Autoantibodies directed against bactericidal/permeability-increasing protein in patients with cystic fibrosis: association with microbial respiratory tract colonization

BACKGROUND: Cystic fibrosis (CF) is associated with the appearance of serum autoantibodies directed against bactericidal/permeability-increasing protein (BPI). OBJECTIVES: To determine the age-specific seroprevalence rates of anti-BPI-IgG and IgA in a population of patients with CF and to correlate anti-BPI antibody concentrations with microbial respiratory tract colonization and pulmonary function variables at the time of serum sampling and 6 years thereafter. METHODS: Determination of BPI antibodies of the IgG and IgA isotypes using a commercial enzyme-linked immunosorbent assay in sera of a CF serum bank of 1992; correlation of anti-BPI antibody concentrations with age, clinical score, pulmonary function variables in 1992 and 1998, total serum immunoglobulin isotype concentrations and respiratory tract colonization with Pseudomonas aeruginosa and Aspergillus spp. RESULTS: Seventy-one patients (age in 1992, 14.1 +/- 7.5 years) were studied. Reactivities for anti-BPI-IgG and IgA were found in 28 (39%) and 26 (37%) patients, respectively. The seroprevalence of anti-BPI-IgA, but not IgG, increased significantly with age. P. aeruginosa colonization was associated with elevated concentrations of anti-BPI-IgG (P = 0.003) and IgA (P = 0.037). There were significant negative correlations between pulmonary function variables (vital capacity, forced expiratory volume in 1 s) in 1992 and 1998, respectively, and concentrations of anti-BPI-IgG or IgA in a multiple regression analysis. Anti-BPI-IgG, but not IgA, remained significantly associated with P. aeruginosa colonization (P = 0.006) and with reduced vital capacity (P = 0.01) in 1998 after correction for total serum isotype concentration. CONCLUSIONS: Anti-BPI-IgG are strongly associated with concurrent P. aeruginosa colonization and with long term restrictive pulmonary function abnormalities.

Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA)

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

Relationships between structural and functional measures of nutritional status in a normally nourished population

Both anthropometric and functional measurements have been used in nutritional assessment and monitoring. Hand dynamometry is a predictor of surgical outcome and peak expiratory flow rate has been used as an index of respiratory muscle function. This study aims to measure in normal subjects the relationship between anthropometric measurements, voluntary muscle strength by hand grip dynamometry and respiratory muscle function by peak expiratory flow rate.

Oesophageal and gastric endoscopic foreign body removal: complications and follow-up of 102 dogs

OBJECTIVES: To assess complication rate, risk factors for complications and outcome in dogs with oesophageal and gastric endoscopic foreign body (FB) removal. METHODS: Medical records of 102 dogs undergoing endoscopic removal of oesophageal and/or gastric FBs from March 2001 to November 2006 were retrospectively reviewed. All owners were contacted by telephone to provide follow-up information. RESULTS: West Highland white terriers, Yorkshire terriers and Bernese mountain dogs were over-represented compared to the hospital population. Endoscopy alone was successful in 92/102 dogs (90.2 per cent), whereas gastrotomy (but no oesophagotomy) was required in 10 dogs (9.8 per cent). Complications in 13/102 dogs (12.7 per cent) were perforation (8), oesophageal stricture (1), oesophageal diverticula (1), perioesophageal abscess (1), pneumothorax and pleural effusion (1) and respiratory arrest (1). Six dogs (all weighing <10 kg) had complications resulting in death or euthanasia. Bone FBs, bodyweight of less than 10 kg, and oesophageal or gastric FB in place for more than three days were significant risk factors for complications. Of the dogs available for follow-up (75/96), 92 per cent had no complications after discharge. CLINICAL SIGNIFICANCE: Endoscopic FB removal is associated with a low overall complication rate with bone FBs and bodyweight of less than 10 kg as significant risk factors.

