Clinical application of ultrashort echo-time MRI for lung pathologies in children.

Lung magnetic resonance imaging (MRI) is considered to be challenging, because the low proton density of the tissue, fast signal decay, and respiratory artefacts hamper adequate image quality. MRI of the lungs and thorax is increasingly used in the paediatric population, because it is a radiation-free alternative to chest CT. Recently, ultrashort echo-time (UTE) sequences have been introduced into clinical MRI protocols, in order to improve the contrast-to-noise ratio due to reduced susceptibility artefacts and to depict structural alterations comparable to CT. The purpose of this review is to provide an overview of various clinical conditions and pathologies in the paediatric chest depicted by an UTE sequence, the so-called three-dimensional (3D) Cones sequence, in comparison with conventional MRI sequences. Besides describing typical features of cystic fibrosis, we present UTE application in other more or less common paediatric lung pathologies, for instance, interstitial pneumopathies, pulmonary infections, and congenital pulmonary malformations.

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial.

INTRODUCTION: Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF). METHODS: The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1). RESULTS: A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group. CONCLUSIONS: In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531).

[Ocular blood flow regulation in glaucoma - examination with the ocular pressure flow analyzer (OPFA)]. / Okuläre Durchblutungsregulation beim Glaukom. Untersuchungen mit dem Ocular Pressure Flow Analyzer (OPFA).

BACKGROUND: The results of studies of ocular blood flow (BF) regulation of patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) and ocular hypertension (OH) are presented. METHODS AND PATIENTS: Examinations were carried out with the "OPFA", a newly developed ocular pressure flow analyzer (producer: tpm Lüneburg) on 92 patients with newly diagnosed glaucomas, among whom 48 patients had POAG, 22 NTG and 22 OH, and compared with age-matched groups of healthy subjects. The OPFA uses pneumatic coupling through special scleral suction cups to record ocular pulses with highly sensitive transducers and a suction pump for simultaneously increasing intraocular pressure (IOP). Following local drop anaesthesia on both eyes, IOP is artificially raised to suprasystolic values. While continuously lowering IOP, the ocular pulse is then recorded with increasing ocular perfusion pressure. We obtain the relative ocular pulse blood volume by correlating the ocular pulse amplitudes with a calibration volume of 1 µl. This enables us to collect reproducible data on intra- and inter-individual pulse blood volume (PVoc). The ocular perfusion pressure pulse blood volume curve characterizes the respective individual ocular circulation as well as systolic and diastolic ocular perfusion pressures. RESULTS: In healthy subjects, the ocular pulse blood volume remains stable over a certain range of ocular perfusion pressure (ppoc) changes. After exceeding a critical point (CP), the ocular pulse blood volume drops. We refer to the difference between the CP and IOP as the autoregulatory capacity (AC). In patients with POAG and in patients with NTG, the AC was reduced significantly compared with the groups of healthy subjects. The mean AC of patients with OH remained within the normal range. The ROC curves showed at an optimal cut-off value for POAG a sensitivity of 75.0 % and a specificity of 97.9 %, for NTG a sensitivity of 77.3 % and a specificity of 100 %. In patients with POAG and OH, the ocular arterial pressures were elevated. In patients with NTG they remained unchanged compared with the healthy subjects. The ocular perfusion pressures did not change in POAG as well as in NTG and OH. CONCLUSIONS: In patients with POAG and in patients with NTG the ocular BF regulation was impaired and detected by the OPFA device with a high level of reliability. Ocular arterial blood pressures were increased as a result of vascular regulation to keep up the ocular perfusion pressure and to maintain ocular perfusion.

Olfactory screening: validation of Sniffin' Sticks in Denmark.

