Variation in the clinical management of self-harm by area-level socio-economic deprivation: findings from the multicenter study of self-harm in England.

BACKGROUND: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. METHODS: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. RESULTS: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71-0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74-0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78-0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79-0.94, p = 0.001). CONCLUSIONS: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

Can postural changes in spirometry in children with Duchenne muscular dystrophy predict sleep hypoventilation?

AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.

Plasma lipidome reveals critical illness and recovery from human Ebola virus disease.

Ebola virus disease (EVD) often leads to severe and fatal outcomes in humans with early supportive care increasing the chances of survival. Profiling the human plasma lipidome provides insight into critical illness as well as diseased states, as lipids have essential roles as membrane structural components, signaling molecules, and energy sources. Here we show that the plasma lipidomes of EVD survivors and fatalities from Sierra Leone, infected during the 2014-2016 Ebola virus outbreak, were profoundly altered. Focusing on how lipids are associated in human plasma, while factoring in the state of critical illness, we found that lipidome changes were related to EVD outcome and could identify states of disease and recovery. Specific changes in the lipidome suggested contributions from extracellular vesicles, viremia, liver dysfunction, apoptosis, autophagy, and general critical illness, and we identified possible targets for therapies enhancing EVD survival.

The α7 and ß2 nicotinic acetylcholine receptor subunits regulate apoptosis in the infant hippocampus, and in sudden infant death syndrome (SIDS).

Apoptosis is increased in the hippocampus of infants who died of sudden infant death syndrome (SIDS), yet it is not known via which mechanism this has occurred. Following existing support for a role of the α7 and ß2 nicotinic acetylcholine receptor (nAChR) subunits in apoptotic regulation, we aimed to determine whether these subunits are altered in the SIDS hippocampus and if they are correlated with cell death markers of active caspase-3 (Casp-3) and TUNEL. Further analyses were run according to the presence of major SIDS risk factors related to hypoxia (bed-sharing and prone sleeping), infection (presence of an upper respiratory tract infection (URTI)), cigarette smoke exposure and gender. Immunohistochemical expression of the markers was studied in 4 regions of the hippocampus (Cornu Ammonis (CA)1, CA2, CA3, CA4) and subiculum amongst 52 infants (aged 1-7 months) who died suddenly and unexpectedly (SUDI) and for whom the cause of death was explained (eSUDI; n = 9), or not and characterised as SIDS I (n = 8) and SIDS II (n = 35) according to the San Diego diagnostic criteria. Results showed that SIDS II infants had widespread increases in TUNEL compared with eSUDI and SIDS I infants, as well as increased α7 and Casp-3 in CA2 compared to eSUDI infants, although these changes were predominant amongst infants who did not bed-share. Cigarette smoke exposure had minimal effects on the markers, while an URTI was associated with changes in all markers (after accounting for bed-sharing). Our findings support the role of nAChRs in regulating apoptosis in the SIDS hippocampus, and highlight the need for separate analysis according to risk factors.

Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the human infant brain and changes in the Sudden Infant Death Syndrome (SIDS).

Pituitary adenylate cyclase activating polypeptide (PACAP) and its complementary receptor, PAC1, are crucial in central respiratory control. PACAP Knockout (KO) mice exhibit a SIDS-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal period. PAC1 KO demonstrate similar attributes to PACAP-null mice, but with the addition of increased pulmonary artery pressure, consequently leading to heart failure and death. This study establishes a detailed interpretation of the neuroanatomical distribution and localization of both PACAP and PAC1 in the human infant brainstem and hippocampus, to determine whether any changes in expression are evident in infants who died of Sudden Infant Death Syndrome (SIDS) and any relationships to risk factors of SIDS including smoke exposure and sleep related parameters. Immunohistochemistry for PACAP and PAC1 was performed on formalin fixed and paraffin embedded human infant brain tissue of SIDS (n=32) and non-SIDS (n=12). The highest expression of PACAP was found in the hypoglossal (XII) of the brainstem medulla and lowest expression in the subiculum of the hippocampus. Highest expression of PAC1 was also found in XII of the medulla and lowest in the midbrain dorsal raphe (MBDR) and inferior colliculus. SIDS compared to non-SIDS had higher PACAP in the MBDR (p<0.05) and lower PAC1 in the medulla arcuate nucleus (p<0.001). Correlations were found between PACAP and PAC1 with the risk factors of smoke exposure, bed sharing, upper respiratory tract infection (URTI) and seasonal temperatures. The findings of this study show for the first time that some abnormalities of the PACAP system are evident in the SIDS brain and could contribute to the mechanisms of infants succumbing to SIDS.

