Literature search from ms 29/4/2010

Wu, H.-T., Y.-N. Su, et al. (2009). "Interaction between PHOX2B and CREBBP mediates synergistic activation: mechanistic implications of PHOX2B mutants." HUMAN MUTATION 30(4): 655-60.

Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system. The genetic defect is usually caused by heterozygous mutations of the PHOX2B gene such as a 20-alanine tract (+5 to+13 alanines) expansion (approximately 95%) and occasional frameshift or missense mutations. Cytoplasmic aggregates were shown in PHOX2B proteins with longer alanine tract (+9 and longer) expansion and impaired DNA binding was observed in PHOX2B proteins with frameshift, missense, or longer alanine tract (+9 and longer) expansion. Defective transactivation activity was shown in certain PHOX2B mutants. However, PHOX2B proteins with short alanine tract (+5 to+7) expansion in the majority of patients (approximately 75%) did not have cytoplasmic aggregates or DNA binding defects. CREB-binding protein (CREBBP/CBP) is a transcriptional coactivator that interacts with multiple transcription factors to cause synergistic activation. Here we show that CBP interacted with PHOX2B and served as its coactivator to mediate synergistic activation. Wild-type PHOX2B and CBP used specific domains to interact with each other. The domains of CBP that interacted with different PHOX2B mutants were different compared to those interacting with wild-type PHOX2B. Transient cotransfection assays using different PHOX2B mutants and CBP showed the impaired synergistic activation caused by different PHOX2B mutants. An interfering effect was observed in certain PHOX2B mutants. These results demonstrated that aberrant interaction of PHOX2B mutants with CBP and/or an interfering effect of certain PHOX2B mutants may be the critical mechanism to impair synergistic activation, thereby contributing to the phenotypes of CCHS. (c) 2009 Wiley-Liss, Inc.

Wuest, J., M. Merritt-Gray, et al. (2007). "Patterns of medication use among women survivors of intimate partner violence." Canadian Journal of Public Health Revue Canadienne de Sante Publique. 98(6): 460-4.

OBJECTIVE: Our objective was to describe patterns of medication use in a convenience sample of 309 women with a history of intimate partner violence (IPV) participating in a study of women's health after leaving an abusive partner (WHES). METHODS: Using data collected through interviews and health assessments, frequencies of past-month use of medications; abuse experienced, health problems and medical diagnoses; and selected demographics were calculated. Associations among abuse history, employment status, health problems, diagnoses, and medications were explored. Comparisons of rates of medication use in women in the WHES and the Canadian Community Health Survey (CCHS) 2.1 were calculated. FINDINGS: Almost half of participants were taking pain and/or psychotropic medications, with almost one third taking antidepressants. Child abuse history, adult sexual assault history and unemployment were associated with taking psychotropic medications. Overall rates of medication use were similar to those of Canadian women of similar age in the CCHS 2.1. However, women in the WHES were more likely to be taking antidepressants, anxiolytics and inhalants, and less likely to be taking oral contraceptives, over-the counter (OTC) pain relievers, and OTC cough and cold medications. CONCLUSION: The pattern of medication use in women who have experienced IPV differs from that in the general population. The complex associations found among health problems, employment, diagnoses, and medication use highlight the need to consider treatment patterns within the context of the impact of lifetime abuse, economic survival, and parenting demands. Medication use must be understood as only one of a range of health interventions available to assist abused women to promote their health.

Xu, Z.-f. and Z.-f. Jiang (2005). "[Congenital central hypoventilation syndrome: report of a case]." Zhonghua Erke Zazhi 43(8): 636-7.

Yamada, A., M. Kamoda, et al. (1993). "[A case of central alveolar hypoventilation syndrome associated with cerebral infarction]." No to Shinkei - Brain & Nerve 45(3): 273-6.