OBJECTIVES: The Sniffin' Sticks 12-identification test (SIT-12) is the most commonly applied Danish olfaction screening tool; however, it has never been validated in a Danish population. The screening score depends on familiarity with descriptors, which is strongly influenced by linguistic and cultural factors, why validation is mandatory. This study aimed to validate the SIT-12 in a Danish population. DESIGN: Prospective controlled study. SETTING: Otorhinolaryngology department. PARTICIPANTS: The SIT-12 was applied to 100 normosmic, healthy adult Danish participants. MAIN OUTCOME MEASURES: Choice of descriptors was registered, along with nasal endoscopic examination, screening for cognitive impairment, depression and sinonasal symptoms. Descriptors of the original version of SIT-12 were evaluated in 50 participants, and misleading descriptors were identified. Modifications to these descriptors were subsequently validated in a comparable group of 50 participants. RESULTS: Mean odorant identification score in the evaluation group was 11.0 of a possible 12, and 11.6 in the validation group (P < 0.0001). Among all odorant identification errors in the evaluation group, 60% were due to two incorrect descriptors having close resemblance to the correct descriptors, lemon and cinnamon. Two additional descriptors were unfamiliar to more than half the participants. There was a significant difference in the distribution of wrong identification answers between odorants in the evaluation group (P < 0.001), but not in the validation group. CONCLUSIONS: The identified systematically wrong descriptors have been modified and validated in the Danish SIT-12.

Reference equations for ultrasound bone densitometry of the radius in Central European children and adolescents.

UNLABELLED: Bone density measurements are important for evaluation and follow-up of children with alterations in their mineral status (increased risk for fractures and osteoporosis subsequently). Interpretation of these measurements relies on the availability of appropriate reference equations. We developed gender-specific, age-dependent reference values of bone density for Central European children. INTRODUCTION: In recent years, there has been an increasing demand for the measurement of bone density in children exposed to an increased risk of early alterations in their bone status. These values must be compared to an adequate reference population. The aim of the present study was to create reference equations of radial speed of sound (SOS) for Central European children and adolescents. METHODS: In this cross-sectional study, SOS values were measured at the distal third of the radius in 581 Swiss children and adolescents (321 girls and 260 boys) aged 6 to 16 years using the Sunlight Omnisense® 7000P quantitative ultrasound system. RESULTS: Gender-specific reference equations for SOS values were derived by polynomial regression and combined a cubic dependence of age and a linear dependence of height. The fitted SOS curves in our study population show a plateau period in both genders for younger ages followed by an increase phase beginning at the age of 12 in girls and 14 in boys. Neither the reported level of physical activity nor additional sport nor self-reported calcium intake influenced the reference equations. CONCLUSIONS: Our results show a good agreement with similar studies using the same measurement technique on other body parts, suggesting a wide applicability of the obtained reference curves over different European populations.

Effect of plyometric training on neural and mechanical properties of the knee extensor muscles.

This study investigated neuromuscular adaptations of the knee extensors after 8 weeks of plyometric training. 23 subjects were randomly assigned to an intervention group and a control group. We measured isometric maximum voluntary torque (iMVT), rate of torque development (RTD) and impulse (IMP) over different time intervals. The neural drive to muscles was estimated with the interpolated twitch technique and normalized root mean square of the EMG signal. Contractile properties, H reflexes as well as jump height in squat jump (SJ) and countermovement jump (CMJ) were evaluated. Neuromuscular testing was performed at 2 knee angles, i. e., 80° and 45° (0° = full extension). The iMVT at 80° knee flexion was 23.1 N · m (95% CI: 0.1-46.1 N · m, P = 0.049) higher at post-test for the intervention group compared with controls. The same was true for RTD and IMP in the time interval 0-50 ms [308.7 N · m · s(-1) (95% CI: 28.8-588.6 N · m · s(-1), P = 0.033) and 0.32 N · m · s (95% CI: 0.05-0.60 N · m · s, P = 0.026), respectively]. These changes were accompanied by enhanced neural drive to the quadriceps muscle. Jump height in SJ and CMJ was higher at post-test for the intervention group compared with controls. Parameters at 45° knee flexion, contractile properties and evoked potentials did not differ between groups. Although hypertrophic changes were not measured, data suggest that the training regime probably induced mainly neural adaptations that were specifically related to the knee angle. The strength gains at 80° knee flexion likely contributed to the enhanced jump height in SJ and CMJ.

Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma.

BACKGROUND: Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age. METHODS: At baseline, IgE and eosinophils were measured in the blood, and FeNO was measured offline in 391 children aged 3-47 months with lower airway symptoms. We developed an asthma predictive index (API) including high FeNO as major criterion. At follow-up, primary outcome was physician-diagnosed asthma based on standardized interviews in those children reaching school age (n = 166). RESULTS: FeNO was significantly elevated in those children with later asthma (68/166) as compared to children not developing asthma. Median (IQR) FeNO was 10.5 (6.6-17.2) vs. 7.4 (5.3-10.3) ppb. Per 5 ppb FeNO increase, the odds ratio (95% CI) for asthma increased by 2.44 (1.61-3.70) without changing when adjusting for confounders. Using the new API, children scored at risk had 58.0% probability for later asthma, whereas the negative predictive value was 78.2%, which was comparable to the classical API. CONCLUSIONS: In this cohort of high-risk preschool children, elevated FeNO is associated with increased risk for school-age asthma. The new API including FeNO identifies children at risk of later asthma comparably to the classical API, but does not require blood sampling.

Effect of exercise-induced muscle damage on neuromuscular function of the quadriceps muscle.

Exercise-induced muscle injury is commonly accompanied by a reduction of muscular strength. It has been suggested that this reduction in voluntary force is attributable to "peripheral" and "central" mechanisms within the neuromuscular system. The quadriceps muscle of 15 subjects was damaged with four bouts of 25 maximal voluntary concentric-eccentric contractions at a speed of 60°/s. In a time period of 7 days, we investigated the contribution of agonist muscle activation and contractile properties (CP) to changes in isometric maximum voluntary torque (iMVT). In order to provide a comprehensive assessment, the neural drive to muscles was estimated with the interpolated twitch technique and root mean square of the EMG signal. CP were evaluated by analysing the twitch torque signal induced by single and doublet stimulation. Furthermore, we measured changes in alpha motoneuron excitability of vastus medialis at the spinal level due to muscle soreness using the H reflex technique. The iMVT was impaired at post, 24 h and 48 h, while rate of torque development and voluntary activation (VA) were only decreased immediately after the intervention. CP were impaired immediately after exercise and at 24 h. Maximal H reflex (Hmax), maximal M wave (Mmax) and the Hmax/Mmax-ratio were not affected. Sensation of muscle soreness assessment revealed impairments at 24 h, 48 h and 72 h. Data suggest that reduced VA and altered CP contribute to the force loss immediately after concentric-eccentric exercise. Thereafter, the impairment of CP seems to be mainly responsible for the reduced iMVT. In addition, there is no evidence for an association between muscle soreness and VA as well as between muscle soreness and spinal excitability.

Monitoring patients at risk of massive transfusion with Thrombelastography or Thromboelastometry: a systematic review.

