Prevalence of gastroesophageal reflux in dogs undergoing MRI for a thoracolumbar vertebral column pathology.

OBJECTIVES: The aims of the study were to investigate the prevalence and extent of gastroesophageal reflux, and the prevalence of regurgitation in dogs undergoing thoracolumbar spine magnetic resonance imaging, and to explore possible associations of reflux and regurgitation with signalment (breed, age, sex, neuter status), bodyweight, body condition score and drugs used in the anaesthetic protocol. MATERIALS AND METHODS: The thoracic part of the oesophagus was retrospectively assessed for presence and quantification of fluid on two T2 weighted sequences. Patient breed, age, sex, neuter status, weight and body condition score were recorded. Anaesthetic records were reviewed for the presence of regurgitation and detailed anaesthetic protocols. RESULTS: Fifty percent (95% confidence interval: 45 to 57%) of included dogs had evidence of gastroesophageal reflux. Reflux was not associated with the individual breed, age, sex, neuter status or body weight. Brachycephalic dogs did not demonstrate significantly higher rates of reflux compared to non-brachycephalic dogs. A larger volume of reflux was associated with a higher chance of regurgitation. CLINICAL SIGNIFICANCE: Gastroesophageal reflux is a common finding in dogs undergoing thoracolumbar spine magnetic resonance imaging. Dogs which regurgitated had higher volumes of reflux. Early detection and quantification of the volume of reflux is helpful as it may allow the anaesthetist to take measures which may reduce the risk of associated complications.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Human bone marrow-derived mesenchymal stem cells rescue neonatal CPAP-induced airway hyperreactivity.

Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.

Respiratory characteristics of the tammar wallaby pouch young and functional limitations in a newborn with skin gas exchange.

A short gestation, low birth weight and presence of cutaneous exchange of O2 and CO2 comprise altricial features of newborn marsupials and that collectively implies a highly immature respiratory system. In the present study, we investigated various respiratory characteristics of the neonatal/postnatal tammar wallaby, a species of marsupial in which > 30% of the newborn's total O2 demands are supported by cutaneous rather than pulmonary gas exchange. The ventilatory response (HVR) to acute hypoxia (10% inspired O2) was absent in the newborn (1 day old) pouch young; a hypoxic hypometabolism contributed entirely to the hyperventilation (increased pulmonary convection requirement). A high (compared to older animals) resting metabolic cost to breathe and an inefficient respiratory system suggest the lack of a HVR might be due to an energetic constraint that impinges on their ability to sustain an increase in ventilation. The latter was supported by the inability of the newborn to tolerate metabolic-ventilatory stimulation following administration of the metabolic uncoupler, 2,4-dinitrophenol (2,4-DNP). At 1 week of age, the cost of breathing was reduced, which coincided with the expression of a significant ventilatory response to hypoxia, a more energetically efficient respiratory system, and tolerance to 2,4-DNP. These data suggest this species of marsupial is born with major respiratory insufficiency, and that their pronounced dependence on the skin for metabolic gas exchange is of critical importance for survival.

Influence of peri-incisional epaxial muscle infiltration with bupivacaine pre- or post-surgery on opioid administration in dogs undergoing thoraco-lumbar hemilaminectomy.

