Utility of cough response during hypertonic histamine challenge in diagnosing asthma

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population. The study population consisted of 25 healthy volunteers, 30 asthmatics, and 82 non-asthmatic subjects with respiratory symptoms due to other diseases. Hypertonic histamine solution was administered with ultrasonic nebuliser with the challenges being videotaped. The cough response was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). The geometric mean (95% CI) of CCR for asthmatics was 302 (166-562) coughs per mg/ml, for the symptomatic controls 29.5 (20.0-43.7) coughs per mg/ml (p<0.001) and for the healthy controls 6.61 (3.02-14.5) (p<0.001) coughs per mg/ml. According to the ROC curve, the optimal cut-off point for logCCR was 2.22, with the specificity and sensitivity to detect asthma among symptomatic subjects being 86% and 70%. Cough response to hyperosmolar challenge may be useful in the differential diagnosis of airway diseases.     

Islet beta-cell-specific T cells can use different homing mechanisms to infiltrate and destroy pancreatic islets

Organ infiltration by T cells depends on the adhesion molecules expressed in these sites and on homing receptors expressed by the T cells. Here, we have studied which form of priming can enable T cells to home to pancreatic islets. To this end, we have used transgenic mice expressing the model autoantigen ovalbumin in pancreatic islets and transgenic ovalbumin-specific CD4 and CD8 T cells. We demonstrate that these T cells were imprinted with homing receptor patterns characteristic for the site of priming, such as alpha4beta7 integrin for mucosal antigen delivery or functionally active alpha4beta1 integrin for islet autoantigens. The adhesion molecules corresponding to these receptors were found to be constitutively expressed in islets, enabling T cells bearing these receptors to infiltrate the islets and to cause diabetes. Disease was prevented only by blockade of the endothelial adhesion molecule, ligand of homing receptors with which the T cells were imprinted. Thus, different priming locations induced different homing mechanisms, allowing T cells to target the islets. This may contribute to the susceptibility of islets to T-cell-mediated attack. Furthermore, it may pertain to the design of adhesion-modulating therapies alone or in combination with external autoantigen administration.     

The effects of irradiation and hyperbaric oxygen on bone formation during rabbit mandibular distraction

[18F-]fluoride positron-emission tomography (PET) was used to assess bone formation during mandibular distraction osteogenesis. There were three study groups: irradiation, irradiation+hyperbaric oxygen and control. The two experimental groups received a tumoricidal dose of irradiation to the mandible, and one group was also given hyperbaric oxygen (2.5 ATA (atmospheres absolute) for 90 min) 18 times preoperatively. Control animals received neither irradiation nor oxygen. A unilateral osteotomy was made and, after a period of latency, bone distraction was started, continued for 2 weeks, and the distraction generated was then allowed to consolidate for 4 weeks. The first PET study was performed at the end of distraction and the second at the end of consolidation. At the end of distraction, the metabolic activity of bone in the distracted area was significantly higher in the controls than in either experimental group; differences between the experimental groups were not statistically significant. By the end of consolidation, activity in the control group had diminished to the same as in the two experimental groups, in which no significant change had occurred. Radioactivity was still significantly higher at second imaging on the distracted than non-distracted side in the control and irradiation+hyperbaric oxygen groups, but not in the group that was only irradiated. The results indicate that previous irradiation disturbs bone formation during mandibular distraction osteogenesis. Hyperbaric oxygen was not able to prevent the suppression of osteogenesis caused by radiotherapy but it might improve bone formation by prolonging high osteogenic activity.     

Aqueous starch acetate dispersion as a novel coating material for controlled release products.

The aim of this study was to evaluate film-formation properties of a novel, organic solvent-free aqueous dispersion of potato starch acetate (SA; degree of substitution 2.8) and its ability to control drug release from a coated tablet. Initially, film-formation mechanisms and drug permeabilities of both organic solvent and dispersion-based SA free films (prepared by cast or spraying techniques) were investigated. The SA dispersion was suitable for the fluid-bed coating process, forming strong films with complete coalescent polymeric spheres. The model compounds predominantly permeated via the micro-pores of SA free films, which resulted from the leaching of water-soluble excipients from the dispersion. Thus, the permeation rate depended on the film structure rather than the physico-chemical properties of the penetrant. In the case of SA-coated tablet, drug release was sustained when the coating level was increased (from 12% to 20%, stated as a weight gain), and also as lipophilicity of the drug increased. When compared to the reference polymer dispersion (Surelease), SA coatings showed better mechanical properties against the osmotic pressure caused by a hydrophilic core tablet. These results clearly demonstrate that SA dispersion has high utility as a novel aqueous coating material for controlled release products.     

Concentrations and number size distribution of fine and nanoparticles in a traditional Finnish bakery

In bakeries, high concentrations of flour dust can exist and ovens release particles into the air as well. Particle concentrations (mass, number) and number size distribution may vary considerably but the variation is not commonly studied. Furthermore, the role of the smallest size fractions is rarely considered in the exposure assessment due to their small mass. The objectives of this work were to find out how concentrations and number size distribution of fine and nanoparticles vary in a traditional Finnish bakery and to determine the exposure of a dough maker to the nanoparticle fraction of the inhalable dust.

Two measurement campaigns were carried out in a traditional, small-scale bakery. Sampling was performed at the breathing zone of the dough maker and three stationary locations: baking area, oven area, and flour depository. Both real-time measurements and conventional gravimetric sampling were conducted. Nanoparticle fraction of the inhalable dust was determined using an IOM sampler with a customized precyclone.

Number concentration of fine and nanoparticles, and mass concentrations of both the inhalable dust and nanoparticles were high. The nanoparticle fraction was 9–15% of the inhalable dust at the breathing zone of the dough maker. Different sources, such as ovens and doughnut baking affected the number size distribution.

Flour dust contained nanoparticles but most of the fine and nanoparticles were released into the air from the oven operations. However, nanoparticles are not a primary concern in bakeries compared to health effects linked to the large flour particles such as flour-induced sensitization or asthma and development of occupational rhinitis.     

Case reports - Injury to the deep femoral artery during proximal locking of a distal femoral nail–a report of 2 cases

No Abstract available.     

Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks’ washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p = 0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p = 0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p = 0.0016). Both the Patient (p = 0.023) and Clinician (p = 0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.     

Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats

The effects of a novel prolyl oligopeptidase (POP) inhibitor KYP-2047 on spatial memory of young (3-month-old) and old (8- to 9-month-old) scopolamine-treated rats (0.4 mg/kg intraperitoneally) was investigated in the Morris water maze. In addition, the concentrations of promnesic neuropeptide substrates of POP, substance P and neurotensin in various brain areas after acute and chronic POP inhibition were measured in young rats. In addition, inositol-1,4,5-trisphosphate (IP(3)) levels were assayed in rat cortex and hippocampus after effective 2.5-day POP inhibition. KYP-2047 (1 or 5 mg/kg 30 min. before daily testing) dose-dependently improved the escape performance (i.e. latency to find the hidden platform and swimming path length) of the young but not the old rats in the water maze. POP inhibition had no consistent effect on substance P levels in cortex, hippocampus or hypothalamus, and only a modest increase in neurotensin concentration was observed in the hypothalamus after a single dose of KYP-2047. Moreover, IP(3) concentrations remained unaffected in cortex and hippocampus after POP inhibition. In conclusion, the behavioural data support the earlier findings of the promnesic action of POP inhibitors, but the mechanism of the memory-enhancing action remains unclear.