Literature search from ms 29/4/2010

Krottmayer, G., R. Kerbel, et al. (1985). "[Congenital central hypoventilation syndrome--loss of chemosensitivity in respiratory control]." Monatsschrift Kinderheilkunde Organ der Deutschen Gesellschaft fur Kinderheilkunde. 133(10): 764-6.

This report describes an infant with congenital central hypoventilation. There is no response to 4% CO2-breathing in sleep and in awake state. Hypoxia, behavioral and "behavioral like" inputs increase ventilation, but not to normal levels. Drugs such as theophylline, naloxone, acetazolamide, methylprogesterone, thyroxine and nicethamide have no effect on the respiratory control. Despite the insertion of a phrenic nerve pacemaker intermittent positive pressure ventilation must be provided in addition.

Kroworsch, B., F. Bullemer, et al. (1999). "Diaphragm pacing in chronic hypoventilation. [German]." MEDIZINISCHE KLINIK 94(SPEC. ISS. 1): 91-92.

Background: Diaphragm pacing in patients with intact phrenic nerve and diaphragm can be used as an alternative to mechanical ventilation. Indications cover diseases caused by central hypoventilation like C2- quadriplegia and Ondine's syndrome. Advantages are physiological ventilation with negative pressure and an improvement in articulation. Case Report: We report our experiences with a patient suffering from chronic hypoventilation caused by a ventilatory pump failure following tetraparesis due to congenital toxoplasmosis.

Kuhle, S. and P. J. Veugelers (2008). "Why does the social gradient in health not apply to overweight?" HEALTH REPORTS 19(4): 7-15.

BACKGROUND: In developed countries, there is a negative association between socioeconomic status (SES) and a variety of health outcomes, known as the social gradient in health. This is contrasted by a weak, absent or even positive gradient for overweight. The objective of this study was to investigate why overweight does not follow the social gradient. DATA AND METHODS: Data from adult respondents to the 2004 Canadian Community Health Survey (cycle 2.2) were used. A series of multivariate models regressing overweight and determinants of overweight on household education and household income were performed, stratified by gender. RESULTS: Except for education among women, negative associations between SES measures and overweight emerged. Respondents from higher household income groups reported more meals away from home, compared with those from lower household income groups. In addition, adults in higher-education households were more likely than those in lower-education households to have quit smoking. INTERPRETATION: Differences in food consumption patterns and smoking cessation between SES groups may have contributed to the lack of a clear negative association between household education and income and overweight in the CCHS.

Kuhn, M., M. Lutolf, et al. (1999). "The eye catcher. Ondine's curse." RESPIRATION 66(3): 265.

Kumar, R., R. Ahdout, et al. (2009). "Reduced caudate nuclei volumes in patients with congenital central hypoventilation syndrome." NEUROSCIENCE 163(4): 1373-9.

Congenital central hypoventilation syndrome (CCHS) children show cognitive and affective deficits, in addition to state-specific loss of respiratory drive. The caudate nuclei serve motor, cognitive, and affective roles, and show structural deficits in CCHS patients, based on gross voxel-based analytic procedures. However, the magnitude and regional sites of caudate injury in CCHS are unclear. We assessed global caudate nuclei volumes with manual volumetric procedures, and regional volume differences with three-dimensional surface morphometry in 14 CCHS (mean age+/-SD: 15.1+/-2.3 years; 8 male) and 31 control children (15.1+/-2.4 years; 17 male) using brain magnetic resonance imaging (MRI). Two high-resolution T1-weighted image series were collected using a 3.0 Tesla MRI scanner; images were averaged and reoriented (rigid-body transformation) to common space. Both left and right caudate nuclei were outlined in the reoriented images, and global volumes calculated; surface models were derived from manually-outlined caudate structures. Global caudate nuclei volume differences between groups were evaluated using a multivariate analysis of covariance (covariates: age, gender, and total intracranial volume). Both left and right caudate nuclei volumes were significantly reduced in CCHS over control subjects (left, 4293.45+/-549.05 vs. 4626.87+/-593.41 mm(3), P<0.006; right, 4376.29+/-565.42 vs. 4747.81+/-578.13 mm(3), P<0.004). Regional deficits in CCHS caudate volume appeared bilaterally, in the rostral head, ventrolateral mid, and caudal body. Damaged caudate nuclei may contribute to CCHS neuropsychological and motor deficits; hypoxic processes, or maldevelopment in the condition may underlie the injury.
Kumar, R., K. Lee, et al. (2009). "Mammillary body and fornix injury in congenital central hypoventilation syndrome." PEDIATRIC RESEARCH 66(4): 429-34.

