Literature search from ms 29/4/2010

Sochala, C., D. Van Deenen, et al. (1999). "Heart block following propofol in a child." PAEDIATRIC ANAESTHESIA 9(4): 349-351.

We present the case of a nine-year-old boy afflicted with Ondine's curse, who developed complete atrioventricular heart block after a single bolus of propofol for induction of anaesthesia for strabismus surgery. Ondine's curse, the other name for congenital central hypoventilation syndrome, is characterized by a generalized disorder of autonomic function. Propofol has no effect on the normal atrioventricular conduction system in humans but it reduces sympathetic activity and can highly potentiate other vagal stimulation factors. Heart block has been documented after propofol bolus use in adults but, to our knowledge, not in children. It would appear that propofol is not a good choice for anaesthesia in congenital central hypoventilation syndrome.

Spengler, C. M., R. B. Banzett, et al. (1998). "Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity." RESPIRATION PHYSIOLOGY 114(1): 65-74.

Breathlessness arises from increased medullary respiratory center activity projecting to the forebrain (respiratory corollary discharge hypothesis). Subjects with congenital central hypoventilation syndrome (CCHS) lack the normal hyperpnea and breathlessness during hypercapnia. The corollary discharge hypothesis predicts that if CCHS subjects have normal hyperpnea during exercise, they will experience normal breathlessness during exercise. To test this, we studied four CCHS subjects and six matched controls during an exhausting constant-load cycling test requiring substantial anaerobiosis. CCHS subjects rated significantly less breathlessness at the end of the test than controls, but ventilation (index of respiratory corollary discharge) was also somewhat lower in CCHS (not significant). In both groups, breathlessness increased disproportionately more than ventilation towards the end of exercise. These data failed to disprove the corollary discharge hypothesis of breathlessness, but do suggest that the relationship between ventilation and breathlessness is non-linear and/or that projections of chemoreceptor afferents to the forebrain (presumed lacking in CCHS) is one source of breathlessness in normals.

Spengler, C. M., D. Gozal, et al. (2001). "Chemoreceptive mechanisms elucidated by studies of congenital central hypoventilation syndrome." RESPIRATION PHYSIOLOGY 129(1-2): 247-55.

Humans born with the condition of central hypoventilation during non-rapid eye movement sleep, termed congenital central hypoventilation syndrome (CCHS), invariably have absent or greatly diminished central hypercapnic ventilatory chemosensitivity. Genetic and pathological studies of CCHS may enable identification of the genes or areas of the central nervous system involved in the syndrome and thus implicated in central hypercapnic ventilatory chemosensitivity. Functional studies of CCHS permit a more quantitative assessment of the importance of ventilatory chemosensitivity in the regulation of breathing during wakefulness and sleep. The experimental evidence suggests that central hypercapnic ventilatory chemosensitivity is crucial in regulating alveolar ventilation during non-rapid eye movement sleep but not during rapid eye movement sleep or during many of the behaviors occurring during wakefulness. Presumably, other neural drives to breathe supervene to enable adequate ventilation. However, although physiological studies in CCHS subjects have been greatly instructive, their accurate interpretation will have to await future determination of the potential genetic and/or neuroanatomic basis of the syndrome. [References: 49]

Sritippayawan, S., R. Hamutcu, et al. (2002). "Mother-daughter transmission of congenital central hypoventilation syndrome." AMERICAN JOURNAL OF RESPIRATORY & CRITICAL CARE MEDICINE 166(3): 367-9.

The cause of congenital central hypoventilation syndrome (CCHS) is unknown, but a genetic etiology is strongly suspected. We report a 25-year-old woman with CCHS (no Hirschsprung's disease) who gave birth to a daughter who also has CCHS. This suggests a dominant mode of inheritance for CCHS in this family. Pregnancy can be associated with physiologic challenges in CCHS. The increase in endogenous progesterone may stimulate breathing and may possibly improve symptoms of hypoventilation. Although this patient did not have any worsening in symptoms, her hyperoxic hypercapnic rebreathing ventilatory response was not different when pregnant versus when not pregnant. Ventilatory support for the patient was successfully managed with diaphragm pacing throughout the pregnancy without the need to adjust settings, despite the enlarged abdomen during pregnancy. We conclude that CCHS may be an inherited disorder. Increased endogenous progesterone during pregnancy has no effect on the ventilatory response, and diaphragm pacing can successfully provide adequate ventilation throughout pregnancy.

