To proceed or not to proceed: ENT surgery in paediatric patients with acute upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection is the most common non-preventable cause of surgery cancellation. Consequently, surgeons and anaesthesiologists involved in elective ENT surgical procedures frequently face a dilemma of whether to proceed or to postpone surgery in affected children. METHODS: A literature review was conducted and a practical assessment algorithm proposed. CONCLUSION: The risk-benefit assessment should take into consideration the impact of postponing the surgery intended to bring relief to the child and the risks of proceeding with general anaesthesia in an inflamed airway. The suggested algorithm for assessment may be a useful tool to support the decision of whether to proceed or to postpone surgery.

The Impact of Partial Vascular Occlusion on Oxidative Stress Markers during Resistance Exercise.

This study sought to examine the effects of partial vascular occlusion (PVO) on oxidative stress markers in response to resistance exercise and at rest in young resistance-trained males. 12 resistance-trained males performed 6 conditions in random counterbalanced order: rest (R), low-intensity (LIRE: 30% 1RM) and moderate-intensity (MIRE: 70% 1RM) resistance exercise with or without PVO. Blood samples were obtained before and immediately after each condition and plasma protein carbonyls (PC), glutathione ratio, oxygen radical absorbance capacity (ORAC), and xanthine oxidase (XO) were evaluated. The addition of PVO resulted in significantly greater plasma PC and glutathione ratio in the rest condition. During LIRE the addition of PVO significantly attenuated plasma PC. The MIRE condition, independent of PVO, resulted in significantly higher PC concentration and glutathione ratio compared to the rest and LIRE conditions. The addition of PVO during MIRE resulted in a significant increase in PC. Thus, this study revealed that PVO increased oxidative stress at rest and enhanced the oxidative stress response to MIRE, but when combined with LIRE oxidative stress was attenuated. These findings suggest that the utilization of PVO during LIRE may alter ROS-induced accumulation in the blood which may influence cellular signaling.

Severity of pneumococcal versus non-pneumococcal acute otitis media in children.

BACKGROUND: Pneumococcal acute otitis media (AOM) has been previously considered as a more severe disease than that caused by other otopathogens, based on clinical and/or otologic scores. We sought to test this hypothesis in the pneumococcal conjugated vaccine (PCV) era. METHODS: Children <6 years who presented with 'severe' AOM episodes with middle ear fluid (MEF) cultures during 2008-2013 were retrospectively identified. 'Severe' AOM episodes were considered if tympanocentesis was required or if spontaneous otorrhea was present. Data were extracted for demographics, clinical and laboratory tests. Children were categorised according to their PCV status as 'unimmunised' or 'PCV7/PCV13 immunised' and according to their MEF culture results into the 'pneumococcal' or the 'non-pneumococcal' group. Leukocytosis was defined as white blood cells (WBC) count >15 000/µL, and elevated C-reactive protein (CRP) level was considered as >50 mg/L. RESULTS: Of 295 eligible AOM episodes, 106 (36%) were culture positive. Children in the pneumococcal group (65, 61%) had a significantly higher WBC counts and higher CRP levels, were more often <2 years old and were more prone to complicate with acute mastoiditis (AM), compared to children in the non-pneumococcal group, P = 0.03, P = 0.02, P = 0.04 and P = 0.03, respectively. In the pneumococcal group, unimmunised children had higher WBC counts when compared with PCV13-immunised children (P = 0.04), but there were no appreciable differences in CRP levels between unimmunised and PCV7/PCV13-immunised children. CONCLUSION: Pneumococcal AOM is associated with higher leukocytosis and CRP levels than non-pneumococcal AOM. Circulating Streptococcus pneumoniae strains causing 'severe' AOM in PCV13-immunised children yielded lower inflammatory responses when compared with unimmunised children.

Oxidative stress and inflammation response following aerobic exercise: role of ethnicity.

African-Americans are at a significantly greater risk for developing several diseases and conditions. These conditions often have underlying oxidative stress mechanisms. Therefore the purpose of this investigation was to ascertain the post-exercise oxidative response to a single bout of aerobic exercise in African-American and Caucasian college-age females. A total of 10 African-American and 10 Caucasian females completed the study. Each subject had her VO2 max measured while exercising on a treadmill. A week later, each subject returned to the laboratory and performed a 30-min run at 70% of her VO2max. Blood samples were taken immediately prior to and following exercise for analysis. Lipid hydroperoxides, protein carbonyls, malondialdehyde, xanthine oxidase, glutathione in the reduced (GSH) and oxidized (GSSG) forms, TNFα and interleukin 6 were measured from blood taken before and after exercise. Significance was set at p≤0.05 a priori. Xanthine oxidase was the only measure that did not significantly increase following exercise. All other markers showed a significant elevation in response to the exercise bout with no difference between groups except that the Caucasian group had significantly higher malondialdehyde post-exercise compared to the African-American group. This cohort of college-age African-American and Caucasian females showed little difference in their response to a single 30-min run at 70% of their max in the markers of oxidative stress within the blood.

Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis.

BACKGROUND: Patients undergoing bariatric surgery are at high risk of postoperative nausea and vomiting (PONV). Despite triple PONV prophylaxis, up to 42.7% of patients require antiemetic rescue medication (AERM). METHODS: This prospective, randomized study was conducted from November 2011 to October 2012. In the Classic group (n=59), patients underwent general anaesthesia with volatile anaesthetics and opioids. In the Total i.v. anaesthesia (TIVA) group (n=60), patients underwent opioid-free TIVA with propofol, ketamine, and dexmedetomidine. The severity of PONV was assessed using a Likert scale (none, mild, moderate, and severe). RESULTS: Patients in both groups had similar clinical characteristics, surgical procedure, and PONV risk scores and required similar amounts of postoperative opioid. In the Classic group, 22 patients (37.3%) reported PONV compared with 12 patients (20.0%) in the TIVA group [P=0.04; risk 1.27 (1.01-1.61)]. The absolute risk reduction was 17.3% (number-needed-to-treat=6). The severity of nausea was statistically different in both groups (P=0.02). The severity of PONV was significantly worse in the Classic group. There was no difference either in the number of patients requiring AERM in the postoperative period or in the number of AERM doses required. CONCLUSIONS: This prospective randomized study demonstrates that opioid-free TIVA is associated with a large reduction in relative risk of PONV compared with balanced anaesthesia. Clinical trial registration NCT 01449708 (ClinicalTrials.gov).

Day to Day Variability and Reliability of Blood Oxidative Stress Markers within a Four-Week Period in Healthy Young Men.

The present study aimed to determine the day to day variability and reliability of several blood oxidative stress markers at rest in a healthy young cohort over a four-week period. Twelve apparently healthy resistance trained males (24.6 ± 3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between visits at the same time of day. Subjects rested 30 minutes prior to blood being obtained by vacutainer. Results. The highest IntraClass correlations (ICC's) were obtained for protein carbonyls (PC) and oxygen radical absorbance capacity (ORAC) (PC = 0.785 and ORAC = 0.780). Cronbach's α reliability score for PC was 0.967 and for ORAC was 0.961. The ICC's for GSH, GSSG, and the GSSG/TGH ratio ICC were 0.600, 0.573, and 0.570, respectively, with Cronbach's α being 0.913, 0.904, and 0.903, respectively. Xanthine oxidase ICC was 0.163 and Cronbach's α was 0.538. Conclusions. PC and ORAC demonstrated good to excellent reliability while glutathione factors had poor to excellent reliability. Xanthine oxidase showed poor reliability and high variability. These results suggest that the PC and ORAC markers were the most stable and reliable oxidative stress markers in blood and that daily changes across visits should be considered when interpreting resting blood oxidative stress markers.

2-Butoxyethanol model of haemolysis and disseminated thrombosis in female rats: a preliminary study of the vascular mechanism of osteoarthritis in the temporomandibular joint.

Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further.

Resistance exercise effects on blood glutathione status and plasma protein carbonyls: influence of partial vascular occlusion.

Seven weight-trained males performed both light resistance with partial occlusion (LRO: 30% 1 RM) and moderate resistance (MR: 70% 1 RM) to failure to ascertain whether blood protein carbonyls (PC) and glutathione status was altered compared to partial occlusion (PO) in a counterbalanced fashion. PO was identical in duration to the LRO session and all sessions were on separate days. PC did not differ for the three conditions at PRE (0.05 nM mg protein(-1)). PC significantly increased for PO and MR over time and was greater than the LRO treatment at POST (0.13 nM mg protein(-1)). The GSSG/TGSH ratio at PRE did not differ across treatments (8%) whereas the ratio at POST was significantly elevated for PO and MR treatments (17%). In contrast, no change occurred for the LRO session at any time. These results indicate that MR to failure and PO can significantly increase blood oxidative stress but LRO did not elicit oxidative stress.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

Transcriptional control of megakaryocyte development.