BACKGROUND: Thrombelastography (TEG) and Thrombelastometry (ROTEM) are viscoelastic whole-blood assays evaluating the haemostatic capacity of blood. These devices are used in algorithms to guide transfusion of haemostatic blood components. METHODS: The methods used for this study were systematic reviews with meta-analyses and trial sequential analyses of randomised clinical trials (RCTs) of TEG/ROTEM-based algorithm compared with standard treatment in patients with bleeding. Primary outcome was all-cause mortality. We searched the literature in seven databases (up to 31 October 2010), reference lists, registers of ongoing trials, and contacted authors and experts. We extracted data from included studies related to study methods, interventions, outcomes, bias risk and adverse events using Cochrane methodology. All trials irrespective of blinding or language status were included. RESULTS: Nine trials involving 776 participants were included. Eight trials involved cardiac surgery with an average blood loss of 390-960 ml, and one trial investigated liver transplantations. One trial was classified as low-risk-of-bias trial. We found two ongoing trials. No impact was identified on mortality, amount of blood transfused, incidence of surgical reinterventions, time to extubation, or length of stay in hospital and intensive care unit. We identified a significant reduction in blood loss favouring the use of TEG/ROTEM {85 ml [95% confidence interval (CI) 29.4-140.7]} and in the proportion of patients receiving freshly frozen plasma and platelets [relative risk 0.39 (95%CI 0.27-0.57)]. CONCLUSION: There is currently weak evidence to support the use of TEG/ROTEM as a tool to guide transfusion in patients with severe bleeding. Further studies need to address other clinical settings and with larger blood losses.

Longitudinal monitoring of pediatric cystic fibrosis lung disease using nitrite in exhaled breath condensate.

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and airway infection. Nitrites in exhaled breath condensate (EBC-NO(2)(-)) have been shown to be increased in children and adults with CF compared to healthy controls suggesting its use as a measure of airway inflammation. This longitudinal study aimed to evaluate if repeated measurements of EBC-NO(2)(-) are helpful in monitoring CF lung disease activity in children. Thirty-two children with mild CF lung disease (age 10.6 +/- 3.3 years) were recruited in two study centers. Follow-up visits occurred every 3 months over a period of 1 year with a total of five visits. Each visit included a clinical assessment incorporating a modified Shwachman-Kulczycki (SK) score, spirometry, an oropharyngeal swab, or sputum sample for bacterial analysis and an EBC sample analyzed for NO(2)(-) using a spectrophotometric assay. Furthermore at the first and the last visit a chest radiograph was done and scored (Chrispin-Norman (CN) score). There was no correlation of EBC-NO(2)(-) and parameters of spirometry, SK-score, or CN-score. Furthermore, increased EBC-NO(2)(-) levels did not predict subsequent pulmonary exacerbations. We conclude that repeated measurements of EBC-NO(2)(-) are not helpful in the longitudinal monitoring of mild CF lung disease in children.

Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease.

Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood mononuclear cells (PBMC) from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls, upon exposure to a thyroid self-antigen, human thyroglobulin (Tg), in the presence of autologous serum. Initially, TNF-alpha and IL-2 were produced in all three groups, accompanied by IL-10. Release of IFN-gamma, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased TNF-alpha, IL-2, IFN-gamma and IL-10 responses, and PBMC from HT patients secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF-alpha production by HT cells also occurred in the presence of pooled normal sera, indicating a dependency on intrinsic cellular factors. Conversely, higher production of TNF-alpha and IL-5 occurred in the presence of autologous sera than in the presence of pooled normal sera in both patient groups, indicating a dependency on serum constituents. Complement appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN-gamma, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells.

Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis.

BACKGROUND: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment. METHODS: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis. RESULTS: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p=0.002 and p=0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis. CONCLUSIONS: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes.

Exhaled nitric oxide is not reduced in infants with cystic fibrosis.

Fractional exhaled nitric oxide (F(eNO)) has been reported to be reduced in cystic fibrosis (CF) patients. However, data from young children are conflicting and it is not clear whether this is a primary feature of the disease or a secondary response. The present study compared F(eNO) between CF and healthy infants using a validated single-breath technique. A total of 23 healthy infants (11 females; mean age 40.1 weeks) and 18 infants with CF (nine females; 64.9 weeks) underwent tests of lung function and F(eNO). Bronchoalveolar lavage (BAL) was collected from all CF infants 2-5 days after lung function testing. There was no significant difference in F(eNO) between the CF and healthy infants (geometric mean: 23.1 parts per billion (ppb) and 17.0 ppb, respectively). There was an inverse relationship between age and F(eNO) in the CF patients, but not in the healthy group. Within the CF group, there was no association between F(eNO) and any marker of airway inflammation measured in the BAL. Exhaled nitric oxide is not reduced in cystic fibrosis infants, but does decrease with age. The current data indicate that F(eNO) is not a good marker of airway inflammation in cystic fibrosis.

