Literature search from ms 29/4/2010

Amankwah, E., E. Ngwakongnwi, et al. (2009). "Why many visible minority women in Canada do not participate in cervical cancer screening." Ethnicity & Health 14(4): 337-49.

OBJECTIVE: To determine a high-risk group of visible minority women in Canada who do not participate in cervical cancer screening and the reasons why they do not participate. DESIGN: We combined two cycles of a large Canadian health survey, Canadian Community Health Survey (CCHS), to obtain a large sample size of visible minority women. Proportions of 'never having a Papanicalaou (Pap) test' and 'not having a Pap test within the last three years' were then calculated for different ethnic groups using sampling weights advised by Statistics Canada to account for the complex sampling procedure used in CCHS. A logistic regression model was developed to test the association between demographic and health-related variables and not having a Pap test. To identify visible minority women who were at a high risk of not having a Pap test, we stratified these women simultaneously on three variables that were significant in the logistic regression model. RESULTS: Visible minority women were more than twice as likely never to have had a Pap test. Among visible minority women, those who recently immigrated to Canada and did not have a regular physician had the highest risk for not having a Pap test. Common reasons reported for not having a Pap test included believing it was not necessary and simply not getting around to it. CONCLUSION: Visible minority women in Canada may not be participating in regular Pap testing because of cultural beliefs and a lack of an understanding of the importance of Pap testing. A culturally appropriate cervical cancer screening intervention program that involves members of visible minority communities may increase participation of this subgroup of Canadian women. This study provides preliminary information on why visible minority women in Canada do not participate in cervical cancer screening. However, the lumping together of all visible minority may obscure differences between different ethnic groups. Therefore, further research on each ethnic group is required to develop tailored culturally appropriate intervention.

Amiel, J., V. Dubreuil, et al. (2009). "PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models." Respiratory Physiology & Neurobiology 168(1-2): 125-32.

Phox2b is a master regulator of visceral reflex circuits. Its role in the control of respiration has been highlighted by the identification of heterozygous PHOX2B mutations as the cause of Central Congenital Hypoventilation Syndrome (CCHS), a rare disease defined by the lack of CO(2) responsiveness and of breathing automaticity in sleep. Phox2b(27Ala/+) mice that bear a frequent CCHS-causing mutation do not respond to hypercapnia and die in the first hour after birth from central apnoea. They are therefore a reliable animal model for CCHS. Neurons of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) were found severely depleted in these mice and no other neuronal loss could be identified. Physiological experiments show that RTN/pFRG neurons are crucial to driving proper breathing at birth and are necessary for central chemoreception and the generation of a normal respiratory rhythm. To date, the reason for the selective vulnerability of RTN/pFRG neurons to PHOX2B protein dysfunction remains unexplained.

Amiel, J., B. Laudier, et al. (2003). "Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome." NATURE GENETICS 33(4): 459-61.

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.

Amiel, J., A. Pelet, et al. (2003). "Exclusion of RNX as a major gene in congenital central hypoventilation syndrome (CCHS, Ondine's curse)." AMERICAN JOURNAL OF MEDICAL GENETICS Part A. 117A(1): 18-20.

Congenital central hypoventilation syndrome (CCHS) is a rare condition for which segregation analyses have suggested genetic factors. The respiratory phenotype of Rnx knock-out mice together with the Rnx expression at the brainstem level prompted us to consider the RNX gene as a candidate for CCHS in human. The screening of the RNX gene in a series of 25 patients with CCHS did not reveal any significant nucleotide variation. We therefore conclude that RNX is not a major gene for CCHS in human. Copyright 2002 Wiley-Liss, Inc.

Amiel, J., R. Salomon, et al. (1998). "Mutations of the RET-GDNF signaling pathway in Ondine's curse." AMERICAN JOURNAL OF HUMAN GENETICS 62(3): 715-7.

Andersen, U. O., J. H. Henriksen, et al. (2002). "Sources of measurement variation in blood pressure in large-scale epidemiological surveys with follow-up." BLOOD PRESSURE 11(6): 357-65.

