Literature search from ms 29/4/2010

Belik, S.-L., M. B. Stein, et al. (2009). "Relation between traumatic events and suicide attempts in Canadian military personnel." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 54(2): 93-104.

OBJECTIVE: To determine whether exposure to particular types of traumatic events was differentially associated with suicide attempts in a representative sample of active military personnel. METHOD: Data came from the Canadian Community Health Survey: Mental Health and Well-Being Canadian Forces Supplement (CCHS-CFS), a cross-sectional survey that provided a comprehensive examination of mental disorders, health, and the well-being of currently active Canadian military personnel (n = 8441; aged 16 to 54 years; response rate 81.1%). Respondents were asked about exposure to 28 traumatic events that occurred during their lifetime. Suicide attempts were measured using a question about whether the person ever "attempted suicide or tried to take [his or her] own life." RESULTS: The prevalence of lifetime suicide attempts for currently active Canadian military men and women was 2.2% and 5.6%, respectively. Sexual and other interpersonal traumas (for example, rape, sexual assault, spousal abuse, child abuse) were significantly associated with suicide attempts in both men (adjusted odds ratios [AORs] ranging from 2.31 to 4.43) and women (AORs ranging from 1.73 to 3.71), even after adjusting for sociodemographics and mental disorders. Additionally, the number of traumatic events experienced was positively associated with increased risk of suicide attempts, indicating a dose-response effect of exposure to trauma. CONCLUSIONS: The current study is the first to demonstrate that sexual and other interpersonal traumatic events are associated with suicide attempts in a representative sample of active Canadian military men and women.

Benfante, R., R. A. Antonini, et al. (2008). "The expression of PHOX2A, PHOX2B and of their target gene dopamine-beta-hydroxylase (DbetaH) is not modified by exposure to extremely-low-frequency electromagnetic field (ELF-EMF) in a human neuronal model." Toxicology in Vitro 22(6): 1489-95.

The homeodomain transcription factors PHOX2A and PHOX2B are vital for development of the autonomic nervous system. Their spatial and temporal expression at the neural crest is instrumental in determining neuronal precursor fate, and by regulating DbetaH expression, the enzyme catalysing noradrenaline synthesis from dopamine, they also play a role in determination of noradrenergic phenotype. Disturbing this finely regulated process leads to disruption of autonomic development and autonomic dysfunction syndromes such as DbetaH deficiency. As it had previously been shown that the catecholamine system is responsive to ELF-EMF, and as this has also been linked to various pathologies and to certain types of cancer, we wondered whether exposure to this type of radiation could affect the expression of PHOX2A, PHOX2B and DbetaH, also during differentiation triggered by retinoic acid. To investigate this possibility we exposed the human SH-SY5Y neuroblastoma cell line to 50 Hz power-line magnetic field at various flux densities and for various exposure times. We measured gene expression in exposed cells compared to control cells and also investigated any changes at protein level. Using our exposure protocol, we found no changes at either transcript or protein level of these important components of the autonomic nervous system and catecholaminergic system.

Berry, R. B. and P. Sriram (2009). "Evaluation of hypoventilation." Seminars in Respiratory & Critical Care Medicine 30(3): 303-14.

Evaluation of a patient with hypoventilation requires a combination of clinical history, physical examination, pulmonary function testing, and chest radiography to help determine the cause. Specialized testing such as measurement of respiratory muscle strength and assessment of ventilatory control may also be needed. Genetic testing may help make the diagnosis of some disorders such as the central congenital hypoventilation syndrome. In some patients the first laboratory clue that chronic hypoventilation is present is to note an unexplained elevation in the serum CO (2) (HCO (3)) on routine electrolyte testing. Nocturnal oximetry and polysomnography are usually required to determine if obstructive or central sleep apnea is present in addition to nocturnal hypoventilation. In addition, the severity of daytime hypoventilation or pulmonary function impairment often does not accurately predict the severity of nocturnal changes in arterial oxygen saturation and the degree of nocturnal hypoventilation. End-tidal PCO (2) and transcutaneous PCO (2) are sometimes utilized to directly estimate the degree of nocturnal hypoventilation during sleep studies. They have limitations but may be especially useful to detect trends in the PCO (2) during the night.