Can daytime measures of lung function predict respiratory failure in children with neuromuscular disease?

Neuromuscular disorders in children are a heterogeneous group of conditions with a variable age of presentation and overlapping clinical manifestations, many of which have progressive respiratory morbidity. Respiratory insufficiency occurs as a consequence of an imbalance between demands on the respiratory system and respiratory muscle capacity. Daytime measures of pulmonary function are used routinely in these children to assess respiratory status and monitor the consequences of the progression of muscle weakness. This review describes the current evidence for daytime pulmonary function tests and their ability to predict imminent respiratory morbidity.

Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta.

Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 ß, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, ß2 and ß4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women.

Shared characteristics of suicides and other unnatural deaths following non-fatal self-harm? A multicentre study of risk factors.

BACKGROUND: Mortality, including suicide and accidents, is elevated in self-harm populations. Although risk factors for suicide following self-harm are often investigated, rarely have those for accidents been studied. Our aim was to compare risk factors for suicide and accidents. METHOD: A prospective cohort (n=30 202) from the Multicentre Study of Self-harm in England, 2000-2007, was followed up to 2010 using national death registers. Risk factors for suicide (intentional self-harm and undetermined intent) and accidents (narcotic poisoning, non-narcotic poisoning, and non-poisoning) following the last hospital presentation for self-harm were estimated using Cox models. RESULTS: During follow-up, 1833 individuals died, 378 (20.6%) by suicide and 242 (13.2%) by accidents. Independent predictors of both suicide and accidents were: male gender, age 35 years (except accidental narcotic poisoning) and psychiatric treatment (except accidental narcotic poisoning). Factors differentiating suicide from accident risk were previous self-harm, last method of self-harm (twofold increased risks for cutting and violent self-injury versus self-poisoning) and mental health problems. A risk factor specific to accidental narcotic poisoning was recreational/illicit drug problems, and a risk factor specific to accidental non-narcotic poisoning and non-poisoning accidents was alcohol involvement with self-harm. CONCLUSIONS: The similarity of risk factors for suicide and accidents indicates common experiences of socio-economic disadvantage, life problems and psychopathology resulting in a variety of self-destructive behaviour. Of factors associated with the accidental death groups, those for non-narcotic poisoning and other accidents were most similar to suicide; differences seemed to be related to criteria coroners use in reaching verdicts. Our findings support the idea of a continuum of premature death.

The development of a population-level clinical screening tool for self-harm repetition and suicide: the ReACT Self-Harm Rule.

BACKGROUND: Self-harm is a common reason for Emergency Department (ED) attendance. We aimed to develop a clinical tool to help identify patients at higher risk of repeat self-harm, or suicide, within 6 months of an ED self-harm presentation. METHOD: The tool, the ReACT Self-Harm Rule, was derived using multicentre data from a prospective cohort study. Binary recursive partitioning was applied to data from two centres, and data from a separate centre were used to test the tool. There were 29 571 self-harm presentations to five hospital EDs between January 2003 and June 2007, involving 18 680 adults aged ⩾16 years. We estimated sensitivity, specificity and positive and negative predictive values to measure the performance of the tool. RESULTS: A self-harm presentation was classified as higher risk if at least one of the following factors was present: recent self-harm (in the past year), living alone or homelessness, cutting as a method of harm and treatment for a current psychiatric disorder. The rule performed with 95% sensitivity [95% confidence interval (CI) 94-95] and 21% specificity (95% CI 21-22), and had a positive predictive value of 30% (95% CI 30-31) and a negative predictive value of 91% (95% CI 90-92) in the derivation centres; it identified 83/92 of all subsequent suicides. CONCLUSIONS: The ReACT Self-Harm Rule might be used as a screening tool to inform the process of assessing self-harm presentations to ED. The four risk factors could also be used as an adjunct to in-depth psychosocial assessment to help guide risk formulation. The use of multicentre data helped to maximize the generalizability of the tool, but we need to further verify its external validity in other localities.

The unfolded protein response and apoptotic regulation in the human placenta due to maternal cigarette smoking and pre-eclampsia.