This study investigated the influence of bupivacaine infiltration before or after hemilaminectomy on peri-operative opioid requirement in dogs. Thirty dogs undergoing T3-L3 hemilaminectomy were randomly assigned to receive peri-incisional infiltration of bupivacaine 2 mg/kg into the epaxial muscles before surgery (Group A), at wound closure (Group B), or no infiltration (Group C). Anaesthesia comprised dexmedetomidine 4 mcg/kg and methadone 0.3 mg/kg IV (premedication), alfaxalone IV (induction), and isoflurane in oxygen (maintenance). All dogs received meloxicam SC/PO prior to induction of general anaesthesia. Response to surgery, defined as a change in autonomic physiological variables >20% above baseline, was treated with fentanyl 2.5 mcg/kg boluses, followed by a continuous rate infusion of fentanyl at 5 mcg/kg/h. The Glasgow Composite Pain Score-Short Form (GCPS-SF) was performed before premedication and at regular intervals until 24 h postoperatively. Methadone 0.2 mg/kg analgesia was given IV if GCPS-SF was ≥5/20. Number of intraoperative, postoperative and total analgesic interventions were recorded. Analgesic interventions were analysed using a chi-squared test using a Pocock approach and statistical significance was set at P < 0.029. The number of intra-operative analgesic interventions in Group A (median, 0; range, 0-2), was significantly lower than in Group B (median, 3; range, 0-5) and Group C (median, 3; range, 0-5; P = 0.019). Regarding postoperative interventions, there were significantly fewer in Group A (median, 0; range, 0-1) and Group B (median, 0; range, 0-1) than in Group C (median, 1; range, 0-2; P = 0.047). Group A (median, 0; range, 0-3), had significantly fewer total analgesic interventions than Group B (median, 3; range, 0-6) and Group C (median, 4; range, 1-7; P = 0.014). Bupivacaine reduced peri-operative opioid administration and pre-surgical peri-incisional infiltration yielded the greatest benefit.

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

Blood and urine biomarkers associated with long-term respiratory dysfunction following neonatal hyperoxia exposure: Implications for prematurity and risk of SIDS.

Former preterm infants, many of whom required supplemental O2 support, exhibit sleep disordered breathing and attenuated ventilatory responses to acute hypoxia (HVR) beyond their NICU stay. There is an increasing awareness that early detection of biomarkers in biological fluids may be useful predictors/identifiers of short- and long-term morbidities. In the present study, we identified serotonin (5-HT), dopamine (DA) and hyaluronan (HA) as three potential biomarkers that may be increased by neonatal hyperoxia and tested whether they would be associated with an impaired HVR in a rat model of supplemental O2 exposure. Neonatal rats (postnatal age (P) 6 days, P6) exposed to hyperoxia (40% FIO2, 24 h/day between P1-P5 days of age) exhibited an attenuated early (1 min), but not the late (4-5 min) phase of the HVR compared to normoxia control rats; the attenuated early phase HVR was associated with increased levels of DA (urine and serum), 5-HT (platelet poor plasma only, PPP), and HA (serum only). At P21, both the early and late phases of the HVR were attenuated, but serum and urine levels of all 3 biomarkers were similar to age-matched control rats. These data indicate that changes in several serum and/or urine biomarkers (5-HT, DA, and HA) following short-term (days) neonatal hyperoxia can signify long-term (weeks) respiratory control dysfunction. Further studies are needed to determine whether early detection of similar biomarkers could be convenient predictors of increased risk of abnormalities in respiratory control including sleep disordered breathing in former preterm infants who had received prior supplemental O2 and who might also be at increased risk of SIDS.

Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event.

The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.

Borderline Q-waves in individuals without overt cardiovascular disease: Relations with adiposity, subclinical atherosclerosis and vascular stiffness.

BACKGROUND: Characteristics and risk factors associated with electrocardiographic borderline Q-waves are not fully elucidated, especially in individuals without overt cardiovascular disease (CVD). Also, the relation of isolated and non-isolated borderline Q-waves with subclinical atherosclerosis and vascular stiffness is unknown. METHODS AND RESULTS: We included 5746 Netherlands Epidemiology of Obesity study participants without overt CVD. Participants were divided in three groups: no Q-waves (93.7%), isolated (4.6%) and non-isolated borderline Q-waves (1.7%). Borderline Q-waves were defined as Minnesota Codes 1.2.x and 1.3.x and non-isolated as ≥1 of abnormal QRS axis, left ventricular hypertrophy or ST/T abnormalities. Several characteristics and measures of body fat were assessed. Vascular stiffness was assessed by pulse wave velocity (PWV) and subclinical atherosclerosis by carotid intima-media thickness (cIMT). Percentage of men, alcohol intake, blood pressure and fasting glucose concentrations were, compared with no Q-waves, higher in the isolated and highest in the non-isolated borderline Q-wave group. Isolated borderline Q-waves were associated with higher body mass index (difference compared with no Q-waves: 1.0 kg/m2; 95%CI: 0.3-1.7; p-value: 0.006), waist circumference (3.4 cm; 1.0-5.8; 0.005), and visceral adipose tissue (21.9 cm2; 7.4-36.3; 0.003) and differences were even larger for non-isolated borderline Q-waves. Compared with no Q-waves, non-isolated borderline Q-waves were associated with higher PWV (1.2 m/s; 0.4-2.0; 0.004) and cIMT (23.4 µm; 3.0-43.8; 0.024), whereas isolated borderline Q-waves were not. CONCLUSION: Cardiovascular risk factors and measures of body fat, especially abdominal adiposity, were higher in participants with isolated borderline Q-waves, compared with no Q-waves, and highest in the non-isolated borderline Q-wave group. Non-isolated borderline Q-waves were associated with subclinical atherosclerosis and vascular stiffness. Future studies should investigate potential added value of borderline Q-waves in CVD prediction.

Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation.

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 1) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O2, 24 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day ( P) 5 ( P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (between P10 and P15). SH between P11 and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.

Enhancement of phrenic long-term facilitation following repetitive acute intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose.

Moderate acute intermittent hypoxia (mAIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with modest protocols of chronic intermittent hypoxia enhances pLTF, demonstrating pLTF metaplasticity. Since "low-dose" protocols of repetitive acute intermittent hypoxia (rAIH) show promise as a therapeutic modality to restore respiratory (and nonrespiratory) motor function in clinical disorders with compromised breathing, we tested 1) whether preconditioning with a mild rAIH protocol enhances pLTF and hypoglossal (XII) LTF and 2) whether the enhancement is regulated by glycolytic flux. In anesthetized, paralyzed, and ventilated adult male Lewis rats, mAIH (three 5-min episodes of 10% O2) elicited pLTF (pLTF at 60 min post-mAIH: 49 ± 5% baseline). rAIH preconditioning (ten 5-min episodes of 11% O2/day with 5-min normoxic intervals, 3 times per week, for 4 wk) significantly enhanced pLTF (100 ± 16% baseline). XII LTF was unaffected by rAIH. When glycolytic flux was inhibited by 2-deoxy-d-glucose (2-DG) administered via drinking water (~80 mg·kg-1·day-1), pLTF returned to normal levels (58 ± 8% baseline); 2-DG had no effect on pLTF in normoxia-pretreated rats (59 ± 7% baseline). In ventral cervical (C4/5) spinal homogenates, rAIH increased inducible nitric oxide synthase mRNA vs. normoxic controls, an effect blocked by 2-DG. However, there were no detectable effects of rAIH or 2-DG on several molecules associated with phrenic motor plasticity, including serotonin 2A, serotonin 7, brain-derived neurotrophic factor, tropomyosin receptor kinase B, or VEGF mRNA. We conclude that modest, but prolonged, rAIH elicits pLTF metaplasticity and that a drug known to inhibit glycolytic flux (2-DG) blocks pLTF enhancement.

Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms.

Daily acute intermittent hypoxia (dAIH) elicits respiratory plasticity, enhancing respiratory motor output and restoring breathing capacity after incomplete cervical spinal injuries (cSCI). We hypothesized that dAIH-induced functional recovery of breathing capacity would occur after both acute (2 weeks) and chronic (8 weeks) cSCI, but through distinct cellular mechanisms. Specifically, we hypothesized that dAIH-induced breathing recovery would occur through serotonin-independent mechanisms 2wks post C2 cervical hemisection (C2Hs), versus serotonin-dependent mechanisms 8wks post C2Hs. In two independent studies, dAIH or sham (normoxia) was initiated 1 week (Study 1) or 7 weeks (Study 2) post-C2Hs to test our hypothesis. Rats were pre-treated with intra-peritoneal vehicle or methysergide, a broad-spectrum serotonin receptor antagonist, to determine the role of serotonin signaling in dAIH-induced functional recovery. Our data support the hypothesis that dAIH-induced recovery of breathing capacity transitions from a serotonin-independent mechanism with acute C2Hs to a serotonin-dependent mechanism with chronic C2Hs. An understanding of shifting mechanisms giving rise to dAIH-induced respiratory motor plasticity is vital for clinical translation of dAIH as a therapeutic modality.