Mechanisms and drug therapy of pulmonary hypertension at high altitude

Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulmonary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension.

Clinical and histological characterization of hair coat and glandular tissue of Chinese crested dogs.

BACKGROUND Two varieties exist in the Chinese crested dog breed, namely hairless Chinese crested dogs presenting with hypotrichosis and dentition abnormalities, and the coated powderpuffs. Hairless Chinese crested dogs are obligate heterozygotes for a FOXI3 mutation, and this phenotype is classified as a form of canine ectodermal dysplasia. OBJECTIVES We provide a detailed histological description of hair follicles and their density for the three subphenotypes (true hairless, semi-coated and powderpuffs) of Chinese crested dogs. Apocrine and exocrine glands of the skin and other tissues were compared with findings reported from dogs with X-linked ectodermal dysplasia. ANIMALS Skin biopsies were collected from 22 Chinese crested dogs. Additionally, the glands of the skin and other tissues were examined from another two dogs available for postmortem examination. METHODS Skin biopsies and tissues were processed, stained and evaluated in a blinded fashion. RESULTS Hair follicular anomalies decreased with increasing number of hairs in the different phenotypes. The FOXI3 mutants had only simple primary hair follicles, whereas the nonmutant powderpuffs had compound follicles identical to other dog breeds. All Chinese crested dogs had an anagen-dominated hair cycle. Furthermore, apocrine glands in the skin and respiratory mucous glands of the mutant Chinese crested dogs were present and normal. CONCLUSIONS AND CLINICAL IMPORTANCE We have identified striking histopathological differences between the three subphenotypes of Chinese crested dogs. We clearly demonstrated distinct differences between the canine ectodermal dysplasia in Chinese crested dogs and dogs with X-linked ectodermal dysplasia.

Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1-0.01 microg/g, days 1-4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19-21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa (day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

The effectiveness of Alexander Technique on music performance and musicians’ health and well-being – a systematic review

Introduction Musicians often suffer injuries related to their music playing. Therefore, some use Alexander Technique (AT), a mental-physical method that facilitates to release unnecessary muscle tension and to re-educate non-beneficial movement patterns through enhanced kinaesthetic awareness. According to a recent review AT may be effective for chronic back pain [1]. This review aimed to evaluate the evidence for the effectiveness of AT lessons on music performance and musicians’ health and well-being. Methods The following electronic databases were searched up to July 2012 for relevant literature: PUBMED, Google Scholar, CINAHL and EMBASE. The search criteria were "Alexander technique" AND "music*" [all fields]. References were searched, and experts and societies of AT or musicians' medicine contacted for further publications. Results 100 studies were identified. 24 studies were included for further analysis, 5 of which were randomised controlled trials (RCTs), 5 controlled but not randomised (CTs), 5 without control group, 2 mixed methods (RCT and case studies), and 7 surveys. 13 to 72 musicians participated per RCT. In 5 RCTs AT groups received between 12 and 20 one-to-one lessons. In 4 RCTs control groups received no interventions. Primary outcomes were performance anxiety, music performance, "use" as well as respiratory function and pain. Performance anxiety decreased by AT in 3 of 4 RCTs and in 3 of 3 CTs. Music performance was improved by AT in 1 RCT, yet in 2 RCTs comparing neurofeedback (NF) to AT, only NF showed improvements. Discussion and Conclusion To investigate the effectiveness of AT in musicians a variety of study designs and outcome measures have been used. Evidence from RCTs suggests that AT may improve performance anxiety in musicians. Effects on music performance, body use and respiratory function yet remain inconsistent. Future trials with scientifically sound study designs are warranted to further and more reliably explore the potential of AT as a relatively low cost and low risk method in the interest of musicians. References [1] Woodman JP, Moore NR. Evidence for the effectiveness of Alexander Technique lessons in medical and health-related conditions: a systematic review. Int J Clin Pract 2012;66(1):98-112.

