Literature search from ms 29/4/2010

PURPOSE: Polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in neuroblastoma can be used to monitor therapy response and to evaluate stem cell harvests. Commonly used PCR markers, tyrosine hydroxylase (TH) and GD2 synthase, have expression in normal tissues, thus limiting MRD detection. To identify a more specific MRD marker, we tested PHOX2B. PATIENTS AND METHODS: To determine PHOX2B, TH, and GD2 synthase expression in normal tissues, it was measured by real-time quantitative PCR in samples of normal bone marrow (BM; n = 51), peripheral blood (PB; n = 37), and peripheral-blood stem cells (PBSCs; n = 24). Then, 289 samples of 101 Dutch patients and 47 samples of 43 German patients were tested for PHOX2B and TH; these samples included 52 tumor, 214 BM, 32 BM, and 38 PBSC harvests. Of the 214 BM samples, 167 were compared with cytology, and 47 BM samples were compared with immunocytology (IC). RESULTS: In contrast to TH and GD2 synthase, PHOX2B was not expressed in any of the normal samples. In patient samples, PHOX2B was detected in 32% cytology-negative and in 14% IC-negative samples and in 94% of cytology-positive and in 90% of IC-positive BM samples. Overall, PHOX2B was positive in 43% compared with 31% for TH. In 24% of all samples, TH expression was inconclusive, which is similar to expression found in normal tissues. In 42% of these samples, PHOX2B expression was positive. CONCLUSION: PHOX2B is superior to TH and GD2 synthase in specificity and sensitivity for MRD detection of neuroblastoma by using real-time quantitative PCR. We propose to include PHOX2B in additional prospective MRD studies in neuroblastoma alongside TH and other MRD markers.

Stutterheim, J., A. Gerritsen, et al. (2009). "Detecting minimal residual disease in neuroblastoma: the superiority of a panel of real-time quantitative PCR markers." CLINICAL CHEMISTRY 55(7): 1316-26.

BACKGROUND: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) patients can be used for initial staging and monitoring therapy response in bone marrow (BM) and peripheral blood (PB). PHOX2B has been identified as a sensitive and specific MRD marker; however, its expression varies between tumors. Therefore, a panel of markers could increase sensitivity. METHODS: To identify additional MRD markers for NB, we selected genes by comparing SAGE (serial analysis of gene expression) libraries of healthy and NB tissues followed by extensive real-time quantitative PCR (RQ-PCR) testing in samples of tumors (n = 56), control BM (n = 51), PB (n = 37), and cell subsets. The additional value of a panel was determined in 222 NB samples from 82 Dutch stage 4 NB patients (54 diagnosis BM samples, 143 BM samples during/after treatment, and 25 PB samples). RESULTS: We identified 2 panels of specific RQ-PCR markers for MRD detection in NB patients: 1 for analysis of BM samples (PHOX2B, TH, DDC, CHRNA3, and GAP43) and 1 for analysis of PB samples (PHOX2B, TH, DDC, DBH, and CHRNA3). These markers all showed high expression in NB tumors and no or low expression in control BM or PB samples. In patients' samples, the PHOX2B marker detected most positive samples. In PB samples, however, 3 of 7 PHOX2B-negative samples were positive for 1 or more markers, and in BM examinations during treatment, 7% (6 of 86) of the PHOX2B-negative samples were positive for another marker. CONCLUSIONS: Because of differences in the sensitivities of the markers in BM and PB, we advise the use of 2 different panels to detect MRD in these compartments.

Sugar, O. (1978). "In search of Ondine's Curse." JAMA 240(3): 236-7.

Suh, J. H., G. H. Barnett, et al. (1999). "Successful conversion from a linear accelerator-based program to a Gamma Knife radiosurgery program: the Cleveland Clinic experience." Stereotactic & Functional Neurosurgery 72 Suppl 1: 159-67.

From August 1989 to January 1997, 307 treatments in 293 patients were performed with a linear accelerator-based (LINAC) stereotactic radiosurgery system. Because of the program s success, the need for a dedicated radiosurgery unit in Ohio and the desire to treat functional disorders, the Cleveland Clinic Health System (CCHS) obtained the first Gamma Knife in the state of Ohio. Based on the previous volume of patients for radiosurgery, it was estimated that 75-100 patients would be treated during the first year of operation. However, during the first calendar year, 214 treatments were performed on 205 patients, which far exceeded expectations. The success of the CCHS Gamma Knife Center can be attributed to an increase in a number of factors. These included marketing efforts, patient awareness, increased use for functional disorders, physician understanding of radiosurgery, use by qualified nonaffiliated radiation oncologists and neurosurgeons, and outpatient delivery (95% with the Gamma Knife vs <5% with the LINAC). With proper planning, education, and awareness, the opening of a Gamma Knife Center can greatly increase the volume of radiosurgery performed when compared with a LINAC-based program.
Swaminathan, S., V. Gilsanz, et al. (1989). "Congenital central hypoventilation syndrome associated with multiple ganglioneuromas." CHEST 96(2): 423-4.

