Synthesis, antichagasic in vitro evaluation, cytotoxicity assays, molecular modeling and SAR/QSAR studies of a 2-phenyl-3-(1-phenyl-1H-pyrazol-4-yl)-acrylic acid benzylidene-carbohydrazide series

Chagas disease (American trypanosomiasis) is one of the most important parasitic diseases with serious social and economic impacts mainly on Latin America. This work reports the synthesis, in vitro trypanocidal evaluation, cytotoxicity assays, and molecular modeling and SAR/QSAR studies of a new series of N-phenylpyrazole benzylidene-carbohydrazides. The results pointed 6k (X = H, Y = p-NO(2), pIC(50) = 4.55 M) and 6l (X = F, Y = p-CN, pIC(50) = 4.27 M) as the most potent derivatives compared to crystal violet (pIC(50) = 3.77 M). The halogen-benzylidene-carbohydrazide presented the lowest potency whereas 6l showed the most promising pro. le with low toxicity (0% of cell death). The best equation from the 4D-QSAR analysis (Model 1) was able to explain 85% of the activity variability. The QSAR graphical representation revealed that bulky X-substituents decreased the potency whereas hydrophobic and hydrogen bond acceptor Y-substituents increased it. (C) 2008 Elsevier Ltd. All rights reserved.

Management of brachial plexus region tumours and tumour-like conditions: relevant diagnostic and surgical features in a consecutive series of eighteen patients

Tumours of the brachial plexus region are rare and most publications are case reports or studies with a small series of patients. The aim of this study is to present our experience in managing these lesions. We review 18 patients with tumours in the brachial plexus region submitted to surgical treatment in a 6 year period, including their clinical presentation, neuro-imaging data, surgical findings and outcome. The tumours comprised a heterogeneous group of lesions, including schwannomas, neurofibromas, malignant peripheral nerve sheath tumour (MPNST), sarcomas, metastases, desmoids and an aneurysmal bone cyst. The most common presentation was an expanding lump (83.33%). Eleven tumours were benign and 7 were malignant. Neurofibromatosis was present in only 2 patients (11.11%). Gross total resection was achieved in 14 patients and sub-total resection in the others. Only 3 patients presented with new post-operative motor deficits. The incidence of complications was low (16.5 %). The majority of tumours were benign and most of them could be excised with a low incidence of additional deficits. Some of the malignant tumours could be controlled by surgery plus adjuvant therapy, but this category is still associated with high morbidity and mortality rates.

Tessier No. 4 Facial Cleft: Evolution of Surgical Treatment in a Large Series of Patients

Background: Tessier no. 4 facial cleft is a rare, complex, and challenging craniofacial malformation. The present article aims to describe different clinical features evidenced in 21 cases of this malformation, discussing a 20-year experience with and evolution of its surgical treatment. Methods: Some demographic data, clinical features, and reconstructive results were evaluated retrospectively. These patients have been evaluated and treated in three specialized Brazilian craniofacial centers. Nineteen were already operated on, with a mean follow-up of 3.5 years (range, 1 to 20 years). Results: Sex distribution showed a male prevalence (2: 1). The average age of initial treatment was 5.4 years. Four cases were affected on the right side of the face, seven on the left, and 10 bilaterally. Six patients had other rare associated facial clefts, including nos. 5 (three patients), 7, 9, and 10. Cleft upper lip was evidenced in all patients, and maxillary hypoplasia was present in five and maxilla cleft in eight. Lower eyelid coloboma was seen in almost every case (19 patients); 10 of these had medial canthus dystopia. Four patients had amniotic bands in the limbs. Surgical repair was individualized to each patient. Surgical experience gained with these patients allowed the authors to develop some technical modifications, which have improved aesthetic results, camouflaging scars into natural folds and anatomical units, without compromising functional outcomes. Conclusions: The great majority of Tessier no. 4 facial clefts can be appropriately treated using local flaps. Classic techniques are extremely useful, but long-term results could be improved if the technical modifications described were adopted. (Plast. Reconstr. Surg. 122: 1505, 2008.)

