Literature search from ms 29/4/2010

Burton, M. D., A. Kawashima, et al. (1997). "RET proto-oncogene is important for the development of respiratory CO₂ sensitivity." JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 63(3): 137-143.

Brain stem muscarinic cholinergic pathways are important in respiratory carbon dioxide (GO,) chemosensitivity. Defects in the muscarinic system have been reported in children with congenital/developmental disorders of respiratory control such as sudden infant death syndrome (SIDS) and congenital central hypoventilation syndrome (CCHS). This early onset of disease suggests a possible genetic basis. The muscarinic system is part of the autonomic nervous system which develops from the neural crest. Ret proto-oncogene is important for this development. Thus, a potential role for ret in the development of respiratory CO₂ chemosensitivity was considered. Using plethysmography, we assessed the ventilatory response to inhaled CO₂ in the unanesthetized offsprings of ret(+/-) mice. Fractional increases in minute ventilation during hypercapnia relative to isocapnia were 5.1 +/- 3.2, 3.0 +/- 1.6 and 1.4 +/- 0.8 for the ret(+/+), ret(+/-) and ret(-/-) mice, respectively. The ret knockout mice have a depressed ventilatory response to inhaled CO₂. Therefore, the ret gene is an important factor in the pathway of neuronal development which allow respiratory CO₂ chemosensitivity.

Butler, G. P., H. M. Orpana, et al. (2007). "By your own two feet: factors associated with active transportation in Canada." Canadian Journal of Public Health Revue Canadienne de Sante Publique. 98(4): 259-64.

OBJECTIVE: The purpose of this study is to examine socio-demographic, geographic and physical activity correlates of walking and cycling for non-leisure purposes, i.e., to work, school, or errands, in Canada. METHODS: Cross-sectional data from the Canadian Community Health Survey (CCHS) 2003 (n = 127,610) were analyzed using logistic regression to identify factors associated with active transportation. The dependent variables were walking 6+ hours per week and any cycling per week. Independent variables were based on age; marital, education, working and immigrant status; income; geographic location; smoking; and other physical activity. RESULTS: Age and income were associated with both walking and cycling, as was geographic location and other physical activity. The results demonstrated that, while similar, walking and cycling are associated with different factors, and that socio-demographic, geographic and health behaviour variables must be taken into consideration when modelling these transportation modes. CONCLUSIONS: Although walking and cycling are relatively easy means to incorporate physical activity in daily life, these results suggest that it is the young and the physically active who engage in them. This research points to a need to address barriers among those who could benefit the most from increased use of both modes of travel.

Cairney, J., L. M. Corna, et al. (2010). "Mental health care use in later life: results from a national survey of Canadians." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 55(3): 157-64.

OBJECTIVE: To estimate the proportion of older adults who have used mental health services in the past 12 months among those who meet the criteria for one or more Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, 12-month psychiatric disorders. We also examine the factors associated with mental health care use in this population. METHOD: We used secondary data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). We first estimated the proportion of adults aged 55 years and older who used a range of mental health services. Next, using logistic regression, we examined the relative contribution of predisposing, enabling, and need characteristics in predicting any service use in this population. RESULTS: Among the 12 792 adults aged 55 years and older in the CCHS 1.2, 513 (4.23%, 95% CI 3.89% to 4.95%) met the criteria for at least one 12-month DSM-IV disorder. Among these respondents, 37% (95% CI 31% to 43%) saw at least one type of mental health care provider in the past 12 months. Visits to a general health care provider for mental health reasons were most common, followed by specialist care. Only psychological distress was significantly and positively associated with using mental health care services. CONCLUSIONS: Over 60% of the older adults who met the criteria for a DSM-IV disorder were not using mental health care services. Social and demographic factors did not predict service use in this population.

Cairney, J., L. M. Corna, et al. (2008). "Comorbid depression and anxiety in later life: patterns of association, subjective well-being, and impairment." AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY 16(3): 201-8.

