Literature search from ms 29/4/2010

Israels, S., J. C. Haworth, et al. (1976). "Lactic acidosis in childhood." ADVANCES IN PEDIATRICS 22: 267-303.

Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an "idiopathic" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders. [References: 106]

Itaranta, P., K. Viiri, et al. (2009). "Lumbo-sacral neural crest derivatives fate mapped with the aid of Wnt-1 promoter integrate but are not essential to kidney development." DIFFERENTIATION 77(2): 199-208.

Neural crest (NC) cells may be involved in kidney organogenesis by providing inductive signals and contributing to cells of the renal stroma. We show here that the lumbo-sacral NC cells fate mapped with the aid of Wnt-1 promoter in the mouse migrate close to the metanephros at the initiation of organogenesis but these cells remain superficial to the condensed Pax2-expressing mesenchymal cells. NC-derived cells enter later into the kidney proper from the midline region. The NC cells contribute also to development of the extra-adrenal para-aortic bodies, Zuckerkandl's bodies and the nerve cord of the sympathetic nervous system. Splotch (Sp2H/Sp2H) embryos, having a NC defect in the lumbo-sacral region, develop a normal metanephros even though the kidney does not express the NC markers Sox10, Phox2b and tyrosine hydroxylase. Consistent with the histological findings, the kidneys of Sp2H/Sp2H embryos also express the stromal genes Foxd1, Hoxa10 and RARbeta normally. Wnt-1 promoter-marked wild-type LacZ NC cells migrate intensely from the heterologous inducer tissue of the embryonic dorsal spinal cord (SPC) to the kidney mesenchyme, but tubule induction does not depend on NC migration, since the Sp2H/Sp2H SPC also induces tubulogenesis. The Sp2H/Sp2H mesenchyme also remains competent for tubulogenesis. We conclude that the NC cells fate mapped with the aid of Wnt-1 promoter migrate to the close to the metanephros and form later derivatives integrating with the kidney, but they may not be essential to the development of the stromal cells nor they may provide critical morphogenetic signals to regulate early kidney development in vivo. copyright 2008 International Society of Differentiation.

Ize-Ludlow, D., J. A. Gray, et al. (2007). "Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood." PEDIATRICS 120(1): e179-88.

OBJECTIVE: The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with hypothalamic dysfunction. METHODS: Individuals with late-onset central hypoventilation with hypothalamic dysfunction who were referred to Rush University Medical Center for clinical or genetic assessment in the past 3 years were identified, and medical charts were reviewed to determine shared characteristics of the affected subjects. Blood was collected for genetic testing of candidate genes (PHOX2B, TRKB, and BDNF) and for high-resolution conventional G-banding, subtelomeric fluorescent in situ hybridization, and comparative genomic hybridization analysis. A subset of these children were studied in the Pediatric Respiratory Physiology Laboratory at Rush University Medical Center. RESULTS: Twenty-three children with what we are now naming rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation were identified. Comprehensive medical charts and blood for genetic testing were available for 15 children; respiratory physiology studies were performed at Rush University Medical Center on 9 children. The most characteristic manifestations were the presentation of rapid-onset obesity in the first 10 years of life (median age at onset: 3 years), followed by hypothalamic dysfunction and then onset of symptoms of autonomic dysregulation (median age at onset: 3.6 years) with later onset of alveolar hypoventilation (median age at onset: 6.2 years). Testing of candidate genes (PHOX2B, TRKB, and BDNF) revealed no mutations or rare variants. High-resolution chromosome analysis, comparative genomic hybridization, and subtelomeric fluorescent in situ hybridization results were negative for the 2 patients selected for those analyses. CONCLUSIONS: We provide a comprehensive description of the clinical spectrum of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in terms of timing and scope of symptoms, study of candidate genes, and screening for chromosomal deletions and duplications. Negative PHOX2B sequencing results demonstrate that this entity is distinct from congenital central hypoventilation syndrome.

Jacob, J., A. L. Ferri, et al. (2007). "Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis." Nature Neuroscience 10(11): 1433-1439.

