RESUMO
Polo-like kinase 1 (PLK1), a member of the serine/threonine protein kinases family, is involved in multiple steps of mitotic progression. It regulates centrosome maturation, mitotic spindle formation, and cytokinesis. While studied extensively in somatic cells, little is known about PLK1 activities in the mammalian preimplantation embryo. We examined the role of PLK1 in the one-cell mouse embryo. Western blotting showed that the PLK1 protein content increased significantly during the S-phase of the one-cell stage and declined during the first mitotic division. Activation of PLK1 preceded nuclear envelope breakdown (NEBD) in both pronuclei at the entry to first embryo mitosis. Immunofluorescence revealed the presence of phosphorylated, active PLK1 (pThr(210) -PLK1) in both male and female pronuclei, and in the microtubule-organizing centers (MTOCs) shortly before NEBD. During the first mitotic metaphase, pThr(210) -PLK1 accumulated at the spindle poles and was also associated with condensed chromosomes. Inhibition of PLK1 activity with a specific PLK1 inhibitor, BI 2536, at the one-cell stage induced the formation of a bipolar spindle that displayed disordered microtubular arrangements and dislocated, condensed chromosomes. Although such embryos entered mitosis, they did not complete mitosis and arrested at metaphase. Time-lapse recording revealed progressive misalignment of condensed chromosomes during first mitotic metaphase. These data indicate that PLK1 activity is not essential for entry into first mitosis, but is required for the events leading up to metaphase-anaphase transition in the one-cell mouse embryo.
Assuntos
Blastocisto/fisiologia , Proteínas de Ciclo Celular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Mitose/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Blastocisto/metabolismo , Western Blotting , Proteínas de Ciclo Celular/antagonistas & inibidores , Feminino , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/genética , Masculino , Camundongos , Centro Organizador dos Microtúbulos/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pteridinas/farmacologia , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/fisiologia , Imagem com Lapso de Tempo , Quinase 1 Polo-LikeRESUMO
BACKGROUND: Patients undergoing emergency surgery continue to be at very high risk, but accurate risk identification for the individual patient remains difficult. This study tested the usefulness of perioperative N-terminal pro B-type natriuretic peptide (NT-proBNP) for in-hospital and long-term risk stratification. METHODS: We conducted a prospective single-centre observational cohort study in an Austrian university hospital. Two hundred and ninety-seven consecutive patients >50 yr of age undergoing a variety of emergency non-cardiac procedures were included. The primary endpoint was a composite of non-fatal myocardial infarction (MI), acute heart failure, or death between index surgery and 3 yr follow-up. The secondary endpoint was in-hospital major adverse cardiac events (MACE), defined as non-fatal MI, acute heart failure, or cardiac death. RESULTS: During a median follow-up of 34 months (inter-quartile range: 16-39), 31% of subjects reached the primary endpoint. A preoperative NT-proBNP ≥725 pg ml(-1) was associated with a 4.8-fold univariate relative risk [95% confidence interval (CI): 3.1-7.6] and a postoperative NT-proBNP ≥1600 pg ml(-1) was associated with a four-fold univariate relative risk (95% CI: 2.7-6.2) for reaching the primary endpoint. Moreover, preoperative NT-proBNP remained a significant and independent (hazards ratio 1.91, 95% CI 1.08-3.37, P=0.027) predictor in a multivariate Cox proportional hazards model. A preoperative NT-proBNP ≥1740 pg ml(-1) was associated with a 6.9-fold univariate relative risk (95% CI: 3.5-13.4) for MACE during the index hospital stay, but did not remain significant in a multivariate logistic regression model. CONCLUSIONS: Preoperative NT-proBNP can help identify patients at high risk for adverse long-term outcome after emergency surgery.