The Copenhagen City Heart Study (CCHS) is a longitudinal epidemiological study of 19698 subjects followed up since 1976. Variation in blood pressure (BP) measurement in the first three CCHS surveys is evaluated by assessing two components, systematic variation and random variation [daytime and seasonally variation, observer bias, non-response bias, variation with explanatory variables, such as diabetes, hypertension, body mass index (BMI), height, plasma cholesterol and smoking] for the purpose of identifying relevant errors in population surveys. BP was measured in the seated position after a 5 min rest, with the cuff around the non-dominating arm, in accordance with recommended guidelines. The participation rate fell from 74% in survey 1 to 63% in survey 3. Significant non-response bias with respect to BP values was not found. No daytime variability was noted either in systolic (SBP) or diastolic (DBP) BPs. A trend towards a lower BP was seen during the summertime. Random variation, expressed as the standard deviation of the measured values, increased with increasing BP values (SBP: 11.9-13.4 to 21.2-25.1 mmHg; DBP: 10.6-11.2 to 11.9-13.4 mmHg). SBP was positively correlated to BMI and plasma cholesterol. SBP was 5-10 mmHg higher in diabetics (p = 0.000-0.04) than in age- and sex-matched non-diabetics. DBP did not differ between the two groups. Smokers from the age of 50 years had a 2-4 mmHg lower SBP (p = 0.000-0.01) and 1-3 mmHg lower DBP (p = 0.000-0.005) than had non-smokers. In addition, significantly fewer smokers took antihypertensive medication than did non-smokers (p = 0.000). In conclusion, judging from the degree of association with BP and/or differences between the three surveys, the most important factors to consider were seasonal variation, BMI, the use of antihypertensive drug therapy, plasma cholesterol, smoking status and diabetes. An inter-survey comparison of BP in population cohorts requires controlling for these factors.
Andersen, U. O. and G. Jensen (2004). "Decreasing population blood pressure: 15 years of follow-up in the Copenhagen City Heart Study (CCHS)." BLOOD PRESSURE 13(3): 176-82.

OBJECTIVE: Population blood pressure (BP) levels from a longitudinal study were analysed for trends during a period of 15 years. Trends from unadjusted data are reported as well as trends adjusted for major cardiovascular (CV) risk factors and use of antihypertensive therapy, thus allowing assessment of independent BP trends. DESIGN: The Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random population sample of both genders aged 20 and above. Three cross-sectional population surveys were performed: 1976-78 (n=14000), 1981-83 (n=12675) and 1991-94 (n=9661). METHODS: BP was measured by a London School of Hygiene Sphygmomanometer. Weight and height were measured and body mass index (BMI) calculated. Non-fasting plasma cholesterol was determined. A questionnaire concerning smoking status and diabetes was completed. Measurement methods were strictly standardized and unchanged in the three cross-sectional surveys. RESULTS: Unadjusted systolic BP (SBP) levels decreased during 15 years of follow-up, and unadjusted diastolic BP (DBP) levels increased. An investigation of the effect of major CV risk factors, both singly and jointly on BP levels, revealed a pattern of correlations contributing to BP variability. Adjustments for BMI, cholesterol, diabetes, use of antihypertensive therapy and smoking status were made in the final analyses of BP trend. The adjusted trend model demonstrated that SBP levels remained lower than SBP levels in the first survey. DBP levels increased slightly. CONCLUSIONS: The results demonstrate a decrease in population SBP. The decrease is independent of major CV risk factors. Possible contributing factors are discussed.

Anderson, R. B., A. L. Stewart, et al. (2006). "Phenotypes of neural-crest-derived cells in vagal and sacral pathways." CELL AND TISSUE RESEARCH 323(1): 11-25.

Enteric neurons arise from vagal and sacral level neural crest cells. To examine the phenotype of neural-crest-derived cells in vagal and sacral pathways, we used antisera to Sox10, p75, Phox2b, and Hu, and transgenic mice in which the expression of green fluorescent protein was under the control of the Ret promoter. Sox10 was expressed prior to the emigration of vagal cells, whereas p75 was expressed shortly after their emigration. Most crest-derived cells that emigrated adjacent to somites 1-4 migrated along a pathway that was later followed by the vagus nerve. A sub-population of these vagal cells coalesced to form vagal ganglia, whereas others continued their migration towards the heart and gut. Cells that coalesced into vagal ganglia showed a different phenotype from cells in the migratory streams proximal and distal to the ganglia. Only a sub-population of the vagal cells that first entered the foregut expressed Phox2b or Ret. Sacral neural crest cells gave rise to pelvic ganglia and some neurons in the hindgut. The pathways of sacral neural crest cells were examined by using DbetaH-nlacZ mice. Sacral cells appeared to enter the distal hindgut around embryonic day 14.5. Very few of the previously demonstrated, but rare, neurons that were present in the large intestine of Ret null mutants and that presumably arose from the sacral neural crest expressed nitric oxide synthase, unlike their counterparts in Ret heterozygous mice. copyright Springer-Verlag 2006.

