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1.
Br J Dermatol ; 178(2): 462-472, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28845516

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Induzidas por Radiação/etiologia , Doenças Profissionais/etiologia , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Relação Dose-Resposta à Radiação , Exposição Ambiental/efeitos adversos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Prevalência , Fatores de Risco , Neoplasias Cutâneas/epidemiologia
2.
Schweiz Arch Tierheilkd ; 160(3): 163-170, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29509139

RESUMO

INTRODUCTION: The aim of this study was to determine reference intervals (RI) for venous blood parameters determined with the RAPIDPoint 500 (RP500) blood gas analyzer using blood gas syringes (BGS) and to determine whether immediate analysis of venous blood collected into lithium heparin (LH) tubes can replace anaerobic blood sampling into BGS. The null hypothesis was that canine venous blood samples collected in BGS and in LH tubes are comparable. Jugular blood was collected from 51 healthy dogs into a BGS and a LH tube. The BGS was immediately analyzed followed by the LH tube. The RI were calculated from BGS results. The BGS and LH tubes results were compared using paired t-test or Wilcoxon matched-pairs signed-rank test and Bland-Altman analysis. To assess clinical relevance, the bias between BGS and LH tubes was compared with the allowable total error (TEa). Values derived from LH tubes showed no significant difference for standard bicarbonate (HCO3std), whole blood base excess (BE B), Na, K, Cl, glucose and hemoglobin (tHb). The pH, partial pressure of carbon dioxide and oxygen, actual bicarbonate, extracellular base excess, ionized Ca, anion gap and lactate were significantly (p.


INTRODUCTION: Le but de la présente étude était de déterminer l'intervalle de référence (RI) de l'analyseur de gaz du sang RAPIDPoint 500 (RP500) pour du sang veineux prélevé dans des seringues pour gaz du sang (BGS) ainsi que de voir si une analyse immédiate du sang collecté dans des tubes à l'héparine de lithium (LH) pouvait remplacer la collecte anaérobe dans des seringues BGS. L'hypothèse était que les échantillons sanguins dans les seringues BGS et dans les tubes LH sont comparables. On a prélevé du sang de la veine jugulaire sur BGS et LH chez 51 chiens en bonne santé, on l'a analysé immédiatement avec l'analyseur RP500 et on a calculé les intervalles de référence pour les résultats des prélèvements sur BGS. Les résultats des prélèvements sur BGS et sur LH ont été comparés au moyen de t-test appariés ou d'un test de Wilcoxon signé ainsi que par une analyse de Bland-Altman. Pour juger de la signification clinique, on a comparé le biais entre BGS et LH avec une erreur globale admissible (TEa). Il n'y avait pas de différence significative entre BGS et LH en ce qui concerne le bicarbonate standard, l'excès basique du sang total, le sodium, le potassium, le glucose et l'hémoglobine. Le pH, les pressions partielles de gaz carbonique et d'oxygène, le bicarbonate effectif, l'excès basique extracellulaire, le calcium ionisé, le trou anionique et le lactate étaient significativement (p.


Assuntos
Gasometria/veterinária , Coleta de Amostras Sanguíneas/veterinária , Cães/sangue , Animais , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Análise Química do Sangue/veterinária , Gasometria/métodos , Gasometria/normas , Coleta de Amostras Sanguíneas/instrumentação , Feminino , Masculino , Valores de Referência
3.
Clin Genet ; 90(4): 343-50, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26916598

RESUMO

The basal transcription of heme oxygenase-1 (HO-1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO-1 gene. We determined the prognostic value of HO-1 promoter polymorphism on the natural postoperative course of complete resected oesophageal cancer. Genomic DNA from 297 patients was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters, disseminated tumour cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25, GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC, the SS genotype presented less advanced tumours with lower rate DTC in bone marrow and relapse compared with L-allele carriers. In contrast, AC patients with the SS genotype displayed a complete opposing tumour characteristic. The disease-free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (p < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (p < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Heme Oxigenase-1/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Análise Mutacional de DNA , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Heme Oxigenase-1/química , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Sequências Repetitivas de Ácido Nucleico , Resultado do Tratamento
4.
World J Surg ; 40(9): 2261-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27138883

