Elevated Cetp Activity During Acute Phase Of Myocardial Infarction Is Independently Associated With Endothelial Dysfunction And Adverse Clinical Outcome.

Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044). An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.

The Clinical Impact Of Cerebellar Grey Matter Pathology In Multiple Sclerosis.

The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS) and cerebellar functional system (FS) score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT) and the Symbol-Digit Modalities Test (SDMT). Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001), cerebellar FS (p = 0.002), arm function (p = 0.049), and for leg function (p<0.001). Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013), while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015). Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.

The Burden Of Eclampsia: Results From A Multicenter Study On Surveillance Of Severe Maternal Morbidity In Brazil.

Maternal mortality (MM) is a core indicator of disparities in women's rights. The study of Near Miss cases is strategic to identifying the breakdowns in obstetrical care. In absolute numbers, both MM and occurrence of eclampsia are rare events. We aim to assess the obstetric care indicators and main predictors for severe maternal outcome from eclampsia (SMO: maternal death plus maternal near miss). Secondary analysis of a multicenter, cross-sectional study, including 27 centers from all geographic regions of Brazil, from 2009 to 2010. 426 cases of eclampsia were identified and classified according to the outcomes: SMO and non-SMO. We classified facilities as coming from low- and high-income regions and calculated the WHO's obstetric health indicators. SPSS and Stata softwares were used to calculate the prevalence ratios (PR) and respective 95% confidence interval (CI) to assess maternal characteristics, clinical and obstetrical history, and access to health services as predictors for SMO, subsequently correlating them with the corresponding perinatal outcomes, also applying multiple regression analysis (adjusted for cluster effect). Prevalence of and mortality indexes for eclampsia in higher and lower income regions were 0.2%/0.8% and 8.1%/22%, respectively. Difficulties in access to health care showed that ICU admission (adjPR 3.61; 95% CI 1.77-7.35) and inadequate monitoring (adjPR 2.31; 95% CI 1.48-3.59) were associated with SMO. Morbidity and mortality associated with eclampsia were high in Brazil, especially in lower income regions. Promoting quality maternal health care and improving the availability of obstetric emergency care are essential actions to relieve the burden of eclampsia.

Vascular Pattern In Enchondroma And Chondrosarcoma: Clinical And Immunohistologic Study.

Although cartilaginous tumors have low microvascular density, vessels are important for the provision of nutrition so that the tumor can grow and generate metastasis. The aim of this study was to assess the value of the vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and its relation with vascular endothelial growth factor (VEGF) expression. This was a retrospective study of 21 enchondromas and 57 conventional CSs. Clinical data and outcome were retrieved from medical files. CSs histologic grades (on a scale of 1 to 3) were determined according to the World Health Organization classification. The vascular pattern (on a scale of A to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also evaluated. Poor outcome was significantly associated with vascular pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a clear correlation was found between VEGF overexpression and B/C vascular patterns. Only 18 (benign and malignant) tumors stained for CD105. The results point to the use of the vascular pattern classification as a prognostic tool in CSs and to differentiate low-grade from moderate-grade/high-grade CSs. Vascular pattern might be also used to complement histologic grade, VEGF immunostaining, and microvascular density, for indicating a patient's prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the slow growth rate of these tumors.

Evaluation Of Different Treatment Methods Against Denture Stomatitis: A Randomized Clinical Study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.

Can We Predict The Clinical Outcomes Of Genitourinary Trauma Patients And Offer Them An Evidence-based Support? The Case For Telemedicine Network.

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The Consequences Of Refractory Epilepsy And Its Treatment.

Seizures in some 30% to 40% of patients with epilepsy fail to respond to antiepileptic drugs or other treatments. While much has been made of the risks of new drug therapies, not enough attention has been given to the risks of uncontrolled and progressive epilepsy. This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research. Eight international epilepsy experts from Europe, the United States, and South America met on May 4, 2013, to present, review, and discuss relevant concepts, data, and literature on the consequences of refractory epilepsy. While patients with refractory epilepsy represent the minority of the population with epilepsy, they require the overwhelming majority of time, effort, and focus from treating physicians. They also represent the greatest economic and psychosocial burdens. Diagnostic procedures and medical/surgical treatments are not without risks. Overlooked, however, is that these risks are usually smaller than the risks of long-term, uncontrolled seizures. Refractory epilepsy may be progressive, carrying risks of structural damage to the brain and nervous system, comorbidities (osteoporosis, fractures), and increased mortality (from suicide, accidents, sudden unexpected death in epilepsy, pneumonia, vascular disease), as well as psychological (depression, anxiety), educational, social (stigma, driving), and vocational consequences. Adding to this burden is neuropsychiatric impairment caused by underlying epileptogenic processes (essential comorbidities), which appears to be independent of the effects of ongoing seizures themselves. Tolerating persistent seizures or chronic medicinal adverse effects has risks and consequences that often outweigh risks of seemingly more aggressive treatments. Future research should focus not only on controlling seizures but also on preventing these consequences.

Clinical Consequences Of Tityus Bahiensis And Tityus Serrulatus Scorpion Stings In The Region Of Campinas, Southeastern Brazil.

