PROWESS-SHOCK TRIAL: A PROTOCOL OVERVIEW AND PERSPECTIVES

Sepsis remains a challenge for intensive care physicians, as it keeps up with high mortality rate in spite of the high costs associated with its treatment. Several studies indicate that the infusion of Drotrecogin-alpha activated (DrotAA) reduce mortality in patients at high risk of death when administered early and secured the appropriate initial treatment of sepsis as recommended by Surviving Sepsis Campaign. Europe and United States of America differ regarding the criteria of high risk of death in sepsis, two or more organ dysfunctions and Acute Physiology and Chronic Health Evaluation 25 or more, respectively. In addition to varied definitions of high risk of death for inclusion of patients in sepsis studies, the possibility of bleeding related to drug use and intrinsic limitations related to study design led the Company to develop a new randomized, multinational, placebo-controlled, double-blind study to assess the effectiveness of drug in patients with septic shock in adults.

The remodeling of collagen fibers in rats ankles submitted to immobilization and muscle stretch protocol

To evaluate the remodeling of collagen fibers in the articular cartilage of rat ankles, with and without immobilization, after application of muscle stretching protocol. Twenty three Wistar rats were divided into four groups: immobilized (I), n = 6; immobilized and stretched (IS), n = 6; stretched (S), n = 6 and control (C), n = 5. The animals in groups I and IS were submitted to immobilization. After the period of immobilization, the animals in groups IS and S were submitted to a muscle stretching protocol. At the end of the experiment, the animals were euthanized and the joints removed, processed and stained with Picrosirius red. The analysis was carried out using a polarized light microscope. The density of collagen fibers were quantified according to the intensity of birefringence displayed. By way of statistical analyses, the right and left hind limbs of the different groups were compared based on the total density of collagen fibers, the density of thick collagen fibers and the density of thin collagen fibers. Immobilization promoted a reduction in density of the thin fibers and of total collagen. The muscle stretching protocol after immobilization promoted a reduction in density of the total collagen and of the thick fibers, but the density of the thin fibers showed the same values as control. The collagen fibers were remodeled by the different stimuli. Immobilization was harmful to the collagen fibers and the muscle stretching protocol only recovered the thin collagen fibers.

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose: The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients. Methods: This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement +/- 150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients` median BG, and the safety outcome was the incidence of hypoglycemia (<= 40 mg/dL). Results: The mean of patients` median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional). Conclusions: The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols. (C) 2009 Elsevier Inc. All rights reserved.

Transvaginal US after Bowel Preparation for Deeply Infiltrating Endometriosis: Protocol, Imaging Appearances, and Laparoscopic Correlation

Deeply infiltrating endometriosis (DIE) is a common gynecologic disease that is characterized by a difficult and delayed diagnosis. Radiologic mapping of the DIE lesion sites is crucial for case management, patient counseling, and surgical planning. Transvaginal ultrasonography (US) is the initial imaging modality for investigating DIE and has been the focus of several recent studies. DIE typically manifests at imaging as hypoechogenic nodules throughout the affected sites and thickening of the intestinal wall, with some lesions showing a mixed pattern due to cystic areas. Transvaginal US performed after bowel preparation improves the ability to diagnose intestinal lesions and provides invaluable details, including which layers of the intestine are affected and the distance between the lesion and the anal border. It is vital that radiologists be familiar with the technical aspects of this modality and with the US manifestations of DIE lesions. Transvaginal US performed after bowel preparation should be the first-line imaging modality for the evaluation of women with suspected endometriosis. (C) RSNA, 2010 . radiographics.rsna.org

Cisplatin and Etoposide in Childhood Germ Cell Tumor: Brazilian Pediatric Oncology Society Protocol GCT-91

Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P = .032), and abnormal lactate dehydrogenase value at diagnosis (P = .001). Conclusion The improvement in survival by the introduction of a standard protocol is an important achievement. This is of particular importance for smaller institutions with previous limited experience in the treatment of childhood germ cell tumors. In addition, the results of a two-agent regimen with PE were favorable (5-year overall survival rate is 83.3% for patients in the high-risk group [n = 36] who received PE v 58.8% for patients in the high-risk patients group who received PE plus ifosfamide, vinblastine, and bleomycin [n = 17; P = .017]). Thus for selected patients, complex three-agent regimens may not be necessary to achieve long-term survival, even for some patients with advanced disease.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death

Background: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. Material/Methods: Ten dogs (21.3 +/- 0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without ally additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. Results: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0 +/- 0.2 VS. 2.8 +/- 2.8 L/min) and PVBF (687 +/- 114 vs. 623 +/- 130 ml/min) was observed, whereas HABF (277 33 vs. 134 28 ml/min, p<0.005) remained lower than baseline values. Conclusions: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Expanded protocol of orofacial myofunctional evaluation with scores: Validity and reliability

Objective: Clinical evaluation of the stomatognathic system is indispensable for the diagnosis of orofacial myofunctional disorders. In order to obtain a more precise diagnosis, the protocol of orofacial myofunctional evaluation with scores (OMES protocol) (Int. J. Pediatr. Otorhinolaryngol. 72 (2008) 367-375) was expanded in terms of number of items and scale amplitude. The proposal of this study is to describe the expanded OMES protocol (OMES-E) for the evaluation of children. Validity of the protocol, reliability of the examiners and agreement between them were analyzed, as also were the sensitivity, specificity and predictive values of the instrument. Methods: The sample consisted of videorecorded images of 50 children, 25 boys (mean age = 8.4 years, SD = 1.8) and 25 girls (mean age = 8.2 years, SD = 1.7) selected at random from 200 samples. Three speech therapists prepared for orofacial myofunctional evaluation participated as examiners (E). The OMES and OMES-E protocols were used for evaluation on different days. E1 evaluated all images, E2 analyzed children with recordings from 1 to 25 and E3 analyzed children with recordings from 26 to 50. The validity of OMES-E was analyzed by comparing the instrument to the OMES protocol using the Pearson correlation test complemented with the split-half reliability test (p < 0.05). The linear weighted Kappa coefficient of agreement (Kw`), the sensitivity, specificity and predictive values and the prevalence of OMD were calculated. Results: There was a statistically significant correlation between the OMES and OMES-E protocols (0.79 > r < 0.94, p < 0.01) and a significant test-retest correlation with the OMES-E (0.75 > r < 0.86, p < 0.01), with a reliability range of 0.86-0.93. The correlation and reliability coefficients between examiners were: E1 x E2 (r = 0.74, 0.84), E1 x E3 (r = 0.70, 0.83) (p < 0.01). Kw` coefficients with moderate and good strength predominated. The OMES-E protocol presented mean sensitivity = 0.91, specificity = 0.77, positive predictive value = 0.87 and negative predictive value = 0.85. The mean prevalence of OMD was 0.58. Conclusion: The OMES-E protocol is valid and reliable for orofacial myofunctional evaluation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Clinical Validity of the Protocol for Multi-Professional Centers for the Determination of Signs and Symptoms of Temporomandibular Disorders. Part II

The aims of this study were to analyze the criterion and construct validity of Part II of the protocol for multi-professional centers for the determination of signs and symptoms of temporomandibular disorders (ProTMDMulti) as a measure of TMD severity. The study was conducted on eight asymptomatic subjects (CG) and 30 subjects with articular TMD (TMDG), according to the Research Diagnostic Criteria for TMD (RDC/TMD). The ProTMDMulti-Part II was validated using the Helkimo Clinical Dysfunction Index (Di). The construct validity was tested using the analysis of the ability of ProTMDMulti-part II to differentiate the CG from the TMDG and to measure the changes that occurred in the TMDG between the period before and after TMD treatment. Correlations between the Di and the ProTMDMulti-Part II scores were calculated using the Spearman test. Inter- and intragroup comparisons were made (p<0.05). There was a statistically significant correlation between the Helkimo Clinical Dysfunction Index (Di) and the severity scores of the ProTMDMulti-Part II. There was a significant difference between TMDG and CG regarding the severity of signs and symptoms. The present study provides statistical evidence of the clinical validity of the ProTMDmulti-Part II as a measure of the severity of TMD symptoms.