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

Intratracheal LPS administration attenuates the acute hypoxic ventilatory response: Role of brainstem IL-1ß receptors.

Perinatal inflammation and infection are commonly associated with various respiratory morbidities in preterm infants including apnea of prematurity. In this study, we investigated whether pulmonary inflammation via intra-tracheal micro-injection of lipopolysaccharide (LPS) into neonatal rats modifies respiratory neural control via an IL-1ß receptor-dependent mechanism. Prior to an intra-tracheal micro-injection of LPS (1mg/kg), 10day old (Postnatal age, P10) rats received an intraperitoneal (i.p.) or intracisternal (i.c.) micro-injection of the IL-1ß receptor antagonist AF12198. Whole-body plethysmography was performed two hours later to assess the magnitude of the acute hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses. Intra-tracheal LPS dose-dependently attenuated the acute HVR compared to saline (control) treated rats, whereas the HCVR was not affected. Pre-treatment with an i.c. (but not i.p.) micro-injection of AF12198 15min prior to LPS prevented the attenuated HVR. These data indicate that intrapulmonary inflammation affects brainstem respiratory neural pathways mediating the ventilatory response to acute hypoxia via an IL-1ß-dependent pathway. These findings are relevant to our understanding of the way that pulmonary inflammation may affect central neural mechanisms of respiratory insufficiency commonly seen in preterm infants.

Cardiorespiratory events in preterm infants: etiology and monitoring technologies.

Every year, an estimated 15 million infants are born prematurely (<37 weeks gestation) with premature birth rates ranging from 5 to 18% across 184 countries. Although there are a multitude of reasons for this high rate of preterm birth, once birth occurs, a major challenge of infant care includes the stabilization of respiration and oxygenation. Clinical care of this vulnerable infant population continues to improve, yet there are major areas that have yet to be resolved including the identification of optimal respiratory support modalities and oxygen saturation targets, and reduction of associated short- and long-term morbidities. As intermittent hypoxemia is a consequence of immature respiratory control and resultant apnea superimposed upon an immature lung, improvements in clinical care must include a thorough knowledge of premature lung development and pathophysiology that is unique to premature birth. In Part 1 of a two-part review, we summarize early lung development and diagnostic methods for cardiorespiratory monitoring.

Cardiorespiratory events in preterm infants: interventions and consequences.

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for sudden infant death syndrome.

KEY POINTS: Neonatal sustained hypoxia exposure modifies brainstem microglia and serotonin expression. The altered brainstem neurochemistry is associated with impaired ventilatory responses to acute hypoxia and mortality. The deleterious effects of sustained hypoxia exposure can be prevented by an inhibitor of activated microglia. These observations demonstrate a potential cause of the brainstem serotonin abnormalities thought to be involved in sudden infant death syndrome. ABSTRACT: We showed previously that the end of the second postnatal week (days P11-15) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH, 11% O2 , 5 days) exposure. In the current study, we investigated whether the vulnerability to SH during the same developmental time period is associated with changes in brainstem serotonin (5-HT) expression and whether it can be prevented by the microglia inhibitor minocycline. Using whole-body plethysmography, SH attenuated the acute (5 min) hypoxic ventilatory response (HVR) and caused a high incidence of mortality compared to normoxia rats. SH also increased microglia cell numbers and decreased 5-HT immunoreactivity in the nucleus of the solitary tract (nTS) and dorsal motor nucleus of the vagus (DMNV). The attenuated HVR, mortality, and changes in nTS and DMNV immunoreactivity was prevented by minocycline (25 mg kg(-1) /2 days during SH). These data demonstrate that the 5-HT abnormalities in distinct respiratory neural control regions can be initiated by prolonged hypoxia exposure and may be modulated by microglia activity. These observations share several commonalities with the risk factors thought to underlie the aetiology of sudden infant death syndrome, including: (1) a vulnerable neonate; (2) a critical period of development; (3) evidence of hypoxia; (4) brainstem gliosis (particularly the nTS and DMNV); and (5) 5-HT abnormalities.