Validation of questions on asthma and wheeze in farming and anthroposophic children.

BACKGROUND: In most epidemiological surveys the estimated prevalence of asthma is based on questionnaire responses, which may depend on the individual's perception as well as medical consulting habits in a given population. Therefore, measurement of bronchial hyper-responsiveness as a key feature of asthma has been suggested as an objective parameter for asthma. OBJECTIVE: The aim of the present study was to validate questionnaire responses on asthma and wheeze against bronchial response to hypertonic saline (HS) (4.5%) in populations previously shown to have a lower prevalence of asthma and allergies: farmers' children and children from anthroposophic families. METHODS: Children whose parents had completed a written questionnaire in the cross-sectional PARSIFAL-study were drawn from the following four subgroups: 'farm children' (n=183), 'farm reference children' (n=173), 'Steiner schoolchildren' (n=243) and 'Steiner reference children' (n=179). Overall, 319 children with wheeze in the last 12 months and 459 children without wheeze in the last 12 months performed an HS challenge. RESULTS: Odds ratios, sensitivity, specificity, likelihood ratios and measures of association did not differ significantly between the four subgroups. The correlation between the bronchial response to HS and wheeze and asthma questions was moderate and similar for farm children, farm reference children, Steiner schoolchildren and Steiner reference children (kappa for 'wheeze': 0.25, 0.33, 0.31, 0.35, respectively, P=0.754, kappa for 'doctor's diagnosis of asthma': 0.33, 0.19, 0.33, 032, respectively, P=0.499). CONCLUSION: The findings from this study suggest that the reliabilitiy of questionnaire responses on asthma and wheeze is comparable between farmers' children, children raised in families with anthroposophic lifestyle and their respective peers.

Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation.

BACKGROUND: Lung disease in cystic fibrosis (CF) is established in early childhood with recurrent bacterial infections and inflammation. Using spirometry, the effect of this early lung damage cannot be measured until a child is 6 years of age when some irreversible lung damage may already have occurred. Techniques for measurement of lung function in infants and young children include raised volume rapid thoracic compression (RVRTC) and low frequency forced oscillation (LFFOT). The aim of this study was to investigate the role of inflammation and infection on a population of infants and young children with CF and to determine whether lung function in this population (measured by LFFOT) is affected by early lung disease. METHODS: Lung function was measured by LFFOT in 24 children undergoing bronchoalveolar lavage (BAL) on 27 occasions as part of an annual programme while still under general anaesthesia. Following lung function testing, three aliquots of saline were instilled into the right middle or lower lobe. The first aliquot retrieved was processed for the detection of microbes, and the remaining aliquots were pooled to assess inflammatory markers (cytology, IL-8, NE, LTB(4)). RESULTS: Inflammation (percentage and number of neutrophils) was significantly higher in children with infections (p<0.001, p = 0.04, respectively), but not in those with symptoms. Several markers of inflammation significantly correlated with LFFOT parameters (R, G, and eta). CONCLUSION: Infections and inflammation are established before symptoms are apparent. Inflammation is correlated with measures of parenchymal changes in lung function measured by LFFOT.

The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma.

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.

Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath.