Central alveolar hypoventilation syndrome (CAH), or Ondine's curse, is a very rare disease characterized by dysfunction of respiratory center in the brain stem. Here, we report a case of CAH associated with cerebral infarction. A 59-year-old man developed right facial sensory deficit at age 56. Then, the facial sensory deficit spread to the left side and dysarthria and dysphagia also developed. Since age 58, he often developed respiratory failure and consciousness disturbance. Arterial blood gas analysis revealed alveolar hypoventilation and respiratory acidosis. Disorders of peripheral organs such as lung, airway, thorax and neuromuscular diseases were ruled out. Brain MRI showed cerebral infarction in the brain stem. We diagnosed him as CAH associated with brain stem infarction.
Yamamoto, N., M. Iwama, et al. (1985). "[Central alveolar hypoventilation as a complication of massive intracerebellar hemorrhage: report of a case treated by diaphragm pacing]." No Shinkei Geka - Neurological Surgery 13(4): 451-6.

The author reported a case of central alveolar hypoventilation (Ondine's curse) which was treated by diaphragm pacing. A 59-year-old man was admitted because of sudden deep coma and tetraparesis. Neurological examination on admission showed miotic pupils with absent light reaction, no oculocephalic reflex, no corneal reflex and tetraparesis. Glasgow scale was evaluated to be E-1 V-1, and M-3 with total of 5 points. Computed tomography confirmed a large hematoma in the cerebellum with ventricular rupture. Immediately, a suboccipital craniectomy was performed and the hematoma was evacuated. His neurological condition was improved gradually within a month after the operation. He responded to verbal orders and moved all his limbs against gravity. His respiration, however, was irregular with a pattern of so-called "cluster breathing" followed by prolonged apnea, that was more pronounced in night. He was suffered from hypoxic hypercapnea and recurrent pneumonia. Therefore, authors decided to employ diaphragm pacing for management of central alveolar hypoventilation. A diaphragm pacemaker (radiofrequency induction) was implanted. A cuff electrode was put around the right phrenic nerve in the right thorax, and the receiver installed subcutaneously in the right anterior chest. Postoperative respiratory study showed ventilation on pacing with satisfactory blood gas and he became able to move around using a wheel chair. In 1966 Glenn demonstrated a new technique to move the diaphragm paced by a receiver through the phrenic nerve, triggered by radio wave from external device.(ABSTRACT TRUNCATED AT 250 WORDS)

Yang, C., H. S. Kim, et al. (1998). "Paired-like homeodomain proteins, Phox2a and Phox2b, are responsible for noradrenergic cell-specific transcription of the dopamine beta-hydroxylase gene." JOURNAL OF NEUROCHEMISTRY 71(5): 1813-26.

Recently, a murine paired-like homeobox gene, Phox2a, has been identified whose product is critical for the development of several major noradrenergic neuron populations, including the locus coeruleus. In noradrenergic neurons, dopamine beta-hydroxylase (DBH) is a hallmark protein and catalyzes the conversion of dopamine to noradrenaline. Our previous studies have shown that a composite promoter (domain IV), residing at -185 to -150 bp upstream of the transcription start site, is critical for DBH transcription and is comprised of multiple cis-acting elements, including a cyclic AMP response element, a YY1 binding site, and two core motifs of the homeodomain (HD)-binding site. Here, we show that the HD-binding site residing within domain IV is a noradrenergic-specific cis-acting element. In contrast, the cyclic AMP response element is active in all cell lines tested. We provide evidence that Phox2a is expressed only in DBH-positive cell lines and interacts with the HD-binding site. Forced expression of Phox2a robustly activates DBH promoter activity in DBH-negative cell lines (>10-fold), but increased it only marginally (<50%) in DBH-positive cell lines. Furthermore, another protein factor with an identical HD, Phox2b, also activates DBH transcription with an efficiency comparable to that of Phox2a. In contrast, neither Phox2a nor Phox2b was able to transactivate tyrosine hydroxylase transcription, indicating that these transcription factors differentially activate catecholamine-synthesizing gene transcription. Together with the Phox2a knockout experiment, the studies described here make Phox2a and Phox2b the first strong candidate transcription factors for determining a neurotransmitter phenotype in vertebrates.

Yang, T.-Y., J.-W. Chang, et al. (2009). "Extreme hypernatremia combined with rhabdomyolysis and acute renal failure." Journal of the Chinese Medical Association: JCMA 72(10): 555-8.