In many regions of the developing CNS, distinct cell types are born at different times. The means by which discrete and stereotyped temporal switches in cellular identities are acquired remains poorly understood. To address this, we have examined how visceral motor neurons (VMNs) and serotonergic neurons, two neuronal subtypes, are sequentially generated from a common progenitor pool in the vertebrate hindbrain. We found that the forkhead transcription factor Foxa2, acting in progenitors, is essential for the transition from VMN to serotonergic neurogenesis. Loss-of-function and gain-of-function experiments indicated that Foxa2 activates the switch through a temporal cross-repressive interaction with paired-like homeobox 2b (Phox2b), the VMN progenitor determinant. This mechanism bears a marked resemblance to the cross-repression between neighboring domains of transcription factors that establish discrete progenitor identities along the spatial axes. Moreover, the subsequent differentiation of central serotonergic neurons required both the suppression of VMN neurogenesis and the induction of downstream intrinsic determinants of serotonergic identity by Foxa2. copyright 2007 Nature Publishing Group.

Jacobsen, S., S. Sonne-Holm, et al. (2004). "Pelvic orientation and assessment of hip dysplasia in adults." ACTA ORTHOPAEDICA SCANDINAVICA 75(6): 721-9.

BACKGROUND: The study was performed to qualify the source material of 4151 pelvic radiographs for the research into the relationship between unrecognised childhood hip disorders and the development of hip osteoarthrosis, and to investigate the effect of varying degrees of pelvic tilt and rotation on the measurements of radiographic indices of hip dysplasia. MATERIAL AND METHODS: We investigated the effect of varying pelvic orientation on radiographic measurements of acetabular dysplasia using a cadaver model. Results from the cadaver study were used to validate the radiographic assessments of acetabular dysplasia in the longitudinal survey cohort of the Copenhagen City Heart Study (CCHS; Osteoarthrosis Sub-study). 1) Cadaver pelvises and proximal femurs from a male and a female donor were mounted anatomically in holding devices allowing independent inclination/reclination and rotation. An AP pelvic radiograph was recorded at each 3 degrees increment. The most widely used radiographic parameters of hip dysplasia were assessed. 2) Critical limits of acceptable rotation and inclination/reclination of pelvises were determined on 4151 standing, standardised pelvic radiographs of the CCHS cohort. RESULTS: Wiberg's CE angle, Sharp's angle, the x-coordinate of Goodman's Cartesian coordinate system, and the acetabular depth ratio were significantly affected by varying rotation and inclination/reclination of the cadaver pelvises. Femoral head extrusion index was not significantly affected within the applied rotation and inclination/reclination of the cadaver study. Application of the corresponding critical limits of Tonnis' foramen obturator index of 0.7-1.8 meant that 188 of 4151 (4.5%) of the CCHS-III pelvic radiographs had to be omitted from further studies. INTERPRETATION: To ensure a neutral starting point and reproducible readings, especially in epidemiological and clinical studies, and when performing preoperative planning and follow-up of patients undergoing redirectional pelvic osteotomies, it is important that all aspects of the radiographic examination are controlled and reproducible. Furthermore, we found that studies of acetabular dysplasia based on supine urograms or colon radiographs without information about pelvic orientation, centering of the X-ray beam and tube to film distance, run a serious risk of erroneous measurements.

Jacobsen, S., S. Sonne-Holm, et al. (2004). "The relationship of hip joint space to self reported hip pain. A survey of 4.151 subjects of the Copenhagen City Heart Study: the Osteoarthritis Substudy." Osteoarthritis & Cartilage 12(9): 692-7.

OBJECTIVES: (1) To evaluate the effect of pelvic orientation on measurements of hip joint space widths (JSW) in cadaver pelvic radiographs, thereby validating the pelvic radiographs of the Copenhagen City Heart Study: The Osteoarthritis Substudy (CCHS III) cohort of 4.152 subjects, and (2) to investigate the relationship between minimal JSW and self reported hip pain of the cohort. METHODS: (1) Cadaver pelves and proximal femora of one male and one female donor were mounted in holding devices permitting independent rotation (total arc of 42 degrees), and inclination/reclination (total arc of 24 degrees). At each 3 degrees increment an anteroposterior radiograph was recorded. Measurements of JSW were performed. (2) Self reported recurrent pain in or around the hip joint during 12 months prior to baseline examinations, and minimum JSW in pelvic radiographs of the cohort were registered. Relationships between minimum JSW and self reported pain were investigated. RESULTS: (1) Measurements of hip JSW in cadaver radiographs were not influenced significantly by rotation. Measurements of JSW were inconclusively influenced by varying inclination/reclination. (2) Minimum JSW< or =2.0 mm was significantly associated to self reported pain in or around the hip joint in both sexes. CONCLUSION: Measurements of minimum hip JSW did not seem to be significantly influenced by varying spatial orientation of the pelvis during X-ray recordings. An inclusion criteria of minimum JSW< or =2.0 mm designating definite degenerative pathology in hips will be used by the current authors in future studies.