OBJECTIVE: Very little epidemiological work has examined comorbidity between depression and anxiety disorders in community-dwelling older adults, despite the fact these disorders are known to co-occur in younger adults and that this co-occurrence is associated with greater clinical severity. In this study, the authors examine psychiatric comorbidity and associated impairment of four disorders (major depression, panic disorder, social phobia, and agoraphobia) in a community-based sample of adults aged 55 and older. SETTING: Population-based sample of older adults (N=12,792) from the Canadian Community Health Survey-Mental Health and Well-Being (CCHS 1.2). METHOD: The World Mental Health Composite International Diagnostic Interview was used to identify cases of 12-month disorder. Descriptive analysis and regression analysis is used to examine patterns of association between disorders and related impairment. RESULTS: Among adults aged 55 years and older, 4.4% met the criteria for at least one disorder and 0.8% had two or more. Social phobia was the most common comorbid disorder among respondents with depression, and depression was the most common comorbid disorder among respondents with any of the anxiety disorders. Respondents who report comorbid disorders reported significantly lower well-being and greater impairment. CONCLUSION: Although comorbidity between physical health conditions and depression, and between dementias and depression, are well documented among older adults, these results suggest that comorbid depression and anxiety are also prevalent in later life. The significant impact of comorbidity on function and well-being underlines the need to screen for comorbid disorders in this population.

Callahan, T., H. M. Young, et al. (2008). "Development of satellite glia in mouse sympathetic ganglia: Gdnf and Gfralpha1 are not essential." GLIA 56(13): 1428-1437.

The phenotypic development of satellite cells in mouse sympathetic ganglia was examined by localizing the transcription factors, Sox10 and Phox2b, the neuronal marker, tyrosine hydroxylase (TH), and brain-derived fatty acid binding protein (B-FABP), which identifies glial precursors and mature glia. In E10.5 mice, most cells in the sympathetic chain expressed both Sox10 and Phox2b, with a minority of cells expressing Sox10 only or Phox2b only. In E11.5 mice, the majority of cells expressed Sox10 only or Phox2b only. B-FABP was colocalized with Sox10 in satellite glial precursors, which were located on the periphery of the ganglion. There was no overlap between B-FABP and Phox2b or B-FABP and TH. During subsequent development, the number of B-FABP+ cells increased and they became more common deep within the ganglion. In E12.5 and E18.5 mice, there was no overlap between Sox10 and Phox2b, and 98% of Sox10 cells were also B-FABP+. Satellite glial precursors in E11.5-E15.5 mice also expressed the GDNF-binding molecule, GFRalpha1. B-FABP immunoreactive cells did not express Ret or NCAM, two potential signaling molecules for GDNF/GFRalpha1. In E12.5 and E18.5 mice lacking GFRalphaJ or GDNF, the development of B-FABP immunoreactive satellite cells was normal, and hence neither GDNF or GFRalpha1 are essential for the development of satellite glia in sympathetic ganglia. copyright 2008 Wiley-Liss, Inc.

Cargnin, F., A. Flora, et al. (2005). "PHOX2B regulates its own expression by a transcriptional auto-regulatory mechanism." JOURNAL OF BIOLOGICAL CHEMISTRY 280(45): 37439-48.

The specification of neuronal identity is a result of interactions between the following two distinct classes of determinants: extrinsic factors that include secreted or cell membrane-associated signals in the local environment, and intrinsic factors that generally consist of ordered cascades of transcription factors. Little is known about the molecular mechanisms underlying the interplay between these extrinsic and intrinsic factors and the transcriptional processes that establish and maintain a given neuronal phenotype. Phox2b is a vertebrate homeodomain transcription factor and a well established intrinsic factor in developing autonomic ganglia, where its expression is triggered by the bone morphogenic proteins secreted by the dorsal aorta. In this study we characterized its proximal 5'-regulatory region and found that it contained five putative DNA sites that potentially bind homeodomain proteins, including PHOX2B itself. Chromatin immunoprecipitation assays showed that PHOX2B could bind its own promoter in vivo, and electromobility gel shift assays confirmed that four of the five sites could be involved in PHOX2B binding. Functional experiments demonstrated that 65% of the transcriptional activity of the PHOX2B promoter in neuroblastoma cells depends on this auto-regulatory mechanism and that all four sites were required for full self-transactivation. Our data provide a possible molecular explanation for the maintenance of PHOX2B expression in developing ganglia, in which initially its expression is triggered by bone morphogenic proteins, but may become independent of external stimuli when it reaches a certain nuclear concentration and sustains its own transcription.