Megakaryocytes are highly specialized cells that arise from a bipotent megakaryocytic-erythroid progenitor (MEP). This developmental leap requires coordinated activation of megakaryocyte-specific genes, radical changes in cell cycle properties, and active prevention of erythroid differentiation. These programs result from upregulation of megakaryocyte-selective transcription factors, downregulation of erythroid-selective transcription factors and ongoing mediation of common erythro-megakaryocytic transcription factors. Unlike most developmental programs, no single lineage-unique family of master regulators exerts executive control over the megakaryocytic plan. Rather, an assemblage of non-unique factors and signals converge to determine lineage and differentiation. In human megakaryopoiesis, hereditary disorders of platelet production have confirmed contributions from three distinct transcription factor families. Murine models have extended this repertoire to include multiple additional factors. At a mechanistic level, the means by which these non-unique factors collaborate in the establishment of a perfectly unique cell type remains a central question.

Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative stress to eccentric exercise.

This study investigated if vitamin C supplementation before and after eccentric exercise could reduce muscle soreness (MS), oxidative stress, and muscle function. Eighteen healthy men randomly assigned to either a placebo (P) or vitamin C (VC) (3 g/d) treatment group took pills for 2 wk prior and 4 d after performing 70 eccentric elbow extensions with their non-dominant arm. MS increased in both groups with significantly reduced MS for the first 24 h with VC. Range of motion was reduced equally in both groups after the exercise (P > or = 0.05). Muscle force declined equally and was unaffected by treatment. VC attenuated the creatine kinase (CK) increase at 48 h after exercise with similar CK after this time. Glutathione ratio (oxidized glutathione/total glutathione) was significantly increased at 4 and 24 h with P but VC prevented this change. These data suggest that vitamin C pretreatment can reduce MS, delay CK increase, and prevent blood glutathione oxidation with little influence on muscle function loss.

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Cold sensitivity of thermophilic and mesophilic RNA polymerases.

RNA polymerase from mesophilic Deinococcus radiodurans displays the same cold sensitivity of promoter opening as RNA polymerase from the closely related thermophilic Thermus aquaticus. This suggests that, contrary to the accepted view, cold sensitivity of promoter opening by thermophilic RNA polymerases may not be a consequence of their thermostability.

Image guided navigation system-a new technology for complex endoscopic endonasal surgery.

PURPOSE: Endoscopic endonasal surgery (EES) has become the standard practice in sinonasal and anterior skull base surgery. The purpose of this manuscript is to describe experience using a new technology-the image guided navigation system (IGNS)-in complex cases undergoing EES. The advantages and disadvantages of computer aided surgery are discussed. PATIENTS AND METHODS: A total of 165 endoscopic endonasal procedures were performed between April 2001 and January 2003. IGNS was used in 34 patients in whom it was assumed that the ability to identify surgical sites accurately could be compromised by previous surgery, massive recurrent polyposis, or abnormal anatomy, or when biopsies had to be taken from specific anatomic locations (for example, clivus, wall of sphenoid sinus, orbital apex). The precision of the navigation system, total operating room time, surgeon's satisfaction and confidence, and intraoperative and postoperative complications were recorded. RESULTS: In 33 out of 34 patients the surgical procedure was uneventful. One patient with an atelectatic maxillary sinus developed a minor complication of preseptal orbital haematoma. In 94% the IGNS provided accurate anatomical localisation with less than 2 mm localisation error (1.1-2.0 mm, mean 1.6 mm). In all cases the surgical team felt that the system increased the intraoperative safety factor for the patient. The overall operating room time at the end of the study was 15 minutes longer than when regular EES was used. CONCLUSIONS: IGNS enables a new level of efficiency and safety in EES. Nevertheless, it is not advised for surgeons who are not familiar with regular EES. For the experienced endoscopist, however, IGNS is a valuable new tool in complex procedures.

Plasma chitotriosidase activity in patients with beta-thalassemia.

Variable increases in chitotriosidase levels have been reported in Italian patients with beta-thalassemia major and intermedia. We measured plasma chitotriosidase levels in Israeli patients with beta-thalassemia to ascertain its use as a universal marker of disease and/or response to therapy. Chitotriosidase levels in 39 adults (16-53 years; 30 with beta-thalassemia major, 9 with intermedia), and in 14 children (0.7-15 years; 12 with beta-thalassemia major, 2 with intermedia) were compared with other measures of disease, such as ferritin, hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels were normal (0.37 +/- 0.04 mU/mL) in all children. Twelve adults (31%) had elevated levels (>1.33 mU/mL): 11 patients (37%) with thalassemia major and 1 patient (11%) with thalassemia intermedia. A significant correlation was only found between plasma chitotriosidase levels and ferritin levels, and with mean number of transfusions per year. The patient with the highest chitotriosidase (1,440 nmol/mL/hr) had the highest ferritin (5,175 microg/L), required the most transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase levels in the pediatric cohort and increased levels in only some adults may reflect status of iron overload in macrophages; thus there may be a role for monitoring chitotriosidase in patients with beta-thalassemia. Our results confirm results of the Italian cohort; however, in the latter, a more universal correlation was noted and chitotriosidase levels were much higher.