Berry-Kravis, E. M., L. Zhou, et al. (2006). "Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype." AMERICAN JOURNAL OF RESPIRATORY & CRITICAL CARE MEDICINE 174(10): 1139-44.

RATIONALE: Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases. OBJECTIVES: To characterize CCHS-associated nonpolyalanine repeat mutations in PHOX2B, evaluate genotype-phenotype relationships, and compare clinical features of CCHS in cases with nonpolyalanine repeat mutations to those with polyalanine expansion mutations. METHODS: DNA from probands was analyzed by polymerase chain reaction for the common polyalanine repeat expansion. If no expansion was present, coding regions and intron-exon boundaries of PHOX2B were sequenced. When possible, parents and siblings were screened for the mutation found in the proband. RESULTS: Fourteen nonpolyalanine repeat mutations, including missense, nonsense, and frameshift mutations, and 170 polyalanine repeat mutations were identified in 184 CCHS probands. Both incomplete penetrance and parental mosaicism were observed within the family members of probands with nonpolyalanine repeat mutations. Increased prevalence of continuous ventilatory dependence, HSCR, and neural crest tumors was seen in the nonpolyalanine repeat group compared to those with polyalanine repeat mutations. CONCLUSIONS: These data suggest that nonpolyalanine repeat mutations produce more severe disruption of PHOX2B function. Patients carrying these mutations should be evaluated for HSCR and neural crest tumors. Because incomplete penetrance can occur in families of CCHS probands with PHOX2B mutations, genetic screening of appropriate family members is indicated to evaluate reproductive risk and because asymptomatic mutation carriers may be at risk for developing alveolar hypoventilation.

Bethell, J. and A. E. Rhodes (2007). "Depressed mood in the suicidal population." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 52(11): 744-8.

OBJECTIVE: To determine whether, and to what extent, those who reported suicidal ideation and (or) attempts in the previous year, without meeting the criteria for major depressive episode (MDE), might still have experienced subthreshold depression. METHOD: Data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2) were examined to estimate and compare the prevalence of depressed mood, a core symptom of MDE and subthreshold depression, within the previous month for the following 4 population groups: MDE within the previous month [D(1 month)], MDE within the previous year but not the previous month [D(1 year)], suicidality without MDE within the previous year (D-S+), and no MDE or suicidality within the previous year (D-S-). RESULTS: As expected, the D(1 month) group showed the highest prevalence of depressed mood in the previous month. However, the D-S+ group had a significantly higher prevalence of depressed mood than the D-S- group and only a slightly lower level than that of the D(1 year) group. CONCLUSIONS: A fraction of those who reported suicidality in the previous year met the criteria for MDE during that time; however, subthreshold depression might be common in the suicidal population. Future epidemiologic research in the areas of suicidality and depression will benefit from a comprehensive assessment of subthreshold depression.

Bieber, R. J. (1977). "[Crux medicorum: Ondine's curse (author's transl)]." ANAESTHESIST 26(11): 628-9.

All known cases of the Ondine's curse syndrome with lifethreatening complications in consequence of narcosis, sedatives or oxygen-administration are reported. The avoidance of accidents requires blood gas analysis and more attention to the less well-known phenomenon--possibly a cause of the sudden-death-syndrome.

Bieber, R. J. (1977). "[Impairment of the respiratory centre: ondines curse (chronic hypoventilation) (author's transl)]." Praxis und Klinik der Pneumologie 31(7): 676-80.

Biering-Sorensen, F., E. Jacobsen, et al. (1990). "[Diaphragm pacing by electric stimulation of the phrenic nerves]." UGESKRIFT FOR LAEGER 152(16): 1143-5.