Antic, N. A., B. A. Malow, et al. (2006). "PHOX2B mutation-confirmed congenital central hypoventilation syndrome: presentation in adulthood." AMERICAN JOURNAL OF RESPIRATORY & CRITICAL CARE MEDICINE 174(8): 923-7.

Congenital central hypoventilation syndrome (CCHS) typically presents in the newborn period. A case series of five adults is presented, each heterozygous for a documented polyalanine expansion mutation in the PHOX2B gene and evidence of nocturnal alveolar hypoventilation. All cases had symptoms in childhood, but survived to adulthood without ventilatory support. After identification of physiologic compromise, artificial ventilation was initiated. These adults have the mildest of the CCHS-related PHOX2B polyalanine expansion mutations, coding for only five extra alanines; three of the adults have affected offspring. Report of these cases should lead to a more rapid identification of CCHS presenting in adulthood.

Arai, H., T. Otagiri, et al. (2007). "De novo polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: unequal sister chromatid exchange during paternal gametogenesis." Journal of Human Genetics 52(11): 921-5.

The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHOX2B in 13 de novo families with CCHS and found that 6 families were informative regarding a parental origin of polyalanine expansion, with all 6 mutants being of paternal origin. Four of them were also informative regarding a chromosomal event and their mutants were derived from unequal sister chromatid exchange. It is probable that de novo expansion of polyalanine repeats in CCHS results mainly from unequal sister chromatid exchange during spermatogenesis due to the secondary DNA structure of imperfect trinucleotide repeats encoding polyalanine tracts.

Arai, H., T. Otagiri, et al. (2010). "Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: rs17884724:A>C is associated with 7-alanine expansion." Journal of Human Genetics 55(1): 4-7.

With congenital central hypoventilation syndrome (CCHS), most patients have a de novo 5-13 polyalanine expansion mutation in PHOX2B. We reported previously that de novo polyalanine expansion mutations were of paternal origin and were derived from unequal sister chromatid exchange during spermatogenesis in six and four informative families, respectively. In this study, we analyzed the relationship between haplotypes and de novo polyalanine expansion in PHOX2B and found that haplotypes carrying rs17884724:A>C were detected frequently in 7-alanine expanded (27-alanine) mutant alleles, which are the most prevalent mutations in CCHS. The allele with rs17884724:A>C made fewer nucleotide mismatches in the misalignment at crossing-over than the allele without rs17884724:A>C. The high frequency of rs17884724:A>C in 7-alanine expansion (27-alanine) mutations also supported the unequal crossover mechanism for polyalanine expansion. We also confirmed the paternal origin of de novo polyalanine expansion mutation and unequal sister chromatid exchange association in three more patients. In spite of paternal bias, the paternal age effect on CCHS incidence was not observed. De novo polyalanine expansion mutations are mainly derived from unequal sister chromatid exchange during spermatogenesis because of replication and/or repair systems that are specific for spermatogenesis.

Archbold, K. H., N. L. Johnson, et al. (2010). "Normative heart rate parameters during sleep for children aged 6 to 11 years." Journal of Clinical Sleep Medicine 6(1): 47-50.

