Outdoor pollen is a trigger of child and adolescent asthma emergency department presentations: A systematic review and meta-analysis.

BACKGROUND: In the context of increased asthma exacerbations associated with climatic changes such as thunderstorm asthma, interest in establishing the link between pollen exposure and asthma hospital admissions has intensified. Here, we systematically reviewed and performed a meta-analysis of studies on pollen and emergency department (ED) attendance. METHODS: A search for studies with appropriate search strategy in MEDLINE, EMBASE, Web of Science and CINAHL was conducted. Each study was assessed for quality and risk of bias. The available evidence was summarized both qualitatively and meta-analysed using random-effects models when moderate heterogeneity was observed. RESULTS: Fourteen studies were included. The pollen taxa investigated differed between studies, allowing meta-analysis only of the effect of grass pollen. A statistically significant increase in the percentage change in the mean number of asthma ED presentations (MPC) (pooled results from 3 studies) was observed for an increase in 10 grass pollen grains per cubic metre of exposure 1.88% (95% CI = 0.94%, 2.82%). Time series studies showed positive correlations between pollen concentrations and ED presentations. Age-stratified studies found strongest associations in children aged 5-17 years old. CONCLUSION: Exposure to ambient grass pollen is an important trigger for childhood asthma exacerbations requiring ED attendance. As pollen exposure is increasingly a problem especially in relation to thunderstorm asthma, studies with uniform measures of pollen and similar analytical methods are necessary to fully understand its impact on human health.

Residential greenness and allergic respiratory diseases in children and adolescents - A systematic review and meta-analysis.

BACKGROUND: The aetiology of allergic respiratory disease in children is not yet fully understood. Environmental factors are believed to play a major part. The amount of green vegetation surrounding the home (residential greenness) has been recently identified as a potentially important exposure OBJECTIVES: Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between residential greenness and allergic respiratory diseases in children. METHODS: Peer-reviewed literature published prior to 1 March 2017 was systematically searched using nine electronic databases. Meta-analyses were conducted if at least three studies published risk estimates for the same outcome and exposure measures. RESULTS: We included 11 articles across broad outcomes of asthma and allergic rhinitis. Reported effects were inconsistent with varying measures to define residential greenness. Only limited meta-analysis could be conducted, with the pooled odds ratios for asthma (OR 1.01 95%CI 0.93, 1.09; I2 68.1%) and allergic rhinitis (OR 0.99 95%CI 0.87, 1.12; I2 72.9%) being significantly heterogeneous. CONCLUSIONS: Inconsistencies between the studies were too large to accurately assess the association between residential greenness and allergic respiratory disease. A standardised global measure of greenness which accounts for seasonal variation at a specific relevant buffer size is needed to create a more cohesive body of evidence and for future examination of the effect of residential greenness on allergic respiratory diseases.

Breastfeeding and childhood acute otitis media: a systematic review and meta-analysis.

AIM: To synthesise the evidence on the association between duration and exclusivity of breastfeeding and the risk of acute otitis media (AOM). METHODS: Systematic review and meta-analysis following searching of PubMed, CINAHL and EMBASE electronic databases. RESULTS: Twenty-four studies, all from the USA or Europe, met the inclusion criteria. In the pooled analyses, any form of breastfeeding was found to be protective for AOM in the first 2 years of life. Exclusive breastfeeding for the first 6 months was associated with the greatest protection (OR 0.57 95% CI 0.44, 0.75), followed by 'more vs less' breastfeeding (OR 0.67; 0.59, 0.76) and 'ever vs never' breastfeeding (OR 0.67; 0.56, 0.80). CONCLUSION: This systematic review and meta-analysis provides evidence that breastfeeding protects against AOM until 2 years of age, but protection is greater for exclusive breastfeeding and breastfeeding of longer duration. Exclusive breastfeeding during the first 6 months was associated with around a 43% reduction in ever having AOM in the first 2 years of life. After 2 years of age, there is no evidence that breastfeeding protects against AOM; however, there were few studies and the evidence quality was low.

Breastfeeding and the risk of dental caries: a systematic review and meta-analysis.