Congenital central hypoventilation syndrome (CCHS) is accompanied by reduced ventilatory sensitivity to CO2 and O2, respiratory drive failure during sleep, impaired autonomic, fluid, and food absorption regulation, and affective and cognitive deficits, including memory deficiencies. The deficits likely derive from neural injury, reflected as structural damage and impaired functional brain responses to ventilatory and autonomic challenges. Brain structures playing essential memory roles, including the hippocampus and anterior thalamus, are damaged in CCHS. Other memory formation circuitry, the fornix and mammillary bodies, have not been evaluated. We collected two high-resolution T1-weighted image series from 14 CCHS and 31 control subjects, using a 3.0-Tesla magnetic resonance imaging scanner. Image series were averaged and reoriented to a standard template; areas containing the mammillary bodies and fornices were over sampled, and body volumes and fornix cross-sectional areas were calculated and compared between groups. Both left and right mammillary body volumes and fornix cross-sectional areas were significantly reduced in CCHS over control subjects, controlling for age, gender, and intracranial volume. Damage to these structures may contribute to memory deficiencies found in CCHS. Hypoxic processes, together with diminished neuroprotection from micronutrient deficiencies secondary to fluid and dietary absorption issues, may contribute to the injury.

Kumar, R., P. M. Macey, et al. (2006). "Elevated mean diffusivity in widespread brain regions in congenital central hypoventilation syndrome." JOURNAL OF MAGNETIC RESONANCE IMAGING 24(6): 1252-8.

PURPOSE: To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). MATERIALS AND METHODS: Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. RESULTS: Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. CONCLUSION: Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS. (c) 2006 Wiley-Liss, Inc.

Kumar, R., P. M. Macey, et al. (2008). "Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome." PEDIATRIC RESEARCH 64(3): 275-80.

Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphe, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

Kumar, R., P. M. Macey, et al. (2005). "Neuroanatomic deficits in congenital central hypoventilation syndrome." JOURNAL OF COMPARATIVE NEUROLOGY 487(4): 361-71.

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation. (c) 2005 Wiley-Liss, Inc.

Kumar, R., H. D. Nguyen, et al. (2009). "Dilated basilar arteries in patients with congenital central hypoventilation syndrome." NEUROSCIENCE LETTERS 467(2): 139-43.

Congenital central hypoventilation syndrome (CCHS) patients show hypoventilation during sleep and severe autonomic impairments, including aberrant cardiovascular regulation. Abnormal sympathetic patterns, together with increased and variable CO(2) levels, lead to the potential for sustained cerebral vasculature changes. We performed high-resolution T1-weighted imaging in 13 CCHS and 31 control subjects using a 3.0-T magnetic resonance imaging scanner, and evaluated resting basilar and bilateral middle cerebral artery cross-sections. Two T1-weighted image series were acquired; images were averaged and reoriented to common space, and regions containing basilar and both middle cerebral arteries were oversampled. Cross-sections of the basilar and middle cerebral arteries were manually outlined to calculate cross-sectional areas, and differences between and within groups were evaluated. Basilar arteries in CCHS were significantly dilated over control subjects, but both middle cerebral artery cross-sections were similar between groups. No significant differences appeared between left and right middle cerebral arteries within either group. Basilar artery dilation may result from differential sensitivity to high CO(2) over other vascular beds, damage to serotonergic or other chemosensitive cells accompanying the artery, or enhanced microvascular resistance, and that dilation may impair tissue perfusion, leading to further neural injury in CCHS.

Kurz, H., W. Sterniste, et al. (1999). "Resolution of obstructive sleep apnea syndrome after adenoidectomy in congenital central hypoventilation syndrome." PEDIATRIC PULMONOLOGY 27(5): 341-6.

We report on a 2 1/2-year-old boy who is currently ventilated at home by positive pressure ventilation through a nasal mask during the night because of congenital central hypoventilation syndrome (CCHS). Up to age 2 he had developed normally. A reevaluation was performed because of symptoms suggestive of obstructive sleep apnea syndrome (OSAS), including snoring, nocturnal sweating, frequent nighttime awakenings, speech impairment, daytime fatigue, and failure to thrive. A sleep study indicated obstructive apnea episodes lasting up to 40 s and arterial desaturations below 50% during spontaneous sleep. During mechanical ventilation snoring persisted, and capillary PCO2 rose to 60 mm Hg. Partial upper airway obstruction, leaking around the mask, and arousal movements developed on passive flexion of the neck to 20 degrees. After adenoidectomy, symptoms of OSAS resolved. There were no more obstructive apneas during spontaneous sleep, but obstructive apneas could be provoked by neck flexion to 20 degrees. During ventilation, neck flexion of 20 degrees was tolerated, but a 40 degrees flexion led to partial obstruction. In CCHS patients, the problem of upper airway obstruction is rarely noted because most patients are ventilated through a permanent tracheostomy. Today, noninvasive ventilation strategies are becoming more common. Reduced activity of upper airway muscles and impaired reflex mechanisms could lead to upper airway obstruction during face mask positive pressure ventilation in children with CCHS. Enlarged adenoids worsened this problem in our patient, leading to insufficient ventilation and OSAS. Adenoidectomy resolved symptoms of OSAS and enabled successful nasal mask ventilation. Close follow-up of the patient avoided hypoxia and sequelae from OSAS such as pulmonary hypertension.