Stanke, M., D. Junghans, et al. (1999). "The Phox2 homeodomain proteins are sufficient to promote the development of sympathetic neurons." DEVELOPMENT 126(18): 4087-4094.

The development of sympathetic neurons is controlled by a network of transcriptional regulators, including the paired homeodomain proteins Phox2a and Phox2b. To understand the role of Phox2 proteins in more detail, the effect of Phox2 overexpression was analysed in the avian peripheral nervous system. Phox2a expression in neural crest cultures elicited a strong increase in the number of sympathoadrenergic cells. Expression of Phox2a in the chick embryo promoted the generation of additional neurons expressing the noradrenergic marker genes DBH and TH, pan-neuronal genes SCG10 and NF160 and cholinergic genes ChAT and VAChT. Phox2a-induced neurons were found in ectopic locations such as dorsal root ganglia and peripheral nerve. Sympathoadrenergic development could be elicited in cultures of E5 dorsal root ganglia, demonstrating the presence of Phox2a-responsive cells in non-autonomic peripheral ganglia. Phox2b induced ectopic neurons in the chick embryo in the same way as Phox2a. These results show that Phox2 proteins are sufficient to promote sympathetic neuron generation and control, directly or indirectly, the expression of a large number of genes characteristic for sympathetic neurons.

Stanke, M., J. Stubbusch, et al. (2004). "Interaction of Mash1 and Phox2b in sympathetic neuron development." Molecular and Cellular Neuroscience 25(3): 374-382.

The transcription factors Mash1 and Phox2b are both essential for sympathetic neuron development. To understand in more detail their function and interaction, Phox2b and Mash1 were ectopically expressed in vivo, in peripheral nerve precursors. Here, we demonstrate that the Phox2b-induced generation of ectopic noradrenergic neurons in chick peripheral nerve involves the induction of Cash1, the chick homolog of Mash1. All Phox2-induced neurons coexpress the noradrenergic marker genes TH and DBH. Conversely, Mash1 induces neuronal differentiation characterized by the expression of generic neuronal genes SCG10, Hu and NF160; however, only a subpopulation of these neurons also displays an autonomic, noradrenergic phenotype. This context-dependent action of Mash1 implicates autonomic codeterminants, required for noradrenergic differentiation in response to Mash1. In contrast, Phox2b coordinates generic and noradrenergic gene expression, recruiting Mash1/Cash1, which may have a major function in the control of pan-neuronal gene expression during noradrenergic neuron development. copyright 2004 Elsevier Inc. All rights reserved.

Stankiewicz, J. A. and J. P. Pazevic (1989). "Acquired Ondine's curse." Otolaryngology - Head & Neck Surgery 101(5): 611-3.

Acquired OC, although rare, can occur as a result of neurologic abnormalities, and its diagnosis is dependent on an understanding of all causes of altered ventilation, including sleep disturbances--central, obstructive, or mixed. A neurologic evaluation, appropriate radiologic studies, and sleep workup will in most cases delineate the problem. Treatment includes a tracheotomy and ventilator support. Phrenic nerve pacing is reserved for patients with long-term disease and viable phrenic nerves.

Steele, L., C. Dewa, et al. (2007). "Socioeconomic status and self-reported barriers to mental health service use." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 52(3): 201-6.

OBJECTIVE: Socially disadvantaged individuals are at high risk for having their mental health service needs unmet. We explored the relations among education level, income level, and self-reported barriers to mental health service use for individuals with a mental illness, using data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). METHODS: Our sample group comprised the 8.3% of adult respondents who met the CCHS 1.2 criteria for an anxiety or affective disorder in the past 12 months (n = 3101). We examined the association between education and income levels and self-reported accessibility, availability, or acceptability barriers to mental health care. RESULTS: Accessibility, availability, and acceptability barriers were reported by 3%, 5%, and 16% of our sample, respectively. Individuals with a high school diploma were less likely than individuals without a high school diploma to report acceptability barriers to care (odds ratio 0.65; 95% confidence interval, 0.45 to 0.93). Higher-income individuals were less likely than lower-income individuals to report acceptability barriers to care (odds ratio 0.69; 95% confidence interval, 0.50 to 0.96). Employment, distress level, age, and family structure were also associated with acceptability barriers. CONCLUSION: Issues related to acceptability explain most of the unmet need for mental health services. Program planners should consider the development of targeted approaches to service delivery and outreach for low-income, working individuals who have not completed high school.