RESUMO

OBJECTIVE: To retrospectively assess the frequency and indications for emergency pancreatoduodenctomies in a tertiary referral center. METHODS: Pancreatoduodenectomies between January 2005 and January 2014 were retrospectively assessed for emergency indications defined as surgery following unplanned hospital admission in less than 24 h. Data on indications and on the intraoperative as well as the post-operative course were collected. RESULTS: Out of 583 pancreatoduodenectomies during the interval, a total of 10 (1.7 %) were performed as an emergency surgery. Indications included uncontrollable bleeding, duodenal and proximal jejunal perforations, and endoscopic retrograde cholangiopancreatography-related complications. Three of the 10 (30.0 %) patients died during the hospital course. In one patient, an intraoperative mass transfusion was necessary. No intraoperative death occurred. All but one patient were American Society of Anesthesiologists class three or higher. In two cases, the pancreatic remnant was left without anastomosis for second-stage pancreatojejunostomy. Median operation time was 326.5 min (SD 100.3 min). Hospital stay of the surviving patients was prolonged (median 43.0 days; SD 24.0 days). CONCLUSION: Emergency pancreatoduodenectomies are non-frequent, have a diverse range of indications and serve as an ultima ratio to cope with severe injuries and complications around the pancreatic head area.


Assuntos
Emergências , Pancreaticoduodenectomia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Duodeno/lesões , Duodeno/cirurgia , Feminino , Hemorragia/cirurgia , Humanos , Perfuração Intestinal/cirurgia , Jejuno/lesões , Jejuno/cirurgia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos
5.
Z Gastroenterol ; 54(6): 566-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27284932

RESUMO

Cement (polymethylmethacrylat) is frequently and increasingly used in vertebral surgery. Complications can occur by spillage of this material; however the vast majority of the patients remain free of symptoms and do not require any specific therapy.Internists, gastroenterologists and radiologists regularly performing abdominal ultrasound and computed tomography should be aware of this complication.A case of spillage of cement in the right hepatic vein is presented.


Assuntos
Cimentos Ósseos/efeitos adversos , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Veias Hepáticas/diagnóstico por imagem , Vertebroplastia/efeitos adversos , Idoso , Diagnóstico Diferencial , Veias Hepáticas/lesões , Humanos , Achados Incidentais , Masculino , Ultrassonografia/métodos
6.
Sci Rep ; 13(1): 3206, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36828941

RESUMO

Pleural empyema is a serious condition leading to a significant burden on health care systems due to protracted hospitalisations. Treatment ranges from non-surgical interventions such as antibiotic therapy and chest tube placement to thoracoscopic or open surgery. Various risk factors which impact outcomes have been investigated. The RAPID (renal, age, purulence, infection source, and dietary factors) score is a clinical risk score which identifies patients at risk of death and may be used to formulate individual treatment strategies accordingly. All patients undergoing surgical interventions for empyema at a major tertiary medical centre in Germany from 2017 to 2020 were analysed. The aim was to identify perioperative risk factors which significantly impact treatment outcomes but are currently not included in the RAPID score. 245 patients with pleural empyema surgically treated at the Department of General, Visceral and Thoracic Surgery at the University Medical Centre, Hamburg, Germany (admitted from January 2017 to April 2020) were retrospectively analysed. All patients which received either minimally invasive or open thoracic surgery were included. Epidemiological as well as perioperative data was analysed to identify risk factors which impact long-term overall outcomes. 90-day mortality rate was the primary endpoint. The mean age was 59.4 years with a bimodal distribution. There was a male predominance across the cohort (71.4% compared to 28.6%), with no significant differences across ages below or above 60 years. 53 (21.6%) patients died within the first 90 days. Diabetes type 1 and 2, renal replacement therapy, immunosuppression, postoperative bleeding, intraoperative transfusion as well as microbiologically confirmed bacterial invasion of the pleura all led to higher mortality rates. Higher RAPID scores accurately predicted higher 90-day mortality rates. Modifying the RAPID score by adding the comorbidities diabetes and renal replacement therapy significantly increased the predictive value of the score. We demonstrated various perioperative and patient related risk-factors not included in the RAPID score which negatively impact postoperative outcome in patients receiving surgical treatment for pleural empyema. These should be taken into consideration when deciding on the best course of treatment. If confirmed in a prospective study including non-surgical patients with a significantly larger cohort, it may be worth considering expanding the RAPID score to include these.


