Troponina cardíaca T para estratificação de risco na insuficiência cardíaca crônica descompensada

FUNDAMENTO: As troponinas cardíacas são marcadores altamente sensíveis e específicos de lesão miocárdica. Esses marcadores foram detectados na insuficiência cardíaca (IC) e estão associadas com mau prognóstico. OBJETIVO: Avaliar a relação da troponina T (cTnT) e suas faixas de valores com o prognóstico na IC descompensada. MÉTODOS: Estudaram-se 70 pacientes com piora da IC crônica que necessitaram de hospitalização. Na admissão, o modelo de Cox foi utilizado para avaliar as variáveis capazes de predizer o desfecho composto por morte ou re-hospitalização em razão de piora da IC durante um ano. RESULTADOS: Durante o seguimento, ocorreram 44 mortes, 36 re-hospitalizações por IC e 56 desfechos compostos. Na análise multivariada, os preditores de eventos clínicos foram: cTnT (cTnT > 0,100 ng/ml; hazard ratio (HR) 3,95 intervalo de confiança (IC) 95%: 1,64-9,49, p = 0,002), diâmetro diastólico final do ventrículo esquerdo (DDVE >70 mm; HR 1,92, IC95%: 1,06-3,47, p = 0,031) e sódio sérico (Na <135 mEq/l; HR 1,79, IC95%: 1,02-3,15, p = 0,044). Para avaliar a relação entre a elevação da cTnT e o prognóstico na IC descompensada, os pacientes foram estratificados em três grupos: cTnT-baixo (cTnT < 0,020 ng/ml, n = 22), cTnT-intermediário (cTnT > 0,020 e < 0,100 ng/ml, n = 36) e cTnT-alto (cTnT > 0,100 ng/ml, n = 12). As probabilidades de sobrevida e sobrevida livre de eventos foram: 54,2%, 31,5%, 16,7% (p = 0,020), e 36,4%, 11,5%, 8,3% (p = 0,005), respectivamente. CONCLUSÃO: A elevação da cTnT está associada com mau prognóstico na IC descompensada, e o grau dessa elevação pode facilitar a estratificação de risco

Different Approaches for Modeling Grouped Survival Data: A Mango Tree Study

Interval-censored survival data, in which the event of interest is not observed exactly but is only known to occur within some time interval, occur very frequently. In some situations, event times might be censored into different, possibly overlapping intervals of variable widths; however, in other situations, information is available for all units at the same observed visit time. In the latter cases, interval-censored data are termed grouped survival data. Here we present alternative approaches for analyzing interval-censored data. We illustrate these techniques using a survival data set involving mango tree lifetimes. This study is an example of grouped survival data.

Nodules Less Than 20 mm and Vascular Invasion are Predictors of Survival in Small Hepatocellular Carcinoma

Background: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. Methods: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. Results: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: I to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P = 0.016), Child-Pugh classification (P = 0.007), alpha-fetoprotein level (P = 0.006), number of nodules (P = 0.041), tumor diameter (P = 0.009), and vascular invasion (P < 0.0001) were significant predictors Of Survival. Cox regression analysis identified vascular invasion (relative risk = 14.60, confidence interval 95% = 3.3-64.56, P < 0.001) and tumor size > 20 mm (relative risk = 2.14, confidence interval 95% = 1.07-4.2, P = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusions: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors Of LIP to 20 mm diameter is related to increased survival.

Extent of Pelvic Lymphadenectomy in Women With Squamous Cell Carcinoma of the Uterine Cervix: Is There Any Prognostic Value?

