2 (3.4) vs 1.2 (0.5) TPU, P=0.029]. The DRP group trended towards better acid-base status with base excess [-5.0 (1.7) vs -8.1 (5.1) mmol litre(-1), P=0.083] and pH [7.42 (0.07) vs 7.35 (0.02), P=0.03]. CONCLUSIONS: Administration of nanomolar concentrations of aloe vera-based DRP prolonged survival time in animals with AMI. DRPs may offer a novel method to treat organ/tissue hypoperfusion.
Assuntos
Aloe , Isquemia Miocárdica/tratamento farmacológico , Fitoterapia/métodos , Doença Aguda , Animais , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Infusões Intravenosas , Masculino , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/fisiopatologia , Oxigênio/sangue , Pressão Parcial , Extratos Vegetais/uso terapêutico , Polímeros/uso terapêutico , Ratos , Ratos Sprague-Dawley , Taxa de SobrevidaRESUMO
Historically, nature has provided the source for the majority of the drugs in use today. More than 20,000 microbial secondary metabolites have been described, but only a small percentage of these have been carried forward as natural product drugs. Natural products are in tough competition with large chemical libraries and with combinatorial chemistries. Hence, each step of a natural product program has to be more efficient than ever, starting from the collection of environmental samples and the selection of strains, to metabolic expression, genetic exploitation, sample preparation and chemical dereplication. This review will focus on approaches for diversifying microbial natural product strains and extract libraries, while decreasing genetic and chemical redundancy.
Assuntos
Bactérias/metabolismo , Produtos Biológicos , Fungos/metabolismo , Farmacognosia/métodos , Bactérias/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Produtos Biológicos/biossíntese , Produtos Biológicos/genética , Produtos Biológicos/isolamento & purificação , Ecossistema , Fungos/química , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificaçãoRESUMO
BACKGROUND: We undertook a multicentre phase II trial to evaluate the safety and efficacy of primary chemotherapy followed by chemoradiation for localised adenocarcinoma or squamous carcinoma of the oesophagus. PATIENTS AND METHODS: Chemotherapy comprised five 3-weekly cycles of cisplatin and protracted continuous infusion 5-fluorouracil, with conformally planned radiotherapy commencing at the start of the fifth cycle. RESULTS: The planned treatment programme was completed by 39 of 72 patients (54%), and a further 13% completed chemotherapy and proceeded to surgical oesophagectomy. Response rates to chemotherapy and to the entire treatment programme were 47% [95% confidence interval (CI) 34% to 60%] and 56% (CI 43% to 68%). The dysphagia score improved in 54% of patients. The median survival duration was 14.6 months with 1- and 2-year survival rates of 58.7% and 44.1%, respectively. Grade III/IV chemotherapy-related toxicity occurred in 38% of patients, and there were no treatment-related deaths. CONCLUSIONS: This is a feasible and active treatment regimen providing palliative benefits for patients with poor-prognosis localised oesophageal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Probabilidade , Doses de Radiação , Radioterapia Adjuvante/métodos , Medição de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , Reino UnidoRESUMO
IMPLICATIONS: Two case reports illustrate errors that can occur during intraoperative red blood cell salvage and emphasize the need for standardized procedures and quality improvement processes for this intervention.