FIBRIN GLUE APPLICATION IN MICROVASCULAR ANASTOMOSIS: COMPARATIVE STUDY OF TWO FREE FLAPS SERIES

Background: Since the first experiments with fibrin glue application in microvascular anastomoses in 1977, several studies have reported its benefits on suture reduction and anastomosis decreased time. In spite of that, clinical experience has been limited to two neurosurgical and two replantation case series, all of them with good results. This study was conducted to evaluate the feasibility and the potential benefits of fibrin glue application in free flaps. Methods: We performed 24 free flaps in 24 patients, from March 2005 to June 2006. Twenty were included in this study. They were divided into two groups according to the anastomosis technique: conventional group (n = 7 patients) and fibrin glue group (n = 13 patients). In the conventional group, the anastomosis was performed with interrupted sutures, whereas in the fibrin glue group, they were performed using less sutures and fibrin glue application. Results: The application of fibrin glue cut by half the number of sutures required to complete the anastomoses. The mean arterial and venous anastomotic times in the conventional group were 27.2 and 24.0 minutes, respectively. In the fibrin glue group, they were 13.6 and 12.6 minutes, respectively. All these differences were statistically significant. There was no significant difference of ischemic time between two groups (P = 0.26). The survival rate of the flaps was similar in both groups: 84.6% (11 of 13) in the fibrin glue group and 85.7% (6 of 7) in the conventional group (P = 1.0). Conclusions: Fibrin glue application in free flaps was feasible and allowed us to complete the anastomoses with fewer sutures and less time. The survival rate of the flaps was not adversely affected by the fibrin glue. (C) 2008 Wiley-Liss, Inc. Microsurgery 29:24-28, 2009.

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

Background: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. Study Design: Retrospective case series. Setting & Participants: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the Sao Paulo University Medical School (Sao Paulo, Brazil). Outcomes & Measurements: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. Results: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P = 0.001), lower gestational age (P = 0.001), and birth weight (P = 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P = 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. Limitations: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. Conclusions: Outcomes of pregnancy in women undergoing hemodialysis often are good. Preeclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight. Am J Kidney Dis 56:77-85. (C) 2010 by the National Kidney Foundation, Inc.Inc

Early Complication Rates in a Single-Surgeon Series of 2500 Robotic-Assisted Radical Prostatectomies: Report Applying a Standardized Grading System

Background: Perioperative complications following robotic-assisted radical prostatectomy (RARP) have been previously reported in recent series. Few studies, however, have used standardized systems to classify surgical complications, and that inconsistency has hampered accurate comparisons between different series or surgical approaches. Objective: To assess trends in the incidence and to classify perioperative surgical complications following RARP in 2500 consecutive patients. Design, setting, and participants: We analyzed 2500 patients who underwent RARP for treatment of clinically localized prostate cancer (PCa) from August 2002 to February 2009. Data were prospectively collected in a customized database and retrospectively analyzed. Intervention: All patients underwent RARP performed by a single surgeon. Measurements: The data were collected prospectively in a customized database. Complications were classified using the Clavien grading system. To evaluate trends regarding complications and radiologic anastomotic leaks, we compared eight groups of 300 patients each, categorized according the surgeon`s experience (number of cases). Results and limitations: Our median operative time was 90 min (interquartile range [IQR]: 75-100 min). The median estimated blood loss was 100 ml (IQR: 100-150 ml). Our conversion rate was 0.08%, comprising two procedures converted to standard laparoscopy due to robot malfunction. One hundred and forty complications were observed in 127 patients (5.08%). The following percentages of patients presented graded complications: grade 1, 2.24%; grade 2, 1.8%; grade 3a, 0.08%; grade 3b, 0.48%; grade 4a, 0.40%. There were no cases of multiple organ dysfunction or death (grades 4b and 5). There were significant decreases in the overall complication rates (p = 0.0034) and in the number of anastomotic leaks (p < 0.001) as the surgeon`s experience increased. Conclusions: RARP is a safe option for treatment of clinically localized PCa, presenting low complication rates in experienced hands. Although the robotic system provides the surgeon with enhanced vision and dexterity, proficiency is only accomplished with consistent surgical volume; complication rates demonstrated a tendency to decrease as the surgeon`s experience increased. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Homeopathic practice in Intensive Care Units: objective semiology, symptom selection and a series of sepsis cases

Homeopathy has been used for more than two hundred years to treat chronic disease using various approaches in a wide range of diseases. However, for acute disease and critical illness, application has been limited by inadequate training of homeopathic physicians and the small number of pertinent clinical studies. In view of the difficulty of practising homeopathy in Intensive Care Units (ICU), a protocol was developed to facilitate description of objective homeopathic symptoms with a ranking of symptoms appropriate for these situations (Protocol for Objective Homeopathic Semiology). Examples of favorable results with individualized homeopathic treatments for a series of cases of Systemic Inflammatory Response Syndrome (sepsis) are described. Homeopathy (2008) 97, 206-213.

Studies of RET gene expression and acetylcholinesterase activity in a series of sporadic Hirschsprung`s disease

The purpose is to present the studies of RET gene expression and acetylcholinesterase activity in 23 patients operated for Hirschsprung`s disease (HD). The patients underwent either transanal endorectal pull-through or Duhamell`s procedure. Full-thickness intestinal samples from the three different segments (ganglionic, intermediate and aganglionic) were collected. Each tissue sample was divided in two portions, one for AChE histochemical staining and the other for examination of RET mRNA expression level. All patients had an uneventful postoperative recovery. In all patients, the AChE stainings demonstrated the absence of activity in the ganglionic area, the marked increase of positive fibers in the aganglionic area, and little increase of positive fibers in the intermediate area. In the ganglionic and intermediate areas, all patients (100%) showed significant RET gene expression. In the aganglionic area, 18 patients (78.3%) did not present gene expression and the other five patients (21.7%) presented gene expression that was similar to the ganglionic and intermediate areas. The results reinforce the conclusion that the method of AChE staining is effective for the diagnosis of intestinal aganglionosis and confirm the knowledge that genes beyond RET may be implicated in the genesis of sporadic cases of HD.