Assuntos
Empiema Pleural , Cirurgia Torácica Vídeoassistida , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Empiema Pleural/microbiologia , Resultado do Tratamento
7.
Surg Endosc ; 25(10): 3235-44, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21573715

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is among the most common dysfunctions of the upper gastrointestinal tract. It interferes with quality of life and is a risk factor for the development of adenocarcinoma in the lower esophagus. Laparoscopic fundoplication is an effective treatment of GERD, but the physiologic mechanisms of the different available procedures had not been investigated to date. METHODS: In this study, 28 German Landrace pigs underwent baseline manometry and 24-h pH monitoring followed by myotomy to induce reflux esophagitis. After new-onset reflux was proved, the pigs were randomized to groups based on four treatments: total fundoplication, anterior hemifundoplication, posterior hemifundoplication, and control. On days 10 and 60 after the intervention, the effectiveness of the different fundoplication modifications was compared with that of the control subjects by 24-h pH monitoring manometry. Finally, the pigs were killed, after which the minimum volume and pressure required to breach the gastroesophageal junction were recorded. RESULTS: After myotomy, a significant increase in the reflux could be confirmed. The findings after fundoplication showed a significant decrease in the fraction of time that the pH fell below four and an increase in the vector volume compared with the measurement after myotomy. Total fundoplication and posterior hemifundoplication were highly effective, whereas measurements after anterior fundoplication still showed increased fraction times. Pharmacologic stimulation with pentagastrin showed an increase in the vector volume of the esophageal sphincter. CONCLUSIONS: Total fundoplication and posterior hemifundoplication are potent operations for the treatment of GERD. Anterior hemifundoplication reduces the reflux as well, but the effects are significantly less than with total and posterior fundoplication. Pharmacologic stimulation showed excellent results after posterior hemifundoplication, and a tendency to overcorrection was shown after total fundoplication.


Assuntos
Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Análise de Variância , Animais , Modelos Animais de Doenças , Monitoramento do pH Esofágico , Manometria , Estudos Prospectivos , Distribuição Aleatória , Suínos
8.
J Occup Med Toxicol ; 15: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944060

RESUMO

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

9.
Science ; 154(3749): 650-1, 1966 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-5923778

RESUMO

Microspectrophotometric DNA determinations on liver nuclei of hylid frogs have revealed the presence of several polyploid classes of DNA in several specimens belonging to five species. All such specimens were breeding.


Assuntos
Anuros/análise , Núcleo Celular/análise , DNA/análise , Fígado/análise , Animais , Feminino , Masculino , Espectrofotometria
10.
J Visc Surg ; 156(5): 405-411, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30745185

RESUMO

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.


Assuntos
Isquemia Mesentérica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Isquemia Mesentérica/sangue , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/terapia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Eur J Surg Oncol ; 43(4): 758-762, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28131667

RESUMO

BACKROUND: The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. Additional markers to better separate low and high-risk lesions would improve patient selection. METHODS: Patients who underwent pancreatic resections for IPMNs between January 2008 and December 2012 with available blood samples were selected and retrospectively assessed. Data on cyst characteristics such as cyst size, duct relation and main-duct dilatation were collected and plasma fibrinogen levels were measured. RESULTS: A total of 73 patients fulfilled the inclusion criteria by pancreatic resection for pathologically confirmed IPMN and available blood sample. Histologically, IPMNs were classified as low-grade and borderline in 52 (71.2%, group 1) and as high-grade and invasive in 21 (28.8%, group 2) of all cases. Fibrinogen levels showed significant differences between the two groups (group 1: mean 3.62 g/L (SD ± 1.14); group 2: mean 4.49 g/L (SD ± 1.57); p = 0.027). A ROC-curve analysis calculated cut-off value of 4.71 g/L separated groups 1 and 2 (p = 0.008). Fibrinogen levels remained as the only significant factor in multivariable analysis, cyst size and duct relation were not significant. CONCLUSION: Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated.