Stene, M. C. A., R. Frikke-Schmidt, et al. (2008). "Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease." JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 52(5): 369-77.

OBJECTIVES: This study was designed to test the hypotheses that single nucleotide polymorphisms (SNPs), in zinc finger protein 202 (ZNF202), predict severe atherosclerosis and ischemic heart disease (IHD). BACKGROUND: ZNF202 is a transcriptional repressor controlling promoter elements in genes involved in vascular maintenance and lipid metabolism. METHODS: We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis (ankle brachial index >0.7 vs. G altered transcriptional activity of the ZNF202 promoter in vitro. RESULTS: Cross-sectionally, ZNF202 g.-660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 (95% confidence interval [CI]: 1.34 to 3.01). Prospectively, GG versus AA homozygosity predicted a hazard ratio for IHD of 1.21 (95% CI: 1.02 to 1.43). In the 2 case-control studies, the equivalent odds ratios for IHD were 1.29 (95% CI: 1.02 to 1.62) and 1.60 (95% CI: 1.34 to 1.92), confirming the results from the prospective study. Only 2 other SNPs, which were highly correlated with g.-660A>G, also predicted risk of severe atherosclerosis and IHD. Finally, ZNF202 g.-660G versus g.-660A was associated with a 60% reduction in transcriptional activity in vitro, whereas none of the 2 correlated SNPs were predicted to be functional. CONCLUSIONS: Homozygosity for a common functional promoter variant in ZNF202 predicts severe atherosclerosis and an increased risk of IHD.

Stern, M., R. Erttmann, et al. (1980). "Total aganglionosis of the colon and Ondine's curse." LANCET 1(8173): 877-8.

Stern, M., H. H. Hellwege, et al. (1981). "Total aganglionosis of the colon (Hirschsprung's disease) and congenital failure of automatic control of ventilation (Ondine's curse)." Acta Paediatrica Scandinavica 70(1): 121-4.

Total aganglionosis of the colon presenting with small intestinal obstruction in the neonatal period was observed in combination with congenital alveolar hypoventilation requiring continuous mechanical ventilation in a boy. The patient died aged 15 months from acute dehydration due to enteritis, long after total resection of the aganglionic bowel had been performed. Pulmonary hypertension was found in the newborn period. There was progressive right ventricular myocardial hypertrophy. This is the fourth case reported with a combination of defects involving nerve cell function of the brain stem and gastrointestinal tract.
St-Jean-Trudel, E., S. Guay, et al. (2009). "[The relationship between social support, psychological stress and the risk of developing anxiety disorders in men and women: results of a national study]." Canadian Journal of Public Health Revue Canadienne de Sante Publique. 100(2): 148-52.

OBJECTIVE: Investigate the links between different types of social support, psychological well-being and distress among individuals with anxiety disorders. METHODS: Data were drawn from the Canadian Community Health Survey (CCHS cycle 1.2) which had 36,984 participants, 1,803 of whom presented with anxiety disorders. Classical linear regression analyses were conducted to examine the links between different social support dimensions and psychological well-being on one hand, and psychological distress on the other hand. RESULTS: Women reported perceiving significantly higher levels of affective, emotional/informational, tangible support and positive social interactions than men. After controlling for potentially confounding variables (socio-demographic variables and the presence of a major depressive disorder), three types of social supports appeared to be predictors for the psychological well-being of women with anxiety disorders: positive social interactions, emotional/informational support, and affective support. For men, none of the social support variables were significantly associated with psychological well-being or distress. The comparisons of Beta coefficients do not show any significant difference between the sexes. CONCLUSION: Social support appears to be a positive predictor for psychological well-being among women with an anxiety disorder. No associations were found between social support variables and the psychological distress perceived by men and women. The results of this study therefore confirm the importance of teaching appropriate support strategies adapted for anxiety disorders. Future studies should assess negative social interactions in addition to social support.