Do tissue spears used to clear ear canal pus improve hearing? A case series study of hearing in remote Australian Aboriginal children with chronic suppurative otitis media before and after dry mopping with tissue spears.

OBJECTIVE: To determine whether the use of tissue spears to remove otorrhoea from Aboriginal children's ear canals improves hearing in the affected ear. DESIGN: Case series study with controls. METHODS: The study comprised 61 Aboriginal children from communities in the remote arid zone of South Australia who had otorrhoea obscuring the tympanic membrane in 1 or both ears. Eighty ears were treated with tissue spears, and hearing was assessed before and after treatment. RESULTS: Forty-two children had unilateral and 19 had bilateral active disease. An additional 13 ears without otorrhoea served as controls. Improvement by 5 dB HL or greater in a four-frequency pure tone average occurred in 41.3 per cent of treated ears. Subsequently, blinded audiologists made qualitative judgements that a functional improvement in hearing had occurred after tissue spear use in 28.4 per cent of ears. CONCLUSION: Tissue spears can improve hearing thresholds in a significant proportion of children with otorrhoea. However, the duration of the effect is unknown.

Comparison of two passive warming devices for prevention of perioperative hypothermia in dogs.

OBJECTIVE: To compare effects of two passive warming methods combined with a resistive heating mat on perioperative hypothermia in dogs. MATERIALS AND METHODS: Fifty-two dogs were enrolled and randomly allocated to receive a reflective blanket (Blizzard Blanket) or a fabric blanket (VetBed). In addition, in the operating room all dogs were placed onto a table with a resistive heating mat covered with a fabric blanket. Rectal temperature measurements were taken at defined points. Statistical analysis was performed comparing all Blizzard Blanket-treated to all VetBed-treated dogs, and VetBed versus Blizzard Blanket dogs within spay and castrate groups, spay versus castrate groups and within groups less than 10 kg or more than 10 kg bodyweight. RESULTS: Data from 39 dogs were used for analysis. All dogs showed a reduction in perioperative rectal temperature. There were no detected statistical differences between treatments or between the different groups. CLINICAL SIGNIFICANCE: This study supports previous data on prevalence of hypothermia during surgery. The combination of active and passive warming methods used in this study prevented the development of severe hypothermia, but there were no differences between treatment groups.

Sleep-disordered breathing and idiopathic pulmonary fibrosis--is there an association?

BACKGROUND: Very little data exists on the prevalence and impact of sleep-disordered breathing (SDB) in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the impact of SDB on newly diagnosed IPF patients and explore associations with lung function parameters. METHODS: From 2005 to 2009, a cohort of 27 newly diagnosed patients with IPF underwent unattended polygraphy. All patients were diagnosed according to ATS 2000 diagnostic criteria and were not on supplemental oxygen or other treatment. Standard statistical analysis was undertaken using SPSS v. 19 (IBM). RESULTS: Of the 27 patients, 19 were men. There was no correlation at baseline of apnoea + hypopnoea per time in bed (AH), oxygen desaturation index, or 4% desaturations with any lung function variables, age, or body mass index. Six patients had significant SDB (AH >20). Two patients were started on CPAP following polygraphy. No variables from the original sleep studies at baseline predicted eventual long-term oxygen therapy (LTOT) use. At 5-year follow-up, 18 of 27 patients had died (67%). Cox regression analysis showed no association of time spent at SpO2 <90% on baseline polygraphy with survival (p = 0.39). There was no association with survival for AH >20 (p = 0.4) or LTOT use (p = 0.19). CONCLUSION: Our results do not support the contention that nocturnal upper airway obstruction in steroid-free patients with IPF is a common problem or correlated with lung function. In this cohort of patients, there was no evidence that significant SDB at baseline was a predictor of survival.