Carriere, G. (2003). "Parent and child factors associated with youth obesity." HEALTH REPORTS 14 Suppl: 29-39.

OBJECTIVES: This article examines relationships between parent and adolescent weight, as well as other selected characteristics and health behaviours of both, and then explores which factors are associated with youth obesity. DATA SOURCE: The analysis is based on cross-sectional household data from cycle 1.1 of the 2000/01 Canadian Community Health Survey (CCHS), conducted by Statistics Canada. The sample comprises 4,803 girls and 4,982 boys who were aged 12 to 19 in 2000/01. ANALYTICAL TECHNIQUES: Estimates of body mass index (BMI) were calculated and selected health behaviours were evaluated for adolescents and a parent who lived in the same household. Multiple logistic regression was used to identify factors associated with youth obesity while controlling for age of the youth and the sex of the reporting parent. MAIN RESULTS: For both sexes, having an obese parent greatly increased the odds for youth obesity. Among girls, former smokers had higher odds for obesity, but smoking behaviour was not associated with obesity for boys. For boys, being physically inactive or even moderately active increased the odds of obesity. And if the responding parent smoked daily, this increased the odds of obesity for boys.

Casey, K. R., K. O. Cantillo, et al. (2007). "Sleep-related hypoventilation/hypoxemic syndromes." CHEST 131(6): 1936-48.

The latest edition of The International Classification of Sleep Disorders: Diagnostic and Coding Manual subsumes a broad range of disorders under the heading "Sleep Related Hypoventilation/Hypoxemic Syndromes." Some are quite common, such as COPD with worsening gas exchange during sleep; while some are exceedingly rare, such as congenital central hypoventilation syndrome. All share the attribute of abnormal gas exchange that worsens, or may only be present, during sleep. The sleep state, the sleeping posture, and the circadian rhythm driving sleep all may affect respiration by altering control of breathing and/or pulmonary mechanics. These changes are largely inconsequential in the normal individual but interact with respiratory, neurologic, or neuromuscular disease to manifest as the sleep-related hypoventilation/hypoxemic syndromes. In addition to optimal treatment of the underlying disorder (when known and when possible), treatment usually involves nocturnal ventilatory support that is now most commonly provided by noninvasive positive pressure ventilation. [References: 135]

Catlin, A. J. (2007). "Home care for the high-risk neonate: success or failure depends on home health nurse funding and availability." Home Healthcare Nurse 25(2): 131-5.

Chang, Y. L. and P. W. Meerstadt (1991). "Congenital central alveolar hypoventilation syndrome (Ondine's Curse): effectiveness of early home ventilation for normal development." POSTGRADUATE MEDICAL JOURNAL 67(787): 471-3.

An 8 month old Caucasian girl, with congenital central alveolar hypoventilation syndrome (Ondine's Curse), was discharged with her home ventilation managed by her parents. Her subsequent neurophysical development assessed at 22 months of age was satisfactory.
Chen, J. (2003). "Age at diagnosis of smoking-related disease." HEALTH REPORTS 14(2): 9-19.

OBJECTIVES: This study assesses the relationship between the age of daily smoking initiation and the age at diagnosis of chronic obstructive pulmonary disease (COPD), heart disease and rheumatoid arthritis. DATA SOURCE: The data are from the 2000/01 Canadian Community Health Survey (CCHS). The sample for the analysis consisted of 34,144 respondents aged 35 to 64 living in private households in the provinces and territories. ANALYTICAL TECHNIQUES: The life table approach was used to estimate the cumulative incidence of smoking-related disease. Cox proportional hazards regression models were used to estimate the relative risks of disease by the age when daily smoking began. MAIN RESULTS: For both sexes, the younger the individuals were when they became daily smokers, the sooner they were diagnosed with COPD, heart disease or rheumatoid arthritis. Even when education, household income and number of cigarettes smoked per day were taken into account, adolescent starters were at increased risk of these diseases, compared with never-smokers.

Chen, L.-R., P.-N. Tsao, et al. (2007). "Congenital central hypoventilation syndrome with PHOX2B gene mutation in a Taiwanese infant." JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION 106(1): 69-73.