Changes in the reducing power of synovial fluid from temporomandibular joints with "anchored disc phenomenon".

PURPOSE: In this study, we examined the hypothesis that uncontrolled oxidative stress causes collapse of the lubrication system, which is considered a major initiator of temporomandibular joint (TMJ) dysfunction. The oxidative stress was evaluated by measuring the overall antioxidant capacity of the low-molecular-weight antioxidants in the TMJ, using cyclic voltammetry (CV), in synovial fluid from normal and anchored disc phenomenon (ADP) TMJs. MATERIALS AND METHODS: Synovial fluids samples were taken from 13 normally functioning and 33 ADP TMJs. The samples were frozen initially on collection and analyzed in CV to measure their overall reducing power. RESULTS: CV measurements of the fluids collected from 90% of the healthy joints showed an anodic waves at peak potential [Ep(a)1/2] of 290 +/- 30 mV. Of the samples 56% showed another wave at 650 +/- 100 mV. These waves were generally absent in the fluid collected from ADP TMJs, but 2 new waves at 465 +/- 90 mV and greater than 750 mV were detected in 68% and 87% of the patients, respectively. CONCLUSIONS: The results show more anodic waves, most of which of higher potentials (greater than 750 mV) in ADP TMJs, indicating that the capacity to cope with oxidative stress is lower in these joints. It is not clear whether this is due to absence of low-molecular-weight antioxidants or their consumption by uncontrolled production of reactive oxygen species, which might be the initial step in the collapse of the lubrication system.

Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients.

Renal involvement as part of systemic lymphoma (LY) is quite frequent, however, primary extranodal renal non-Hodgkin's lymphoma (NHL) is extremely rare, and only about 65 cases have been reported in the world literature. In a retrospective study of renal manifestations in 700 patients with documented LY and chronic lymphocytic leukemia (CLL) seen at our hospital during 1986-95, 83 patients had signs of acute renal failure. Only five of these had proven renal infiltration, but none of them satisfied the criteria for primary renal LY. Glomerulonephritis (GN) has also rarely been reported in association with LY and CLL, and only 37 glomerular lesions in NHL and 42 in CLL have been documented, respectively. GN may precede, coexist, or follow the diagnosis of LY by several years. Of the 42 cases of CLL reported worldwide, 36 had nephrotic syndrome. Renal failure was seen in about one third. The most common glomerular lesion reported is membranoproliferative GN, followed by membranous GN. In our study, we found only five biopsy-proven cases with GN amongst the 700 patients seen. In this report we also briefly describe some rare interesting associated renal syndromes in CLL and NHL.

Stromal inhibition of megakaryocytic differentiation correlates with blockade of signaling by protein kinase C-epsilon and ERK/MAPK.

Contact with bone marrow stromal cells maintains normal and leukemic hematopoietic progenitors in an undifferentiated state. Recently, stromal contact has been shown to diminish the yield of megakaryocytes in cultures of primary human hematopoietic stem cells. This inhibition may explain the poor megakaryocytic engraftment frequently observed after bone marrow transplantation. In the current study, stromal co-culture is shown to render K562 cells refractory to megakaryocytic induction. This stromal inhibition correlated with the selective down-regulation in K562 cells of protein kinase C-epsilon (PKC-epsilon), which has recently been implicated in regulation of megakaryocytic lineage commitment. In addition, the stromal inhibition correlated with inactivation of the ERK/MAPK pathway, which has also been implicated in promoting megakaryocytic development. Forced expression of PKC-epsilon by retroviral transduction was insufficient to reverse the stromal blockade of ERK/MAPK signaling or of megakaryocytic induction. Thus stromal interruption of ERK/MAPK signaling occurred independently of PKC-epsilon levels and correlated more closely with megakaryocytic blockade. These findings provide potential mechanisms for stromal inhibition of hematopoietic differentiation and possibly for the poor megakaryocytic engraftment seen after bone marrow transplantation.