Assuntos
Serviços Médicos de Emergência , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Comorbidade , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Hematócrito , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Período Pós-Operatório , Período Pré-Operatório , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Procedimentos Cirúrgicos Operatórios/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Troponina T/sangueRESUMO
The aim of this study was to evaluate the possible effect of maternal poisoning by BASTA-15 on developmental capacities and quality of preimplantation embryos in a mouse model. During in vivo tests, fertilized mice were fed with various doses of BASTA-15 for several days. During in vitro tests, isolated embryos were cultured in a medium with the addition of herbicide or its main compound glufosinate ammonium. Stereomicroscopic evaluation of embryonic pools obtained from treated dams showed that BASTA-15 at dose 58 µl/kg bw negatively affected their ability to reach the blastocyst stage. Moreover, as shown by morphological evaluation, based on cell counting and cell death assay, even the application of herbicide at the lowest dose (approx. 1/100 LD50) had a negative effect on obtained embryo quality. In vitro tests proved the direct ability of BASTA-15 to negatively affect embryo growth and quality. On the other hand, the addition of glufosinate ammonium at equivalent concentrations (from 0.015 to 15 µg/ml) had almost no damaging effect on embryos. It was harmful only at very high doses. Results show that maternal intoxication with BASTA-15 might affect the development of preimplantation embryos and suggest that the responsibility for this effect lies probably not solely with glufosinate ammonium, but in combination with the herbicide's secondary compounds.
Assuntos
Aminobutiratos/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Herbicidas/toxicidade , Exposição Materna/efeitos adversos , Teratogênicos/toxicidade , Aminobutiratos/administração & dosagem , Animais , Blastocisto/efeitos dos fármacos , Blastocisto/patologia , Contagem de Células , Morte Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Forma do Núcleo Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Embrião de Mamíferos/patologia , Feminino , Herbicidas/administração & dosagem , Imageamento Tridimensional , Camundongos , Camundongos Endogâmicos ICR , Mórula/efeitos dos fármacos , Mórula/patologia , Necrose , GravidezRESUMO
Scanning X-ray microprobes are unique tools for the nanoscale investigation of specimens from the life, environmental, materials and other fields of sciences. Typically they utilize absorption and fluorescence as contrast mechanisms. Phase contrast is a complementary technique that can provide strong contrast with reduced radiation dose for weakly absorbing structures in the multi-keV range. In this paper the development of a segmented charge-integrating silicon detector which provides simultaneous absorption and differential phase contrast is reported. The detector can be used together with a fluorescence detector for the simultaneous acquisition of transmission and fluorescence data. It can be used over a wide range of photon energies, photon rates and exposure times at third-generation synchrotron radiation sources, and is currently operating at two beamlines at the Advanced Photon Source. Images obtained at around 2 keV and 10 keV demonstrate the superiority of phase contrast over absorption for specimens composed of light elements.
Assuntos
Espectrometria por Raios X/instrumentação , Diatomáceas/ultraestrutura , Microscopia de Contraste de Fase/métodos , Microesferas , Miócitos Cardíacos/ultraestrutura , Poliestirenos , Proteínas/químicaRESUMO
BACKGROUND: Numerous medical and physiological conditions that might alter electroencephalography (EEG), such as hypoglycaemia, hypothermia or hypovolaemia, were shown to result in the bispectral Index (BIS) indicating an incorrect hypnotic state. Recently, acute normovolaemic haemodilution (ANH) was shown to be associated with significant impairment of cognitive functions that could alter EEG and consequently BIS monitoring, an EEG derived parameter. METHODS: In a randomised clinical study, we assessed the effect of ANH on BIS monitoring before induction and after propofol target controlled infusion (TCI) anaesthesia in 45 unmedicated patients randomly allocated to ANH with oxygen insufflation (oxygen group), ANH with air insufflation (air group), or control group. RESULTS: With ANH, mean BIS values briefly declined in the oxygen group (82+/-4) and air group (84+/-3) before returning to baseline values. The