AIM: To synthesise the current evidence for the associations between breastfeeding and dental caries, with respect to specific windows of early childhood caries risk. METHODS: Systematic review, meta-analyses and narrative synthesis following searches of PubMed, CINAHL and EMBASE databases. RESULTS: Sixty-three papers included. Children exposed to longer versus shorter duration of breastfeeding up to age 12 months (more versus less breastfeeding), had a reduced risk of caries (OR 0.50; 95%CI 0.25, 0.99, I(2) 86.8%). Children breastfed >12 months had an increased risk of caries when compared with children breastfed <12 months (seven studies (OR 1.99; 1.35, 2.95, I(2) 69.3%). Amongst children breastfed >12 months, those fed nocturnally or more frequently had a further increased caries risk (five studies, OR 7.14; 3.14, 16.23, I(2) 77.1%). There was a lack of studies on children aged >12 months simultaneously assessing caries risk in breastfed, bottle-fed and children not bottle or breastfed, alongside specific breastfeeding practices, consuming sweet drinks and foods, and oral hygiene practices limiting our ability to tease out the risks attributable to each. CONCLUSION: Breastfeeding in infancy may protect against dental caries. Further research needed to understand the increased risk of caries in children breastfed after 12 months.

Breastfeeding and asthma and allergies: a systematic review and meta-analysis.

AIM: To systematically review the association between breastfeeding and childhood allergic disease. METHODS: Predetermined inclusion/exclusion criteria identified 89 articles from PubMed, CINAHL and EMBASE databases. Meta-analyses performed for categories of breastfeeding and allergic outcomes. Meta-regression explored heterogeneity. RESULTS: More vs. less breastfeeding (duration) was associated with reduced risk of asthma for children (5-18 years), particularly in medium-/low-income countries and with reduced risk of allergic rhinitis ≤5 years, but this estimate had high heterogeneity and low quality. Exclusive breastfeeding for 3-4 months was associated with reduced risk of eczema ≤2 years (estimate principally from cross-sectional studies of low methodological quality). No association found between breastfeeding and food allergy (estimate had high heterogeneity and low quality). Meta-regression found differences between study outcomes may be attributable to length of breastfeeding recall, study design, country income and date of study inception. Some of the protective effect of breastfeeding for asthma may be related to recall bias in studies of lesser methodological quality. CONCLUSION: There is some evidence that breastfeeding is protective for asthma (5-18 years). There is weaker evidence for a protective effect for eczema ≤2 years and allergic rhinitis ≤5 years of age, with greater protection for asthma and eczema in low-income countries.

The role of seasonal grass pollen on childhood asthma emergency department presentations.

BACKGROUND: Few studies have focused on the role of grass pollen on asthma emergency department (ED) presentations among children. None have examined whether a dose-response effect exists between grass pollen levels and these asthma exacerbations. OBJECTIVES: To examine the association between increasing ambient levels of grass pollen and asthma ED presentations in children. To determine whether these associations are seen only after a thunderstorm, or whether grass pollen levels have a consistent influence on childhood asthma ED visits during the season. METHODS: A short time series ecological study was conducted for asthma presentations to ED among children in Melbourne, Victoria, and grass pollen, meteorological and air quality measurements recorded during the selected 2003 period. A semi-parametric Poisson regression model was used to examine dose-response associations between daily grass pollen levels and mean daily ED attendance for asthma. RESULTS: A smoothed plot suggested a dose-response association. As ambient grass pollen increased to about 19 grains/m(3) , the same day risk of childhood ED presentations also increased linearly (P < 0.001). Grass pollen levels were also associated with an increased risk in asthma ED presentations on the following day (lag 1, P < 0.001). CONCLUSION: This is the first study to establish a clear relationship between increased risk of childhood asthma ED attendance and levels of ambient grass pollen below 20 grains/m(3) , independent of any impact of thunderstorm-associated asthma. These findings have important implications for patient care, such as asthma management programs that notify the general public regarding periods of high grass pollen exposure, as well as defining the timing of initiation of pollen immunotherapy.

Reporting dental trauma and its inclusion in an injury surveillance system in Victoria, Australia.

BACKGROUND: This study investigated the frequency, patterns and causes of dental trauma in patients seeking emergency treatment at a dental hospital, and evaluated the impact of an electronic structured injury history form to collect key information. METHODS: A retrospective audit was undertaken of all emergency presentations at the Royal Dental Hospital of Melbourne from 2009 to 2012. Dental trauma and injury surveillance data were collected and evaluated with reference to the criteria of the Victorian Emergency Minimum Dataset. Statistical analysis included chi-squared and Fisher's exact tests. RESULTS: A total of 88,610 new emergency courses of care were created, with 3642 (4.1%) identified as new dental trauma cases in 3574 patients. A total of 6001 teeth were injured with a mean of 1.7 teeth per patient (range: 1-8 teeth). The improvement of injury surveillance information collected using the electronic form compared with the paper form was statistically significant (p<0.001). CONCLUSIONS: The dental trauma findings of this study are consistent with other studies regarding age, gender, location, cause and injury type. This study also confirmed the benefits of electronic collection of dental injury surveillance data that can assist policy planners and health service providers in designing and delivering effective dental injury prevention and management services.