Kwong, J. C. and D. G. Manuel (2007). "Using OHIP physician billing claims to ascertain individual influenza vaccination status." VACCINE 25(7): 1270-4.

The objective of this study was to validate physician billing claims against self-reported influenza vaccination to assess individual-level vaccination status. We compared responses to the Canadian Community Health Survey 1.1 (CCHS) and Ontario Health Insurance Plan (OHIP) physician billing claims and found moderate agreement. Using self-report as the gold standard, OHIP claims based on using both influenza-specific and general vaccination codes have high specificity and positive predictive value (PPV), reasonable negative predictive value (NPV), but only fair sensitivity. OHIP physician billing claims are suboptimal for ascertaining the vaccination status of individuals because many individuals receive their vaccinations outside doctor's offices, but may be used as the backbone for the creation of an immunization registry.

Kwong, J. C., L. C. Rosella, et al. (2007). "Trends in influenza vaccination in Canada, 1996/1997 to 2005." HEALTH REPORTS 18(4): 9-19.

OBJECTIVES: This article reports recent trends in influenza vaccination rates in Canada, provides data on predictors of vaccination in Canada for 2005, and examines longer-term effects of Ontario's universal influenza immunization program on vaccine uptake. DATA SOURCES: Data are from the 1996/1997 National Population Health Survey (NPHS) and the 2000/2001, 2003, and 2005 Canadian Community Health Survey (CCHS). ANALYTICAL TECHNIQUES: NPHS and CCHS data were used to estimate influenza vaccination rates of the population aged 12 or older. The Z test was used to assess differences between surveys, and the chi-squared test for trend was used to examine trends over time. Logistic regression was used to identify predictors of vaccination and to compare the odds of being vaccinated in Ontario versus other provinces. MAIN RESULTS: Nationally, influenza vaccination rates rose from 15% in 1996/1997 to 27% in 2000/2001, stabilized between 2000/2001 and 2003, and increased further to 34% by 2005. Vaccination rates for most high-risk groups still fall short of national targets. Ontarians continue to be more likely to be vaccinated than are residents of any other province, while residents of two of the territories--Nunavut and the Northwest Territories--are even more likely to be vaccinated than are Ontarians.

Lahorgue Nunes, M., M. A. G. Friedrich, et al. (1999). "Association of misoprostol, Moebius syndrome and congenital central alveolar hypoventilation." ARQUIVOS DE NEURO-PSIQUIATRIA 57(1): 88-91.

We report a case showing the association of Moebius syndrome, the use of misoprostol during pregnancy and the development of central congenital alveolar hypoventilation. Pathophysiological aspects of these three diseases are discussed and also the unfavorable prognosis of this association.

Lahteenmaki, M., J. Kupari, et al. (2007). "Increased apoptosis of parasympathetic but not enteric neurons in mice lacking GFRalpha2." DEVELOPMENTAL BIOLOGY 305(1): 325-332.

Enteric neurons, unlike sympathetic and sensory neurons that require target-derived neurotrophins for survival, do not undergo classical caspase-3-mediated programmed cell death (PCD) during normal development. Whether parasympathetic neurons in the pancreas, which originate from a subpopulation of enteric nervous system (ENS) precursors, or other parasympathetic neurons undergo PCD during normal mammalian development is unknown. In GFRalpha2-deficient mice, many submandibular and intrapancreatic parasympathetic neurons are missing but whether this is due to increased neuronal death is unclear. Here we show that activated caspase-3 and PGP9.5 doubly positive neurons are present in wild-type mouse pancreas between embryonic day E15 and birth. Thus, in contrast to ENS neurons, intrapancreatic neurons undergo PCD via apoptosis during normal development. We also show that, in GFRalpha2-deficient mice, most intrapancreatic neurons are lost during this late fetal period, which coincides with a period of increased apoptosis of the neurons. Since the percentage of BrdU and Phox2b doubly positive cells in the fetal pancreas and the number of intrapancreatic neurons at E15 were similar between the genotypes, impaired precursor proliferation and migration are unlikely to contribute to the loss of intrapancreatic neurons in GFRalpha2-KO mice. Caspase-3-positive neurons were also found in GFRalpha2-deficient submandibular ganglia around birth, suggesting that parasympathetic neurons depend on limited supply of (presumably target-derived neurturin) signaling via GFRalpha2 for survival. copyright 2007 Elsevier Inc. All rights reserved.