loss of consciousness time was significantly shorter, with fewer propofol TCI dose requirements, and BIS was significantly higher in the oxygen group (1.3+/-0.5 min, 2.41+/-0.15 microg/ml, 73+/-7) and air group (1.2+/-0.6 min, 2.44+/-0.17 microg/ml, 75+/-5), compared with the control group (1.7+/-0.4 min, 2.75+/-0.17 microg/ml, 61+/-5), respectively. Whereas, there was no significant difference in BIS values between the oxygen group (38+/-7), air group (36+/-5) and control group (40+/-6) at propofol TCI 4 microg/ml anaesthesia maintenance. CONCLUSIONS: BIS values briefly declined with ANH before returning to baseline values before anaesthesia induction. Despite transient ANH enhancement of propofol effect during induction, there was no significant difference in BIS values with or without ANH during propofol maintenance of anaesthesia.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Estado de Consciência/efeitos dos fármacos , Eletroencefalografia , Hemodiluição , Propofol/administração & dosagem , Adulto , Análise de Variância , Anestesia Geral/métodos , Anestesia Intravenosa/métodos , Gasometria , Relação Dose-Resposta a Droga , Feminino , Hematócrito , Hemodiluição/métodos , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Components of plant essential oils have been reported to have health benefit properties, including antioxidative, anti-tumour, antimicrobial, anti-stress, and immunomodulative activities. We examined the anti-inflammatory effects of thymoquinone, the active ingredient in the volatile oil of Nigella sativa seeds, and borneol, the active component of Salvia officinalis essential oil, on TNBS-induced colitis in mice. Thymoquinone was added to the commercial diet at a concentration of 0.05 % and borneol at two concentrations (0.09% and 0.18%) and fed to ICR mice 5 days before induction of TNBS colitis. Seven days after TNBS administration the mice were killed and macroscopic and histological scores were evaluated. Cytokine mRNA expression in colonic tissue was assessed using quantitative realtime RT-PCR. We did not detect any significant changes in macroscopic and histological scores between experimental and control groups, but we observed a significant decrease in proinflammatory cytokine (IL-1beta and IL-6) mRNA expression in colon tissue in the 0.09% and 0.18% borneol-treated groups of mice in comparison to the control group. Surprisingly, we were not able to confirm anti-inflammatory effects of thymoquinone in TNBS colitis. In conclusion, our data show that borneol is able to significantly suppress proinflammatory cytokine mRNA expression in colonic inflammation, although no significant morphological changes are visible.
Assuntos
Benzoquinonas/farmacologia , Canfanos/farmacologia , Colite/induzido quimicamente , Colite/patologia , Ácido Trinitrobenzenossulfônico/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/genética , Citocinas/metabolismo , DNA/metabolismo , Enzimas de Restrição do DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: The severity of hepatic encephalopathy is currently graded clinically using West Haven criteria and psychometric tests. OBJECTIVE: To assess the discriminative power of the bispectral index (BIS) monitor to classify the degree and progression of hepatic encephalopathy. DESIGN: A consecutive, multicentre, observer blinded validation study. SETTING: Medical University of Graz (Graz, Austria), Zhejiang University First Affiliated Hospital (Hang Zhou, China), and Cairo University (Cairo, Egypt). PATIENTS: 28 consecutive patients with hepatic encephalopathy were first enrolled at Medical University of Graz as a test set. The estimated BIS cut off values were subsequently tested in a validation set of 31 patients at Zhejiang University First Affiliated Hospital and 26 patients at Cairo University; 18 patients were reassessed later in a longitudinal study. Fifteen of 85 patients (18%) were excluded from the final analysis (11 became too agitated with high electromyographic activity; four fell asleep during the recording). RESULTS: Applying the Austrian BIS cut off values of 85, 70, and 55 for discriminating West Haven grades 1 to 4 yielded agreement between BIS classification and West Haven grades in 40 of the 46 validation patients (87%), and in 16 of the 18 follow up patients (89%). Mean (SD) BIS values differed significantly between patients with West Haven grade 1 (90.2 (2.5)), grade 2 (78.4 (6.6)), grade 3 (63.2 (4.8)), and grade 4 (45.4 (5.0)). CONCLUSIONS: BIS is a useful measure for grading and monitoring the degree of involvement of the central nervous system in patients with chronic liver disease.