Rhabdomyolysis is a life-threatening condition that involves muscle cell destruction. Among its etiologies, severe hypernatremia is a less common cause. We report a teenage girl with congenital central hypoventilation syndrome and hypothalamus dysfunction syndrome who presented with extreme hypernatremia (sodium, 211 mmol/L) with rhabdomyolysis (creatine kinase, 32,850 U/L) and acute renal failure (creatinine, 6.1 mg/dL) following gastroenteritis with 7-kg weight loss. Rhabdomyolysis subsequently led to acute renal failure and hyperkalemia. Acute hemodialysis was initiated on hospital day 3 for hyperkalemia. This resulted in a 13 mmol/L fall in serum sodium in 3 hours despite using a 156 mmol/L sodium bath, but without the development of cerebral edema or neurological defect. This report highlights an unusual cause of rhabdomyolysis in children and the experience of managing such a difficult clinical situation.

Yasuma, F., H. Nomura, et al. (1987). "Congenital central alveolar hypoventilation (Ondine's curse): a case report and review of the literature." EUROPEAN JOURNAL OF PEDIATRICS 146(1): 81-3.

Congenital central alveolar hypoventilation (C-CAH), so called Ondine's curse, is known to be quite a rare neuropathology that has been reported in only 23 cases to date. C-CAH was diagnosed in a 2-year-5-month-old infant. In the treatment of C-CAH, we implanted a right unilateral diaphragm pacemaker in the infant and his respiratory status was remarkably improved after diaphragm pacing. Twenty-three reported cases of this disorder are reviewed in the literature.

Yasuma, F., A. Okada, et al. (1998). "Ondine's curse and its inverse syndrome. Respiratory failure in autonomic vs. voluntary control." ADVANCES IN EXPERIMENTAL MEDICINE & BIOLOGY 450: 179-84.

Yon, C., H. Aoki, et al. (1978). "A case of Ondine's curse - congenital dysfunction of central chemoreceptor." Yokohama Medical Bulletin 29(5-6): 151-159.

You, C.-M., W.-H. Fu, et al. (2009). "[One case report of congenital central hypoventilation syndrome]." Zhongguo Dangdai Erke Zazhi 11(6): 498-9.

Young, H. M., A. J. Bergner, et al. (2003). "Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine." JOURNAL OF COMPARATIVE NEUROLOGY 456(1): 1-11.

Enteric neurons and glia arise from the neural crest. The phenotype of crest-derived cells was examined as they differentiated into neurons or glia in the mouse small and large intestine. Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b⁺/Ret⁺/p75⁺/Sox10⁺, and at embryonic day (E) 10.5, about 10-15% of the crest-derived cells in the small intestine have started to differentiate into neurons. In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b⁺ cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward. The differentiation of crest-derived cells into neurons in the colon lagged behind that in the small intestine by several days. Differentiating enteric neurons showed high Ret, low p75, and undetectable Sox10 immunostaining. Glial precursors were identified by the presence of brain-specific fatty acid binding protein (B-FABP) and detected first in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B-FABP⁺/Sox10⁺/p75⁺ but showed low Ret immuno-staining. S100b was not detected until E14.5. Adult glial cells were B-FABP⁺/Sox10⁺/p75⁺ S100b⁺. A nucleic acid stain (to identify all ganglion cells) was combined with immunostaining for PGP9.5 and S100b to detect neurons and glial cells, respectively, in the postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in myenteric ganglia of the small and large intestine, respectively, were neither PGP9.5⁺ nor S100b⁺. Because some classes of neurons are not present in significant numbers until after birth, the expression of PGP9.5 by developing enteric neurons appeared to precede the expression of neuron type-specific markers. copyright 2002 Wiley-Liss, Inc.
Young, H. M., D. Ciampoli, et al. (1999). "Expression of Ret-, p75(NTR)-, phox2a-, phox2b-, and tyrosine hydroxylase-immunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut." DEVELOPMENTAL DYNAMICS 216(2): 137-152.