Stornetta, R. L., T. S. Moreira, et al. (2006). "Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat." JOURNAL OF NEUROSCIENCE 26(40): 10305-10314.

Central congenital hypoventilation syndrome is caused by mutations of the gene that encodes the transcription factor Phox2b. The syndrome is characterized by a severe form of sleep apnea attributed to greatly compromised central and peripheral chemoreflexes. In this study, we analyze whether Phox2b expression in the brainstem respiratory network is preferentially associated with neurons involved in chemosensory integration in rats. At the very rostral end of the ventral respiratory column (VRC), Phox2b was present in many VGlut2 (vesicular glutamate transporter 2) mRNA-containing neurons. These neurons were functionally identified as the respiratory chemoreceptors of the retrotrapezoid nucleus (RTN). More caudally in the VRC, many fewer neurons expressed Phox2b. These cells were not part of the central respiratory pattern generator (CPG), because they were typically cholinergic visceral motor neurons or catecholaminergic neurons (presumed C1 neurons). Phox2b was not detected in serotonergic neurons, in the A5, A6, and A7 noradrenergic cell groups nor within the main cardiorespiratory centers of the dorsolateral pons. Phox2b was expressed by many solitary tract nucleus (NTS) neurons including those that relay peripheral chemoreceptor information to the RTN. These and previous observations by others suggest that Phox2b is expressed by an uninterrupted chain of neurons involved in the integration of peripheral and central chemoreception (carotid bodies, chemoreceptor afferents, chemoresponsive NTS neurons projecting to VRC, RTN chemoreceptors). The presence of Phox2b in this circuit and its apparent absence from the respiratory CPG could explain why Phox2b mutations disrupt breathing automaticity during sleep without causing major impairment of respiration during waking. Copyright copyright 2006 Society for Neuroscience.

Stornetta, R. L., D. Spirovski, et al. (2009). "Galanin is a selective marker of the retrotrapezoid nucleus in rats." JOURNAL OF COMPARATIVE NEUROLOGY 512(3): 373-383.

The rat retrotrapezoid nucleus (RTN) contains CO2-activated neurons that contribute to the central chemoreflex and to breathing automaticity. These neurons have two known markers, the transcription factor Phox2b and vesicular glutamate transporter 2 (VGLUT2). Noncatecholaminergic galanin-immunoreactive (ir) neurons within a region of the lower brainstem that seems identical to what is currently defined as the RTN have been previously described. Here we ask whether these galanin-expressing neurons are the same cells as the recently characterized CO2-sensitive neurons of the RTN. By using in situ hybridization, we found that pre-pro-galanin (PPGal) mRNA is expressed by an isolated cluster of neurons that is co-extensive with the RTN as defined by a population of strongly Phox2b-ir neurons devoid of tyrosine hydroxylase (Phox2b+/TH- neurons). This bilateral structure contains about 1,000 PPGal mRNA-positive neurons in the rat. The PPGal mRNA-positive neurons were Phox2b+/TH- and as susceptible to destruction by the toxin [Sar9, Met (O2)11]-substance P as the rest of the RTN/TH- cells of the RTN. CO2-activated neurons were recorded in the RTN of anesthetized rats and were labeled with biotinamide. Many of those cells (7/17, 41%, five rats) contained PPGal-mRNA. In conclusion, galanin mRNA is a very specific marker of the glutamatergic Phox2b+/TH- neurons of the RTN, but galanin mRNA identifies only half of these putative central respiratory chemo-receptors. copyright 2008 Wiley-Liss, Inc.

Stovroff, M., F. Dykes, et al. (1995). "The complete spectrum of neurocristopathy in an infant with congenital hypoventilation, Hirschsprung's disease, and neuroblastoma." JOURNAL OF PEDIATRIC SURGERY 30(8): 1218-21.