Scorpion stings account for most envenomations by venomous animals in Brazil. A retrospective study (1994-2011) of the clinical consequences of Tityus scorpion stings in 1327 patients treated at a university hospital in Campinas, southeastern Brazil, is reported. The clinical classification, based on outcome, was: dry sting (no envenoming), class I (only local manifestations), class II (systemic manifestations), class III (life-threatening manifestations, such as shock and/or cardiac failure requiring inotropic/vasopressor agents, and/or respiratory failure), and fatal. The median patient age was 27 years (interquartile interval = 15-42 years). Scorpions were brought for identification in 47.2% of cases (Tityus bahiensis 27.7%; Tityus serrulatus 19.5%). Sting severity was classified and each accounted for the following percentage of cases: dry stings - 3.4%, class I - 79.6%, class II - 15.1%, class III - 1.8% and fatal - 0.1%. Pain was the primary local manifestation (95.5%). Systemic manifestations such as vomiting, agitation, sweating, dyspnea, bradycardia, tachycardia, tachypnea, somnolence/lethargy, cutaneous paleness, hypothermia and hypotension were detected in class II or class III + fatal groups, but were significantly more frequent in the latter group. Class III and fatal cases occurred only in children <15 years old, with scorpions being identified in 13/25 cases (T. serrulatus, n = 12; T. bahiensis, n = 1). Laboratory blood abnormalities (hyperglycemia, hypokalemia, leukocytosis, elevations in serum total CK, CK-MB and troponin T, bicarbonate consumption and an increase in base deficit and blood lactate), electrocardiographic changes (ST segment) and echocardiographic alterations (ventricular ejected fraction <54%) were frequently detected in class III patients. Seventeen patients developed pulmonary edema, 16 had cardiac failure and seven had cardiogenic shock. These results indicate that most scorpion stings involved only local manifestations, mainly pain; the greatest severity was associated with stings by T. serrulatus and in children <15 years old.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Cd8+ Tumour-infiltrating Lymphocytes And Cox2 Expression May Predict Relapse In Differentiated Thyroid Cancer.

There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients. Retrospective cohort study. We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas. Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis. Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0·001) and expression of COX2 (P =0·01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2. In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures.

Pyrimidine-5'-nucleotidase Campinas, A New Mutation (p.r56g) In The Nt5c3 Gene Associated With Pyrimidine-5'-nucleotidase Type I Deficiency And Influence Of Gilbert's Syndrome On Clinical Expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Evolution Of The Deaths Registry System In Brazil: Associations With Changes In The Mortality Profile, Under-registration Of Death Counts, And Ill-defined Causes Of Death.

This paper examines the spatial pattern of ill-defined causes of death across Brazilian regions, and its relationship with the evolution of completeness of the deaths registry and changes in the mortality age profile. We make use of the Brazilian Health Informatics Department mortality database and population censuses from 1980 to 2010. We applied demographic methods to evaluate the quality of mortality data for 137 small areas and correct for under-registration of death counts when necessary. The second part of the analysis uses linear regression models to investigate the relationship between, on the one hand, changes in death counts coverage and age profile of mortality, and on the other, changes in the reporting of ill-defined causes of death. The completeness of death counts coverage increases from about 80% in 1980-1991 to over 95% in 2000-2010 at the same time the percentage of ill-defined causes of deaths reduced about 53% in the country. The analysis suggests that the government's efforts to improve data quality are proving successful, and they will allow for a better understanding of the dynamics of health and the mortality transition.

Surgical Site Infections In Women And Their Association With Clinical Conditions.

Surgical site infections (SSIs) can affect body tissues, cavities, or organs manipulated in surgery and constitute 14% to 16% of all infections. This study aimed to determine the incidence of SSIs in women following their discharge from a gynecology outpatient clinic, to survey different types of SSIs among women, and to verify the association of SSIs with comorbidities and clinical conditions. Data were collected via analytical observation with a cross-sectional design, and the study was conducted in 1,026 women who underwent gynecological surgery in a teaching hospital in the municipality of Teresina, in the northeast Brazilian State of Piauí, from June 2011 to March 2013. The incidence of SSIs after discharge was 5.8% among the women in the outpatient clinic. The most prevalent surgery among the patients was hysterectomy, while the most prevalent type of SSI was superficial incisional. Comorbidities in women with SSIs included cancer, diabetes mellitus, and hypertension. Surveillance of SSIs during the post-discharge period is critical for infection prevention and control. It is worth reflecting on the planning of surgical procedures for patients who have risk factors for the development of SSIs.

[child Protection Network And The Intersector Implementation Of The Circle Of Security As Alternatives To Medication].

To describe the clinical history of a child with aggressive behavior and recurring death-theme speech, and report the experience of the team of authors, who proposed an alternative to medication through the establishment of a protection network and the inter-sector implementation of the circle of security concept. A 5-year-old child has a violent and aggressive behavior at the day-care. The child was diagnosed by the healthcare center with depressive disorder and behavioral disorder, and was medicated with sertraline and risperidone. Side effects were observed, and the medications were discontinued. Despite several actions, such as talks, teamwork, psychological and psychiatric follow-up, the child's behavior remained unchanged. A unique therapeutic project was developed by Universidade Estadual de Campinas' Medical School students in order to establish a connection between the entities responsible for the child's care (daycare center, healthcare center, and family). Thus, the team was able to develop a basic care protection network. The implementation of the inter-sector circle of security, as well as the communication and cooperation among the teams, produced very favorable results in this case. This initiative was shown to be a feasible and effective alternative to the use of medication for this child.