Cells of the enteric nervous system are derived from the neural crest. Probes to a number of molecules identify neural crest-derived cells within the gastrointestinal tract of embryonic mice prior to their differentiation into neurons and glial cells. However, it is unclear whether the different markers are identifying all neural crest-derived cells. In this study the distribution of p75(NTR)-immunoreactivity was compared with that of Ret-, Phox2a-, Phox2b-, and tyrosine hydroxylase (TH) in undifferentiated neural crest-derived cells in the E10.5-E13.5 mouse intestine. Neural crest-derived cells colonise the embryonic mouse gut in a rostral-to-caudal wave between E9.5-E14, and differentiation into enteric neurons also occurs in a rostral- to-caudal wave. Thus, the most caudal neural crest-derived cells within the gut are undifferentiated. These most caudal neural crest-derived cells co- expressed p75(NTR)-, Phox2b- and Ret-immunoreactivity; at E10.5 a sub- population was also TH-positive. The most caudal cells did not show Phox2a- immunoreactivity at any stage. However, a sub-population of cells, which was rostral to the undifferentiated neural crest-derived cells, was Phox2a- positive, and these are likely to be cells beginning to differentiate along a neuronal lineage. The expression of Ret-, Phox2a-, Phox2b- and p75(NTR)- immunoreactivity by two classes of enteric neurons that differentiate prior to birth was also examined. Nitric oxide synthase (NOS) neurons showed Phox2b and Ret immunoreactivity at all ages, and Phox2a and p75(NTR) immunoreactivity only transiently. Calcitonin gene-related peptide (CGRP) neurons showed Phox2b and Ret-immunoreactivity, but not Phox2a immunoreactivity. It is concluded that all undifferentiated neural crest- derived cells initially express Phox2b, Ret, and p75(NTR); a subpopulation of these cells also expresses TH transiently. Those cells that are beginning to differentiate along a neuronal lineage maintain their expression of Phox2b and Ret, and they start to express Phox2a, but down-regulate p75(NTR); those cells that differentiate along a glial lineage downregulate Ret and maintain their expression of p75(NTR).

Young, H. M., C. J. Hearn, et al. (1998). "A single rostrocaudal colonization of the rodent intestine by enteric neuron precursors is revealed by the expression of Phox2b, Ret, and p75 and by explants grown under the kidney capsule or in organ culture." DEVELOPMENTAL BIOLOGY 202(1): 67-84.

The colonization of the rodent gastrointestinal tract by enteric neuron precursors is controversial due to the lack of specific cellular markers at early stages. The transcription factor, Phox2b, is expressed by enteric neuron precursors (Pattyn et al. Development 124, 4065-4075, 1997). In this study, we have used an antiserum to Phox2b to characterize in detail the spatiotemporal expression of Phox2b in the gastrointestinal tract of adult mice and embryonic mice and rats. In adult mice, all enteric neurons (labeled with neuron-specific enolase antibodies), and a subpopulation of glial cells (labeled with GFAP antibodies), showed immunoreactivity to Phox2b. In embryonic mice, the appearance of Phox2b-immunoreactive cells was mapped during development of the gastrointestinal tract. At Embryonic Days 9.5-10 (E9.5-10), Phox2b-labeled cells were present only in the stomach, and during subsequent development, labeled cells appeared as a single rostrocaudal wave along the gastrointestinal tract; at E14 Phox2b-labeled cells were present along the entire length of the gastrointestinal tract. Ret and p75 have also been reported to label migratory-stage enteric neuron precursors. A unidirectional, rostral-to-caudal colonization of the gastrointestinal tract of embryonic mice by Ret- and p75-immunoreactive cells was also observed, and the locations of Ret- and p75-positive cells within the gut were very similar to that of Phox2b-positive cells. To verify the location of enteric neuron precursors within the gut, explants from spatiotemporally defined regions of embryonic intestine, 0.3-3 mm long, were grown in the kidney subcapsular space, or in catenary organ culture, and examined for the presence of neurons. The location and sequence of appearance of enteric neuron precursors deduced from the explants grown under the kidney capsule or in organ culture was very similar to that seen with the Phox2b, Ret, and p75 antisera. Previous studies have mapped the rostrocaudal colonization of the rat intestine by enteric neuron precursors using HNK-1 as a marker. In the current study, all HNK-1-labeled cells in the gastrointestinal tract of rat embryos showed immunoreactivity to Phox2b, but HNK-1 cells comprised only a small subpopulation of the Phox2b-labeled cells. In addition, in rats, Phox2b-labeled cells were present in advance of (more caudal to) the most caudal HNK-1-labeled cells by 600-700 mum in the hindgut at E15. We conclude that the neural crest cell population that arises from the vagal level of the neural axis and that populates the stomach, midgut, and hindgut expresses Phox2b, Ret, and p75. In contrast, the sacral-level neural crest cells that populate the hindgut either do not express, or show a delayed expression of, all of the known markers of vagal- and trunk-level neural crest cells.