Background and Objectives: Some authors states that the removal of lymph node would only contribute towards assessing the lymph node status and regional disease control, without any benefit for the patients` survival. The aim of this paper was to assess the influence of the number of surgically dissected pelvic lymph nodes (PLN) on disease-free Survival. Methods: Retrospective cohort study on 42 women presenting squamous cell carcinoma (SCC) of the uterine cervix, with metastases in PLN treated by radical surgery. The Cox model was used to identify risk factors for recurrence. The model variables were adjusted for treatment-related factors (year of treatment, surgical margins and postoperative radiotherapy). The cutoff value for classifying the lymphadenectomy as comprehensive (15 PLN or more) or non-comprehensive (<15 PLN) was determined from analysis of the ROC curve. Results: Fourteen recurrences (32.6%) were recorded: three pelvic, eight distant, two both pelvic and distant, and one at an unknown location. The following risk factors for recurrence were identified: invasion of the deep third of the cervix and number of dissected lymph nodes <15. Conclusions: Deep invasion and non-comprehensive pelvic lymphadenectomy are possible risk factors for recurrence of SCC of the uterine cervix with metastases in PLN. J. Surg. Oncol. 2009;100:252-257. (C) 2009 Wiley-Liss, Inc.

Benefit of antiretroviral therapy on survival of human immunodeficiency virus-infected patients admitted to an intensive care unit

Objective: To evaluate the impact of antiretroviral therapy (ART) and the prognostic factors for in-intensive care unit (ICU) and 6-month mortality in human immunodeficiency virus (HIV)-infected patients. Design: A retrospective cohort study was conducted in patients admitted to the ICU from 1996 through 2006. The follow-up period extended for 6 months after ICU admission. Setting: The ICU of a tertiary-care teaching hospital at the Universidade de Sao Paulo, Brazil. Participants: A total of 278 HIV-infected patients admitted to the ICU were selected. We excluded ICU readmissions (37), ICU admissions who stayed less than 24 hours (44), and patients with unavailable medical charts (36). Outcome Measure: In-ICU and 6-month mortality. Main Results: Multivariate logistic regression analysis and Cox proportional hazards models demonstrated that the variables associated with in-ICU and 6-month mortality were sepsis as the cause of admission (odds ratio [OR] = 3.16 [95% confidence interval [CI] 1.65-6.06]); hazards ratio [HR] = 1.37 [95% Cl 1.01-1.88)), an Acute Physiology and Chronic Health Evaluation 11 score >19 [OR = 2.81 (95% CI 1.57-5.04); HR = 2.18 (95% CI 1.62-2.94)], mechanical ventilation during the first 24 hours [OR = 3.92 (95% CI 2.20-6.96); HR = 2.25 (95% CI 1.65-3.07)], and year of ICU admission [OR = 0.90 (95% CI 0.81-0.99); HR = 0.92 [95% CI 0.87-0.97)]. CD4 T-cell count <50 cells/mm(3) Was only associated with ICU mortality [OR = 2.10 (95% Cl 1.17-3.76)]. The use of ART in the ICU was negatively predictive of 6-month mortality in the Cox model [HR = 0.50 (95% CI 0.35-0.71)], especially if this therapy was introduced during the first 4 days of admission to the ICU [HR = 0.58 (95% CI 0.41-0.83)]. Regarding HIV-infected patients admitted to ICU without using ART, those who have started this treatment during ICU, stay presented a better prognosis when time and potential confounding factors were adjusted for [HR 0.55 (95% CI 0.31-0.98)]. Conclusions: The ICU outcome of HIV-infected patients seems to be dependent not only on acute illness severity, but also on the administration of antiretroviral treatment. (Crit Care Med 2009; 37: 1605-1611)

Genetic Analysis of Age-at-Onset for Cardiovascular Risk Factors in a Brazilian Family Study

Background/Aims: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. Methods: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. Results: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. Conclusions: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI. Copyright (C) 2008 S. Karger AG, Basel

Coronary reserve impairment prevents the improvement of left ventricular dysfunction and adversely affects the long-term outcome of patients with hypertensive dilated cardiomyopathy