Maternal cigarette smoking (CS) and pre-eclampsia (PE) alter placental function and expression of important proteins which maintain homeostasis. Two interlinked pathways of interest are the unfolded protein response (UPR) and apoptosis. The UPR is upregulated in the PE placenta, but no data is available on the effects of CS and how it correlates with apoptotic expression. Samples of human placental tissue from normotensive non-smokers (n = 8), women with PE (n = 8), and CS (n = 8) were analysed using immunohistochemistry for 3 UPR markers (phosphorylated PKR-like endoplasmic reticulum (ER) kinase (pPERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6)), and an antibody microarray for 19 apoptotic and stress regulating markers. For the PE group compared to the normotensive group, staining for pPERK was increased in decidual tissue and villi, and for IRE1, the overall percentage of stained villi per field of view was increased. There were no differences in UPR expression comparing CS to controls. Of the apoptotic markers, only IκBα (Ser32/36), which is part of an inhibitory pathway, showed a significant decrease in the PE and CS groups compared to controls. These findings suggest UPR regulation is more evident in PE with a general increase in ER stress due to decreased inhibition of apoptosis as compared to CS for which UPR was not altered.

Contribution of cellulosic fibre filter on atmosphere moisture content in laser powder bed fusion additive manufacturing.

Cellulosic materials are commonly used to manufacture the particulate filters used in laser powder bed fusion (LPBF) additive manufacturing (AM) equipment. An experimental approach has been used to calculate the moisture quantity and kinetics of sorption in a cellulosic filter at varying relative humidity (RH) levels. A prediction of the amount of moisture which can be theoretically held within a filter during storage before its use has been obtained. Subsequently, the quantity and the rate of moisture desorption which can be transferred into the build chamber during LPBF is presented. This work highlights the importance of filter storage and conditioning prior to use in additive manufacturing processing.

Use of non-invasive ventilation in children with congenital tracheal stenosis.

INTRODUCTION: Congenital tracheal stenosis (CTS) is a rare airway condition characterized by complete tracheal rings. Most patients undergo a slide tracheoplasty, which greatly reduces mortality but significant morbidity remains. The assessment of sleep disordered breathing (SDB) and use of non-invasive ventilation (NIV) in these children has not been described. AIM: To describe the presence of SDB and use of NIV in children diagnosed with CTS over a 10-year period (2005-2015). DESIGN: Retrospective case series at a tertiary children's hospital. RESULTS: There were 16 patients identified with CTS with a median [range] age at diagnosis of 2.5 months (0-9 months). One child died in the immediate post-operative period following a slide tracheoplasty, leaving 15 survivors. There were no later deaths during follow-up while using NIV for up to 3 years after surgery. Slide tracheoplasty was undertaken in (12/15) with long-segment tracheal stenosis. 3/15 patients had a short-segment tracheal stenosis and were managed conservatively. The use of NIV occurred in 10/15 (66.67%) patients, all of whom had long-segment CTS. Pre-operative polysomnography (PSG) showed a median (±SD) obstructive apnoea/hypopnoea index (OAHI) of 14.6/hr (±6.2) which reduced to 7.2/hour (±4.2) on NIV prior to slide tracheoplasty. The median oxygen desaturation index (ODI) before NIV use was 15.3 (±19.4) episodes/hour, which reduced to 6.3 (±11) on NIV. The median period of NIV use was 5 [1-24 months] months. CONCLUSION: Patients with CTS have obstructed sleep disordered breathing. Trials of NIV are well-tolerated and improve sleep disordered breathing.

Indoor versus Outdoor Air Quality during Wildfires.

The human behavioral modification recommendations during wildfire events are based on particulate matter and may be confounded by the potential risks of gas-phase pollutants such as polycyclic aromatic hydrocarbons (PAHs). Moreover, the majority of adults spend over 90 percent of their time indoors where there is an increased concern of indoor air quality during wildfire events. We address these timely concerns by evaluating paired indoor and outdoor PAH concentrations in residential locations and their relationship with satellite model-based categorization of wildfire smoke intensity. Low-density polyethylene passive air samplers were deployed at six urban sites for 1 week in Eugene, Oregon with matched indoor and outdoor samples and 24 h time resolution. Samples were then quantitatively analyzed for 63 PAH concentrations using gas-chromatography-tandem mass spectrometry. A probabilistic principal components analysis was used to reduce all 63 PAHs into an aggregate measure. Linear regression of the first principal component against indoor versus outdoor shows that indoor gas-phase PAH concentrations are consistently equal to or greater than outdoor concentrations. Regression against a satellite-based model for wildfire smoke shows that outdoor, but not indoor gas-phase PAH concentrations are likely associated with wildfire events. These results point toward the need to include gas-phase pollutants such as PAHs in air pollution risk assessment.

Are children just small adults? The differences between paediatric and adult sleep medicine.