The Effectiveness of Alexander Technique on Music Performance and Musicians' Health and Well-being – a Systematic Review

Purpose Musicians often suffer injuries related to their music playing. Therefore, some use the Alexander Technique (AT), a psycho-physical method that helps to release unnecessary muscle tension and re-educates non-beneficial movement patterns through enhanced kinaesthetic awareness. According to a recent review AT may be effective for chronic back pain. This review aimed to evaluate the evidence for the effectiveness of AT lessons on music performance and musicians’ health and well-being. Methods The following electronic databases were searched up to July 2012 for relevant literature: PUBMED, Google Scholar, CINAHL and EMBASE. The search criteria were "Alexander technique" AND "music*" [all fields]. References were searched, and experts and societies of AT or musicians' medicine contacted for further publications. Results 100 studies were identified. 35 studies were included for further analysis, 5 of which were randomised controlled trials (RCTs), 5 controlled but not randomised, 5 not controlled, 5 qualitative case studies, 2 mixed-models (RCT and case studies), 7 surveys, 4 qualitative case reports and 2 unpublished pilot studies. 13 to 72 musicians participated per RCT. In 5 RCTs AT groups received between 12 and 20 one-to-one lessons. In 4 RCTs control groups received no interventions. Primary outcomes were performance anxiety, performance, "use" as well as respiratory function and pain. Performance anxiety decreased by AT in 3 of 4 RCTs. Music performance was improved by AT in 1 RCT, yet in 2 RCTs comparing neurofeedback (NF) to AT, only NF showed improvements. Conclusions To investigate the effectiveness of AT in musicians a variety of study designs and outcome measures have been used. Evidence from RCTs suggests that AT may improve performance anxiety in musicians. Effects on music performance, body use and respiratory function yet remain inconsistent. Future trials with well-established study designs are warranted to further and more reliably explore the potential of AT as a relatively low cost and low risk method in the interest of musicians.

Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

OBJECTIVE To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. STUDY DESIGN Prospective, experimental cross-over trial. ANIMALS Nine Norwegian Fjord research foals. METHODS Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. RESULTS We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine. CONCLUSION AND CLINICAL RELEVANCE These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.

Immunization against gonadotropin-releasing hormone in dairy cattle: Antibody titers, ovarian function, hormonal levels, and reversibility

Suppression of cyclic activity in cattle is often desired in alpine farming and for feedlot cattle not intended for breeding. A cattle-specific anti-GnRH vaccination (Bopriva, Zoetis Australia Ltd., West Ryde, Australia) is approved for use in heifers and bulls in New Zealand, Australia, Mexico, Brazil, Argentina, Turkey, and Peru. Eleven healthy, cyclic Swiss Fleckvieh cows were included in the study and vaccinated twice with Bopriva 4wk apart. Injection site, rectal body temperature, and heart and respiratory rates were recorded before and 3d following each vaccination. Blood samples were taken weekly for progesterone and estrogen analysis and to determine GnRH antibody titer. Ovaries were examined weekly, using ultrasound to count the number of follicles and identify the presence of a corpus luteum. Thirty weeks after the first vaccination, the cows were subjected to a controlled internal drug-releasing device-based Select-Synch treatment. The GnRH antibody titers increased after the second vaccination and peaked 2wk later. Estrogen levels were not influenced by vaccination, and progesterone level decreased in 7 of 11 cows up to 3wk after the second vaccination and remained low for 10 to 15wk following the second vaccination. The number of class I follicles (diameter ≤5mm) was not influenced by vaccination, whereas the number of class II follicles (diameter 6-9mm) decreased between 7 and 16wk after the first vaccination. Class III follicles (diameter >9mm) were totally absent during this period in most cows. The median period until recurrence of class III follicles was 78d from the day of the second vaccination (95% confidence interval: 60-92d). After vaccination, all cows showed swelling and pain at the injection site, and these reactions subsided within 2wk. Body temperature and heart and respiratory rates increased after the first and second vaccinations and returned to normal values within 2d of each vaccination. The cows in our study were not observed to display estrus behavior until 30wk after the first vaccination. Therefore, a Select-Synch protocol was initiated at that time. Ten cows became pregnant after the first insemination (the remaining cow was reinseminated once until confirmed pregnancy). Bopriva induced a reliable and reversible suppression of reproductive cyclicity for more than 2mo. The best practical predictor for the length of the anestrus period was the absence of class III follicles.