Assuntos
Encefalopatia Hepática/diagnóstico , Idoso , Amônia/sangue , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Análise Espectral/métodos , Análise Espectral/normasRESUMO
A new imaging device for dynamic electron microscopy is in great demand. The detector should provide the experimenter with images having sufficient spatial resolution at high speed. Immunity to radiation damage, accumulated during exposures, is critical. Photographic film, a traditional medium, is not adequate for studies that require large volumes of data or rapid recording and charge coupled device (CCD) cameras have limited resolution, due to phosphor screen coupling. CCD chips are not suitable for direct recording due to their extreme sensitivity to radiation damage. This paper discusses characterization of monolithic active pixel sensors (MAPS) in a scanning electron microscope (SEM) as well as in a transmission electron microscope (TEM). The tested devices were two versions of the MIMOSA V (MV) chip. This 1M pixel device features pixel size of 17 x 17 microm(2) and was designed in a 0.6 microm CMOS process. The active layer for detection is a thin (less than 20 microm) epitaxial layer, limiting the broadening of the electron beam. The first version of the detector was a standard imager with electronics, passivation and interconnection layers on top of the active region; the second one was bottom-thinned, reaching the epitaxial layer from the bottom. The electron energies used range from a few keV to 30 keV for SEM and from 40 to 400 keV for TEM. Deterioration of the image resolution due to backscattering was quantified for different energies and both detector versions.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Microscopia Eletrônica/métodos , Elétrons , Microscopia Eletrônica/instrumentaçãoRESUMO
Plant essential oils (EOs) have been reported to have health benefit properties and their preventive and therapeutic use in animals is expected to increase in the future. We evaluated the influence of five essential oils obtained from plant species which are known to have positive antimicrobial, antioxidative and anti-inflammatory effects--sage EO from Salvia officinalis L. (Lamiaceae), oregano EO from Origanum vulgare L. (Lamiaceae), thyme EO from Thymus vulgaris L. (Lamiaceae), clove EO from Syzygium aromaticum L. (Myrtaceae) and cinnamon EO from Cinnamomum zeylanicum Blume (Lauraceae) on the growth and development of mouse preimplantation embryos in vivo. Essential oils were added to commercial diet at concentrations of 0.25% for sage EO, thyme EO, clove EO, cinnamon EO and 0.1% for oregano EO, and fed to ICR female mice for 2 weeks ad libitum. Females were then mated with males of the same strain. Embryos obtained on Day 4 of pregnancy at the blastocyst stage were stained by morphological triple staining (Hoechst, PI, Calcein-AM) and evaluated using fluorescent microscopy. The effects of essential oils were estimated by the viability of embryos, number of nuclei and distribution of embryos according to nucleus number. Cinnamon EO significantly decreased the number of nuclei and the distribution of embryos according to nucleus number was significantly altered. Sage EO negatively influenced the distribution of embryos according to nucleus number. Clove and oregano EOs induced a significantly increased rate of cell death. Only thyme EO had no detectable effects on embryo development. In conclusion, none of the essential oils had any positive effect on embryo development, but some of them reduced the number of cells and increased the incidence of cell death.
Assuntos
Blastocisto/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cinnamomum zeylanicum , Relação Dose-Resposta a Droga , Feminino , Morte Fetal/induzido quimicamente , Morte Fetal/patologia , Marcação In Situ das Extremidades Cortadas , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Origanum , Gravidez , Salvia , Syzygium , Thymus (Planta)RESUMO
BACKGROUND: Since nursing staff in the hospital are frequently the first to witness a cardiac arrest, they may play a central role in the effective management of in-hospital cardiac arrest. In this retrospective study the first 500 in-hospital cardiac arrests in non-monitored areas, which were treated initially by nursing staff equipped with automated external defibrillators (AEDs) are reported. METHODS AND RESULTS: Between April 2001 and December 2004, 500 in-hospital cardiac arrest calls were made: there were false arrests in 61 patients, so a total of 439 patients (88%) were evaluated using the Utstein style of data collection. ROSC occurred in 256 patients (58%), 125 (28%) were discharged from hospital and 95 (22%) were still alive 6 months after discharge. Among the 73 patients with VF/VT 63 (86%) had ROSC, 34 (47%) were discharged from hospital and 28 (38%) were alive after 6 months. The chance of survival was not influenced by the time between the call of the arrest team and the 1st defibrillation but was slightly higher with physicians as in-hospital first responders (p=0.078). In contrast, 366 patients with non-VF/VT, 193 (53%) had ROSC, but only 91 (25%) were discharged from hospital and 67 (18%) were alive after 6 months. The risk of dying was significantly higher in patients with non-VF/VT (p<0.001), and there was a trend to a higher risk ratio in patients older than 65 years and in patients with non-witnessed cardiac arrest (p=0.056 and 0.079, respectively). CONCLUSION: This observational study supports the concept of hospital-wide first responder resuscitation performed by nursing staff before the arrival of the CPR-team. Among these patients survival rate was higher in those with VF/VT defibrillated at an early stage. Consequently, it may be assumed that patients may die unnecessarily due to sudden cardiac arrest if proper in-hospital resuscitation programmes are not available.