Assuntos
Adenocarcinoma Mucinoso/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Papilar/sangue , Fibrinogênio/metabolismo , Neoplasias Pancreáticas/sangue , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Curva ROC , Estudos Retrospectivos
13.
Curr Drug Metab ; 7(1): 1-14, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16454689

RESUMO

Strategies and standards for predicting the likelihood of pharmacokinetically significant inhibitory drug-drug interactions for drug development purposes which rely primarily on projected in vivo concentrations of cytochrome P450 (CYP) or transporter inhibitors, [I], and in vitro estimates of their inhibitory constants, K(i), were specified in several commentaries based upon a conference held by the European Federation of Pharmaceutical Sciences (EUFEPS) several years ago. Since then the application of those strategies and standards has met with varying degrees of success. Many of the vexing issues that were identified in the EUFEPS Conference Report remain, while other issues are systematically being resolved. This article briefly reviews the underlying strategy in the prediction of the significance of inhibitory DDIs using [I]/K(i) ratios; some of the difficulties or pitfalls associated with the predictive application of [I]/K(i) ratios; and some of the recent refinements of the general strategy.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Interações Medicamentosas , Farmacocinética , Animais , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/farmacologia , Hepatócitos/efeitos dos fármacos , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Valor Preditivo dos Testes
14.
Biochim Biophys Acta ; 395(1): 67-73, 1975 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-1138934

RESUMO

The DNA of aseptically grown protocorms of a Cymbidium hybrid and in vitro developed leaves, as well as DNA of leaves and flower buds of Cymbidium ceres from the greenhouse, was analysed by analytical ultracentrifugation and thermal denaturation. Upon ultracentrifugation a satellite DNA with a buoyant density of 1.682 g/cm-3 appears as a shoulder on the main band (density 1.694 g/cm-3). Thermal denaturation reveals an inhomogeneous main peak with the major component melting at 84 degrees C and a separate peak melting at 75 degrees C. This is the first demonstration of a satellite DNA in a monocot, and one of the rare examples of a major A + T-rich DNA fraction in a plant.


Assuntos
DNA , Plantas/análise , Adenina/análise , Centrifugação com Gradiente de Concentração , DNA/análise , Temperatura Alta , Cinética , Peso Molecular , Desnaturação de Ácido Nucleico , Timina/análise , Fatores de Tempo
15.
Endocrinology ; 117(3): 1084-9, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-4017957

RESUMO

A microcalorimetric study of perifused tissue samples obtained from hypothyroid thyroidectomized rats killed 15 h after a single injection of T3 was conducted in order to observe at the tissue level, and in a constant environment, the T3-dependent thermogenesis induced in fed, starved, and refed states. When 9 micrograms T3/100 g BW had been administered to fed animals, tissue heat production rate (E) increased in liver, soleus muscle, and myocardium. In kidney cortex an increase in E was observed only after 90 micrograms T3. A dose-response study was performed with liver samples, in which both oxygen consumption and heat production rates were measured. Liver and soleus muscle were then further investigated. T3-dependent thermogenesis could not be demonstrated in tissues obtained from rats which had been starved for 3 days before receiving 9 micrograms T3/100 g BW. After a small carbohydrate intake corresponding to about 60 kJ/rat (refed state; 1 kJ congruent to 0.4 kcal) given over a 3-h period preceding the injection of T3, T3-dependent thermogenesis was again present. It is concluded that differences in T3 dependent thermogenesis similar to those previously observed in animals under different nutritional states continue to exist in vitro, when tissues are no longer exposed to differing levels of humoral factors.


