Literature search from ms 29/4/2010

Weese-Mayer, D. E., J. M. Silvestri, et al. (1996). "Diaphragm pacing with a quadripolar phrenic nerve electrode: an international study." Pacing & Clinical Electrophysiology 19(9): 1311-9.

We sought to determine the international experience with the quadripolar diaphragm pacer system and to test two hypotheses: the incidence of pacer complications would be (1) increased among pediatric as compared to adult patients; and (2) highest among active pediatric patients with idiopathic congenital central hypoventilation syndrome (CCHS). Data were collected via a questionnaire coupled with the Atrotech Registry data for a total of 64 patients (35 children and 29 adults) from 14 countries. Thoracic implantation of electrodes and bilateral pacer use each occurred in 94% of all subjects. Tetraplegic (vs pediatric CCHS) patients were more typically paced 24 hours/day (P = 0.001). Pacing duration averaged 2.0 +/- 1.0 years among children and 2.2 +/- 1.1 years among adults. Infections occurred among 2.9% of surgical procedures, all in pediatric CCHS patients (vs pediatric tetraplegic patients, P = 0.01). The incidence of mechanical trauma was 3.8%, without significant differences among patient groups. The incidence of presumed electrode and receiver failure were 3.1% and 5.9%, respectively, with internal component failure greater among pediatric CCHS than pediatric tetraplegic patients (P < 0.01). Intermittent or absent function of 0-4 electrode combinations occurred among 19% of all patients, with increased frequency among pediatric CCHS than pediatric tetraplegic patients (P < 0.03). Complication-free successful pacing occurred in 60% of pediatric and 52% of adult patients. In all, 94% of the pediatric and 86% of the adult patients paced successfully after the necessary intervention. Although pacer complications were not increased among pediatric as compared to adult patients, the incidence of complications was highest among the active pediatric patients with CCHS. Longitudinal study of these patients will provide invaluable information for modification and improvement of the quadripolar system.

Weese-Mayer, D. E., J. M. Silvestri, et al. (1993). "Congenital central hypoventilation syndrome: inheritance and relation to sudden infant death syndrome." AMERICAN JOURNAL OF MEDICAL GENETICS 47(3): 360-7.

We evaluated the families of 50 children with idiopathic congenital central hypoventilation syndrome (CCHS) to 1) test genetic hypotheses, 2) explore the relationship to Hirschsprung disease (HD), and 3) examine other clinical findings including sudden infant death syndrome (SIDS) in relatives of CCHS patients. A questionnaire was administered to parents of each proband to determine a detailed pedigree and medical history for 3 generations including 1,482 relatives. The data were analyzed under the unified mixed model method (assumes individual genotype composed of multifactorial [MF] and major locus [ML] components). Analysis was made of the Total dataset and on subdivided data sets: HIR1 = families of probands with HD (n = 8) vs. HIR2 = families of probands without HD; then under a premise that severe, chronic constipation may be a milder form of HD (i.e., ganglion cells present but dysfunctional), CON1 = families of probands with HD or constipation (n = 13) vs. CON2 = families of probands without HD or constipation. By statistical genetic analysis of the Total, HIR1, and CON1 datasets, the MF and ML hypotheses were about equally likely, with the MF model slightly more parsimonious. Although HIR2 and CON2 datasets indicated no familiality, statistical evidence of heterogeneity between the results of HIR1 and HIR2, or between CON1 and CON2 was lacking. A SIDS incidence of 11.2/1,000 was documented among the relatives of CON1 vs. 1.8/1,000 among relatives of CON2. Our results are consistent with familiality by either MF or ML models. Recurrence risk is likely < 5%. The relationship of CCHS to the high familial incidence of SIDS is intriguing and demands further investigation. [References: 41]

Weese-Mayer, D. E., J. M. Silvestri, et al. (1992). "Congenital central hypoventilation syndrome: diagnosis, management, and long-term outcome in thirty-two children." JOURNAL OF PEDIATRICS 120(3): 381-7.