Coffee stimulation of cholecystokinin release and gallbladder contraction in humans.

We studied the effect of the ingestion of 400 mL regular coffee on plasma cholecystokinin (CCK) concentrations and of 165 mL regular and decaffeinated coffee on plasma CCK and gallbladder contraction in six healthy regular coffee drinkers. Plasma CCK concentrations rose 3.3 +/- 0.4 pmol/L after 400 mL and 2.8 +/- 0.9 pmol/L after 165 mL regular coffee compared with 1.8 +/- 0.6 pmol/L after 165 mL decaffeinated coffee. These plasma CCK increments were greater than those after 400 and 165 mL of an isosmotic and isothermic sodium chloride solution (0.6 +/- 0.2 and 0.4 +/- 0.1 pmol/L, respectively). An average gallbladder contraction of 33 +/- 7% was observed after 165 mL regular coffee and 29 +/- 10% after 165 mL decaffeinated coffee, whereas after 165 mL sodium chloride the contraction was only 10 +/- 12%. We conclude that both regular coffee and decaffeinated coffee give rise to increments in plasma CCK and contractions of the gallbladder.

Vestibulo-oculomotor behaviour in rats following a transient unilateral vestibular loss induced by lidocaine.

The effects of a transient vestibular nerve blockade, achieved by intra-tympanic instillation of lidocaine, were studied in rats by recording horizontal eye movements in darkness. Evaluation of the dose-response relationship showed that a maximal effect was attained with a concentration of 4% lidocaine. Within 15 min of lidocaine instillation, a vigorous spontaneous nystagmus was observed which reached maximal frequency and velocity of the slow phase after about 20 min. Subsequently, the nystagmus failed for approximately half an hour before it reappeared. This could be avoided by providing visual feedback in between the recordings in darkness or by a contralateral instillation of 2.5% lidocaine. It is suggested that the failure reflects an overload of the vestibulo-oculomotor circuits. After recovery from the nerve blockade, when the gaze was stable, dynamic vestibular tests were performed. They revealed that a decrease of the slow phase velocity gain and the dominant time constant during, respectively, sinusoidal- and step stimulation toward the unanaesthetised side, had developed with the nerve blockade. These modulations were impaired by a nodulo-uvulectomy but not by bilateral flocculectomy, which is consistent with the concept of vestibular habituation. A GABA(B) receptor antagonist, CGP 56433A, given systemically during the nerve blockade, aggravated the vestibular asymmetry. The same effect has previously been demonstrated in both short- (days) and long-term (months) compensated rats, by antagonising the GABA(B) receptor. In summary, this study provides the first observations of vestibulo-oculomotor disturbances during the first hour after a rapid and transient unilateral vestibular loss in the rat. By using this method, it is possible to study immediate behavioural consequences and possible neural changes that might outlast the nerve blockade.

Early compensation of vestibulo-oculomotor symptoms after unilateral vestibular loss in rats is related to GABA(B) receptor function.