Lai, D. and B. Schroer (2008). "Haddad syndrome: a case of an infant with central congenital hypoventilation syndrome and Hirschsprung disease." JOURNAL OF CHILD NEUROLOGY 23(3): 341-3.

This report presents an otherwise healthy infant who developed unexplained apnea and long-segment Hirschsprung disease. After extensive evaluation that included a paired-like homeobox 2b gene (PHOX2B) analysis, he was found to have Haddad syndrome, a congenital disorder that features central congenital hypoventilation syndrome in conjunction with Haddad syndrome. Recent work has associated polyalanine repeats within the PHOX2B gene on chromosome 4p12 with central congenital hypoventilation syndrome, whereas PHOX2B knockout mice develop aganglionic bowels.

Lan, M. S. and M. B. Breslin (2009). "Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation." FASEB Journal 23(7): 2024-33.

Zinc-finger transcription factors are DNA-binding proteins that are implicated in many diverse biological functions. INSM1 (formerly IA-1) contains five zinc-finger motifs and functions as a transcription factor. INSM1 protein structure is highly conserved in homologues of different species. It is predominantly expressed in developing neuroendocrine tissues and the nervous system in mammals. INSM1 represents an important player in early embryonic neurogenesis. In pancreatic endocrine cell differentiation, Ngn3 first activates INSM1 and subsequently NeuroD/beta2. Conversely, INSM1 exerts a feedback mechanism to suppress NeuroD/beta2 and its own gene expression. INSM1 gene ablation in the mouse results in the impairment of pancreatic endocrine cell maturation. Further, deletion of INSM1 severely impairs catecholamine biosynthesis and secretion from the adrenal gland that results in early embryonic lethality. Genetically, INSM1 acts as a downstream factor of Mash 1 and Phox2b in the differentiation of the sympatho-adrenal lineage. In the developing neocortex, mouse embryos lacking INSM1 expression contain half the number of basal progenitors and show a reduction in cortical plate radial thickness. Cell signaling studies reveal that INSM1 contributes to the induction of cell cycle arrest/exit necessary to facilitate cellular differentiation. INSM1 is highly expressed in tumors of neuroendocrine origin. Hence, its promoter could serve as a tumor-specific promoter that drives a specific targeted cancer gene therapy for the treatment of neuroendocrine tumors. Taken together, all of these features of INSM1 strongly support its role as an important regulator during neuroendocrine differentiation. [References: 55]

Landing, B. H., A. L. Recalde, et al. (1994). "Cardiomyopathy in childhood and adult life, with emphasis on hypertrophic cardiomyopathy." Pathology, Research & Practice 190(8): 737-49.

Over 60 entries in the genetic catalog have cardiomyopathy features--32 autosomal dominant, 35 autosomal recessive and X-linked. Over 40 present in, or can have survival into, adult life. Major clinicopathologic categories of these cardiomyopathic disorders included: sudden death (13 entities); cardiac conduction disturbance important feature; associated myopathy or motor dysfunction; storage diseases with cardiac involvement; cardiac amyloidoses; and, other categories. Genes, abnormality of which can cause hypertrophic cardiomyopathy (HCM), have been identified on chromosomes 1, 14 and 15, the locus on chromosome 14 involving the B-myosin heavy chain gene, but at least one unidentified locus is known to exist and there is a suggestive locus on chromosome 16, so that HCM is not a single disease but a group of disorders with clinicopatholopic similarities. To investigate these aspects of HCM in some detail, sixty-six patients with "sharply demarcated" differential myocardial fiber bundle hypertrophy (DMBH), considered to be of significant degree, from a pediatric autopsy data base of approximately 8,000 cases, were reviewed. Twenty-three of the patients died suddenly, without antecedent significant cardiac dysfunction, seven had clinical congestive heart failure of varying duration, three were stillborn, six showed evidence of aspiration of amniotic sac content (three had history of fetal distress), five had ischemic bowel disease, three (two with clinical cerebral palsy and one with Ondine's curse syndrome) had cerebral atrophy and sclerosis and one had extensive more acute encephalomalacia, and a variety of other major "causes of death" were present. Whether all infants and children with DMBH meeting the criteria used, who do not have congenital heart disease, have dominant hypertrophic cardiomyopathy (HCM) cannot be established by studies of this type, but the "concentration" of a gene or genes for HCM in pediatric autopsy series because the strong effect of HCM on life expectancy is relevant to this possibility. The data raise the question that stillbirth, fetal distress with aspiration of amniotic sac content, ischemic bowel disease and cerebral atrophy and sclerosis may be hitherto underappreciated features of HCM in childhood, and that patients with HCM may be peculiarly liable to die with certain types of septic shock, such as acute meningococcemia. In the material of this study, sudden death was statistically more frequent in females than in males in childhood (p < .029).