Neuroblastoma, Hirschsprung's disease, and central hypoventilation (Ondine's curse) are considered aberrations of neural crest cell growth, migration, or differentiation, and as such are considered to be under the general heading of neurocristopathy. Their combined occurrence in a newborn infant presenting with total colonic aganglionosis, central hypoventilation, and multifocal neuroblastoma had not been reported previously. A 2.3-kg white full-term girl required endotracheal intubation because of persistent apnea in the first hours of life. She had progressive abdominal distension and failure to pass meconium; a barium enema was performed, which showed microcolon with meconium pellets at the distal ileum. During laparotomy the distal ileum was found to be obstructed with inspissated meconium; an ileostomy and appendectomy were performed. The resected specimens were aganglionic. An additional 20 cm of aganglionic ileum was removed, and a normally innervated ileostomy was constructed. Numerous attempts at extubation failed because of apnea. The results of an extensive apnea workup, including electroencephalogram, magnetic resonance imaging (MRI), bronchoscopy, and pH probe study, were normal. Sleep studies showed congenital central hypoventilation syndrome, and the patient underwent a tracheostomy. At 3 months, an abdominal ultrasound examination performed within a septic workup showed a right suprarenal mass extending across the midline. Thoracic and abdominal MRI scans showed large bilateral adrenal and posterior mediastinal masses. The serum catecholamines and ferritin level were markedly elevated, suggestive of neuroblastoma. In light of the child's multiple problems, the family chose to forgo further workup (including a tissue biopsy) and therapy. In the following 2 months her tumor load rapidly progressed, and she died of respiratory insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Strauser, L. M., M. A. Helikson, et al. (1999). "Anesthetic care for the child with congenital central alveolar hypoventilation syndrome (Ondine's curse)." JOURNAL OF CLINICAL ANESTHESIA 11(5): 431-7.

Idiopathic congenital central alveolar hypoventilation syndrome, otherwise known as Ondine's curse, is a rare neuropathologic syndrome characterized by an inadequate respiratory drive with hypoventilation and periods of prolonged apnea resulting in hypercarbia and hypoxemia. Although no definite pathologic abnormality has been identified to account for the disorder, it is thought to represent a primary defect related to altered function of central chemoreceptors resulting in defective control of minute ventilation. Associated problems related to neural crest cell migration, including neuroblastoma formation and Hirschsprung's disease, suggest that the primary defect is defective neural crest cell migration and function. Problems that may impact on perioperative care include the defective central control of ventilation and defective control of upper respiratory musculature, which may lead to upper airway obstruction. Although many patients will have previously undergone tracheostomy and chronic mechanical ventilation, problems in other organ systems can impact on perioperative care. Cardiovascular issues include the possible presence of cor pulmonale and autonomic nervous system dysfunction. Central nervous system issues include the frequent occurrence of seizures and mental retardation. The preoperative work-up, premedication, and the intraoperative/postoperative care and monitoring of these patients is reviewed. [References: 33]

Streiner, D. L., J. Cairney, et al. (2005). "Psychiatric epidemiology in Canada and the CCHS study." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 50(10): 571-2.

Streiner, D. L., J. Cairney, et al. (2006). "The epidemiology of psychological problems in the elderly.[Erratum appears in Can J Psychiatry. 2006 May;51(6):404]." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 51(3): 185-91.

OBJECTIVE: To determine the prevalence of mood, anxiety, and other disorders in the population of Canadians aged 55 years and over. METHOD: We undertook an analysis of the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). RESULTS: There was a linear decrease for all disorders after age 55 years. This was true for men and women; for anglophones, francophones, and allophones; and for both people born in Canada and people who immigrated to Canada after age 18 years. Consistent with previous research, the prevalences were higher for women than men. Immigrants reported fewer problems than nonimmigrants, with the differences decreasing with age. Francophones of both sexes reported more mood disorder than anglophones, but francophone men had less anxiety disorder than anglophone men. CONCLUSIONS: Unlike other studies that have found an upturn in the prevalence of depression and anxiety in the elderly, our results indicate a steady decrease in these disorders. Our findings are discussed in terms of explanations for age-related differences in psychiatric disorders.
Stutterheim, J., A. Gerritsen, et al. (2008). "PHOX2B is a novel and specific marker for minimal residual disease testing in neuroblastoma." JOURNAL OF CLINICAL ONCOLOGY 26(33): 5443-9.