Assuntos
Reanimação Cardiopulmonar/métodos , Desfibriladores , Parada Cardíaca/terapia , Enfermeiras e Enfermeiros , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitais , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
BACKGROUND: The goal of the study was to determine activated thrombelastographic (TEG(R)) parameters with the rotational TEG(R) (ROTEG or ROTEM) device (Pentapharm GmbH, Munich, Germany) in neonates and infants <1 yr with complex congenital heart disease (CCHD) and to compare them with those of healthy children. METHODS: A total of 59 children were included: Group I (Gr I) 24 children, ASA I, scheduled for minor surgery; and Group II (Gr II) 35 children with CCHD, ASA III-IV, scheduled for cardiac surgery. Each group was subdivided into four age groups. Blood samples were obtained before the surgical procedure. RESULTS: Statistically significant differences (two-way anova analysis) between Gr I and Gr II [mean (SD); P-value] were found in INTEG-CT [Gr I 175(19), Gr II 271(162); P=0.049], EXTEG-MCF [Gr I 63(8), Gr II 56(8); P=0.013], EXTEG-MCE [Gr I 186(65), Gr II 137(41); P=0.003], FIBTEG-MCF [Gr I 24(7), Gr II 19(5); P=0.012], FIBTEG-MCE [Gr I 32(13), Gr II 24(8); P=0.012] and EXTEG-MCE-FIBTEG-MCE [Gr I 155(55), Gr II 113(37); P=0.003]. Clotting time via contact activation was prolonged in Gr II and varied widely, mainly in the age group 0-1 month and to a lesser extent in 1-3 months, and maximum clot firmness was reduced in the same age groups. In comparison with Gr II, the healthy children showed relatively homogenous TEG values with a tendency to hypercoagulability; the maximum was found in age group 1-3 months, decreasing towards adult values in the course of the first year of life. CONCLUSIONS: These preliminary TEG results indicate that the coagulation-fibrinolytic system in CCHD patients <1 yr is functionally intact and balanced but at a lower level than in healthy children. This could be interpreted as a reduction in the haemostatic potential with less reserve.
Assuntos
Coagulação Sanguínea , Cardiopatias Congênitas/sangue , Tromboelastografia , Envelhecimento/sangue , Feminino , Fibrinólise , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Cuidados Pré-Operatórios/métodos , Estudos ProspectivosRESUMO
BACKGROUND: Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation. METHODS: More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay. RESULTS: PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay. CONCLUSIONS: PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.
Assuntos
Calcitonina/sangue , Estado Terminal/terapia , Complicações Pós-Operatórias/sangue , Precursores de Proteínas/sangue , Sepse/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Peptídeo Relacionado com Gene de Calcitonina , Cuidados Críticos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/terapia , Complicações Pós-Operatórias/terapia , Prognóstico , Curva ROC , Sepse/microbiologia , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
We report on results of a measurement of meson production in central Pb-Au collisions at E(lab) = 158A GeV. For the first time in the history of high energy heavy-ion collisions, phi mesons were reconstructed both in the K+K- and the dilepton decay channels in the same experiment. This measurement yields rapidity densities near midrapidity, from the two decay channels, of 2.05 +/- 0.14(stat) +/- 0.25(syst) and 2.04 +/- 0.49(stat) +/- 0.32(syst), respectively. The shape of the measured transverse momentum spectrum is also in close agreement in both decay channels. The data rule out a possible enhancement of the phi yield in the leptonic over the hadronic decay channel of a factor 1.6 or larger at the 95% C.L. This rules out the discrepancy reported in the literature between measurements of the hadronic and dimuon decay channels by two different experiments.