Congenital central hypoventilation syndrome (CCHS) is a rare disease that is characterized by failure in the autonomic control of breathing. Recent reports have identified mutation of the paired mesoderm homeobox protein 2b (PHOX2B) gene as playing a major role in CCHS. Increasing polyalanine repeat number is associated with a more severe clinical phenotype. We report a newborn male infant with the clinical manifestations of apnea and cyanosis requiring immediate endotracheal intubation at the age of 1 day. Recurrent hypoventilation with hypercapnia and hypoxemia occurred during sleep after weaning from the ventilator. No primary cardiopulmonary disease was identified. These clinical manifestations are compatible with CCHS. PHOX2B gene mutation analysis performed at the age of 4 months revealed expanded alleles containing polyalanine 26 repeats, further supporting the diagnosis of CCHS. Continuous ventilator support was necessary and tracheostomy was ultimately performed at the age of 5 months due to ventilator dependence. He was discharged with home ventilator support at the age of 6 months.

Chen, M. L. and T. G. Keens (2004). "Congenital central hypoventilation syndrome: not just another rare disorder." Paediatric Respiratory Reviews 5(3): 182-9.

Congenital central hypoventilation syndrome (CCHS) is a rare syndrome, present from birth, and is defined as the failure of automatic control of breathing. Patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxaemia during sleep and wakefulness. Therefore, especially while asleep, children with CCHS experience progressive hypercapnia and hypoxaemia. They lack arousal responses and sensations of dyspnoea to the endogenous challenges of isolated hypercapnia and hypoxaemia and to the combined stimulus of hypercapnia and hypoxaemia. Patients with CCHS do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis is one of exclusion, ruling out any primary pulmonary, cardiac, metabolic or neurologic cause for central hypoventilation. CCHS is associated with other manifestations of autonomic nervous system dysfunction, including Hirschsprung's disease. All patients with CCHS require lifelong ventilatory support during sleep but some will be able to maintain adequate ventilation without assistance while awake once past infancy. However, some CCHS patients require ventilatory support for 24h/day. Modalities of home mechanical-assisted ventilation include positive pressure ventilation via tracheostomy, non-invasive positive pressure ventilation (bi-level ventilation), negative pressure ventilation and diaphragmatic pacers. Supplemental oxygen alone is inadequate treatment. With early diagnosis and adequate ventilatory support, these children can have good outcomes and lead productive lives. [References: 50]

Chen, M. L., M. A. Tablizo, et al. (2005). "Diaphragm pacers as a treatment for congenital central hypoventilation syndrome." Expert Review of Medical Devices 2(5): 577-85.

Congenital central hypoventilation syndrome is a rare syndrome present from birth, and is defined as the failure of automatic control of breathing. All patients with congenital central hypoventilation syndrome require life-long ventilatory support during sleep, although approximately a third of patients require ventilatory support 24 h per day. Diaphragm pacers offer a modality of ventilatory support that affords congenital central hypoventilation syndrome patients with maximal mobility for full-time ventilatory patients, and they may allow for a more normal lifestyle in the appropriate patient. They may permit tracheostomy decannulation in those requiring only support during sleep. Diaphragm pacing entails surgical placement of an electrode onto the phrenic nerve, connected to a subcutaneous receiver. There is an external battery-operated transmitter and antenna placed on the skin over the receiver. The transmitter emits energy, similar to radio transmission, which is converted into an electrical current by the receiver. This stimulates the phrenic nerve resulting in a diaphragmatic contraction. Settings on the transmitter include respiratory rate and electrical voltage, and are adjusted to give enough tidal volume to allow for adequate oxygenation and ventilation. Therefore, diaphragm pacing is an attractive alternative mode of mechanically assisted ventilation for many patients with congenital central hypoventilation syndrome. [References: 36]

Chen, M. L., S. B. Turkel, et al. (2006). "Alcohol use in congenital central hypoventilation syndrome." PEDIATRIC PULMONOLOGY 41(3): 283-5.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there is failure of automatic control of breathing. With improved recognition of CCHS, more children are appropriately diagnosed and treated in infancy, allowing survival into adult years. Because most of these children are able to participate in regular school, they are exposed to common adolescent behaviors, such as abusing alcohol and drugs. Alcohol and many illicit substances are known respiratory depressants. We report on 3 cases of adolescents/young adults with CCHS who had severe adverse events related to alcohol, including coma and death. This series illustrates the dangers of alcohol abuse in CCHS. We speculate that adolescents with CCHS may be less able to perceive the risks of substance abuse and impulsive behavior, leading to increased morbidity and mortality. Patients with CCHS appear to lack anxiety and the awareness that their inability to perceive physiologically dangerous levels of hypercarbia and hypoxia deprives them of important protective mechanisms. (c) 2006 Wiley-Liss, Inc.