Zeitlhofer, J., B. Mamoli, et al. (1982). "[Differential diagnostic problems and polygraphic studies in a case of Pickwickian syndrome]." WIENER KLINISCHE WOCHENSCHRIFT 94(16): 434-8.

The case report of a male patient with the Pickwickian syndrome is presented. The results of the relevant neurophysiological examinations (polygraphic registration of EEG, electrocardiogram, respiration, thorax excursions, submental and intercostal electromyogram, electrooculogram) give an insight into the pathomechanisms and enable the differential diagnosis to be made between this condition and narcolepsy and also the Kleine-Levin syndrome; respiratory investigations (spirometry, hypercapnic ventilatory response: mouth occlusion pressure) make it possible to differentiate between the Pickwickian and Ondine's curse syndrome. The therapeutic management is discussed.

Zelko, F. A., M. N. Nelson, et al. (2010). "Congenital central hypoventilation syndrome: neurocognitive functioning in school age children." PEDIATRIC PULMONOLOGY 45(1): 92-8.

OBJECTIVE: Examine indices of neurocognitive functioning in children with PHOX2B mutation-confirmed neonatal onset congenital central hypoventilation syndrome (CCHS) and relate them to indices of PHOX2B genotype, demographics, and disease severity. METHODS: Subjects were 20 patients with PHOX2B mutation-confirmed CCHS diagnosed as neonates who had undergone neurocognitive assessment in the course of clinical care at the Rush Children's Hospital CCHS Center between 1990 and 2006. Neurocognitive variables of interest included Full Scale IQ (FSIQ) and Wechsler-derived marker indices (subtests) of verbal comprehension (Vocabulary), visuoperceptual reasoning (Block Design), working memory (Digit Span), and clerical/processing speed (Coding). RESULTS: Single sample t-tests revealed participants' general intelligence index (FSIQ; mean 84.9, SD 23.6) to be lower than the general population, though the range of FSIQ observed was broad. Visuoperceptual reasoning and clerical/visuographic speed marker indices were similarly depressed. These deficits were related to special education participation but not to PHOX2B genotype status or other demographic and clinical risk factors. CONCLUSIONS: PHOX2B mutation-confirmed CCHS confers risk for adverse neurocognitive outcome, though the range of functioning observed raises questions about factors that may contribute to neurocognitive variability. Visuoperceptual reasoning and clerical/visuographic speed appear particularly vulnerable. PHOX2B genotype and disease severity indicators were unrelated to neurocognitive indices, possibly due to our modest sample. Future research should employ comprehensive neurocognitive assessment emphasizing visuoperceptual ability, mental speed, attention, and information processing efficiency. Increased recognition and expedited diagnosis with PHOX2B testing should allow larger studies of the relationship between neurocognitive functioning, PHOX2B genotype/mutation, and disease severity and management. (c) 2009 Wiley-Liss, Inc.

Zeluff, G. W., B. F. Orman, et al. (1977). "Grand rounds in critical care: Ondine's curse." Heart & Lung 6(6): 1057-63.

Zhang, T., B. C. Carleton, et al. (2009). "The added burden of comorbidity in patients with asthma." JOURNAL OF ASTHMA 46(10): 1021-6.