OBJECTIVE: Normative values for pediatric heart rates during sleep are not known. The purpose of this study was to describe the average sleeping heart rate of children and to determine if age, sex, body mass index (BMI) or ethnicity is related to sleeping heart rate. METHODS: Electrocardiogram (ECG) data were obtained from healthy children during in-home polysomnography in the Tucson Children's Assessment of Sleep Apnea study (TuCASA) or home cardiorespiratory sleep studies in the Cleveland Children's Sleep and Health Study (CCSHS). Data were described then compared in separate cohort analyses using least square means from analysis of variance models that controlled for age, sex, ethnicity, and BMI. Student t tests were used to compare groups within cohorts for significant differences. RESULTS: In the cohort of 470 TuCASA children, 50.3% were female, 41% were Hispanic; mean age (SD) was 8.7 (1.7) years. Hispanics and Caucasians did not differ significantly on mean sleeping heart rate. The CCSHS cohort consisted of 561 children; 50.2% female and 33% African American, aged 8.9 (0.6) years. African Americans had significantly faster sleeping heart rates than Caucasians in the CCSHS cohort. In both cohorts, younger children demonstrated significantly faster sleeping heart rates than older children; girls had significantly faster sleeping heart rates than boys (TuCASA: girls 77.6 [9.9] vs boys 73.6 [8.2]; CCHS: girls 81.5 [8.4] vs boys 78.4 [8.1]) and obese children (BMI > or = 95th percentile for age) had significantly faster sleeping heart rates than nonobese children (TuCASA: obese children: 79.3 [12.3] vs nonobese children 75.0 [8.7]; CCHS: obese children: 83.3 [8.4] vs nonobese children 79.4 [8.31]). CONCLUSIONS: Children aged 6 to 11 years have sleeping heart rates that decrease significantly with age. African American ethnicity, female sex, and obesity were associated with faster sleeping heart rates.

Aroca, P., B. Lorente-Canovas, et al. (2006). "Locus coeruleus neurons originate in alar rhombomere 1 and migrate into the basal plate: Studies in chick and mouse embryos." JOURNAL OF COMPARATIVE NEUROLOGY 496(6): 802-818.

We investigated in the mouse and chick the neuroepithelial origin and development of the locus coeruleus (LoC), the most important noradrenergic neuronal population in the brain. We first studied the topography of the developing LoC in the hindbrain, using as markers the key noradrenergic marker gene Dbh and the transcription factors Phox2a and Phox2b (upstream of Dbh). In both mouse and chicken, LoC neurons first appear arranged linearly along the middle one-third of the alar plate of rhombomere 1 (r1), collinear to a reference ventricular longitudinal band that early on expresses Phox2a and Phox2b in the alar plate of r2 and later expands to rl. Double-labeling experiments with LoC markers (Dbh or Phox2a) and either alar (Pax7 and Rnx3) or basal (Otp) genetic markers suggested that LoC cells migrate from their origin in the alar plate to a final position in the lateral basal plate. To corroborate these suggestions experimentally and determine the precise origin of the LoC, we fate mapped the LoC in the chick at stage HH11 by using quail-chick homotopic grafts. The experimental results confirmed that the LoC originates in the alar plate throughout the rostrocaudal extent of r1 and ruled out a rostrocaudal translocation. They also corroborated a ventralward tangential migration of LoC cells into the lateral basal plate, where the postmigratory LoC primordium is located. Comparisons with neighboring alar r1-derived cell populations established that LoC neurons originate outside the cerebellum, in a matrix area intercalated dorsoventrally between the sources of the prospective vestibular and trigeminal columns. copyright 2006 Wiley-Liss, Inc.

Asferg, C., R. Mogelvang, et al. (2010). "Leptin, not adiponectin, predicts hypertension in the Copenhagen City Heart Study." AMERICAN JOURNAL OF HYPERTENSION 23(3): 327-33.

BACKGROUND: Leptin and adiponectin are hormones secreted by adipose tissue, and both hormones are candidate intermediaries between adipose tissue and overweight-related diseases. So far, no prospective study has been published where the independent effects of these two hormones on the development of hypertension have been directly compared. The objective of this study was to investigate the relationships between plasma levels of leptin and adiponectin and new-onset hypertension in the Copenhagen City Heart Study (CCHS). METHODS: In a prospective study design, we examined new-onset hypertension in 620 women and 300 men who were normotensive in the third CCHS examination, which was performed in 1991-1994. RESULTS: Between the third and the fourth CCHS examination, which was performed in 2001-2003, 254 had developed hypertension, defined as systolic blood pressure (SBP) > or = 140 mm Hg, or diastolic blood pressure (DBP) > or = 90 mm Hg, or use of antihypertensive medication. Using logistic regression analysis, adjusting for age, sex, estimated glomerular filtration rate, triglycerides, high-density lipoprotein cholesterol (HDL-C), fibrinogen, and glucose, and with leptin and adiponectin included in the same model, leptin was significantly associated with new-onset hypertension with an odds ratio (95% confidence interval) of 1.28 (1.08-1.53; P < 0.005) for 1 s.d. higher level of log-transformed leptin, whereas adiponectin was not significantly associated with new-onset hypertension having an odds ratio of 1.02 (0.84-1.24; P = 0.83) for 1 s.d. higher level of log-transformed adiponectin. CONCLUSIONS: In the CCHS, leptin, but not adiponectin, was a significant independent predictor of new-onset hypertension.