RESUMO
The biological significance of squamous and glandular differentiation and different patterns of invasion in upper urinary tract urothelial carcinoma is unclear. We reviewed 268 cases of consecutive upper urinary tract carcinomas with respect to the presence of squamous and/or glandular differentiation and different patterns of invasion (nodular, trabecular, and infiltrative) and correlated data with patient outcome. Squamous or glandular differentiation occurred in 47/268 (18%) tumors and its presence correlated with high tumor stage (P<0.001) and grade (P<0.001). Invasive patterns were nodular in 49/227 (22%), trabecular in 95/227 (42%), and infiltrative in 83/227 (37%) tumors. The nodular pattern prevailed in low stage (P<0.001) and low-grade (P<0.001) tumors, whereas the infiltrative pattern prevailed in high stage (P<0.001) and high-grade (P<0.001) tumors. Multivariate analysis proved that tumor stage (P<0.001) and the infiltrative pattern (P<0.001) are independent predictors of metastasis-free survival, whereas tumor grade and squamous and glandular differentiation lacked independent influence on patient outcome. In conclusion, the infiltrative pattern of invasion significantly correlated with advanced disease and poor patient outcome. In contrast, the presence of squamous and/or glandular invasion did not prove independent influence on patient outcome. The pattern of invasion should be commented upon separately in the pathology report.
Assuntos
Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: Overweight is defined with a body mass index (BMI) >25. A BMI >25 is known as an independent risk factor for increased morbidity and mortality. The influence of an increased BMI on the development of diabetes and on survival after heart transplantation (HTX) was investigated. METHODS: A total of 137 patients (116 men, 21 women), who underwent HTX at our Department from 1986 to 2002, were included in the study. For group stratification, the pre-operative BMI values were taken (group I: BMI 25). Groups were compared for primary disease, age and sex, development of renal failure, development of diabetes, and survival. The probability of survival and the freedom-from-diabetes interval were calculated by the use of Kaplan-Meier method. RESULTS: No significant differences between groups I and II were found concerning primary disease, age and sex, and occurrence of renal failure. There was a tendency towards increased survival (p = 0.18) in group I. Patients of group II developed diabetes after HTX more frequently than those of group I (p < 0.001). Cox regression revealed that pre-operative BMI >25 is a highly significant independent risk factor for post-operative development of diabetes mellitus (DM) (p < 0.001). CONCLUSION: Overweight prior to HTX appears to negatively influence long-term survival after HTX, although this difference did not reach statistical significance. Pre-operative overweight is a significant and independent risk factor for the development of post-transplant diabetes.
Assuntos
Peso Corporal , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/epidemiologia , Transplante de Coração , Complicações Pós-Operatórias/epidemiologia , Adulto , Índice de Massa Corporal , Feminino , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
Supraglottic airway devices such as the ProSeal Laryngeal Mask Airway (PLMA) and Laryngeal Tube-Suction Airway (LTS) that provoke the least stress responses could be beneficial in many situations, especially in patients with cardiovascular disease. We compared the haemodynamic and catecholamine stress response of the LTS and PLMA in a randomised study of 36 patients. Mean arterial pressure, heart rate, epinephrine and norepinephrine levels were all reduced following induction of anaesthesia with no significant differences between the two groups. Following insertion of LTS, mean arterial pressure, heart rate, epinephrine and norepinephrine levels increased to pre-induction levels. However, following the insertion of the PLMA, mean arterial pressure, heart rate, epinephrine and norepinephrine levels remained significantly lower than pre-induction values. Mean arterial pressure, heart rate and epinephrine were significantly greater in the LTS group than in the PLMA group. We conclude that the LTS produces a greater and more sustained haemodynamic and catecholamine stress response than does the PLMA.
