Teenage asthma after severe early childhood wheezing: an 11-year prospective follow-up

The role of factors related to early wheezing and their associations with subsequent development of asthma are controversial. We reevaluated 81 children who had been prospectively followed up since hospitalization for wheezing at less than 2 years of age. The baseline data on characteristics of the children, family-related factors, and viral causes of wheezing were collected on entry into the study. At the median age of 12.3 years, current symptoms suggestive of asthma and allergy were recorded. As part of the clinical examination, an outdoor exercise challenge test and skin prick tests to common inhalant allergens were performed. Asthma, as indicated by current inhaled anti-inflammatory medication or repeated wheezing and positive result in the challenge test, was present in 32 (40%) children, and 90% of them were sensitized to at least one allergen. Early asthma-predictive factors were atopic dermatitis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.2-10.1) and the presence of specific IgE to inhalant allergens (OR, 11.3; 95% CI, 1.9-67.6). Respiratory syncytial virus (RSV) identification during wheezing in infancy was relatively rare (20%) among later asthmatics compared with other or no viral identification (52%) or rhinovirus identification (58%). Since the prevalence of childhood asthma in our area is 4.0-5.0%, we conclude that the increased risk of asthma persists until the teenage years after hospitalization for wheezing in infancy. The risk was about 5-fold after respiratory syncytial virus-induced wheezing, and more than 10-fold after rhinovirus-induced wheezing in the present study.     

Periodic properties of the histaminergic system of the mouse brain

Brain histamine is involved in the regulation of the sleep–wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1‐methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine‐N‐methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24‐h periodicity was observed. Brain tissue 1‐methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine‐N‐methyltransferase in the striatum and cortex did not show a 24‐h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12‐h periodicity. These results show that the activities of histamine‐metabolizing enzymes are not under simple direct circadian regulation. The complex and non‐uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness.     

Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity

Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3 h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid β (Aβ42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p = 0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aβ42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood–brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer’s pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.     

Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial

Open in a separate window OBJECTIVESCardiac surgery is associated with risk of cerebral injury and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) is suggested to be associated with cerebral injury. The ‘Perfusion Pressure Cerebral Infarcts’ (PPCI) trial randomized patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement to a MAP of 40–50 or 70–80 mmHg during CPB and found no difference in clinical or imaging outcomes between the groups. We here present PPCI trial predefined secondary end points, consisting of biomarkers of brain injury.METHODSBlood was collected from PPCI trial patients at baseline, 24 and 48 h after induction of anaesthesia and at discharge from the surgical ward. Blood was analysed for neuron-specific enolase, tau, neurofilament light and the glial marker glial fibrillary acidic protein. Linear mixed models were used to analyse differences in biomarker value changes from baseline between the 2 MAP allocation groups.RESULTSA total of 193 (98%) patients were included. We found no differences in biomarker levels over time from baseline to discharge between the 2 MAP allocation groups (P_NSE = 0.14, P_Tau = 0.46, P_NFL = 0.21, P_GFAP = 0.13) and the result did not change after adjustment for age, sex and type of surgery.CONCLUSIONSWe found no significant differences in levels of biomarkers of neurological injury in patients undergoing elective or subacute CABG and/or aortic valve replacement randomized to either a target MAP of 40–50 mmHg or a target MAP of 70–80 mmHg during CBP.     

Activated mast cells increase the level of endothelin-1 mRNA in cocultured endothelial cells and degrade the secreted Peptide

Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism.     