Artificial ventilation by electric stimulation of the phrenic nerves has become clinically significant within the past 20 years and, in the world as a whole, approximately 700 patients have been treated with implanted diaphragmatic pacemakers. The two first patients in whom diaphragmatic pacemakers were implanted in Denmark, had sustained accidental fractures of the second cervical vertebra with subsequent high cervical spinal cord lesions with not only tetraplegia but also respiratory arrest. In both patients, diaphragmatic pacemakers were implanted bilaterally and these were employed for 12-14 hours daily while ventilation with a respirator was employed at night. The main indications for diaphragmatic pacing are paralysis of respiration following high cervical spinal traumata and the chronic central hypoventilation syndrome (sleep apnoea of Undine's curse). Diaphragmatic pacing may improve the mode of ventilation and the quality of life for patients with tetraplegia and respiratory insufficiency. On account of the potential technical problems, the risk of complications and the limited number of patients in whom this operation is suitable, implantation of diaphragmatic pacemakers should be concentrated in a few centres and probably only one in Denmark.
Bilodeau, M. L., T. Boulineau, et al. (2001). "Differential expression of sympathoadrenal lineage-determining genes and phenotypic markers in cultured primary neural crest cells." In Vitro Cellular & Developmental Biology Animal. 37(3): 185-92.

Bone morphogenetic protein-2 (BMP-2) promotes the development of primary neural crest cells grown in tissue culture to the sympathoadrenal (SA) lineage. Independent studies have characterized the expression patterns of SA-lineage genes in developing chicken embryo; however, studies using cultured primary neural crest cells have characterized only the expression patterns of the catecholaminergic markers, tyrosine hydroxylase (TH) and catecholamines (CAs). To further explore the molecular mechanisms that control SA-cell development using the in vitro model system, it is crucial to define the expression patterns of both the catecholaminergic markers and the genes regulating SA-lineage determination. Accordingly, we defined, in the absence and presence of BMP-2, the temporal expression patterns of TH and CA, the SA lineage-determining genes ASH-1, Phox2a, and Phox2b, the GATA-2 gene, and the pan-neuronal SCG10 gene. Comparison of these data with the reported temporal and spatial patterns of expression in vivo demonstrate that the inductive steps of SA-lineage determination, including the specification of neurotransmitter identity and neuronal fate, are recapitulated in the neural-crest culture system.

Bogousslavsky, J., R. Khurana, et al. (1990). "Respiratory failure and unilateral caudal brainstem infarction." ANNALS OF NEUROLOGY 28(5): 668-73.

We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (PaCO2 62 mm Hg, PaO2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses.

Boland, R. A. and R. D. Adams (1998). "The effects of arm elevation and overnight head-up tilt on forearm and hand volume." Journal of hand therapy : official journal of the American Society of Hand Therapists(3): 180-90.

Methods to reduce increased fluid volume, or swelling, were evaluated as short- and long-term interventions. Forearm and hand volumes were measured in 45 fit and healthy subjects using a water displacement device with previously established reliability. Volumes were measured before and after 2 hours of recumbency and before and after overnight sleep under different conditions of arm elevation or head-up tilt. No arms-at-side lying-down position, whether after 2 hours awake or after overnight sleep or with bed-head elevated or not, resulted in significant changes in forearm and hand volume. Only 2 hours in a supine lying-down position with 30 degrees of arm elevation caused a significant effect, with an average decrease of 51 ml in forearm and hand volume.

Bolk, S., M. Angrist, et al. (1996). "Congenital central hypoventilation syndrome: mutation analysis of the receptor tyrosine kinase RET." AMERICAN JOURNAL OF MEDICAL GENETICS 63(4): 603-9.

Congenital central hypoventilation syndrome (CCHS) usually occurs as an isolated phenotype. However, 16% of the index cases are also affected with Hirschsprung disease (HSCR). Complex segregation analysis suggests that CCHS is familial and has the same inheritance pattern with or without HSCR. We postulate that alteration of normal function of the receptor tyrosine kinase, RET, may contribute to CCHS based on RET's expression pattern and the identification of RET mutations in HSCR patients. To further explore the nature of the inheritance of CCHS, we have undertaken two main routes of investigation: cytogenetic analysis and mutation detection. Cytogenetic analysis of metaphase chromosomes showed normal karyotypes in 13 of the 14 evaluated index cases; one index case carried a familial pericentric inversion on chromosome 2. Mutation analysis showed no sequence changes unique to index cases, as compared to control individuals, and as studied by single strand conformational polymorphism (SSCP) analysis of the coding region of RET. We conclude that point mutations in the RET coding region cannot account for a substantial fraction of CCHS in this patient population, and that other candidate genes involved in neural crest cell differentiation and development must be considered.

Bolk, S., M. Angrist, et al. (1996). "Endothelin-3 frameshift mutation in congenital central hypoventilation syndrome." NATURE GENETICS 13(4): 395-6.

Borghini, S., T. Bachetti, et al. (2006). "The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells." BIOCHEMICAL JOURNAL 395(2): 355-61.

The TLX2 (HOX11L1, Ncx, Enx) and PHOX2B genes encode transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages. Moreover, they share a similar expression pattern and are both involved in downstream steps of BMP (bone morphogenetic protein) signalling. In an attempt to reconstruct the gene network sustaining the correct development of the ANS, we have undertaken an in vitro experimental strategy to identify direct upstream regulators of the TLX2 gene. After characterizing a sequence displaying enhancer property in its 5' flanking region, we confirmed the functional link between the human PHOX2B and TLX2 genes. Transient transfections and electrophoretic-mobility-shift assays suggested that PHOX2B is able to bind the cell-specific element in the 5' regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells. Such interaction was also confirmed in vivo by means of chromatin immunoprecipitation assay and, in addition, up-regulation of endogenous TLX2 mRNA level was demonstrated following PHOX2B over-expression, by quantitative real-time PCR. Finally, PHOX2B proteins carrying mutations responsible for CCHS (congenital central hypoventilation syndrome) development showed a severe impairment in activating TLX2 expression, both in vitro and in vivo. Taken together, these results support the PHOX2B-TLX2 promoter interaction, suggesting a physiological role in the transcription-factor cascade underlying the differentiation of neuronal lineages of the ANS during human embryogenesis.
Borghini, S., T. Bachetti, et al. (2009). "Functional characterization of a minimal sequence essential for the expression of human TLX2 gene." BMB reports 42(12): 788-93.

TLX2 is an orphan homeodomain transcription factor whose expression is mainly associated with tissues derived from neural crest cells. Recently, we have demonstrated that PHOX2A and PHOX2B are able to enhance the neural cell-type specific expression of human TLX2 by binding distally the 5'-flanking region. In the present work, to deepen into the TLX2 transcription regulation, we have focused on the proximal 5'- flanking region of the gene, mapping the transcription start site and identifying a minimal promoter necessary and sufficient for the basal transcription in cell lines from different origin. Site-directed mutagenesis has allowed to demonstrate that the integrity of this sequence is crucial for gene expression, while electrophoretic mobility shift assays and chromatin immunoprecipitation experiments have revealed that such an activity is dependent on the binding of a PBX factor. Consistent with these findings, such a basal promoter activity has resulted to be enhanced by the previously reported PHOX2-responding sequence.

Borghini, S., M. Di Duca, et al. (2007). "Transcriptional regulation of TLX2 and impaired intestinal innervation: possible role of the PHOX2A and PHOX2B genes." EUROPEAN JOURNAL OF HUMAN GENETICS 15(8): 848-55.

TLX2 (also known as HOX11L1, Ncx and Enx) is a transcription factor playing a crucial role in the development of the enteric nervous system, as confirmed by mice models exhibiting intestinal hyperganglionosis and pseudo-obstruction. However, congenital defects of TLX2 have been excluded as a major cause of intestinal motility disorders in patients affected with intestinal neuronal dysplasia (IND) or pseudo-obstruction. After demonstrating the direct regulation of TLX2 expression by the homeoprotein PHOX2B, in the present work, we have focused on its paralogue PHOX2A. By co-transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation, we have demonstrated that PHOX2A, like PHOX2B, is involved in the cascade leading to TLX2 transactivation and presumably in the intestinal neuronal differentiation. Based on the hypothesis that missed activation of the TLX2 gene induces the development of enteric nervous system defects, PHOX2A and PHOX2B have been regarded as novel candidate genes involved in IND and pseudo-obstruction and consequently analyzed for mutations in a specific set of 26 patients. We have identified one still unreported PHOX2A variant; however, absence of any functional effect on TLX2 transactivation suggests that regulators or effectors other than the PHOX2 genes must act in the same pathway, likely playing a non redundant and direct role in the pathogenesis of such enteric disorders.