Assuntos
Epinefrina/sangue , Máscaras Laríngeas/efeitos adversos , Norepinefrina/sangue , Estresse Fisiológico/etiologia , Adolescente , Adulto , Pressão Sanguínea , Remoção de Dispositivo , Feminino , Frequência Cardíaca , Humanos , Complicações Intraoperatórias , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estresse Fisiológico/sangueRESUMO
AIMS: The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer. METHODS: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n = 7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome. RESULTS: Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p = 0.01). CONCLUSIONS: The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor IGF Tipo 1/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
BACKGROUND AND OBJECTIVE: To prevent neurological complications, low-flow antegrade cerebral perfusion (ACP) is used during repair of complex congenital heart defects. To overcome technical problems, continuous monitoring of cerebral blood flow and oxygenation is mandatory. The aim of the study was to evaluate the effect of different ACP flow rates on cerebral oxygen saturation obtained by near infrared spectroscopy. METHODS: Ten consecutive neonates undergoing Norwood stage I were included. In addition to near infrared spectroscopy (Invos 5100; Somanetics Corp., USA) on both hemispheres, mean arterial pressure and transcranial Doppler flow velocity were measured continuously and arterial and jugular venous oxygen saturation intermittently. Cerebral oxygen extraction ratio was calculated. Measurement points were obtained after starting bypass, during ACP with flow rates of 30, 20 and 10 mL kg(-1) min(-1) and immediately after ACP. ANOVA and Tukey-Kramer multiple comparison test were used for statistics. RESULTS: The near infrared spectroscopy signal could be obtained in all children at all measurement points, whereas transcranial Doppler failed in 1 neonate at a flow rate of 30 mL kg(-1)min(-1), in 3 neonates at 20 mL kg(-1) min(-1) and in 4 neonates at 10 mL kg(-1)min(-1). With the reduction of flow there was a significant decrease of cerebral oxygen saturation on both hemispheres (right: 78+/-8 to 72+/-9 and 66+/-8, P < 0.001; left: 71+/-7 to 65+/-7 and 60+/-7, P < 0.001), of jugular venous oxygen saturation (94+/-6 to 89+/-13 and 83+/-15, P < 0.001) and a significant increase in oxygen extraction ratio (9.1+/-8 to 14.8+/-14 and 21+/-16, P < 0.001) respectively, for 30, 20, 10 mL kg(-1)min(-1). CONCLUSION: Near infrared spectroscopy reliably detects flow alterations during ACP with profound hypothermia.
Assuntos
Síndromes do Arco Aórtico/cirurgia , Circulação Cerebrovascular/fisiologia , Monitorização Intraoperatória/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Anestesia Geral , Síndromes do Arco Aórtico/congênito , Cateterismo Cardíaco , Feminino , Humanos , Recém-Nascido , Masculino , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Ultrassonografia Doppler TranscranianaRESUMO
AIMS: To determine the diagnostic and prognostic value of CD10 immunoreactivity in renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs). METHODS AND RESULTS: CD10 expression was investigated in primary (n = 180) and metastatic (n = 58) RCCs and upper urinary tract TCCs (n = 53) using a tissue microarray technique. One hundred and fifty-four of 172 (90%) evaluable primary and 48/56 (86%) evaluable metastatic RCCs expressed CD10. Extensive immunoreactivity (positivity of >50% cancer cells) decreased with rising tumour grade in conventional RCCs [G1/G2 72/81 (89%), G3/G4 33/48 (69%); P = 0.009]. Chromophobe RCCs showed a significantly lower overall and extensive immunoreactivity compared with conventional tumours (P < 0.001). In papillary RCCs immunoreactivity of more than 10% of cancer cells for CD10 was seen more often in type 2 (7/8, 88%) compared with type 1 (5/12, 42%; P =0.054) tumours. In conventional RCCs, pure apical membranous staining was associated with low tumour stage (P = 0.003), low grade (P = 0.004) and improved prognosis on univariate analysis (P = 0.031). TCCs were less frequently stained (51%). Extensive staining, however, was associated with high-stage tumours (P = 0.024), high-grade (P = 0.073) tumours, and was associated with shorter disease-free survival in univariate analysis (P = 0.003). CONCLUSIONS: CD10 proved to be an additional marker for renal malignancies with predominantly diagnostic potential.