The diagnosis, management, and long-term outcome of 32 patients with congenital central hypoventilation syndrome are summarized. Sleep hypoventilation was severe in all cases, resulting in an alveolar carbon dioxide pressure (mean +/- SEM) of 62 +/- 2.5 mm Hg and a hemoglobin saturation of 65% +/- 3.3% without ventilatory or arousal response. Awake hypoventilation on initial assessment was present in 12 of the 32 patients, resulting in an alveolar carbon dioxide pressure of 58 +/- 2.2 mm Hg and a hemoglobin saturation of 59% +/- 7%. Associated conditions included pulmonary hypertension or cor pulmonale or both (78%), heart block and sick sinus syndrome requiring a cardiac pacemaker (two patients), mild atrophy by cranial imaging evidence (40%), seizures (72%), normal brain-stem auditory evoked responses in all but one patient tested, ganglioneuroblastomas (one patient), Hirschsprung disease (16%), and ophthalmologic abnormalities (60%). Growth was deficient in 44% of patients; hypotonia or major motor delay or both were apparent in all. Twenty-two patients are living; 12 of them require continuous ventilatory support and 10 breathe spontaneously while awake and require ventilatory support while asleep. Ten patients have died. Autopsy performed in six cases indicated diffuse central nervous system astrocytosis, gliosis, and atrophy but no primary brain-stem abnormality. Although these data support a diffuse central nervous system process, the specific cause and the mode of inheritance remain unclear. With early diagnosis and careful ventilatory management, the sequelae of hypoxia and morbidity should be minimized and long-term outcome improved.

Wells, H. H., J. Kattwinkel, et al. (1980). "Control of ventilation of Ondine's curse." JOURNAL OF PEDIATRICS 96(5): 865-7.

Wen, G., J. Wessel, et al. (2007). "An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension." HUMAN MOLECULAR GENETICS 16(14): 1752-64.

Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
White, D. P. (1985). "Central sleep apnea." MEDICAL CLINICS OF NORTH AMERICA 69(6): 1205-19.

Central sleep apnea is a disorder characterized by apneic episodes during sleep with no associated ventilatory effort. More commonly than not these apneas are seen in patients who also have obstructive and mixed events. Although patients with this disorder frequently complain of insomnia and depression, frank hypersomnolence is rarely encountered. As these complaints are common ones seen in numerous clinical situations, and since sleep studies are rarely conducted to investigate their etiology, the true incidence of central sleep apnea has not been determined. The etiology of central apnea remains unknown, although the association between these breathing events and a number of other disease processes has increased our understanding of the disorder. Central apneas during sleep commonly occur after hyperventilation with the associated hypocapnic alkalosis. This occurs at high altitude when hyperventilation is induced by hypoxia and at sea level when spontaneous nocturnal hyperventilation occurs. This suggests that PCO2 is the primary stimulus to ventilation during sleep and that loss of this drive, as occurs with hypocapnia, may produce dysrhythmic breathing. Patients with complete absence of ventilatory chemosensitivity such as occurs with Ondine's curse (central alveolar hypoventilation) or the obesity-hypoventilation syndrome may also have central apneas. For reasons that remain unexplained, central sleep apnea is commonly seen in patients with congestive heart failure, nasal obstruction, and certain neurologic disorders. However, in most patients with central sleep apnea no obvious cause or association can be found. The treatment of this disorder is not entirely satisfactory. If it is severe, mechanical ventilation during sleep can be provided by any one of a number of techniques. However, for the patient who simply complains of insomnia and is found to have a moderate number of central apneas, the treatment choices are limited. Acetazolamide has been shown to decrease central apneas during short-term use, but results have been variable with prolonged administration. Other ventilatory stimulants seem to have little efficacy. Interestingly, oxygen administration has been shown to reduce central apneas considerably in a number of studies, although the explanation for its success is unknown. Central sleep apnea therefore remains a relatively rare disorder whose etiology is not fully understood and whose treatment is not completely satisfactory. [References: 58]

Wiesel, S. and G. S. Fox (1990). "Anaesthesia for a patient with central alveolar hypoventilation syndrome (Ondine's Curse)." CANADIAN JOURNAL OF ANAESTHESIA 37(1): 122-6.

The perioperative anaesthetic management of an adult patient with central alveolar hypoventilation syndrome (CAHS), Ondine's Curse, is described for anterior resection of a carcinoma of the bowel. This rare syndrome results in alveolar hypoventilation, hypercarbia, hypoxaemia with secondary polycythaemia, pulmonary artery hypertension, and cor pulmonale. Epidural morphine was used for postoperative analgesia in an attempt to improve postoperative respiratory function. However, postoperative mechanical ventilation was required until recovery of the respiratory drive, which was ablated by anaesthetic drugs, epidural morphine and high inspired oxygen concentrations. The pathophysiology and treatment of this syndrome are reviewed.

Wilkins, K., M. Shields, et al. (2009). "Smokers' use of acute care hospitals--a prospective study." HEALTH REPORTS 20(4): 75-83.

BACKGROUND: Previous Canadian estimates of hospital use by smoking history have been derived by applying disease-specific "smoking-attributable fractions" to administrative data. For this analysis, health survey data were linked to hospitalization data at an individual level, permitting prospective measures of hospital use by smoking status and age. DATA AND METHODS: Data for 28,255 respondents (outside Quebec) to the 2000/2001 Canadian Community Health Survey (CCHS) were linked to the Hospital Person-Oriented Information Database. Days in hospital over four years were quantified for each respondent and examined in relation to smoking status in 2000/2001. Multiple logistic regression was used to examine the association between smoking and hospitalization, while controlling for confounders. RESULTS: During the four years after their CCHS interview, current daily smokers and former daily smokers who had quit in the past five years averaged more than twice as many days in hospital as did never-daily smokers. Altogether, excess hospital days for current and former smokers aged 45 to 74 numbered 7.1 million over four years, and accounted for 32% of all hospital days used by people in this age group.

Wilzen, A., S. Nilsson, et al. (2009). "The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A." International Journal of Oncology 34(3): 697-705.

Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common solid tumor in childhood. By microarray expression analysis (Affymetrix HU133A) important players in the noradrenalin biosynthesis pathway (DBH, DDC, GATA2, GATA3, PHOX2A, PHOX2B, SLC6A2 SLC18A1 and TH) were found to be among the top ranked genes in showing lower expression in unfavorable NB tumor types as compared to favorable ones. By quantitative PCR with TaqMan, this result was significantly verified for all transcripts (p<0.05, one-tailed) in a new set of 11 primary NB tumors (5 favorable vs. 6 unfavorable). PHOX2A, a downstream target of Phox2b, was found to be the sixth ranked gene from the microarray gene list. Since the PHOX2A gene is localized in a tumor suppressor candidate region at 11q, we screened this gene for mutations by DNA sequencing in 47 tumors of different stages. However, no critical changes were found that could support its role in tumor development or progression. Overall, the findings in this study either suggest that expression of this pathway could be a predictive differentiation marker of NB tumors, or our results could also imply that the noradrenalin biosynthesis pathway is involved in tumor pathogenesis.

Windhorst, U., W. Koehler, et al. (1987). "Event-related cross-correlations between spike trains illustrated on interactions between motor units and muscle spindle afferents." Pflugers Archiv European Journal of Physiology 408(2): 196-203.

A method is presented for computing correlation coefficients of two (or more) output spike trains in temporal relation to one (or more) input event trains. These event-related correlation functions are computed by convolving the output spike trains, represented as point processes, with rectangular pulses of selectable width, and by then calculating linear correlation coefficients for the pairs of amplitude values obtained from the two convolved processes in temporal relation to the input events. The merits of this technique are illustrated on stimulus trains delivered to motor units (MUs) and output spike trains recorded from muscle spindle afferents of the same cat hindlimb muscle. The correlation functions obtained show the temporal course of the correlated firings of the two afferents (mostly Ia afferents from primary muscle spindle endings) as a function of time from MU activation; they are compared with the conventional cross-correlation histograms (CCHs) between afferents and with peri-stimulus time histograms (PSTHs) between stimulus and afferent firing patterns. Stimulus-related cross-correlation functions as displayed here can be calculated for any three spike trains. Possible extensions of the method to larger numbers of input and output channels are also discussed.

Windisch, W., E. Hennings, et al. (2004). "Long-term survival of a patient with congenital central hypoventilation syndrome despite the lack of continuous ventilatory support." RESPIRATION 71(2): 195-8.

Untreated idiopathic congenital central hypoventilation syndrome (CCHS) is thought to cause infant death within 1-2 months. Here we present an adult patient with CCHS who survived without continuous ventilatory support, despite hypoventilation from early childhood onward. The diagnosis was confirmed at the age of 22 years, when the patient presented with hypoventilation during the night (PaCO2 60 mm Hg, PaO2 56 mm Hg, pH 7.32 HCO3- 30 mmol/l) but hyperventilation when awake (PaCO2 26 mm Hg, PaO2 81 mm Hg, pH 7.56, HCO3- 23 mmol/l). The maximal hematocrit was 77%. Despite mental retardation, noninvasive positive pressure ventilation (NPPV) could be successfully established. NPPV-supported ventilation during the night (PaCO2 36, PaO2 84 mm Hg, pH 7.47, HCO3- 25 mmol/l) reduced hematocrit values (40.6 to 36.8%) over a period of 4 years. In conclusion, long-term survival with CCHS is possible without continuous ventilatory support. Spontaneous improvement of hypoventilation during sleep throughout childhood is possible and hyperventilation during wakefulness may occur in patients with CCHS. CCHS can be managed with NPPV despite mental retardation, even over a long-term period. Copyright 2004 S. Karger AG, Basel

Winters, M., M. C. Friesen, et al. (2007). "Utilitarian bicycling: a multilevel analysis of climate and personal influences." AMERICAN JOURNAL OF PREVENTIVE MEDICINE 32(1): 52-8.

BACKGROUND: Increasing utilitarian bicycling in urban areas is a means to reduce air and noise pollution, increase physical activity, and reduce the risk of chronic diseases. We investigated the impact of individual- and city-level characteristics on bicycling in Canadian cities to inform transportation and public health policies. METHODS: The study population included 59,899 respondents to the 2003 Canadian Community Health Survey (CCHS) living in cities with populations greater than 50,000. In 2005, data on individual characteristics were drawn from the CCHS, and city-level climate data from Environment Canada records. Separate multilevel logistic regression models were developed for the general (nonstudent) and student populations. RESULTS: The proportion of the urban population reporting bicycling in a typical week was 7.9%, with students cycling more than nonstudents (17.2% vs 6.0%). In the general population, older age, female gender, lower education, and higher income were associated with lower likelihood of cycling. More days of precipitation per year and more days of freezing temperatures per year were both associated with lower levels of utilitarian cycling (odds ratios [ORs] for every 30-day increase in precipitation=0.84, 95% confidence interval [CI]=0.74-0.94, and for every 30-day increase in freezing temperatures OR=0.91, 95% CI=0.86-0.97). There was less variation in the proportion of students who cycled by age and income, and only the number of days with freezing temperatures influenced bicycling. CONCLUSIONS: Bicycling patterns are associated with individual demographic characteristics and the climate where one lives. This evidence might be useful to guide policy initiatives for targeted health promotion and transportation infrastructure.

Wolfson, C., P. S. Raina, et al. (2009). "The canadian community health survey as a potential recruitment vehicle for the canadian longitudinal study on aging." Canadian Journal on Aging 28(3): 243-9.

ABSTRACTThe goal of the Canadian Longitudinal Study on Aging (CLSA) is to recruit 50,000 participants aged 45 to 85 years of age and follow them for at least 20 years. The sampling and recruitment processes for a study of this scope and magnitude present important challenges. Statistics Canada was approached to collaborate with the CLSA with the goal of determining whether the Canadian Community Health Survey (CCHS) could be used as a recruitment vehicle for the CLSA. In this pilot study conducted in 2004, it was determined that 63.8 per cent and 75.8 per cent of the respondents agreed to share their contact information and their survey responses with the CLSA, respectively. The most commonly reported concerns were confidentiality/privacy issues, lack of interest, and commitment issues. This pilot study identified some challenges to the use of the CCHS as a recruitment vehicle for the CLSA.

Woo, M. A., P. M. Macey, et al. (2005). "FMRI responses to hyperoxia in congenital central hypoventilation syndrome." PEDIATRIC RESEARCH 57(4): 510-8.