Several important physiological and maturational changes occur in sleep development during the paediatric age range, particularly during infancy and in early childhood. As the pathology of sleep apnoea is superimposed onto a developing and often plastic physiological system, children often show a different pathophysiology to their adult counterparts. These factors need to be incorporated into the evaluation of a child's sleep problems. Particular attention should be paid to the developmental stage of the child. Investigation, interpretation and subsequent management provide further unique challenges and during successive reviews predicted normal changes must also be taken into account. This review article discusses the important physiological and maturational changes that occur in sleep during childhood, some common paediatric sleep conditions and their presentation and the appropriate evaluation and management of these conditions. In the course of the discussion, we have stressed important differences between paediatric and adult sleep medicine.

Hypoxia and nicotine effects on Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the developing piglet brainstem.

Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping and cigarette smoke exposure. Using piglet models of these risk factors, intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position) and nicotine (main reinforcing element of cigarettes), this study aimed to determine their effects on PACAP and PAC1 protein expression in the medulla. IHH was delivered for 1 (n=7), 2 (n=6), 3 (n=6) and 4 (n=7) days prior to euthanasia at 13-14days of age, while nicotine (n=7) was continuous for the first 14days of life. An additional group of combined nicotine and 1day IHH (1DIHH) was studied to determine the combined effects of the risk factors. Changes in expression were seen after the acute 1DIHH exposure (none after repeated daily exposures) and included a decrease in PACAP in the dorsal motor nucleus of vagus (DMNV; p=0.024), nucleus of the solitary tract (NTS; p=0.024) and the gracile nucleus (GRAC; p=0.001), and a decrease in PAC1 in the NTS (p=0.01). No PACAP change was noted in the nicotine-exposed piglets, however, a decrease in PAC1 was found in the DMNV (p=0.02). IHH exposure in piglets with pre-exposure to nicotine led to a significant decrease in PACAP in the Grac (p=0.04) but had no effect on PAC1. These findings show for the first time, the vulnerability of PACAP in the brainstem during early development to an acute hypercapnic hypoxic exposure and that those effects are greater than from nicotine exposure.

A cross-sectional analysis of daytime versus nocturnal polysomnographic respiratory parameters in cystic fibrosis during early adolescence.

BACKGROUND: In Cystic Fibrosis (CF), early detection and treatment of respiratory disease is considered the standard for respiratory care. Overnight polysomnography (PSG) may help identify respiratory deterioration in young patients with CF. METHODS: A prospective cohort study of 46 patients with CF, aged 8-12years, from a specialist clinic in a tertiary paediatric hospital. Daytime pulmonary function, shuttle test exercise testing and overnight PSG were studied. RESULTS: Of 81 children aged 8-12years, 46 (57%) agreed to participate. FEV1 (% predicted, mean 74.6%) was normal in 23 (50%), mildly abnormal in 12 (26.1%), moderately abnormal in 10 (21.7%) and severely abnormal in 1 (2.2%). Amongst sleep study parameters, FEV1 (% predicted) showed significant correlation with the respiratory rate (RR) in slow wave sleep (SWS), CO2 change in REM, baseline SaO2, and the arousal index (h-1). Backward, stepwise linear regression modelling for FEV1 (% predicted) included the entire group with a wide spectrum of clinical severity. From sleep, variables remaining in the multivariate model for FEV1 (F=16.81, p<0.001) were the RR in SWS (min-1) and the CO2 change in REM (p=0.003, and 0.014, respectively). When daytime tests were included, the variables remaining were RR in SWS and SD score for BMI (BMIsds) (F=18.70, p<0.001). CONCLUSIONS: Respiratory abnormalities on overnight sleep studies included elevated respiratory rates during SWS and mild CO2 retention in REM sleep, and these incorporated into a model correlating with FEV1 (% predicted). Thus, mild mechanical impairment of ventilation is evident on overnight sleep studies in children with cystic fibrosis although the significance of this finding will require further investigation.

Postnatal nicotine and/or intermittent hypercapnic hypoxia effects on apoptotic markers in the developing piglet brainstem medulla.