The horizontal vestibulo-oculomotor reflex was studied in pigmented rats during the first 5 days after a unilateral chemical or surgical vestibular deafferentation. Spontaneous eye movements in darkness and slow phase velocity gain of compensatory eye movements during horizontal sinusoidal rotation were evaluated. The most evident vestibulo-oculomotor symptom immediately after a unilateral vestibular loss was a spontaneous nystagmus, which gradually abated during the following days. Further, an asymmetry between ipsi- and contra-lesional gains was evident during sinusoidal vestibular stimulation. Single systemic doses of the GABA(B) receptor antagonist [3-[1-(S)-[[3-(cyclohexylmethyl)-hydroxyphosphinoyl]-2-(S)-hydroxypropyl]amino]ethyl]-benzoic acid (CGP 56433A), the agonist baclofen, or the GABA(A) receptor agonist (4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were given at different intervals after unilateral vestibular deafferentation. CGP 56433A highly aggravated the vestibulo-oculomotor symptoms, observed as an increase in spontaneous nystagmus and slow phase velocity gain asymmetry. This effect was most pronounced during the first 2 days after unilateral vestibular loss, when CGP 56433A even decompensated the vestibular system to the extent that all vestibular responses were abolished. Baclofen caused no effect during the first days after unilateral vestibular loss, but in parallel with the abatement of spontaneous nystagmus, the drug equilibrated or even reversed the remaining spontaneous nystagmus with corresponding effects on the slow-phase velocity gain asymmetry. The effects of baclofen were very similar after both chemical and surgical deafferentation. THIP caused a slight depression of all vestibular responses. All single dose effects of the drugs were transient. Altogether these results reveal that endogenous stimulation of GABA(B) receptors in GABA-ergic vestibulo-oculomotor circuits are important for reducing the vestibular asymmetry during the early period after unilateral vestibular deafferentation. A possible role for GABA(B) receptors in the reciprocal inhibitory commissural pathways in the vestibular nuclei is suggested.

Mediastinitis with fistula formation to the left main bronchus. A complication of wisdom tooth extraction.

We describe a 23-year-old patient who after extraction of four wisdom teeth developed a descending necrotizing mediastinitis with a spontaneous fistula to the left main bronchus. Because of this fistula, treatment was limited to surgical drainage of the neck region and antibiotics. Recovery was uneventful.

Effects of GABAB activation and inhibition on vestibulo-ocular and optokinetic responses in the pigmented rat.

The effects of the GABAB agonist baclofen and the GABAB antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABAB receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABAB receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceleratory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.

Effects of the GABA agonists baclofen and THIP on long-term compensation in hemilabyrinthectomised rats.

Horizontal eye movements, elicited by sinusoidal rotation in darkness, were recorded with a magnetic search coil technique in pigmented rats, hemilabyrinthectomised 8-12 weeks before the investigation. Separate gains during rotation towards the lesioned side (LS) and the intact side (IS) were calculated by a computer program, demonstrating an asymmetry. Systemic single administration of the GABAB agonist baclofen caused a dose-related temporary rebalancing of the compensatory eye movements to the LS and the IS. At an optimal dose of 14 micromol/kg b.wt symmetry was achieved by excitation of eye movements during rotation to the LS and depression during rotation to the IS. Administration of the GABAA agonist THIP did not obviously reduce the asymmetry. It is suggested that stimulation of GABAB receptors modifies the tonic imbalance between the bilateral vestibular nuclei and/or the central processing of the input from the peripheral sensory organs.

Modulation of vestibular function by nociceptin/orphanin FQ: an in vivo and in vitro study.

The effects of nociceptin (orphanin FQ) on medial vestibular nucleus (MVN) neurons in vitro, and on vestibulo-ocular reflex (VOR) function in vivo, were investigated in order to determine the role of 'opioid-like orphan' (ORL1) receptors in modulating vestibular reflex function in the rat. Nociceptin (100 nM-1 microM) potently inhibited the spontaneous discharge of the majority (86%) of MVN neurons tested in the rat dorsal brainstem slice preparation in vitro. This inhibition was dose-dependent and persisted after blockade of synaptic transmission in low Ca2+/Co2+ medium. The inhibitory effects were insensitive to the opioid antagonist naloxone, but were effectively antagonised by the selective ORL1 receptor antagonist, [Phe1Psi(CH2-NH)Gly2]Nociceptin(1-13)NH2. The majority of MVN neurons ( approximately 70%) were inhibited by both nociceptin and the delta-opioid receptor agonist, [D-ala2, D-leu5]-enkephalin (DADLE), while a minority of cells (approximately 30%) were selectively responsive either to DADLE or to nociceptin, but not both. Co-application of nociceptin and DADLE to neurons that were responsive to both agonists, resulted in an inhibitory response that was the same as or less than the inhibition evoked by either agonist alone. Intracellular whole-cell patch clamp recordings from identified Type A and Type B MVN cells showed that both these cell types are responsive to nociceptin, which induced membrane hyperpolarisation and decrease in input resistance consistent with its known effects on membrane K currents in other cell types. In alert rats, i.c.v. injection of nociceptin caused a significant decrease in the gain of the hVOR and resulted in a prolongation of post-rotatory nystagmus in darkness. The decrease in VOR gain and the increase in the VOR time-constant was significant even at low doses of nociceptin which did not cause other observable behavioural effects. These findings demonstrate that endogenously released nociceptin may have a hitherto unexplored role in the functional modulation of the neural pathways that mediate vestibular reflexes in vivo.