Chen, Y., Q. Yi, et al. (2008). "Cluster of liver cancer and immigration: a geographic analysis of incidence data for Ontario 1998-2002." International Journal of Health Geographics [Electronic Resource] 7: 28.

BACKGROUND: Liver cancer is not common in Canada in general; however, clustering of the disease causes a concern. We conducted a spatial analysis to determine the geographic variation of liver cancer and its association with the proportion of immigration in Ontario. Liver cancer incidence data between 1998 and 2002 were obtained from the Ontario Cancer Registry. The Canadian Community Health Survey (CCHS) in 2001 provided information on potential risk factors. RESULTS: Age standardized incidence ratios (SIR) for liver cancer and prevalence of potential risk factors were calculated for each of 35 health regions. The SIRs for liver cancer varied across the 35 health regions (p < 0.01). Toronto and York health regions had a significantly higher SIR than other regions, indicated by the Scan method (p < 0.001). Poisson models with and without random effects were fitted to determine independent ecological contributors. After adjustment for sex, age and spatial location, the proportion of immigrants remained a significant determinant. Smoking, alcohol drinking, physical activity, education, income, obesity and diabetes did not substantially explain the geographic variation of liver cancer in Ontario. CONCLUSION: Immigration is an important reason for the clustering of liver cancer in Ontario. More attention should be paid to areas with a high proportion of immigrants.

Chernick, V. (1981). "Endorphins and ventilatory control." NEW ENGLAND JOURNAL OF MEDICINE 304(20): 1227-1228.

The hypothesis that endogenous opioids may be implicated in such disorders of ventilatory control as sudden-infant-death syndrome, Ondine's curse, apnea of prematurity, and COPD may yet be proved correct. However, carefully controlled trials comparing the drug and placebo are required, probably along with more direct evidence, such as elevated endorphin levels.

Cheung, I. Y., Y. Feng, et al. (2008). "Exploiting gene expression profiling to identify novel minimal residual disease markers of neuroblastoma." Clinical Cancer Research 14(21): 7020-7.

PURPOSE: Minimal residual disease (MRD) presents a significant hurdle to curing metastatic neuroblastoma. Biological therapies directed against MRD can improve outcome. Evaluating treatment efficacy requires MRD measurement, which serves as surrogate endpoint. Because of tumor heterogeneity, no single marker will likely be adequate. Genome-wide expression profiling can uncover potential MRD markers differentially expressed in tumors over normal marrow/blood. EXPERIMENTAL DESIGN: Gene expression array was carried out on 48 stage 4 tumors and 9 remission marrows using the Affymetrix U95 gene chip. Thirty-four genes with a tumor-to-marrow expression ratio higher than tyrosine hydroxylase were identified. Quantitative reverse transcription-PCR was done on all 34 genes to study the dynamic range of tumor cell detection and the expression of these genes in normal marrow/blood samples and in stage 4 neuroblastoma tumors. Top ranking markers were then tested for prognostic significance in the marrows of stage 4 patients collected from the same treatment protocol after two cycles of immunotherapy. RESULTS: Based on sensitivity assays, 8 top-ranking markers were identified: CCND1, CRMP1, DDC, GABRB3, ISL1, KIF1A, PHOX2B, and TACC2. They were abundantly expressed in stage IV neuroblastoma tumors (n=20) and had low to no detection in normal marrow/blood samples (n=20). Moreover, expression of CCND1, DDC, GABRB3, ISL1, KIF1A, and PHOX2B in 116 marrows sampled after two treatment cycles was highly prognostic of progression-free and overall survival (P<0.001). CONCLUSIONS: Marker discovery based on differential gene expression profiling, stringent sensitivity and specificity assays, and well-annotated patient samples can rapidly prioritize and identify potential MRD markers of neuroblastoma.