The most important risk factors currently identified for the sudden infant death syndrome (SIDS) are prone sleeping and cigarette smoke exposure. In this study, we investigated the neuropathological sequelae of these risk factors by exposing piglets to intermittent hypercapnic-hypoxia (IHH) and/or nicotine (nic) in the early postnatal period. Our hypothesis was that either nic or IHH exposure could increase neuronal cell death, and that combined exposure (nic+IHH) would be additive. Four exposure patterns were studied: controls (n=14), IHH (n=10), nic (n=14), and nic+IHH (n=14). All groups had equal gender ratios. Nic exposure via an implanted osmotic minipump commenced within 48 h of birth and continued until age 13-14 days when animals were killed and brains collected. A total of 48 min of hypercapnic-hypoxia was delivered on the day immediately prior to killing in a pattern comprising 6 min of HH (8% O(2), 7% CO(2), balance N(2)) alternating with 6 min of air. Immunohistochemistry was performed to identify neurons positive for active caspase-3 and DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, TUNEL) in seven nuclei of the caudal medulla. Staining quantification showed that: 1. IHH induced neuronal death (increased both TUNEL and casapse-3) in more brainstem nuclei than nicotine. 2. Females were more severely affected by IHH than males. 3. Where IHH and nicotine were combined, TUNEL expression was approximately 5% less than IHH alone, but changes in caspase-3 were variable. We conclude that acute exposure to IHH in the postnatal period is more neurotoxic than exposure to nicotine alone. Combined exposure to IHH and nicotine produced variable responses with some results suggesting that nicotine can be neuroprotective. These results indicate that environmental insults attributable to prone sleeping can produce neurotoxic sequelae in SIDS, with some regional specificity in the response. However, no consistent relationship is evident when combining the two insults.

N-methyl-D-aspartate receptor 1 changes in the piglet braintem after nicotine and/or intermittent hypercapnic-hypoxia.

Prone sleeping and cigarette smoke exposure are two major risk factors for the sudden infant death syndrome (SIDS). Utilizing piglet models of early postnatal nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the hypothesis that these exposures, separately or combined, increase N-methyl-D-aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla. We also tested for gender-specific effects. Three piglet exposure groups were compared against 14 controls; 1, nicotine [n = 14], 2, IHH [n = 10], and 3, nicotine+IHH [n = 14], with equal gender proportions in each group. Non-radioactive in situ hybridization and immunohistochemistry were performed for NR1 mRNA and protein expression, respectively, and were quantified in seven nuclei of the brainstem medulla. NR1 mRNA was significantly increased in the gracile and inferior olivary nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH exposure, and in three of seven nuclei after nicotine+IHH. The increased mRNA changes were accompanied by increased protein only in the ION after IHH and nicotine+IHH (P = 0.019, and P = 0.008 respectively). By gender, control females had greater NR1 mRNA than males in the dorsal motor nucleus of vagus (P = 0.05) and for protein in the ION (P = 0.02). This gender difference was maintained after nicotine exposure in the ION with additional gender differences observed including greater mRNA in the cuneate nucleus (P = 0.04) and nucleus of the spinal trigeminal tract (P = 0.03) of males compared with females. Overall, more changes occurred at the mRNA level than protein, and IHH exposure induced more changes than nicotine or nicotine+IHH exposures. Together, these findings suggest that hypercapnic-hypoxic exposures (modeling prone sleeping or sleep apnea) are more likely to induce NMDA receptor changes in the developing brainstem than nicotine exposure alone.

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Management of paediatric thyroid carcinoma: recent experience with recombinant human thyroid stimulating hormone in preparation for radioiodine therapy.

BACKGROUND: Thyroid carcinoma in children is rare and raises unique management issues. Although metastatic disease is more common in this age group, prognosis remains good with appropriate treatment. The aim of the study was to report recent experience in the management of differentiated thyroid carcinoma in children, especially in the use of radioiodine after recombinant human thyroid stimulating hormone (rhTSH) stimulation. METHODS: Eight patients, aged 5-17 years (five were boys) presented following total thyroidectomy for thyroid carcinoma between May 2003 and June 2005. Seven had papillary carcinoma and one had follicular carcinoma. Five had known lymph node metastases and one had pulmonary metastases at presentation. Four patients had previously received therapeutic irradiation for malignancy. All eight underwent diagnostic iodine scans, seven with rhTSH stimulation. Seven went on to receive radioiodine treatment as hospital inpatients, comanaged by the paediatric and nuclear medicine units. The dosage of 131I ranged from 1.5 to 3.7 x 10(9) Bq. All except one were prepared by rhTSH stimulation. RESULTS: Seven of eight patients had significant uptake in the neck on diagnostic scan and two had pulmonary abnormalities. Six of seven evaluable patients achieved complete thyroid ablation. Both patients with pulmonary abnormalities had scan resolution, although one of them only after a second radioiodine treatment. All patients had thyroxine replacement in doses to suppress TSH and all remain alive and well at time of carrying out this study. CONCLUSION: Optimal management of paediatric thyroid carcinoma necessitates a multidisciplinary approach. Radioiodine therapy under rhTSH is an effective and safe adjuvant treatment in this special subgroup.