Occupational health in Central America

The 12.4 million economically active population (EAP) of the seven Central American countries includes a large informal sector. Social security covers only 14-60%. No surveillance of occupational safety and health (OSH) hazards or accidents exists. Extrapolating the incidence of occupational accidents among insured Costa Rican workers to the Central American EAP yields two million accidents yearly, still a gross underestimate. Occupational diseases are underreported, misdiagnosed, and not recognized as such. A number of regional OSH programs aim at modernization of the labor administrations and address the formal sector, in particular textile maquila, in connection with free trade agreements. The weak role of the ministries of health is expected to strengthen under the Pan American Health Organization OSH program. Employers largely influence new policies. Workers' influence on OSH policies has been weak, with only about 10% unionization rate and scarce resources and OSH knowledge. Informal workers, however, are getting organized. OSH research is underdeveloped and not linked to policy making. Construction, agriculture, and general un/underemployment are considered priorities for intervention. The informal sector needs to be included in national and regional OSH policies. Regional collaboration and international development support are of strategic importance to achieve sustainable improvement in OSH.     

Autogenous bone graft and ePTFE membrane in the treatment of peri-implantitis. I. Clinical and radiographic observations in cynomolgus monkeys

The purpose of the study was to examine the effect of autogenous bone graft particles and expanded polytetrafluoroethylene (ePTFE) membrane in the treatment of peri-implantitis. The treatment outcome was evaluated by clinical and radiographic methods including quantitative digital subtraction radiography. A total of 64 implants with a titanium plasma-sprayed (TPS) surface was inserted in eight cynomolgus monkeys (Macaca fascicularis). After a 3-month healing period with plaque control, experimental peri-implantitis characterized by a bone loss of 4-6 mm was established during 14-22 months. Plaque control was then re-implemented and surgical treatment involving autogenous bone+membrane (B+M), autogenous bone (B), membrane (M), or a conventional flap procedure alone (control) (C) was performed. The animals were killed 6 months after treatment. Healthy peri-implant tissue was established irrespective of the applied surgical procedure. A mean bone gain of 4.7 mm was identified around implants treated with B+M, while, respectively, 4.0, 3.0, and 1.9 mm were recorded within the B, M, and C groups. Quantitative digital subtraction radiography confirmed considerable bone gain within defects treated with autogenous bone with or without membrane coverage. The bone gain, especially for defects treated with B+M, seemed to be almost to the level before development of peri-implantitis. By contrast, 38 and 25% of the defect was on average characterized by bone gain when, respectively, M or C was used alone. The present study of implants with a TPS surface in cynomolgus monkeys thus demonstrates considerable bone regeneration after treatment of experimental peri-implantitis with autogenous bone graft particles with or without ePTFE membrane coverage. Further stereologic and histologic evaluation of the treatment outcome is necessary before final conclusions about the effect of autogenous bone graft and ePTFE membrane can be made.     

Implant surface preparation in the surgical treatment of experimental peri-implantitis with autogenous bone graft and ePTFE membrane in cynomolgus monkeys

The aim of the present investigation was to assess the effect of four implant surface preparation methods used in the surgical treatment of experimental peri-implantitis with autogenous bone graft and expanded polytetrafluoroethylene (ePTFE) membrane. The methods were air-powder abrasive unit+citric acid, air-powder abrasive unit, gauze soaked in saline+citric acid, and gauze soaked alternately in chlorhexidine and saline. A total of 64 implants with a titanium plasma-sprayed (TPS) surface was placed in eight cynomolgus monkeys (Macaca fascicularis). After a 3-month period with plaque control, experimental peri-implantitis was induced. A bone loss of 4-6 mm was established after 9-17 months and plaque control was re-implemented. The peri-implantitis defects were surgically exposed, granulation tissue was removed, and each implant surface was prepared by one of the above-mentioned procedures. The defects were then filled with autogenous bone graft particles and covered by an ePTFE membrane. The animals were sacrificed after 6 months. Evaluation by clinical parameters, radiography including quantitative digital subtraction radiography, histology, and stereology did not reveal significant differences between the methods. Almost total bone regeneration and considerable re-osseointegration were obtained irrespective of the method applied. A mean bone-to-implant contact of 39-46% was observed within the defects. Therefore, the present study of implants with a TPS surface in cynomolgus monkeys indicates that the simplest method involving gauze soaked alternately in chlorhexidine and saline should be the preferred implant surface preparation method in the surgical treatment of peri-implantitis involving autogenous bone graft and ePTFE membrane.