Janoueix-Lerosey, I., D. Lequin, et al. (2008). "Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma." NATURE 455(7215): 967-70.

Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.

Janssen, I., M. Lam, et al. (2009). "Influence of overweight and obesity on physician costs in adolescents and adults in Ontario, Canada." Obesity reviews 10(1): 51-7.

The study purpose was to perform an obesity cost-of-illness analysis for individuals living in the province of Ontario, Canada. The participants consisted of a representative sample of 25 038 adults and 2440 adolescents (aged 12-17 years) who participated in the 2000/2001 Canadian Community Health Survey (CCHS). The CCHS data set includes measures of body mass index (BMI) (classified as normal weight, overweight or obese) and relevant covariates (age, income, smoking, alcohol, physical activity). The CCHS data set was linked to the Ontario Health Insurance Plan providers' database to obtain physician costs for 2002-2003. A two-part modelling approach was used to calculate and compare the average annual physician cost according to BMI. After adjusting for the covariates, physician costs were not significantly higher in overweight men and women compared with those with a normal weight. Physician costs were 14.7% higher in obese men and 18.2% higher in obese women than in men and women with a normal weight. Average physician costs were comparable in normal-weight and overweight/obese adolescents ($233 per year in both groups). Because Ontario operates a publicly funded healthcare system, the findings of this study have relevance for other provinces/states and countries that operate similar healthcare systems. [References: 27]

Jardine, E., M. O'Toole, et al. (1999). "Current status of long term ventilation of children in the United Kingdom: questionnaire survey." BMJ 318(7179): 295-9.

OBJECTIVES: To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs. DESIGN: Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom. SUBJECTS: All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing. RESULTS: 141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school. CONCLUSIONS: A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.

Jensen, T. H., P. B. Hansen, et al. (1988). "Ondine's curse in listeria monocytogenes brain stem encephalitis." ACTA NEUROLOGICA SCANDINAVICA 77(6): 505-6.

A case of necrotizing brain stem encephalitis due to listeria monocytogenes is described in a 48-year-old man who had brain stem encephalitis of complicated course and with selective destruction of the vasomotoric and respiratory centers. He developed that very rare Ondine's curse syndrome, being only able to breathe when awake. The literature on Ondine's curse and brain stem encephalitis due to LM is reviewed. Brain stem encephalitis has a mortality near 100%. The only treatment for Ondine's curse is lifelong artificial ventilation.

Jermakowicz, W. J., X. Chen, et al. (2009). "Relationship between spontaneous and evoked spike-time correlations in primate visual cortex." JOURNAL OF NEUROPHYSIOLOGY 101(5): 2279-2289.

Coincident spikes have been implicated in vision-related processes such as feature binding, gain modulation, and long-distance communication. The source of these spike-time correlations is unknown. Although several studies have proposed that cortical spikes are correlated based on stimulus structure, others have suggested that spike-time correlations reflect ongoing cortical activity present even in the absence of a coherent visual stimulus. To examine this issue, we collected singleunit recordings from primary visual cortex (V1) of the anesthetized and paralyzed prosimian bush baby using a 100-electrode array. Spike-time correlations for pairs of cells were compared under three conditions: a moving grating at the cells' preferred orientation, an equiluminant blank screen, and a dark condition with eyes covered. The amplitudes, lags, and widths of cross-correlation histograms (CCHs) were strongly correlated between these conditions although for the blank stimulus and dark condition, the CCHs were broader with peaks lower in amplitude. In both preferred stimulus and blank conditions, the CCH amplitudes were greater when the cells within the pair had overlapping receptive fields and preferred similar orientations rather than nonoverlapping receptive fields and different orientations. These data suggest that spike-time correlations present in evoked activity are generated by mechanisms common to those operating in spontaneous conditions. Copyright copyright 2009 The American Physiological Society.

Jiang, Y., T. Matsuo, et al. (2005). "ARIX and PHOX2B polymorphisms in patients with congenital superior oblique muscle palsy." ACTA MEDICA OKAYAMA 59(2): 55-62.