Protocol of orofacial myofunctional evaluation with scores

Objective: In the literature there is no validated instrument for the clinical evaluation of the orofacial myofunctional condition of children that will permit the examiner to express numerically his perception of the characteristics and behaviors observed. The proposal of this study is to describe a protocol for the evaluation of children aged 6-12 years in order to establish relations between the orofacial. myofunctional conditions and numerical scales. The protocol validity, reliability of the examiners and agreement between them was analyzed. Methods: Eighty children aged 6-12 years participated in the study. All were evaluated and 30 were selected at random for the analyses (age range: 72-149 months, mean = 103.3, S.D. = 23.57). Individuals with and without orofacial myofunctional. disorders were included. The examiners were two speech therapists property calibrated in orofacial myofunctional evaluation. Two protocols were constructed. One, based on traditional models, was called traditional orofacial. myofunctional. evaluation (TOME), and the other, with the addition of numerical scales, was called orofacial myofunctional. evaluation with scores (OMES). The clinical conditions included were: appearance, posture and mobility of lips, tongue, cheeks and jaws, respiration, mastication and deglutition. Statistical analysis was performed using the split-half reliability method. Means, standard deviations and the Spearman correlation coefficient were also calculated. Results: There was a statistically significant correlation between the evaluations of 30 children assessed with the TOME and OMES protocols (r = 0.85, p < 0.01). The reliability between protocols was 0.92. The test-retest reliability of the OMES instrument was 0.99 and the correlation was 0.98. Reliability between examiners 1 and 2 using the OMES protocol was 0.99, and the correlation was 0.98 (P < 0.01). Conclusion: The OMES protocot proved to be a valid and reliable instrument for orofacial myofunctional evaluation, permitting the grading of orofacial myofunctional conditions within the limits of the selected items. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group Protocol ALL-99

Purpose To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MIX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. Patients and Methods Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n=544) were randomly allocated to receive either continuous 6-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (200 mg/m(2) every 3 weeks; group 2, n = 272). Results The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P=.28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P=.089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P=027), while no difference was seen for girls (87.0% v 88.8% SE; P=.78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P=.002), and 772 and 636 for hematologic episodes (P=.005). Deaths on maintenance were: seven (group 1) and one (group 2). Conclusion The intermittent use of 6-MP and MIX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Evaluation of the performance of normal elderly in a limb praxis protocol: Influence of age, gender, and education

Limb praxis can be influenced by age, gender, and education. The present Study investigated the influence of these variables on gesture production by healthy elderly Subjects. We evaluated 96 individuals divided into two age groups (60-74 and 75-88 years). Each group contained 48 men and 48 women and was subdivided into four groups according to education: illiterates and 1-3, 4-7, and 8 or more years of education. Individuals were requested to carry Out tasks oil verbal command and imitation. There were no differences between the performance of men and women, while older individuals performed worse than their younger counterparts. Regarding educational level, three major groups emerged: illiterates, individuals with 1-7 years of education, and those with 8 or more years of education. In conclusion, age and education significantly influenced the performance of individuals in limb praxis tests. (JINS, 2009, 157 618-622.)