In hypertension, left ventricular (LV) hypertrophy develops as an adaptive mechanism to compensate for increased afterload and thus preserve systolic function. Associated structural changes such as microvascular disease might potentially interfere with this mechanism, producing pathological hypertrophy. A poorer outcome is expected to occur when LV function is put in jeopardy by impaired coronary reserve. The aim of this study was to evaluate the role of coronary reserve in the long-term outcome of patients with hypertensive dilated cardiomyopathy. Between 1996 and 2000, 45 patients, 30 of them male, with 52 +/- 11 years and LV fractional shortening <30% were enrolled and followed until 2006. Coronary flow velocity reserve was assessed by transesophageal Doppler of the left anterior descending coronary artery. Sixteen patients showed >= 10% improvement in LV fractional shortening after 17 +/- 6 months. Coronary reserve was the only variable independently related to this improvement. Total mortality was 38% in 10 years. The Cox model identified coronary reserve (hazard ratio = 0.814; 95% CI = 0.72-0.92), LV mass, low diastolic blood pressure, and male gender as independent predictors of mortality. In hypertensive dilated cardiomyopathy, coronary reserve impairment adversely affects survival, possibly by interfering with the improvement of LV dysfunction. J Am Soc Hypertens 2010;4(1):14-21. (C) 2010 American Society of Hypertension. All rights reserved.

Transformed symmetric models

For the first time, we introduce a class of transformed symmetric models to extend the Box and Cox models to more general symmetric models. The new class of models includes all symmetric continuous distributions with a possible non-linear structure for the mean and enables the fitting of a wide range of models to several data types. The proposed methods offer more flexible alternatives to Box-Cox or other existing procedures. We derive a very simple iterative process for fitting these models by maximum likelihood, whereas a direct unconditional maximization would be more difficult. We give simple formulae to estimate the parameter that indexes the transformation of the response variable and the moments of the original dependent variable which generalize previous published results. We discuss inference on the model parameters. The usefulness of the new class of models is illustrated in one application to a real dataset.

Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism

Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible antineoplastic drugs are cyclooxygenase-2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were evaluated in rats bearing Walker-256 (W256) tumor. W256 carcinosarcoma cells were inoculated subcutaneously (10(7) cells/rat) in rats submitted to treatment with celecoxib (25 mg kg(-1)) or vehicle for 14 days. Tumor growth, body-weight gain, and survival data were evaluated. The mechanisms, such as COX-2 expression and activity, oxidative stress, by means of enzymes and lipoperoxidation levels, and apoptosis mediators were also investigated. A reduction in tumor growth and an increased weight gain were observed. Celecoxib provided a higher incidence of survival compared with the control group. Cellular effects are probably COX-2 independent, because neither enzyme expression nor its activity, measured by tumoral PGE(2), showed significant difference between groups. It is probable that this antitumor action is dependent on an apoptotic way, which has been evaluated by the expression of the antiapoptotic protein Bcl-xL, in addition to the cellular changes observed by electronic microscopy. Celecoxib has also a possible involvement with redox homeostasis, because its administration caused significant changes in the activity of oxidative enzymes, such as catalase and superoxide dismutase. These results confirm the antitumor effects of celecoxib in W256 cancer model, contributing to elucidating its antitumoral mechanism and corroborating scientific literature about its effect on other types of cancer.

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model

Objective: To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis. Design: Pharmacologic interventions in an experimental model of peritoneal endometriosis. Setting: Research laboratory in the Federal University of Rio de Janeiro. Animal(s): Twenty female Sprague-Dawley rats with experimentally induced endometriosis. Intervention(s): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days. Main Outcome Measure(s): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed. Result(s): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2). Conclusion(s): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity. (Fertil Steril (R) 2010; 93: 2674-9. (C) 2010 by American Society for Reproductive Medicine.)