BACKGROUND: The fractional concentration of nitric oxide (NO) in exhaled breath (FeNO) is increased in asthma. There is a general assumption that NO synthase (NOS) 2 in epithelium is the main source of NO in exhaled breath. However, there is no direct evidence to support the assumption and data from animal models suggest that non-inducible NOS systems have important roles in determining airway reactivity, regulating inflammation, and might contribute significantly to NO measured in exhaled breath. METHODS: Bronchial epithelial cells were obtained from healthy, atopic, and asthmatic children by non-bronchoscopic brushing. Exhaled NO (FeNO) was measured directly using a fast response chemiluminescence NO analyser. RNA was extracted from the epithelial cells and real time polymerase chain reaction was used to determine the expression of NOS isoenzymes. NOS2 was examined in macrophages and epithelial cells by immunohistochemistry. RESULTS: NOS1 mRNA was not detectable. NOS3 mRNA was detected in 36 of 43 samples at lower levels than NOS2 mRNA which was detectable in all samples. The median FeNO was 15.5 ppb (95% CI 10 to 18.1). There was a significant correlation between FeNO and NOS2 expression (R = 0.672, p<0.001). All epithelial cells exhibited NOS2 staining, whereas staining in the macrophages was variable and not related to phenotype. CONCLUSIONS: Only NOS2 expression was associated with FeNO in respiratory epithelial cells obtained from children (R = 0.672; p<0.001). This suggests that FeNO variability is largely determined by epithelial NOS2 expression with little contribution from other isoforms.

Affective disorder and 'psychopathy' in a sample of younger male delinquents.

OBJECTIVE: The authors' goal was to determine the prevalence of affective disorder, a history of traumatic events and the prevalence of post-traumatic stress disorder (PTSD) diagnosis in their relationship to 'psychopathy' in a sample of younger male delinquents admitted to a correctional institution. METHOD: As part of routine mental health screening, the SCID-1 and Psychopathy Checklist (PCL-R) were administered to 102 inmates aged 17-27 years. RESULTS: Affective disorder was found in 28% and 29% had a history of suicidal attempts. The PCL-R-score was significantly correlated with the number of prior threatening events, but PTSD could not be diagnosed in the 'psychopathic' group. The prevalence of affective disorder was significantly higher in the 'non-psychopathic' group. CONCLUSION: The inverse relationship between threatening events and the PTSD diagnosis seems to indicate other coping modalities than those found in 'non-psychopaths'. That finding is discussed against the background of psychophysiological data and psychosocial learning models.

Is risk associated with drinking water in Australia of significant concern to justify mandatory regulation?

Presently in Australia there are no mandatory drinking water standards. Here we argue that the risk associated with drinking water in Australia is of a dimension discernible to warrant mandatory regulations. The catchments that supply the major metropolitan areas of Sydney and Adelaide, and the groundwater for the city of Perth have been seriously compromised by the encroachment of development and activities. Melbourne in the past has generally relied on a closed catchment reservoir system; however, population growth in the near future will sequester the full online operation of additional reservoirs, which have multiple land use catchments. In addition to the current landscape circumstances, the management of a water system in itself proposes significant issues of risk. Two critical assumptions that are unique to a mass medium substance like water and dramatically alter the appraisal of risk are: (1) very large numbers of people are potentially exposed, and (2) small changes in contaminant levels may have adverse population outcomes. It is also known that water reticulation systems frequently suffer from contamination problems caused solely by the distribution system, and optimal management of these facilities would best be served by statutory protected transparency and dedicated water quality programs. In 1979, an Australian parliamentary committee stated that an "uncontaminated water supply is" a "basic requirement for the obtainment of good health"; however, recent surveys of Australian water systems show many are not meeting basic water quality criteria, and many communities are not receiving regular monitoring or testing as required by government authorized Australian drinking water guidelines. Exacerbating this situation is the lack of reporting and statutory endorsed standardized procedures to ensure information is properly and promptly recorded and that data are centralized for maximum benefit. The evaluation of risk associated with drinking water in Australia is often hampered by inadequate or incomplete data. Lastly, regional and rural water supplies face a vast array of contemporary problems and experiences that include widespread usage of pesticides and agricultural chemicals. In recent years, the Darling River has experienced the worst algal bloom known to man, and this river system not only supplies a number of regional and rural towns with water, but eventually connects with the River Murray, which supplies the State of South Australia with approximately 50% of its water requirements.