Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis-related, such as pulmonary hypertension. However, contemporary human studies in HbSS have used only surrogate markers of hemolysis rather than direct measurements of RBC survival. We directly quantified hemolysis in HbSS by measuring survival of an age cohort of RBCs labeled with a stable isotope, administered orally as 15N-glycine, a metabolic precursor of heme. The atomic excess of 15N in heme extracted from blood was monitored by mass spectrometry over time. We performed 13 labeling experiments in 11 individuals with HbSS. Mean RBC survival was 31.9 days (range 14.1 – 53.6). Both HbF level, a known determinant of hemolysis, and absolute reticulocyte count (ARC), an index of the marrow’s response to hemolysis, correlated with directly measured RBC survival (r=0.61, P<0.002; r=−0.84, P<0.001). However, commonly used biochemical surrogates of hemolysis (LDH, AST, bilirubin and plasma free hemoglobin) did not correlate with directly measured RBC survival. These biochemical surrogates should be interpreted cautiously, at best, in clinical trials and human physiologic studies in HbSS. ARC was the best correlate of total hemolysis, but only 70% of the variation in RBC survival was reflected in this marker. If greater accuracy is required in human studies, 15N-glycine RBC labeling can directly and accurately quantify hemolysis.

Background:Application of upper lip catch test (ULCT) for airway evaluation in edentulous patients.Methods:This research is an evaluation of a clinical diagnostic test in edentulous patients prior to operation. Five hundred eighty eight edentulous patients in a referral university hospital, between March 2008 and June 2011 scheduled for elective surgery under general anesthesia were enrolled. Those unable to open the mouth and those with pharyngo-laryngeal pathology were excluded. ULCT was assessed and compared with Cormack-Lehane grading as a gold standard for airway evaluation.Results:A high negative predictive value of 99.4% was a notable finding for the ULCT. The results also showed a high specificity (89.4%), high sensitivity (75.0%) and a high accuracy (89.3%) in a comparatively higher range for the ULCT.Conclusion:The ULCT proved to be a useful predictor for airway assessment in edentulous patients in this setting. Further studies are needed to reconfirm its validity in other ethnic groups.

SUMMARY The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing sympathetic nervous system input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here, we demonstrate that reduction of brain-melanocortin signaling actively promotes fat mass gain by activating the lipogenic program and adipocyte and endothelial cell proliferation in white fat depots independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. Those vagally regulated obesogenic signals also contribute to the fat mass gain following chronic high-fat diet feeding. These data reveal a physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6±2.25 years, and the mean followup was 5.3±4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.

Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS.

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Background:Unanticipated difficult tracheal intubation remains a primary concern of anaesthesiologists and upper lip bite test (ULBT) is one of the assessments used in predicting difficult intubation. In this study, we aimed to check the utility of lateral neck X-ray measurements in improving the diagnostic value of the ULBT.Methods:In a prospective study conducted from January 2007 until December 2010, we recorded personal and demographic data of 4500 patients who entered the study and subjected them to standard lateral neck radiography. Before the induction of anaesthesia, clinical examination and ULBT results were recorded and during induction of anaesthesia laryngoscopic grading was evaluated and recorded in questionnaires. All the compiled data were analysed by SPSS 14.0 (SPSS Inc., Chicago, IL, USA) software. Diagnostic value for each test was calculated and compared.Results:Negative predictive values (NPVs) were high in all tests. ULBT had the highest specificity and NPV compared with the other tests. The positive predictive value for all the tests had been low, but marginally high in the ULBT.Conclusion:Although all the tests used had relatively acceptable predictive values, combination of tests appeared to be more predictive. Highest sensitivities were observed with ULBT, mandibulohyoid distance and thyromental distance respectively. Use of radiological parameters may not be suitable as screening tools, but may help in anticipating and preparing for a difficult scenario.

Perioperative effects of oral midazolam premedication in children undergoing skin laser treatment. A double-blinded randomized placebo-controlled trial 1Efeitos peroperatórios da premedicação oral de midazolam em crianças submetidas a tratamento de pele por laser. Estudo duplo-cego randomizado e controlado. Mehrdad Shoroghi ABSTRACT Purpose:To investigate and compare the efficacy of oral midazolam with two different dosages in orange juice on perioperative hemodynamics and behavioral changes in children who underwent skin laser treatment in an academic educational Hospital. Methods: Ninety children, candidates for skin laser treatment were randomly assigned to 1 of 3 groups of 30 each: the placebo group received 0.1 ml/kg orange flavored juice, group 2 and 3 receiving 0.5 and 1 mg/kg of injectable midazolam mixed with an equal volume of orange juice, respectively. The main outcome measures included the mask acceptance, patients' behavioral scales and postoperative events. Results: There were no significant differences in heart rate, respiratory rate, and systolic blood pressure among the three groups. However, arterial oxygen saturation was significantly reduced in those given 1 mg.kg -1 midazolam. The median scores of anxiety, separation from parent, preparing an intravenous line, acceptance of the oxygen mask, good sedation, crying reduction and consciousness level were better in midazolam group. Postoperative agitation and re-crying were also more frequent in placebo receivers. Those given 1 mg.kg -1 midazolam were significantly more optimal for sedation, crying, consciousness, preparing an intravenous line, and postoperative re-crying compared with 0.5 mg.kg -1 midazolam receivers. Conclusion: As a preanaesthetic medication, the 1 mg.kg -1 dose of orally given midazolam especially in a volume of orange juice and can optimize the children's behavior during skin laser treatment with no serious adverse effects, enhancing their parents' satisfactions about the sedative protocol. Key words: Midazolam. Premedication. Anesthesia. Laser Therapy. Skin. RESUMO Objetivo:Investigar e comparar a eficácia do uso oral de midazolam com duas diferentes doses de suco de laranja na hemodinâmica peropeatória e mudanças de desempenho em crianças submetidas tratamento de pele por laser em Hospital educacional e acadêmico. Métodos: Noventa crianças candidatas a tratamento de pele por laser foram distribuídas aleatóriamente em três grupos de 30 cada: o grupo placebo recebeu 0.1mg/kg de suco de laranja, grupos dois e três receberam 0.5 e 1mg/kg de midazolam injetável misturado em igual volume de suco de laranja respectivamente. Os principais registros incluíam a aceitação da máscara, escalas de comportamento e eventos pós-operatórios. Resultados: Não houve diferenças significantes cardíacas, respiratórias e pressão sanguinea sistólica nos três grupos. Contudo, o nível de saturação de oxigênio foi reduzido significantemente nos que receberam 1mg.kg -1 de midazolam. Os níveis médios de ansiedade, separação dos pais, preparo intraveno...