To identify ARIX gene and PHOX2B gene polymorphisms in patients with congenital superior oblique muscle palsy, 3 exons of the ARIX gene and PHOX2B gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 31 patients with congenital superior oblique muscle palsy and in 54 normal individuals. A family with a father and one daughter each having congenital superior oblique muscle palsy was also included in this study. Eleven patients with congenital superior oblique muscle palsy had heterozygous nucleotide changes in the ARIX gene, including 4 patients reported on previously. One patient with atrophy of the superior oblique muscle had a new change of T-4G in the promoter region of the ARIX gene. The other 6 patients had a heterozygous nucleotide change of G153A in the 5'-untranslated region (UTR) of the exon 1 of the ARIX gene. These nucleotide changes of the ARIX gene, taken together, had a significant association with congenital superior oblique muscle palsy(P = 0.0022). One patient and 5 patients had heterozygous nucleotide changes of A1106 C and A1121 C in exon 3 of the PHOX2B gene, respectively, while these changes were absent in the normal individuals. Two patients had both the G153A change in the 5'-UTR of exon 1 of the ARIX gene and the A1121 C change in exon 3 of the PHOX2B gene. In conclusion, the polymorphisms of the ARIX gene and PHOX2B gene may be genetic risk factors for the development of congenital superior oblique muscle palsy.

Johnson, P. L., R. Moratalla, et al. (2005). "Are tuberomammillary histaminergic neurons involved in CO ₂-mediated arousal?" EXPERIMENTAL NEUROLOGY 193(1): 228-233.

An increase in arousal in response to hypercapnia [elevated arterial PCO₂ (partial pressure of CO₂) levels] during awake or sleep states is an important component of mechanisms designed to maintain acid-base homeostasis. Since central histaminergic neurons are crucial for maintaining waking states and vigilance, a nonresponsive or dysfunctional histaminergic system could contribute to the lack of arousal in response to hypercapnia in some sleep-related disorders [e.g., sudden infant death syndrome (SIDS) and Ondine's curse]. Therefore, the present study attempted to determine if histaminergic neurons display functional responses to acute exposure to hypercapnic gas (i.e., gas with elevated CO₂ concentrations). Healthy adult male rats were placed in flow cages during the light cycle, or inactive phase, and exposed to either atmospheric air or to environmental CO₂ concentrations increasing from baseline up to 20% CO₂ over a 5-min period. The expression of the protein product of the immediate-early gene c-fos was used as a measure of functional cellular responses within subpopulations of histaminergic neurons. Among the histaminergic subgroups (E1-E5), only the ventral tuberommamillary nucleus (VTMn)/E2 cell group showed significant increases in c-Fos expression following brief exposure to hypercapnic gas. These data are consistent with the hypothesis that histaminergic neuronal cell groups are heterogeneous and are involved in physiological and/or behavioral responses to acute hypercapnic challenge, potentially increasing vigilance during active waking and awakening from sleep during hypercapnic states. copyright 2004 Elsevier Inc. All rights reserved.

Johnson, S., J. T. McDonald, et al. (2010). "Socio-economic status and head and neck cancer incidence in Canada: a case-control study." ORAL ONCOLOGY 46(3): 200-3.

In an earlier study we identified an increased incidence of head and neck cancer (HNC) in individuals with lower socio-economic status (SES) in the United States. The objective of this study was to determine if lower SES is associated with a similar increase in the incidence of HNC in Canadian patients. We obtained data on SES (income, education and immigration status), demographic characteristics, frequency of dental visits and smoking behavior for adult patients residing in the Eastern Ontario region who were referred to the Ottawa Regional Cancer Centre with HNC. We compared the SES and frequency of dental visits of these HNC patients with the SES and frequency of dental visits of a control sample in the same region from the 2004-2005 Statistics Canada Canadian Community Health Survey (CCHS 3.1). We then performed a logistic regression analysis on the combined sample of patients and controls using incidence of HNC as the dependent variable. This allowed us to eliminate confounding variables such as tobacco intake and to isolate the effect of SES, frequency of dental visits, and immigration status on HNC incidence. There was a statistically significant decrease in the incidence of HNC among adults with a higher median family income (OR=0.5429, CI=[.3352, .8795]). Also, adults with less than grade 8 education had significantly higher rates of HNC than adults who had completed high school (OR 3.65, CI=[1.88, 7.08]). As well, immigrants had a significantly lower incidence of HNC than Canadian born adults (OR=0.3825, CI=[.2063, .7090]). Lastly, we found that individuals who typically visited a dentist less than once per year had a significantly higher incidence of HNC than individuals who typically visited a dentist at least once per year (OR=1.69, CI=[1.01, 2.83]). Even when controlling for tobacco intake, the incidence of HNC in Eastern Ontario was higher in patients with lower median family income and less than grade 8 education. It was higher in individuals who visited a dentist less than once per year, and lower in immigrants to Canada. This was similar to what has been observed in the United States. Further study into the reason for this increased incidence of HNC in patients with lower SES is warranted. (c) 2009 Elsevier Ltd. All rights reserved.