Boubred, F., V. Lethel, et al. (2002). "[Central alveolar hypoventilation syndrome and cerebral venous thrombosis: fortuitous association?]." ARCHIVES DE PEDIATRIE 9(3): 266-70.

Central hypoventilation syndrome is defined as the failure of automatic control of breathing. Secondary central hypoventilation syndrome should distinguish from congenital central hypoventilation syndrome by brainstem abnormalities, place of respiratory control. CASE REPORTS: We report two clinical cases characterized by late onset central hypoventilation syndrome (three years--six months, and five years old): in the first case the diagnosis was made after general anesthesia and the second one presented with acute nocturnal comatose state. Neuroradiologic investigations showed bilateral cerebral sinus veinous thrombosis without any brainstem lesions. Moreover these children had severe behavior disorders: psychomotor instability, alterations of social relations, language dysfunction, and neurocognitive deficit. This symptomatology seems independent from central hypoventilation syndrome and cerebral venous thrombosis. CONCLUSION: Late onset central hypoventilation syndrome may be associated with cerebral venous thrombosis. Ischemia of central chemoreceptors or integration of their informations could be one of mechanism.

Bouchard, L., I. Gaboury, et al. (2009). "Health in language minority situation. [French]." Healthcare Policy 4(4): 36-42.

Literature suggests the hypothesis that there is a health differential for minority Frenchspeaking groups in Canada. The effect of minority on perceived health has been measured using the 2001 and 2003 Canadian Community Health Survey (CCHS). The sequential multivariate logistic regression analysis shows that the minority Frenchspeaking groups - men and women - are more likely to declare a poorer health condition than the majority English-speaking groups. Contrary to women, this disparity among men groups remains significant even when adjustments are made according to some of the key health determinants. The study shows that the action of health determinants can be modulated by the minority/majority ratio. The identified disparities remind the need for a reflection on linguistic healthcare access policies.

Bourdeaut, F., I. Janoueix-Lerosey, et al. (2009). "Cholinergic switch associated with morphological differentiation in neuroblastoma." JOURNAL OF PATHOLOGY 219(4): 463-72.

The morphology of malignant cells distinguishes between undifferentiated, poorly differentiated and differentiating neuroblastomas and constitutes a strong prognostic factor. Spontaneous or treatment-induced maturation characterizes a subset of neuroblastomas. It constitutes the basis of retinoic acid treatment to improve survival in aggressive neuroblastomas. However, the molecular events that drive differentiation are poorly understood. In the present study we have investigated the relationships between gene expression profiles and differentiation criteria in stroma-poor neuroblastomas. This study included three undifferentiated (UN), 20 poorly differentiated (PDN) and 11 differentiating (DN) neuroblastomas. These groups could be clearly separated using unsupervised clustering methods, which further enabled a major classification impact of genes involved in neural development, differentiation and function to be identified. UNs are characterized by high ASCL1, high PHOX2B, low GATA2, low TH and low DBH expressions. Most PDNs harbour a clear adrenergic phenotype, even in the presence of missense PHOX2B mutations. Finally, all DN tumours demonstrate cholinergic features. Depending upon their association with adrenergic characteristics, this enables dual 'cholinergic/adrenergic' and 'fully cholinergic' neuroblastomas to be defined. This suggests that the cholinergic switch, a final specification process that occurs physiologically in a minority of sympathetic neurons, is a critical step of differentiation in some neuroblastic tumours. This switch is associated with a down regulation of DBH that is apparently not strictly dependent upon PHOX2B. Conversely, GATA2 and TFAP2B may play critical roles in maintaining adrenergic features in poorly differentiated tumours.