Modulation of B-1 and B-2 kinin receptors expression levels in the hippocampus of rats after audiogenic kindling and with limbic recruitment, a model of temporal lobe epilepsy

Epileptic seizures are hypersynchronous, paroxystic and abnormal neuronal discharges. Epilepsies are characterized by diverse mechanisms involving alteration of excitatory and inhibitory neurotransmission that result in hyperexcitability of the central nervous system (CNS). Enhanced neuronal excitability can also be achieved by inflammatory processes, including the participation of cytokines, prostaglandins or kinins, molecules known to be involved in either triggering or in the establishment of inflammation. Multiple inductions of audiogenic seizures in the Wistar audiogenic rat (WAR) strain are a model of temporal lobe epilepsy (TLE), due to the recruitment of limbic areas such as hippocampus and amygdata. In this study we investigated the modulation of the B-1 and B-2 kinin receptors expression levels in neonatal WARs as well as in adult WARs subjected to the TLE model. The expression levels of pro-inflammatory (IL-1 beta) and anti-inflammatory (IL-10) cytokines were also evaluated, as well as cyclooxygenase (COX-2). Our results showed that the B-1 and B-2 kinin receptors mRNAs were up-regulated about 7- and 4-fold, respectively, in the hippocampus of kindled WARs. On the other hand, the expressions of the IL-1 beta, IL-10 and COX-2 were not related to the observed increase of expression of kinin receptors. Based on those results we believe that the B, and B2 kinin receptors have a pivotal role in this model of TLE, although their participation is not related to an inflammatory process. We believe that kinin receptors in the CNS may act in seizure mechanisms by participating in a specific kininergic neurochemical pathway. (c) 2007 Elsevier B.V. All rights reserved.

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL. (C) 2011 Elsevier Inc. All rights reserved.

Validation of an experimental polyurethane model for biomechanical studies on implant supported prosthesis - tension tests

OBJECTIVES: The complexity and heterogeneity of human bone, as well as ethical issues, frequently hinder the development of clinical trials. The purpose of this in vitro study was to determine the modulus of elasticity of a polyurethane isotropic experimental model via tension tests, comparing the results to those reported in the literature for mandibular bone, in order to validate the use of such a model in lieu of mandibular bone in biomechanical studies. MATERIAL AND METHODS: Forty-five polyurethane test specimens were divided into 3 groups of 15 specimens each, according to the ratio (A/B) of polyurethane reagents (PU-1: 1/0.5, PU-2: 1/1, PU-3: 1/1.5). RESULTS: Tension tests were performed in each experimental group and the modulus of elasticity values found were 192.98 MPa (SD=57.20) for PU-1, 347.90 MPa (SD=109.54) for PU-2 and 304.64 MPa (SD=25.48) for PU-3. CONCLUSION: The concentration of choice for building the experimental model was 1/1.

Validation of an experimental polyurethane model for biomechanical studies on implant-supported prosthesis: compression tests

OBJECTIVES: The complexity and heterogeneity of human bone, as well as ethical issues, most always hinder the performance of clinical trials. Thus, in vitro studies become an important source of information for the understanding of biomechanical events on implant-supported prostheses, although study results cannot be considered reliable unless validation studies are conducted. The purpose of this work was to validate an artificial experimental model based on its modulus of elasticity, to simulate the performance of human bone in vivo in biomechanical studies of implant-supported prostheses. MATERIAL AND METHODS: In this study, fast-curing polyurethane (F16 polyurethane, Axson) was used to build 40 specimens that were divided into five groups. The following reagent ratios (part A/part B) were used: Group A (0.5/1.0), Group B (0.8/1.0), Group C (1.0/1.0), Group D (1.2/1.0), and Group E (1.5/1.0). A universal testing machine (Kratos model K - 2000 MP) was used to measure modulus of elasticity values by compression. RESULTS: Mean modulus of elasticity values were: Group A - 389.72 MPa, Group B - 529.19 MPa, Group C - 571.11 MPa, Group D - 470.35 MPa, Group E - 437.36 MPa. CONCLUSION: The best mechanical characteristics and modulus of elasticity value comparable to that of human trabecular bone were obtained when A/B ratio was 1:1.

Short-Term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans

Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p<0.05). The percentage of remaining deep pockets (>7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents potential effect as an adjunct of periodontal disease treatment, but long-term clinical trials are necessary to confirm its efficacy.