Effects of toluene on tonic firing and membrane properties of rat medial vestibular nucleus neurones in vitro.

The effects of toluene on discharge rate and membrane properties of tonically active medial vestibular nucleus (MVN) neurones were investigated in an in vitro slice preparation of the dorsal brainstem of the rat. The majority of the cells (50/56) were inhibited in a dose-dependent manner by toluene. The inhibitory effects of toluene persisted after blockade of synaptic transmission. Complementary patch-clamp recordings showed that toluene caused a hyperpolarisation of 2-5 mV associated with an increase in membrane conductance. These findings indicate that toluene might interfere with specific ion channels or the receptors regulating them along the cell membrane. The effective toluene concentrations used in this experiment are comparable to the concentrations producing vestibulo-ocular disturbances in vivo.

The effect of loxiglumide (CR-1505) on basal and bombesin-stimulated gallbladder volume in man.

This study was undertaken in 5 normal subjects to determine the role of cholecystokinin (CCK) in the regulation of basal gallbladder volume and gallbladder contraction stimulated by infusion of bombesin. Administration of the CCK-receptor antagonist, loxiglumide (CR-1505), led to doubling of the gallbladder volume (increase 104 +/- 26%; P less than 0.05) and reduced the bombesin-stimulated gallbladder contraction from 69 +/- 17 to 19 +/- 17% (P less than 0.05). The findings provide evidence suggesting that CCK plays an important role in the regulation of basal gallbladder tone and in mediating the gallbladder contraction induced by the administration of bombesin.

Late anaphylactic shock after hysterosalpingography.

We observed a patient who had a severe anaphylactic reaction 1 hour after HSG. Allergic symptoms recurred several hours after antiallergic therapy was stopped. The initial complaints of pain and vomiting could have been due to peritoneal irritation or alternatively to an early anaphylactic reaction. Patients who are at risk should be carefully evaluated before performing HSG. These patients and those with complaints after HSG should stay under observation for 1 or 2 hours after HSG.

Magnetic resonance imaging in Paget disease of the skull.

Four cases of Paget disease of the skull were studied with magnetic resonance (MR) imaging. With optimal use of projection and technical factors, MR permits simultaneous demonstration of osseous deformity and its relation to the underlying soft tissues. Effects on the brain caused by thickened calvaria and brainstem compression from basilar impression can be detected readily on a single sagittal scan.

Are the effects of toluene on the vestibulo and opto-ocular motor system inhibited by the action of GABAB antagonist CGP 35348?

The acute effects of toluene and a selective GABAB-antagonist, CGP 35348, on the vestibulo and opto-ocular motor (VOOM) system in rats were investigated by recording of compensatory eye-movements during vestibular and optokinetic stimulations. It has previously been demonstrated that toluene enhances the performance of the basic vestibulo-oculomotor reflex (VOR) and depresses the effects of the visual input to this reflex. It has been proposed that these effects are caused by alterations of the GABA-transmission system in the cerebellum. It has now been demonstrated that the exaggerating effects of toluene on the VOR, tested by angular horizontal acceleration/deceleration of the animals in darkness, are inhibited by CGP 35348 in a dose related way. On the contrary, the depressing effects on the visual input, tested by optokinetic stimulation, by angular acceleration/deceleration with a simultaneous conflicting visual stimulation and by eliciting saccades, could not be prevented by CGP 35348. The results support the hypothesis that toluene causes some of the effects on the VOOM system by influence on the GABA-transmission. The findings are in agreement with a recent report of increased levels of extracellular GABA in the cerebellar cortex during exposure to toluene.

The effect of toluene on the vestibulo- and opto-oculomotor system in rats, pretreated with GABAergic drugs.

Toluene, an aromatic solvent, prolongs the duration of nystagmus induced by a rotatory acceleration or by an optokinetic stimulation in the pigmented rat. Baclofen, an agonist of GABAB receptors, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP), an agonist of GABAA receptors are able to block this toluene effect on the vestibular system. On the contrary diazepam, which by itself causes an evident reduction of the duration of acceleratory nystagmus, is not able to block the toluene effect. The results indicate that the toluene effect is related to GABA transmission and that the solvent interacts by a rather receptor specific mechanism of action.