Assuntos
Transfusão de Sangue Autóloga , Erros Médicos , Idoso , Humanos , Período Intraoperatório , Masculino , Cloreto de SódioRESUMO
The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg x m(-2)) was given every 2 weeks and PVI 5-FU (300 mg x m(-2) x day(-1)) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15-46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n = 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3-4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7-73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/farmacologia , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/patologia , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamenteAssuntos
Adjuvantes Imunológicos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Quimioterapia Combinada , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Levamisol/uso terapêutico , Análise de SobrevidaAssuntos
Transfusão de Sangue Autóloga , Cesárea , Hemorragia Pós-Parto/terapia , Adulto , Feminino , Humanos , Gravidez , Terapia de SalvaçãoAssuntos
Linfoma Folicular/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Tionucleotídeos/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Ensaios Clínicos Fase I como Assunto , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Linfoma Folicular/genética , Linfoma não Hodgkin/genética , Camundongos , Camundongos SCID , Oligonucleotídeos Antissenso/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Indução de Remissão , Tionucleotídeos/efeitos adversos , Tionucleotídeos/toxicidade , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the effect of third-trimester calcium supplementation on maternal hemodynamic function. METHODS: Pregnant women were randomized to receive either 1.5 g of elemental calcium or placebo for 6 weeks during the third trimester. Using Doppler technique, maternal hemodynamic characteristics were measured at baseline, at 2 hours after the first dose of study drug, and at the completion of 6 weeks. Serum, dietary, and urinary calcium levels were also assessed. Power calculation indicated the need to study ten subjects in each group to detect a 1.2 L (20%) difference in cardiac output between groups, assuming a mean of 6.2 +/- 1.0 L/minute. Data were analyzed by analysis of variance for repeated measures, Student t test, Mann-Whitney U test, and Fisher exact test. RESULTS: Twenty-three women enrolled, and 18 completed the study. There were no statistically significant differences in demographic characteristics or in serum, dietary, or urinary calcium levels between the two groups. There were also no statistically significant differences in hemodynamic function over time within the calcium supplementation or placebo group (P > .05; analysis of variance for repeated measures). After 6 weeks, there were no significant differences between the calcium- and placebo-treated subjects in any hemodynamic measurement. Specifically, there was not a statistically significant difference in cardiac output (7.3 +/- 1.2 L/minute versus 8.0 +/- 0.9 L/minute; P = .09) between the calcium- and placebo-treated groups. CONCLUSION: These findings suggest that third-trimester calcium supplementation does not significantly alter cardiac output. The mechanism by which calcium supplementation lowers blood pressure remains to be elucidated.
Assuntos
Carbonato de Cálcio/uso terapêutico , Débito Cardíaco/efeitos dos fármacos , Gravidez/fisiologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Cálcio da Dieta/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez , Fatores de TempoRESUMO
The changing face of health care delivery continues to challenge public hospitals, and many of these hospitals are in danger of closing. Increasing numbers of uninsured patients, coupled with state and federal cuts in Medicaid spending, threaten to worsen the situation. These facilities' survival may well depend upon their ability to create integrated delivery systems (IDSs). However, public hospitals are likely to face significant barriers in forming and participating in IDSs. This article present some of the barriers facing public hospitals as they attempt to form an IDS. Additionally, the authors present a brief case study of a public hospital whose successful efforts to form an IDS began before the IDS concept became popular. In forming an IDS this public hospital has strengthened its commitment to research, education, and the delivery of quality public health care.
Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Administração Financeira de Hospitais , Reestruturação Hospitalar/organização & administração , Hospitais Públicos/economia , Redes Comunitárias , Relações Hospital-Médico , Hospitais Públicos/organização & administração , Humanos , Equipes de Administração Institucional , Programas de Assistência Gerenciada , North Carolina , Cultura Organizacional , Inovação OrganizacionalRESUMO
Methods have been developed for culturing a dividing population of morphologically differentiated rat parotid, lacrimal, and pancreatic acinar cells in vitro. Isolated acinar cells were plated onto tissue culture dishes coated with a three-dimensional, reconstituted basement membrane gel. After attachment in Ham's nutrient mixture F12, the cells were cultured at 35 degrees C in F12 supplemented with 10% heat inactivated rat serum, epidermal growth factor, dexamethasone, insulin, transferrin, selenium, putrescine, reduced glutathione, ascorbate, penicillin, streptomycin, and the appropriate secretagogue. Under these conditions, the cells attached rapidly and DNA synthesis was initiated within 2 to 3 d. Although the cells flattened on the substratum, they continued to maintain their differentiated morphology. The cells contained secretory granules, and the secretory enzymes peroxidase and amylase could be detected. The use of a reconstituted basement membrane gel proved critical for the attachment and growth of exocrine acinar cells.