Pompe disease in a Brazilian series: clinical and molecular analyses with identification of nine new mutations

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18_25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.

Time series evaluation of traumatic lesions and airsacculitis at one poultry abattoir in the state of Sao Paulo, Brazil (1996-2005)

Ten year official condemnation records of one officially inspected poultry abattoir in state of Sao Paulo. Brazil, were analyzed. Seasonal and cyclical trends were analyzed in relation to traumatic lesions and airsacculitis. which were the most relevant official condemnation causes Time series analysis of the records, seasonal indexes and moving averages was used to describe the adherence to the mathematical model and to offer preventive management strategies for the slaughter house industry Although cause-effect relationships were not defined, some insight was given into the causal mechanisms that generated the series (C) 2010 Elsevier B V All rights reserved

Efficacy of Profile .04 taper series 29 in removing filling materials during root canal retreatment-an in vitro study

Objective. The aim of this study was to compare Profile .04 taper series 29 instruments and hand files for gutta-percha removal. Study design. Twenty maxillary central incisors with a single straight canal were instrumented and filled. The teeth were divided into 2 groups of 10 specimens each, according to gutta-percha removal techniques: Group 1- Profile series 29 and Group 2- hand files and solvent. The amount of time for gutta-percha removal and the number of fractured instruments were evaluated. Radiographs were taken and the teeth were grooved longitudinally and split. The area of residual debris was measured using computer software. Results. The time for filling material removal was significantly shorter when Profile series 29 was used (P = .00). Regarding cleanliness, there were no statistical differences in the teeth halves evaluations (P = .05). Hand instruments cleaned the canals significantly better than Profiles, in the radiographic analysis considering the whole canal. Overall, the radiographic analysis showed a smaller percentage of residual debris than the teeth halves analysis. Conclusion. The Profile series 29 instruments proved to be faster than hand instruments in removing root filling materials; however, hand instruments yielded better root canal cleanliness. Some residual debris was not visualized by radiographs. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e46-e50)

Experience With Lacosamide in a Series of Children With Drug-Resistant Focal Epilepsy

We report our pediatric experience with lacosarnide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n = 3), vagus nerve stimulation (n = 9), and ketogenic diet (n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (>= 50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with >= 50% seizure reduction) without severe adverse events. (C) 2011 Elsevier Inc. All rights reserved.

A Time-Series Analysis of the H alpha Emission Line in V3885 Sagitarii

Flickering is a phenomenon related to mass accretion observed among many classes of astrophysical objects. In this paper we present a study of flickering emission lines and the continuum of the cataclysmic variable V3885 Sgr. The flickering behavior was first analyzed through statistical analysis and the power spectra of lightcurves. Autocorrelation techniques were then employed to estimate the flickering timescale of flares. A cross-correlation study between the line and its underlying continuum variability is presented. The cross-correlation between the photometric and spectroscopic data is also discussed. Periodograms, calculated using emission-line data, show a behavior that is similar to those obtained from photometric datasets found in the literature, with a plateau at lower frequencies and a power-law at higher frequencies. The power-law index is consistent with stochastic events. The cross-correlation study indicates the presence of a correlation between the variability on Ha and its underlying continuum. Flickering timescales derived from the photometric data were estimated to be 25 min for two lightcurves and 10 min for one of them. The average timescales of the line flickering is 40 min, while for its underlying continuum it drops to 20 min.

Uranium series disequilibria in ground waters from a fractured bedrock aquifer (Morungaba Granitoids-Southern Brazil): Implications to the hydrochemical behavior of dissolved U and Ra

Activity concentrations of dissolved U-234, U-238, Ra-226 and Ra-228 were determined in ground waters fromtwo deep wells drilled in Morungaba Granitoids (Southern Brazil). Sampling was done monthly for little longer than 1 year. Significant disequilibrium between U-238, U-234 and Ra-226 were observed in all samples. The variation of U-238 and U-234 activity concentrations and U-234/U-238 activity ratios is related to seasonal changes. Although the distance between the two wells is short (about 900m), systematic differences of activity concentrations of U isotopes, as well as of U-234/U-238, Ra-226/U-234 and Ra-228/Ra-226 activity ratios were noticed, indicating distinct host rock-water interactions. Slightly acidic ground water percolation through heterogeneous host rock, associated with different recharge processes, may explain uranium and radium isotope behavior. (c) 2008 Elsevier Ltd. All rights reserved.