Is routine pathological examination required in South African children undergoing adenotonsillectomy?

Objective. We aimed to determine the incidence of abnormalpathological findings in the tonsils and/or adenoids of children undergoing tonsillectomy and/or adenoidectomy, and the incidence of tuberculosis of the tonsils and adenoids; suggest criteria to identify children at risk for adenotonsillar tuberculosis; and investigate the association between HIV and adenotonsillar abnormality, the cost-effectiveness of routine pathological examination of adenotonsillectomy specimens, and criteria to decide which specimens to send for histological examination.Methods. We undertook an 8-month prospective study on all children (.12 years) undergoing consecutive tonsillectomy or adenotonsillectomy (T&A) at Red Cross War Memorial Childrenfs Hospital. Patients were assessed pre-operatively and tonsil sizes graded pre- and intra-operatively. Blood was taken for HIV testing, and all tonsils and adenoids were examined histologically. A cost-benefit analysis was done to determine the cost-effectiveness of adenotonsillectomy routine pathology.Results. A total of 344 tonsils were analysed from 172 children (102 boys, 70 girls); 1 patient had nasopharyngeal tuberculosis, and 1 lymphoma of the tonsils; 13 (7.6%) patients had clinically asymmetrically enlarged tonsils but no significant abnormal  pathological finding. The average cost of detecting a clinically significant abnormality was R22 744 (R45 488 € 2 abnormalities).Conclusions. The following criteria could improve cost-effectiveness of pathological examination of adenotonsillectomy specimens: positive tuberculosis contact at home, systemic symptoms of fever and weight loss, cervical lymphadenopathy >3 cm, suspicious nasopharyngealappearance, HIV-positive patient, rapid tonsillar enlargement or significant tonsillar asymmetry. On our evidence, routine pathological investigation for South African children does not seem to be justified

ICAR: endoscopic skull‐base surgery

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Reassessment of pre-industrial fire emissions strongly affects anthropogenic aerosol forcing

Uncertainty in pre-industrial natural aerosol emissions is a major component of the overall uncertainty in the radiative forcing of climate. Improved characterisation of natural emissions and their radiative effects can therefore increase the accuracy of global climate model projections. Here we show that revised assumptions about pre-industrial fire activity result in significantly increased aerosol concentrations in the pre-industrial atmosphere. Revised global model simulations predict a 35% reduction in the calculated global mean cloud albedo forcing over the Industrial Era (1750–2000 CE) compared to estimates using emissions data from the Sixth Coupled Model Intercomparison Project. An estimated upper limit to pre-industrial fire emissions results in a much greater (91%) reduction in forcing. When compared to 26 other uncertain parameters or inputs in our model, pre-industrial fire emissions are by far the single largest source of uncertainty in pre-industrial aerosol concentrations, and hence in our understanding of the magnitude of the historical radiative forcing due to anthropogenic aerosol emissions

Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index

Contains fulltext : 103595.pdf (publisher's version ) (Open Access)Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects