Literature search from ms 29/4/2010

Dick, T. E., F. J. Kong, et al. (1987). "Correlation of recruitment order with axonal conduction velocity for supraspinally driven diaphragmatic motor units." JOURNAL OF NEUROPHYSIOLOGY 57(1): 245-259.

1. Spontaneous activities of pairs of single diaphragmatic motor units (MUs) were recorded via two electrodes in anesthetized cats, ventilated with CO₂ added to the inspired gas, which slightly enhanced respiratory drive (end-tidal CO₂ <6%). These MUs were characterized by their axonal conduction velocities (CVs) and relative onset times (defined as the time after onset of phrenic nerve activity until the MU began discharging divided by the duration of inspiration). Motor unit axonal CV was estimated by the conduction time and the distance between two points on the phrenic nerve. Results were compared from two experimental preparations: one with dorsal roots intact and the other with dorsal roots transected bilaterally between fouth (C₄) and seventh (C₇) cervical segments. 2. Estimated mean CV for phrenic MUs was 46.2 m/s (n = 180 MU). Motor units were classified as early and late recruited MUs depending on their relative onset times. 3. We correlated MU axonal CV with its relative recruitment time. A highly significant (P < 0.0001), positive correlation between axonal CV and relative recruitment time was established for those diaphragmatic MUs recruited with this respiratory drive. Correlation coefficients were r = 0.70 for intact animals, r = 0.72 for dorsal rhizotomized animals, and r = 0.72 overall population. 4. For pairs of MUs, the CV of the earlier recruited unit was compared with the CV of the later recruited unit. In 96% of pairs from intact animals and 92% of pairs from dorsal rhizotomized animals, the first MU had a lower CV than the MU recruited later. Difference in relative times of recruitment was directly related to difference in axonal CVs. However, a portion of the motor pool with high axonal CVs was not sampled. 5. Under conditions of these experiments, afferent input in cervical dorsal roots, including that from diaphragmatic receptors, did not influence the distribution of MU relative onset times. Further, a similar proportion of MU pairs wherein the earlier recruited MU had a CV lower than the later recruited unit was observed in intact and dorsal rhizotomized animals. 6. We also cross-correlated 31 pairs of simultaneously recorded MUs to assess common input onto phrenic motoneurons. Common input was characterized by the presence of peaks having widths of [greater-than or equal to]3 ms in the cross-correlation histograms (CCHs) and occurring within 20 ms of the trigger event. Peaks were judged significant if the bin with the largest number of occurrences was significantly greater than base line and if neighboring bins were above base line. Peaks were present in 17 of 31 CCHs. This ratio of CCHs, indicating common input, was comparable for both homogeneous (similar relative onset times) and heterogeneous (dissimilar relative onset times) pairs of MUs. 7. Henneman's size principle predicted recruitment order correctly based on difference in axonal CV for 93.4% of MU pairs. There was no difference in the ability of axonal CV to predict recruitment order in intact and dorsal rhizotomized animals.
Diedrich, A., B. A. Malow, et al. (2007). "Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation-confirmed congenital central hypoventilation syndrome." CLINICAL AUTONOMIC RESEARCH 17(3): 177-85.

BACKGROUND: Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control. METHODS AND RESULTS: An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted. CONCLUSION: In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS.

Dieterle, L., T. Staudacher, et al. (1991). "Ondine's curse: Impaired respiratory control with convulsive syncope. [German]." NERVENARZT 62(12): 754-759.

In a 31 years old woman with primary alveolar hypoventilation (Ondine's curse) and noctural seizures the arterial blood gases, EEG and blood flow velocity in the middle cerebral artery were measured before, during and after a phase of apnea terminated by a convulsive syncope. The blood flow velocity abruptly increased to the 2.5 fold of the initial value with the beginning of the convulsions, which is interpreted as a break down of the cerebral autoregulation.

Doebelin, B., J. L. Estival, et al. (2005). "Impetigo herpetiformis and Ondine curse. [French]." ANNALES DE DERMATOLOGIE ET DE VENEREOLOGIE 132(6-7 I): 559-561.

Introduction. Impetigo herpetiformis is a rare dermatitis that occurs during pregnancy and may be life threatening for both mother and child. In this case report, we present an Ondine curse involving the baby, and the good response to isotretinoine. Case report. A first pregnancy, 26 year-old woman developed at 8 months a widespread skin lesion involving the medial side of the thighs, abdomen and intertriginous areas, with a severe systemic toxic condition and fever. Diagnosis of impetigo herpetiformis was made and corticosteroids, methotrexate and cyclosporine were unsuccessful. Isotretinoine rapidly improved the patient with good control of the disease. The full term baby had an Ondine curse. Discussion. Our case is typical of impetigo herpetiformis. Maternal and infant complication may be life threatening and we report a real Ondine curse the etiology of which remains unknown. Moreover, this observation is unusual because the lesions did not clear despite delivery and good treatment. In our opinion, the great improvement with isotretinoine would suggest it could be used as first line treatment.

Dogra, S., B. A. Meisner, et al. (2008). "Psychosocial predictors of physical activity in older aged asthmatics." Age & Ageing 37(4): 449-54.

BACKGROUND: there is little information available on physical activity (PA) patterns and the psychosocial determinants of PA in older adults with asthma. OBJECTIVE: to quantify the prevalence of PA in older asthmatics and to explore the potential psychosocial determinants of PA in this population. STUDY DESIGN AND SETTING: cross-sectional data available from the Canadian Community Health Survey (CCHS), cycle 2.1, were used. There was a total of 1,772 older asthmatics in the sample. RESULTS: there were significant differences in the prevalence of PA between older asthmatic females compared to middle-aged asthmatic females (chi(2) = 23.65, P < 0.0001) and older asthmatics compared to older non-asthmatics (chi(2) = 38.1, P < 0.0001). Logistic regression revealed a significant association between PA and perceived health in older asthmatic males (OR = 5.39, CI = 1.36-21.33) and females (OR = 4.81, CI = 1.41-16.38). Being a member of a volunteer organisation was also significantly associated with PA in older asthmatic females (OR = 1.59, CI = 1.11-2.30). CONCLUSION: older asthmatics were less active than their non-asthmatic peers. Perceived health was an important predictor of PA in both older asthmatic males and females. Exercise interventions in this population should make an effort to improve self-perceived health.

Doherty, L. S., J. L. Kiely, et al. (2007). "Late-onset central hypoventilation syndrome: a family genetic study." EUROPEAN RESPIRATORY JOURNAL 29(2): 312-6.

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.

Dooling, E. C. and E. P. Richardson, Jr. (1977). "Ophthalmoplegia and Ondine's curse." ARCHIVES OF OPHTHALMOLOGY 95(10): 1790-3.

Ocular abnormalities and psychomotor difficulties were prominent in two unrelated children; in addition, the older child had respiratory irregularity during sleep. The pathologic findings included lesions of the optic nerve in the case with available material and established the diagnosis of Leigh's subacute necrotizing encephalopathy. This disorder is thought to result from inhibition of a thiamine-dependent enzymatic process and may be modified by greatly increased thiamine intake. Suspicion of the diagnosis in a child with ophthalmoplegia or other ocular abnormalities may lead to earlier recognition and more successful treatment of the disease.

Doyle, S., E. Fasoli Susan, et al. (2007) Interventions for sensory impairment in the upper limb after stroke. Cochrane Database of Systematic Reviews Volume, DOI: 10.1002/14651858.CD006331

This is the protocol for a review and there is no abstract. The objectives are as follows:The objectives of this review are to determine the effectiveness of interventions that target upper limb sensory function after stroke. The primary outcomes considered for this review will be those related to sensory function but outcomes related to body impairments, activity limitations, and participation will be included if available.

D'Souza, S. and R. P. Khubchandani (2003). "Haddad syndrome--congenital central hypoventilation associated with Hirschsprung's disease." INDIAN JOURNAL OF PEDIATRICS 70(7): 597-9.

The combination of Congenital Central Hypoventilation with Hirschsprung's disease belongs to the family of diseases now designated as Neurocristopathies. The authors report a polysomnographically documented case and review literature on this disorder.

Dubreuil, V., J. Barhanin, et al. (2009). "Breathing with phox2b." Philosophical Transactions of the Royal Society of London - Series B: Biological Sciences 364(1529): 2477-83.

In the last few years, elucidation of the architecture of breathing control centres has reached the cellular level. This has been facilitated by increasing knowledge of the molecular signatures of various classes of hindbrain neurons. Here, we review the advances achieved by studying the homeodomain factor Phox2b, a transcriptional determinant of neuronal identity in the central and peripheral nervous systems. Evidence from human genetics, neurophysiology and mouse reverse genetics converges to implicate a small population of Phox2b-dependent neurons, located in the retrotrapezoid nucleus, in the detection of CO(2), which is a paramount source of the 'drive to breathe'. Moreover, the same and other studies suggest that an overlapping or identical neuronal population, the parafacial respiratory group, might contribute to the respiratory rhythm at least in some circumstances, such as for the initiation of breathing following birth. Together with the previously established Phox2b dependency of other respiratory neurons (which we review briefly here), our new data highlight a key role of this transcription factor in setting up the circuits for breathing automaticity. [References: 56]

Dubreuil, V., M. R. Hirsch, et al. (2002). "The role of Phox2b in synchronizing pan-neuronal and type-specific aspects of neurogenesis." DEVELOPMENT 129(22): 5241-5253.

Within the developing vertebrate nervous system, specific subclasses of neurons are produced in vastly different numbers at defined times and locations. This implies the concomitant activation of a program that controls pan-neuronal differentiation and of a program that specifies neuronal subtype identity, but how these programs are coordinated in time and space is not well understood. Our previous loss- and gain-of-function studies have defined Phox2b as a homeodomain transcription factor that coordinately regulates generic and type-specific neuronal properties. It is necessary and sufficient to impose differentiation towards a branchio- and viscero-motoneuronal phenotype and at the same time promotes generic neuronal differentiation. We have examined the underlying genetic interactions. We show that Phox2b has a dual action on pan-neuronal differentiation. It upregulates the expression of proneural genes (Ngn2) when expressed alone and upregulates the expression of Mash1 when expressed in combination with Nkx2.2. By a separate pathway, Phox2b represses expression of the inhibitors of neurogenesis Hes5 and Id2. The role of Phox2b in the specification of neuronal subtype identity appears to depend in part on its capacity to act as a patterning gene in the progenitor domain. Phox2b misexpression represses the Pax6 and Olig2 genes, which should inhibit a branchiomotor fate, and induces Nkx6.1 and Nkx6.2, which are expressed in branchiomotor progenitors. We further show that Phox2b behaves like a transcriptional activator in the promotion of both, generic neuronal differentiation and expression of the motoneuronal marker Islet1. These results provide insights into the mechanisms by which a homeodomain transcription factor through interaction with other factors controls both generic and type-specific features of neuronal differentiation.

Dubreuil, V., M. R. Hirsch, et al. (2000). "The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity." DEVELOPMENT 127(23): 5191-5201.

In the vertebrate neural tube, cell cycle exit of neuronal progenitors is accompanied by the expression of transcription factors that define their generic and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly understood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic. In the absence of Phox2b, post-mitotic neuronal precursors are not generated in proper numbers. Conversely, forced expression of Phox2b in the embryonic chick spinal cord drives ventricular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation characterised by expression of Islet1 and of the cholinergic transmitter phenotype, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons. These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.

Dubreuil, V., N. Ramanantsoa, et al. (2008). "A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105(3): 1067-72.

Breathing is maintained and controlled by a network of neurons in the brainstem that generate respiratory rhythm and provide regulatory input. Central chemoreception, the mechanism for CO(2) detection that provides an essential stimulatory input, is thought to involve neurons located near the medullary surface, whose nature is controversial. Good candidates are serotonergic medullary neurons and glutamatergic neurons in the parafacial region. Here, we show that mice bearing a mutation in Phox2b that causes congenital central hypoventilation syndrome in humans breathe irregularly, do not respond to an increase in CO(2), and die soon after birth from central apnea. They specifically lack Phox2b-expressing glutamatergic neurons located in the parafacial region, whereas other sites known or supposed to be involved in the control of breathing are anatomically normal. These data provide genetic evidence for the essential role of a specific population of medullary interneurons in driving proper breathing at birth and will be instrumental in understanding the etiopathology of congenital central hypoventilation syndrome.

Dubreuil, V., M. Thoby-Brisson, et al. (2009). "Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons." JOURNAL OF NEUROSCIENCE 29(47): 14836-14846.

The retrotrapezoid nucleus (RTN) is a group of neurons in the rostral medulla, defined here as Phox2b-, Vglut2-, neurokinin1 receptor-, and Atoh1-expressing cells in the parafacial region, which have been proposed to function both as generators of respiratory rhythm and as central respiratory chemoreceptors. The present study was undertaken to assess these two putative functions using genetic tools. We generated two conditional Phox2b mutations, which target different subsets of Phox2b-expressing cells, but have in common a massive depletion of RTN neurons. In both conditional mutants as well as in the previously described Phox2b27Ala mutants, in which the RTN is also compromised, the respiratory-like rhythmic activity normally seen in the parafacial region of fetal brainstem preparations was completely abrogated. Rhythmic motor bursts were recorded from the phrenic nerve roots in the mutants, but their frequency was markedly reduced. Both the rhythmic activity in the RTN region and the phrenic nerve discharges responded to a low pH challenge in control, but not in the mutant embryos. Together, our results provide genetic evidence for the essential role of the Phox2b-expressing RTN neurons both in establishing a normal respiratory rhythm before birth and in providing chemosensory drive. Copyright copyright 2009 Society for Neuroscience.

Duhoux, A., L. Fournier, et al. (2009). "Guideline concordance of treatment for depressive disorders in Canada." Social Psychiatry & Psychiatric Epidemiology 44(5): 385-92.

BACKGROUND: Depression is one of the most prevalent mental health problems worldwide with considerable social and economic burdens. While practice guidelines exist, their adherence is inconsistent in clinical practice. OBJECTIVE: To provide up-to-date national estimates of the adequacy of treatment received by Canadians having suffered a major depressive disorder (MDD) and examine factors associated with this adequacy. To evaluate the impact of different definitions of guideline-concordant treatment on the results. SUBJECTS: Data were drawn from the Canadian Community Health Survey, cycle 1.2: Mental Health and Well-Being (CCHS 1.2), a nationally representative survey conducted in 2002 and targetting persons aged 15 years or older living in private dwellings. In order to calculate the prevalence of treatment adequacy, we used a sample of 1,563 individuals meeting the criteria for MDD in the 12 months preceding the survey. A subset of 831 subjects who reported having used health services for mental health purposes at least once during that time served to identify the factors associated with treatment adequacy. MEASUREMENTS: Four definitions of minimally adequate treatment were considered and covariates were selected according to a well-known behavioral model. The analyses consisted of prevalence estimates and logistic regression models. RESULTS: Among selected subjects, 55% received guideline-concordant treatment according to the Canadian guidelines. Inadequacy was more prevalent in rural settings, for less complex cases, and in the general medical sector. Depending on the definition, prevalence of guideline-concordant treatment ranged between 48 and 71%, and factors associated with guideline-concordant treatment were mainly need factors and sector of care. CONCLUSIONS: A large proportion of people with a depressive disorder do not receive minimally adequate treatment. Improved access to and quality of treatment is required, especially in primary care settings.

Durand, E., S. Dauger, et al. (2005). "Sleep-disordered breathing in newborn mice heterozygous for the transcription factor phox2b." AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 172(2): 238-243.

Rationale: Central congenital hypoventilation syndrome (CCHS) is a rare autosomal dominant syndrome present from birth, and characterized by depressed ventilation during sleep. Heterozygous mutations of the homeobox gene Phox2b were recently found in a very high proportion of patients. Objectives: To determine whether newborn mice with heterozygous targeted deletion of the transcription factor Phox2b would display sleep-disordered breathing. Methods: We measured breathing pattern using whole-body plethysmography in wild-type and mutant 5-day-old mice, and we classified sleep-wake states using nuchal EMG and behavioral scores. Results: We found that sleep apnea total time was approximately six times longer (8.9 +/- 12 vs. 1.5 +/- 2.2 seconds, p < 0.0015), and ventilation during active sleep was 21% lower (18.4 +/- 5.1 vs. 23.3 +/- 5.5 ml/g/second, p < 0.006) in mutant than in wild-type pups. During wakefulness, apnea time and ventilation were not significantly different between mutant and wild-type pups. Mutant and wild-type pups showed highly similar sleep-wake states. Conclusion: Although their respiratory phenotype was much less severe than CCHS, the Phox2b^+/- mutant mice showed sleep-disordered breathing, which partially modeled the key feature of CCHS.

Dyson, G., R. Frikke-Schmidt, et al. (2007). "An application of the patient rule-induction method for evaluating the contribution of the Apolipoprotein E and Lipoprotein Lipase genes to predicting ischemic heart disease." GENETIC EPIDEMIOLOGY 31(6): 515-27.

Different combinations of genetic and environmental risk factors are known to contribute to the complex etiology of ischemic heart disease (IHD) in different subsets of individuals. We employed the Patient Rule-Induction Method (PRIM) to select the combination of risk factors and risk factor values that identified each of 16 mutually exclusive partitions of individuals having significantly different levels of risk of IHD. PRIM balances two competing objectives: (1) finding partitions where the risk of IHD is high and (2) maximizing the number of IHD cases explained by the partitions. A sequential PRIM analysis was applied to data on the incidence of IHD collected over 8 years for a sample of 5,455 unrelated individuals from the Copenhagen City Heart Study (CCHS) to assess the added value of variation in two candidate susceptibility genes beyond the traditional, lipid and body mass index risk factors for IHD. An independent sample of 362 unrelated individuals also from the city of Copenhagen was used to test the model obtained for each of the hypothesized partitions. Copyright (c) 2007 Wiley-Liss, Inc.