Nasal cytokine responses to natural colds in asthmatic children.

BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1ß, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.

A third blind test of crystal structure prediction.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

Serum erythropoietin and erythropoiesis in patients with myelodysplastic syndromes.

Ineffective erythropoiesis is an early feature of the myelodysplastic syndromes (MDS), usually accompanying an hypercellular marrow. In a previous study, concentrations of serum erythropoietin (EPO) in MDS have been shown to correlate inversely both with haemoglobin concentration and with % bone marrow erythroblasts. We have measured erythroid production using a radioisotopic technique in 20 patients with MDS. Although haemoglobin concentration shows a weak inverse relationship with serum EPO concentration there is considerable variation in EPO concentration at a given haemoglobin level. There is no correlation between serum EPO and total erythroid production, though there is a weak correlation with effective erythropoiesis. The data suggests that control mechanisms of erythropoiesis in patients with MDS are complex.

The effect of advancing age on the sympathetic response to laryngoscopy and tracheal intubation.

The effect of aging on the hemodynamic and sympathetic response to tracheal intubation was evaluated in 27 patients aged 18 to 80 years, ASA Class I and II, given atropine 0.4 mg and diazepam 10 mg as premedication and thiopental, 4.0 mg/kg, and succinylcholine 100 mg for anesthesia induction. Laryngoscopy and tracheal intubation was performed 60 seconds after induction. The elderly had significantly less chronotropic response to intubation 2, 3, 4, and 5 minutes after induction so that the maximum increase in heart rate above awake values was negatively correlated with age (R = -0.66, P less than 0.001). Baseline systolic blood pressure (SBP) and mean BP increased significantly with age (R = 0.81, P less than 0.001 and R = 0.76, P less than 0.001, respectively) but age was not significantly related to increases in SBP and mean BP following intubation. Baseline plasma norepinephrine (NE) levels increased with age ( R = 0.51, P less than 0.01). Following intubation, mean plasma NE concentrations were significantly higher in elderly patients than young patients, despite the diminished heart rate response. Heart rate (HR) per pg/ml of NE, a measure of cardiac sensitivity to beta stimulation, was therefore significantly less 2, 3, and 4 mins after induction in elderly patients than in younger patients. To determine if this alteration in cardiac sensitivity to endogenous catecholamines was reflected by changes in beta receptor function on lymphocytes, beta receptor density and the proportion of receptor binding agonist with high affinity (%RH) were measured. No significant correlation between beta-receptor affinity for agonist, %RH, or receptor density was found with age, HR, or HR per pg/ml NE.(ABSTRACT TRUNCATED AT 250 WORDS)

A radiologic and anatomic study of internal derangements of the temporomandibular joint.

Fifteen temporomandibular joints (TMJs) in unfixed cadavers were examined clinically and then arthrograms were made. Eleven of the TMJ disks were mechanically displaced anteriorly before the arthrograms were made. The joints were removed, fixed, frozen, and sectioned perpendicular to the long axis of the condyle in 2 mm slices. The arthrograms of the joint were compared with arthrograms of each individual section and the original tissue slices to determine whether there was a definite correlation with true anatomic relationships. Because of the complexity of the internal morphology of the hard and soft tissues in the TMJ, no accurate or consistent conclusions about the actual physical relationships could be made by means of arthrogram.