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Alimentos , Hipotireoidismo/fisiopatologia , Inanição/fisiopatologia , Tri-Iodotironina/farmacologia , Animais , Coração/fisiopatologia , Hipotireoidismo/complicações , Córtex Renal/fisiopatologia , Fígado/fisiopatologia , Masculino , Músculos/fisiopatologia , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Inanição/complicações
16.
Clin Pharmacol Ther ; 25(3): 309-15, 1979 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-761442

RESUMO

Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.


Assuntos
Fumar , Varfarina/metabolismo , Adulto , Feminino , Meia-Vida , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Tiocianatos/sangue , Varfarina/sangue
17.
Clin Pharmacol Ther ; 65(6): 653-60, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10391671

RESUMO

Cyclooxygenase (COX) exists as constitutive (COX-1) and inducible (COX-2) isoforms. Nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen and diclofenac inhibit both COX-1 and COX-2. The role of COX-2 in the genesis of fever in monkeys and humans was examined with use of the specific COX-2 inhibitor rofecoxib. Rofecoxib was administered to monkeys made febrile by 6 microg/kg intravenous lipopolysaccharide. Induced pyrexia was followed by oral rofecoxib (1 or 3 mg/kg), diclofenac (3 mg/kg), or vehicle. Rofecoxib and diclofenac rapidly reversed the elevated temperature (P < .05 versus vehicle for 3 mg/kg rofecoxib and diclofenac at 70 to 90 minutes after dosing). A single-dose, parallel-group, double-blind randomized trial was conducted in 94 patients with fever caused by a viral-type illness. Mean baseline temperature was similar for all groups (-38.5 degrees C). Patients received oral doses of 12.5 mg rofecoxib, 25 mg rofecoxib, 400 mg ibuprofen, or placebo and the mean +/- SE change in oral temperature at 4 hours after dosing was -0.97 degrees C +/- 0.11 degrees C, -1.19 degrees C +/- 0.09 degrees C, -1.20 degrees C +/- 0.11 degrees C, and 0.01 C +/- 0.17 C, respectively (P < .001 for active treatments versus placebo). Specific inhibition of COX-2 by rofecoxib results in antipyretic activity in monkeys and humans comparable to dual COX-1/COX-2 inhibitors such as diclofenac or ibuprofen. The data support the hypothesis that it is the COX-2 isoform that is primarily involved in the genesis of fever in humans.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/uso terapêutico , Febre/tratamento farmacológico , Febre/enzimologia , Isoenzimas/efeitos dos fármacos , Lactonas/uso terapêutico , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Administração Oral , Análise de Variância , Animais , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/efeitos adversos , Diclofenaco/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Febre/etiologia , Febre/virologia , Ibuprofeno/uso terapêutico , Lactonas/administração & dosagem , Lactonas/efeitos adversos , Lipopolissacarídeos/administração & dosagem , Saimiri , Sulfonas , Resultado do Tratamento
18.
Curr Drug Metab ; 2(3): 299-314, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11513332

RESUMO

With the dramatic change underway in the process of drug discovery and development it has become increasingly important to define, both qualitatively and quantitatively, the dispositional features of new chemical entities (NCEs) as early in the process as possible. To that end strategies have emerged that are designed to enable reasonable predictions about a NCE's absorption from the gastrointestinal tract, systemic bioavailability and likelihood for significant pre-systemic clearance, character of metabolic processing both within the gastrointestinal tract and the liver, in vivo pharmacokinetics (PK), and likelihood for clinically significant interactions with other drugs. To some extent these strategies have embraced interspecies allometric scaling in which findings in animals are extrapolated to predict outcomes in humans. However, a greater emphasis in recent years has been placed on predicting human PK and the likelihood of clinically significant drug-drug interactions for NCEs solely from in vitro experiments. These general strategies have been methodologically streamlined so that hundreds or even thousands of experiments on a given NCE can be conducted within several days. Dispositional data from these pre-clinical experiments is useful for rapidly identifying potential marketing advantages for NCEs, and for screening out those substances that should not be placed into more expensive and labor-intensive animal experiments or brought to clinical trial. The key issue in these strategies is the accuracy with which pre-clinical findings predict clinical outcomes. Based largely on retrospective analyses the current state of the art exhibits a high percentage of useful predictions. However, there are many examples in which the prediction of either human PK or clinical drug-drug interactions from pre-clinical data has failed. The reasons for inaccurate predictions are manifold, and may include the actual in vitro methodology used, inappropriate model selection, and errant scale-up factors. Additionally, in vitro methods may fail to account for complex hepatobiliary processing including transport phenomena and Phase II metabolism. Progress has been made in establishing humanized methodologies that accurately describe these processes, with a view toward reconstituting the contributions of each into a more complex and accurate depiction and prediction of in vivo PK and drug-interaction potential.


Assuntos
Interações Medicamentosas , Farmacocinética , Animais , Humanos , Preparações Farmacêuticas/metabolismo , Valor Preditivo dos Testes , Especificidade da Espécie
19.
Biotechniques ; 24(5): 796-800, 802, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9591129

RESUMO

To exploit the polymorphism of repeat numbers in short tandem repeat (STR) sequences (microsatellites) as molecular markers, STRs must be isolated and PCR primers must be developed in flanking sequences. In species with large genomes such as Allium cepa L. (onion and shallot), an efficient selection procedure for genomic fragments containing STRs is a crucial step. Here we describe a nonradioactive method for microsatellite isolation based on affinity capture of single-stranded restriction fragments annealed to biotinylated microsatellite oligonucleotides (CA)10, (GAA)8 and (AAC)8 followed by adapter-mediated genomic PCR. Cloning of the products in E. coli and plasmid sequencing revealed more than 60% positive clones. Primers were designed in STR-flanking regions, and one or two bands were amplified in 13 diploid onion and five shallot accessions. Allelism of the bands was confirmed by product sequencing.


Assuntos
Repetições de Dinucleotídeos , Genoma de Planta , Cebolas/genética , Repetições de Trinucleotídeos , Biblioteca Genômica , Reação em Cadeia da Polimerase , Polimorfismo Genético , Análise de Sequência de DNA
20.
Am J Cardiol ; 61(9): 7E-11E, 1988 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-3126638

RESUMO

Twenty patients were studied angiographically before and after administration of glyceryl trinitrate (NTG) spray at a single oral dose of 0.8 mg in either a hydrosoluble (NTG-h) or liposoluble (NTG-I) solution. The assessment was by a randomized double-blind trial involving quantitative coronary angiography and pharmacological stress testing using ergonovine maleate. The peak effect and duration of NTG-induced coronary dilatation were evaluated in 2 groups of 10 patients each, in whom NTG oral spray was given either under resting conditions (group A) or for the release of ergonovine-increased coronary vasomotor tone (group B). The study demonstrates that the 2 different galenic formulations of NTG spray are equally efficacious in dilating the conductance coronary arteries under both conditions. When NTG-h and NTG-I oral spray were given subsequent to ergonovine-testing, the diameters of extramural coronary arteries are not only reset to their dimensions at baseline but furthermore increase above resting values by 15.1% and 15.5%, respectively. Ergonovine-induced coronary vasoconstriction was released significantly for a period of at least 30 minutes. Both the NTG-h and NTG-I oral spray are potent coronary vasodilators in patients with increased coronary vasomotor tone.


Assuntos
Angina Pectoris/tratamento farmacológico , Angiografia Coronária , Nitroglicerina/administração & dosagem , Administração Oral , Adulto , Aerossóis , Idoso , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/fisiopatologia , Ensaios Clínicos como Assunto , Vasos Coronários/fisiopatologia , Método Duplo-Cego , Ergonovina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vasoconstrição/efeitos dos fármacos
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