Immunolocalization of nitric oxide synthase isoforms in human archival and rat tissues, and cultured cells

Nitric oxide (NO) exerts important physiological and pathological roles in humans. The study of NO requires the immunolocalization of its synthesizing enzymes, neuronal, endothelial and inducible NO synthases (NOS). NOS are labile to formalin-fixation and paraffin-embedding, which are used to prepare human archival tissues. This lability has made NOS immunohistochemical studies difficult, and a detailed protocol is not yet available. We describe here a protocol for the immunolocalization of NOS isoforms in human archival cerebellum and non-nervous tissues, and in rat tissues and cultured cells. Neuronal NOS antigenicity in human archival and rat nervous tissue sections was microwave-retrieved in 50 mM Tris-HCl buffer, pH 9.5, for 20 min at 900W. Neuronal NOS was expressed in stellate, basket, Purkinje and granule cells in human and rat cerebellum. Archival and frozen human cerebellar sections showed the same neuronal NOS staining pattern. Archival cerebellar sections not subjected to antigen retrieval stained weakly. Antigenicity of inducible NOS in human lung was best retrieved in 10 mM sodium citrate buffer, pH 6.0, for 15 min at 900W. Inflammatory cells in a human lung tuberculoma were strongly stained by anti-inducible NOS antibody. Anti-endothelial NOS strongly stained kidney glomeruli. Cultured PC12 cells were strongly stained by anti-neuronal NOS without antigen retrieving. The present immunohistochemistry protocol is easy to perform, timeless, and suitable for the localization of NOS isoforms in nervous and non-nervous tissues, in human archival and rat tissues. It has been extensively used in our laboratory, and is also appropriate for other antigens. (C) 2011 Elsevier B.V. All rights reserved.

Equine chorionic gonadotropin and gonadotropin-releasing hormone enhance fertility in a norgestomet-based, timed artificial insemination protocol in suckled Nelore (Bos indicus) cows

Two experiments were conducted to investigate the effects of equine chorionic gonadotropin (eCG) at progestin removal and gonadotropin-releasing hormone (GnRH) at timed artificial insemination (TA!) on ovarian follicular dynamics (Experiment 1) and pregnancy rates (Experiment 2) in suckled Nelore (Bos indicus) cows. Both experiments were 2 x 2 factorials (eCG or No eCG, and GnRH or No GnRH), with identical treatments. In Experiment 1, 50 anestrous cows, 134.5 +/- 2.3 d postpartum, received a 3 mg norgestomet ear implant se, plus 3 mg norgestomet and 5 mg estradiol valerate im on Day 0. The implant was removed on Day 9, with TAI 54 h later. Cows received 400 IU eCG or no further treatment on Day 9 and GnRH (100 mu g gonadorelin) or no further treatment at TAI. Treatment with eCG increased the growth rate of the largest follicle from Days 9 to 11 (means +/- SEM, 1.53 +/- 0.1 vs. 0.48 +/- 0.1 mm/d; P < 0.0001), its diameter on Day 11(11.4 +/- 0.6 vs. 9.3 +/- 0.7 mm; P = 0.03), as well as ovulation rate (80.8% vs. 50.0%, P = 0.02), whereas GnRH improved the synchrony of ovulation (72.0 +/- 1.1 VS. 71.1 +/- 2.0 h). In Experiment 2 (n = 599 cows, 40 to 120 d postpartum), pregnancy rates differed (P = 0.004) among groups (27.6%, 40.1%, 47.7%, and 55.7% for Control. GnRH, eCG, and eCG + GnRH groups). Both eCG and GnRH improved pregnancy rates (51.7% vs. 318%, P = 0.002; and 48.0% vs 37.6%, P = 0.02, respectively), although their effects were not additive (no significant interaction). In conclusion, eCG at norgestomet implant removal increased the growth rate of the largest follicle (LF) from implant removal to TAI, the diameter of the LF at TAI, and rates of ovulation and pregnancy rates. Furthermore, GnRH at TAI improved the synchrony of ovulations and pregnancy rates in postpartum Nelore cows treated with a norgestomet-based TAI protocol. (C) 2010 Elsevier Inc. All rights reserved.