Cardiac lipid levels show diurnal changes and long-term variations in healthy human subjects

(1) H-MRS is regularly applied to determine lipid content in ectopic tissue - mostly skeletal muscle and liver - to investigate physiological and/or pathologic conditions, e.g. insulin resistance. Technical developments also allow non-invasive in vivo assessment of cardiac lipids; however, basic data about methodological reliability (repeatability) and physiological variations are scarce. The aim of the presented work was to determine potential diurnal changes of cardiac lipid stores in humans, and to put the results in relation to methodological repeatability and normal physiological day-to-day variations. Optimized cardiac- and respiratory-gated (1) H-MRS was used for non-invasive quantification of intracardiomyocellular lipids (ICCL), creatine, trimethyl-ammonium compounds (TMA), and taurine in nine healthy young men at three time points per day on two days separated by one week. This design allowed determination of (a) diurnal changes, (b) physiological variation over one week and (c) methodological repeatability of the ICCL levels. Comparison of fasted morning to post-absorptive evening measurements revealed a significant 37 ± 19% decrease of ICCL during the day (p = 0.0001). There was a significant linear correlation between ICCL levels in the morning and their decrease during the day (p = 0.015). Methodological repeatability for the ICCL/creatine ratio was excellent, with a coefficient of variance of ~5%, whereas physiological variation was found to be considerably higher (22%) in spite of a standardized physiological preparation protocol. In contrast, TMA levels remained stable over this time period. The proposed (1) H-MRS technique provides a robust way to investigate relevant physiological changes in cardiac metabolites, in particular ICCL. The present results suggest that ICCL reveal a diurnal course, with higher levels in the morning as compared to evening. In addition, a considerable long-term variation of ICCL levels, in both the morning and evening, was documented. Given the high methodological repeatability, these effects should be taken into account in studies investigating the metabolic role of ICCL.

[Air pollution and asthma in childhood].

Exposure to outdoor air pollutants and passive tobacco smoke are common but avoidable worldwide risk factors for morbidity and mortality of individuals. In addition to well-known effects of pollutants on the cardiovascular system and the development of cancer, in recent years the association between air pollution and respiratory morbidity has become increasingly apparent. Not only in adults, but also in children with asthma and in healthy children a clear harmful effect of exposure towards air pollutants has been demonstrated in many studies. Among others increased pollution has been shown to result in more frequent and more severe respiratory symptoms, more frequent exacerbations, higher need for asthma medication, poorer lung function and increased visits to the emergency department and more frequent hospitalisations. While these associations are well established, the available data on the role of air pollution in the development of asthma seems less clear. Some studies have shown that increased exposure towards tobacco smoke and air pollution leads to an increase in asthma incidence and prevalence; others were not able to confirm those findings. Possible reasons for this discrepancy are different definitions of the outcome asthma, different methods for exposure estimation and differences in the populations studied with differing underlying genetic backgrounds. Regardless of this inconsistency, several mechanisms have already been identified linking air pollution with asthma development. Among these are impaired lung growth and development, immunological changes, genetic or epigenetic effects or increased predisposition for allergic sensitisation. What the exact interactions are and which asthmatic phenotypes will be influenced most by pollutants will be shown by future studies. This knowledge will then be helpful in exploring possible preventive measures for the individual and to help policy makers in deciding upon most appropriate regulations on a population level.