Congenital Central Hypoventilation Syndrome (CCHS) patients show partial retention of peripheral chemoreception despite impaired ventilatory responses to CO2 and hypoxia. The condition allows examination of central responses to hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2) period in 14 CCHS and 15 control subjects. After partitioning gray matter and correcting for global effects, the images were analyzed using volume-of-interest time trends followed by repeated-measures ANOVA and conventional cluster analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in control subjects; CCHS heart rate increased in the first minute, and then decreased in the second minute, as in controls, but with muted rise and extent of decline. Multiple sites within the cerebellum, midbrain, and pons responded similarly to the challenge in both groups. Response patterns differed early in the right amygdala, paralleling initial respiratory pattern deficits, and late in the right insula, concomitant with cardiac rate differences. Signals also differed between groups in the medial and anterior cingulate, hippocampus, head of caudate, and lentiform nuclei, as well as pontine and midbrain structures and regions within the superior temporal and inferior frontal cortical gyri. The findings emphasize that structures that can alter respiratory timing, such as the amygdala, and modulate sympathetic outflow, such as the right insula, are deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are also affected.

Woo, M. S., M. A. Woo, et al. (1992). "Heart rate variability in congenital central hypoventilation syndrome." PEDIATRIC RESEARCH 31(3): 291-6.

Heart rate variability was assessed in 12 patients with congenital central hypoventilation syndrome (CCHS) and in age- and sex-matched controls using SD of time intervals between R waves (R-R intervals), R-R interval histograms, spectral analysis, and Poincare plots of sequential R-R intervals over a 24-h period using ambulatory monitoring. Mean heart rates in patients with CCHS were 103.3 +/- 17.7 SD and in controls were 98.8 +/- 21.6 SD (p greater than 0.5, NS). SD analysis of R-R intervals showed similar results in both groups (CCHS 102.2 +/- 36.0 ms versus controls 126.1 +/- 43.3 ms; p greater than 0.1, NS). Spectral analysis revealed that, for similar epochs sampled during quiet sleep and wakefulness, the ratios of low-frequency band to high-frequency band spectral power were increased for 11 of 12 patients with CCHS during sleep, whereas a decrease in these ratios was consistently observed in all controls during comparable sleep states (chi 2 = 20.31; p less than 0.000007). During wakefulness, the ratios of low-frequency band to high-frequency band spectral power were similar in both patients with CCHS and controls. Poincare plots displayed significantly reduced beat-to-beat changes at slower heart rates in the CCHS patients (chi 2 = 24.0; p less than 0.000001). The scatter of points in CCHS Poincare plots was easily distinguished from controls. All CCHS patients showed disturbed variability with one or more measures. The changes in moment-to-moment heart rate variability suggest that, in addition to a loss of ventilatory control, CCHS patients exhibit a dysfunction in autonomic nervous system control of the heart.

Wright, R. F., R. B. Hatfield, et al. (1999). "Procedure for construction of a custom tracheostomal obturator: a clinical report." JOURNAL OF PROSTHETIC DENTISTRY 82(4): 387-90.

Wrobel, L. J., M. Ogier, et al. (2007). "Abnormal inspiratory depth in Phox2a haploinsufficient mice." NEUROSCIENCE 145(1): 384-392.

Mutations of genes encoding Phox2a or Phox2b transcription factors induce modifications of different brainstem neuronal networks. Such modifications are associated with defects in breathing behavior at birth. In particular, an abnormal breathing frequency is observed in Phox2a^-/- mutant mice, resulting from abnormal development of the locus coeruleus (LC) nucleus. However, the role of Phox2a proteins in the establishment of respiratory neuronal pathways is unknown, largely because mutants die shortly after birth. In the present study, we examined the effects of a haploinsufficiency of the Phox2a gene. Phox2a heterozygotes survive and exhibit a significantly larger inspiratory volume both during normoxic breathing and in response to hypoxia and a delayed maturation of inspiratory duration compared to wild-type animals. This phenotype accompanied by an unaltered frequency is evident at birth and persists until at least postnatal day 10. Morphological analyses of Phox2a^+/- animals revealed no anomaly in the LC region, but highlighted an increase in the number of cells expressing tyrosine hydroxylase enzyme, a marker of chemoafferent neurons, in the petrosal sensory ganglion. These data indicate that Phox2a plays a critical role in the ontogeny of the reflex control of inspiration. copyright 2006 IBRO.