NONINVASIVE MONITORING OF ANDROGENS IN MALE AMAZONIAN MANATEE (TRICHECHUS INUNGUIS): BIOLOGIC VALIDATION

The Amazonian manatee (Trichechus inunguis) is endemic in the Amazonian basin and is the only exclusively fresh water sirenian. Historically hunted on a large scale, this species is now considered endangered, and Studies on the reproductive physiology are critical for the improvement of reproductive management of captive and wild Populations of manatees. The aim of this Study was to verify the viability of androgen measurement in saliva, lacrimal, urine, and fecal samples of the Amazonian manatee by conducting a hormone challenge. Two adult male manatees (A-1 and A-2) were Submitted to an experimentation protocol of 12 day (D1 to D10). On D0, the animals received an intramuscular injection of gonadotropin-releasing hormone (GnRH)-analogue. Salivary, lacrimal, urinary, and fecal samples were collected daily (between 0800 hours and 0900 hours) and frozen at -20 degrees C until assayed. Fecal samples were lyophilized, extracted with 80% methanol, and diluted in buffer before the radioimmunoassay (RIA). Urine samples underwent acid hydrolysis and were diluted in depleted bovine serum. Salivary and lacrimal samples were assayed without the extraction step. Hormonal assays were conducted with a commercial testosterone RIA kit. An androgen peak (>median + 2 interquartile range [IQR]) was observed in all matrices of both animals, although it was less prominent in the lacrimal samples of A-2. However, the fecal androgen peak (A-1 peak = 293.78 ng/g dry feces, median [IQR] = 143.58 [32.38] ng/g dry feces; A-2 peak = 686.72 ng/g dry feces, median [IQR] = 243.82 [193.16] ng/g dry feces) occurred later than urinary (A-1 peak = 648.16 ng/mg creatinine [Cr], median [IQR] = 23.88 [30.44] ng/mg Cr; A-2 peak = 370.44 ng/mg Cr, median [IQR] = 113.87 [117.73] ng/mg Cr) and salivary (A-1 peak = 678.89 pg/ml, median [IQR] = 103.69 [119.86] pg/ml; A-2 peak = 733.71 pg/ml, median [IQR] = 262.92 [211.44] pg/ml) androgen peaks. These intervals appear to be correlated with the long digesta passage time in this species. The salivary and urinary peaks were closely associated. These results demonstrate that androgen concentrations in saliva, urine, or feces samples reflect reliably physiologic events and are a powerful tool for noninvasive reproductive monitoring of Amazonian manatees.

Effects of equine chorionic gonadotropin and type of ovulatory stimulus in a timed-AI protocol on reproductive responses in dairy cows

The objectives were to evaluate the effects of equine chorionic gonadotropin (eCG) supplementation (with or without eCG) and type of ovulatory stimulus (GnRH or ECP) on ovarian follicular dynamics, luteal function, and pregnancies per AI (P/AI) in Holstein cows receiving timed artificial insemination (TAI). On Day 0, 742 cows in a total of 782 breedings, received 2 mg of estradiol benzoate (EB) and one intravaginal progesterone (P4) insert (CIDR). On Day 8, the CIDR was removed, and all cows were given PGF2 alpha and assigned to one of four treatments in a 2 x 2 factorial arrangement: (1) CG: GnRH 48 h later; (2) CE: ECP; (3) EG: eCG + GnRH 48 It later; (4) EE: eCG + ECP. There were significant interactions for eCG x ovulatory stimulus and eCG x BCS. Cows in the CG group were less likely (28.9% vs. 33.8%; P < 0.05) to become pregnant compared with those in the EG group (odds ratio [OR] = 0.28). There were no differences in P/AI between CE and EE cows (30.9% vs. 29.1%; OR = 0.85; P = 0.56), respectively. Thinner cows not receiving eCG had lower P/AI than thinner cows receiving eCG (15.2% vs. 38.0%; OR = 0.20; P < 0.01). Treatment with eCG tended to increase serum progestesterone concentrations during the diestrus following synchronized ovulation (P < 0.10). However, the treatment used to induce ovulation did not affect CL volume or serum progesterone concentrations. In conclusion, both ECP and GnRH yielded comparable P/AI. However, eCG treatment at CIDR removal increased pregnancy rate in cows induced to ovulate with GnRH and in cows with lower BCS. (C) 2009 Elsevier Inc. All rights reserved.