OBJECTIVE: Compare the prevalence of comorbidities in adults with and without asthma in Canada and investigate the association between comorbidities in patients with asthma and the occurrence of asthma symptoms or attacks. METHODS: Survey data from the 2005 Canadian Community Health Survey (CCHS) were analyzed. A total of 132,221 Canadians participated in the national survey; 10,089 adult respondents from 10 Canadian provinces and 3 territories reported having asthma. Analyses focused on 11 major chronic comorbidities. RESULTS: Respondents with asthma were more likely to have comorbidities except cancer; 31% of respondents with asthma and comorbidities reported their health status to be fair or poor. For respondents with asthma, non-asthma chronic respiratory disease, mental illness, and allergy were significantly associated with having asthma symptoms or attacks. CONCLUSIONS: Many Canadians with asthma report a high comorbidity burden. These patients will likely require more health services and more complex health management strategies. Comorbid conditions should be clearly identified with particular emphasis on management of mood disorders and anxiety because these conditions are likely to increase asthma symptomatology and may be unrecognized by clinicians.
Zhao, J., T. Stockwell, et al. (2009). "Non-response bias in alcohol and drug population surveys." Drug & Alcohol Review 28(6): 648-57.

INTRODUCTION AND AIMS: This proposed study was to assess non-response bias in the 2004 Canadian Addictions Survey (CAS). DESIGN AND METHODS: Two approaches were used to assess non-response bias in the CAS which had a response rate of only 47%. First, the CAS sample characteristics were compared with the 2002 Canadian Community Health Survey (CCHS, response rate 77%) and the 2001 Canada Census data. Second, characteristics of early and late respondents were compared. RESULTS: People with lowest income and less than high-school education and those who never married were under-represented in the CAS compared with the Census, but similar to the CCHS. Substance use was more prevalent in the CAS than the CCHS sample, but most of the CAS and CCHS estimates did not exceed +/-3% points. Late respondents were also significantly more likely to be male, young adult, highly educated, used, have high income, live in different provinces and report substance use. Multivariate logistic regression found significant non-response bias for lifetime, past 12 months, chronic risky, acute risky and heavy monthly alcohol use, lifetime and past year cannabis use, lifetime hallucinogen use, any illicit drug uses of lifetime and past year. Adjustment for non-response bias substantially increased prevalence estimates. For example, the estimates for lifetime and past 12 month illicit drug use increased by 5.22% and 10.34%. DISCUSSION AND CONCLUSIONS: It is concluded that non-response bias is a significant problem in substance use surveys with low response rates but that some adjustments can be made to compensate.

Zhu, M. Y., W. P. Wang, et al. (2005). "Age-associated changes in mRNA levels of Phox2, norepinephrine transporter and dopamine beta-hydroxylase in the locus coeruleus and adrenal glands of rats." JOURNAL OF NEUROCHEMISTRY 94(3): 828-838.

Age-related changes in the gene expression of the transcription factors, Phox2a and 2b, and two marker proteins, norepinephrine transporter (NET) and dopamine beta-hydroxylase (DBH), of noradrenergic neurons were characterized in the locus coeruleus (LC) and adrenal glands using in situ hybridization. Analysis of changes was performed in rats that were 1-23 months of age. Compared to 1-month-old rats, there was a 62% increase of Phox2a messenger RNA (mRNA) in the LC of 3-month-old rats, and a decline of 37% in 23-month-old rats. In contrast, levels of Phox2b mRNA in the LC remained unchanged in 3-month-old rats, but declined to a 30% reduction in 23-month-old rats. Interestingly, mRNA levels of NET in the LC decreased with increasing age to a reduction of 29%, 30% and 43% in 3-, 8- and 23-month-old rats, respectively. Similarly, DBH mRNA in the LC declined with increasing age to a 56% reduction in 23-month-old rats. mRNA levels of Phox2a, Phox2b, NET and DBH in the adrenal medulla of 23-month-old rats were significantly lower than those of 1-month-old rats. Semi-quantitative reverse transcription assays of the same genes yielded data similar to in situ hybridization experiments, with beta-actin mRNA levels being unchanged across the ages. Taken together, these data reveal that reduced Phox2 mRNAs in the LC and adrenal medulla of aging rats are accompanied by a coincidental decline in mRNA levels of NET and DBH and suggest a possible relationship between Phox2 genes and the marker genes in noradrenergic neurons after birth. copyright 2005 International Society for Neurochemistry.