Auer, R. N., C. G. Rowlands, et al. (1996). "Multiple sclerosis with medullary plaques and fatal sleep apnea (Ondine's curse)." CLINICAL NEUROPATHOLOGY 15(2): 101-5.

We report 2 patients with multiple sclerosis (MS) who were symptomatic but ambulatory, and died in their sleep. Sleep studies in 1 patient showed hypercarbia and hypoxia accompanying sleep. In both cases autopsy showed plaques of multiple sclerosis in the medulla oblongata, incompletely involving the neuroanatomic areas of the medullary reticular formation controlling automatic breathing. A systematic analysis of the location of the plaques in relation to areas known to be important in breathing control revealed that the regions corresponding to the ventral nuclear complex of respiratory control in animals were incompletely and unilaterally involved in both cases. Close correlation with nuclei that have been demonstrated in animal experiments to be important in descending respiratory control of phrenic and intercostal musculature was not possible due to possible differences in anatomy between animals and humans, and the fact that plaques of MS affect axons of passage and spare neuronal cell bodies. Nevertheless, the cases clearly illustrate that patchy, unilateral lesions of the medullary reticular formation in humans can give rise to sleep disordered breathing. The cases also illustrate the risk of death during sleep in MS patients with demyelination in the medulla oblongata, and demonstrate the need to carefully examine the medulla in MS patients if they die unexpectedly during sleep.

Babak, V. G., F. Baros, et al. (2008). "Dilational viscoelasticity and relaxation properties of interfacial electrostatic complexes between oppositely charged hydrophobic and hydrophilic polyelectrolytes." Colloids and Surfaces B: Biointerfaces 65(1): 43-49.

Strongly adsorbing hydrophobic cationic polyelectrolyte, Eudragit RS, containing [similar to]2.5 mol% of pendent hydrophilic trimethylammonium (TMA) groups irreversibly adsorbs from its methylene chloride (MCl) solution at the MCl/water interface and forms solid-like adsorption layers (ALs). Submitted to periodic dilational deformations with the standard radial frequency omega₀ = 0.63 rad/s, these ALs exhibit relatively high dilational storage modulus E' [similar to] 20 mN/m and practically zero loss modulus E'' at the bulk concentration C_Eud = 4 x 10^-3 g/L. The frequency scanning of these ALs in the diapason omega = 0.01-0.63 rad/s and the approximation of the experimental dependences E'(omega) and E''(omega) by two relaxation times rheological model makes it possible to estimate the crossing frequency of these ALs determined from the condition E'(omega_c) = E''(omega_c) as omega_c [similar to] 5 x 10^-4 rad/s. Upon dissolving the hydrophilic anionic polyelectrolyte, chitosan sulfate (ChS), in the water phase (C_ChS = 3 x 10^-2 g/L) the electrostatic interpolyelectrolyte complexes form at the MCl/water interface. The elasticity moduli E' and E'' of these mixed AL did not undergo remarkable variations, but the crossing frequency is sharply increased by [similar to]10 times becoming equal to omega_c [approximately equal to] 3 x 10^-3 rad/s. The increase of omega_c certifies for the liquefaction of mixed Eudragit RS/ChS adsorption layers. A remarkable decrease of the storage modulus down to E' = 8 mN/m and simultaneous increase of the crossing frequency up to omega_c [approximately equal to] 10^-2 rad/s occurs upon increasing the concentrations of both components, Eudragit RS and ChS, up to 0.1 g/L. The liquefaction effect in the mixed ALs of oppositely charged polyelectrolytes was explained on the basis of the proposed relaxation mechanism. The effect of the liquefaction of adsorption layers of strongly adsorbing hydrophobic polyelectrolytes by formation of interpolyelectrolyte complexes with hydrophilic polyelectrolytes must be taken into account in the production of nano-capsules and nano-fibers. copyright 2008 Elsevier B.V. All rights reserved.