A five-year-old girl had congenital central hypoventilation syndrome and mediastinal and adrenal tumors. The mediastinal mass was though to be present, retrospectively, for at least four years prior to surgery. Pathology of the excised tumors revealed benign ganglioneuromas. This is the first case reported of an association between CCHS and multiple ganglioneuromas. This suggests that CCHS, like neural crest tumors, may result from maldevelopment of the embryonic neural crest.

Swift, P. G. (1976). "Letter: Ondine's curse." LANCET 2(7985): 588-9.

Sybrecht, G. W. (1988). "SIDS, Ondine's curse, and Pickwickian syndrome. [German]." Intensivbehandlung 13(4): 145-148.

Taitz, L. S. and C. W. Redman (1971). "Ondine's curse with recovery: alveolar hypoventilation." Proceedings of the Royal Society of Medicine 64(12): 1222.

Takahashi, M. and N. Osumi (2005). "Identification of a novel type II classical cadherin: rat cadherin19 is expressed in the cranial ganglia and Schwann cell precursors during development." DEVELOPMENTAL DYNAMICS 232(1): 200-8.

To identify a novel type II classical cadherin, we searched the genome database and found rat cadherin19 (cad19) with high similarity to human cadherin19. We also found nucleotide sequences corresponding to rat cad19 in mouse and chicken genomes. In situ hybridization of rat cad19 revealed that rat cad19 mRNA was initially expressed in cephalic neural crest cells, and then in the cranial ganglia, migrating trunk neural crest cells, the nascent dorsal root ganglia, and the sympathetic ganglia. Expression of cad19 overlapped with that of neural crest markers, including Sox10 and AP-2, but cad19 expression was confined to subpopulations of the neural crest-derived cells, those typically observed in the satellite glia at the periphery of the ganglia and Schwann cell precursors along the peripheral nerves. cad19 mRNA was not detected in cells expressing Phox2b, an epibranchial placode-derived neurons, nor in those expressing neuronal markers such as Hu protein. These observations suggest that cad19 is expressed in neural crest-derived, non-neuronal cells. Although the expression of cad19 mRNA persisted in Schwann cell precursors at E14.5, it was no longer detected in maturing Schwann cells at later stages. These results suggest that cad19 is an evolutionarily conserved cadherin and may be involved in the early development of Schwann cells in the peripheral nervous system.
Takahashi, R., H. Kakizawa, et al. (2000). "Peculiar respiratory response observed during sleep-onset REM sleep of an infant with Ondine's curse." NEUROPEDIATRICS 31(5): 269-72.

We treated an infant with congenital central hypoventilation syndrome ("Ondine's curse"). She was cyanotic and given ventilatory support at the first hour after birth. An investigation of sleep state and respiration performed at the age of 3 months led to this diagnosis. Hypoventilation persisted in all sleep stages, with the most severely reduced tidal volumes occurring during delta-wave sleep (stages 3 and 4). In addition, severe secondary reduction in tidal volumes occurred in sleep-onset REM sleep. This phenomenon was absent in non sleep-onset REM sleep. At 4 months of age, her respiratory treatment was successfully converted to positive-pressure ventilation via a nasal mask, thus avoiding tracheotomy. This transition to noninvasive ventilatory support dramatically improved her quality of life during wakefulness. This report may be a clue to discuss the function of sleep-onset REM sleep seen in the early stage of life and suggests that nasal mask ventilation is a viable option in selected cases with congenital central hypoventilation syndrome (CCHS).

Takakura, A. C., T. S. Moreira, et al. (2008). "Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats." JOURNAL OF PHYSIOLOGY 586(12): 2975-2991.

Injection of the neurotoxin saporin-substance P (SSP-SAP) into the retrotrapezoid nucleus (RTN) attenuates the central chemoreflex in rats. Here we ask whether these deficits are caused by the destruction of a specific type of interneuron that expresses the transcription factor Phox2b and is non-catecholaminergic (Phox2b⁺TH^-). We show that RTN contains around 2100 Phox2b⁺TH^- cells. Injections of SSP-SAP into RTN destroyed Phox2b⁺ TH^- neurons but spared facial motoneurons, catecholaminergic and serotonergic neurons and the ventral respiratory column caudal to the facial motor nucleus. Two weeks after SSP-SAP, the apnoeic threshold measured under anaesthesia was unchanged when fewer than 57% of the Phox2b⁺TH^- neurons were destroyed. However, destruction of 70 +/- 3.5% of these cells was associated with a dramatic rise of the apnoeic threshold (from 5.6 to 7.9% end-expiratory P_CO2). In anaesthetized rats with unilateral lesions of around 70% of the Phox2b⁺TH^- neurons, acute inhibition of the contralateral intact RTN with muscimol instantly eliminated phrenic nerve discharge (PND) but normal PND could usually be elicited by strong peripheral chemoreceptor stimulation (8/12 rats). Muscimol had no effect in rats with an intact contralateral RTN. In conclusion, the destruction of the Phox2b⁺TH^- neurons is a plausible cause of the respiratory deficits caused by injection of SSP-SAP into RTN. Two weeks after toxin injection, 70% of these cells must be killed to cause a severe attenuation of the central chemoreflex under anaesthesia. The loss of an even greater percentage of these cells would presumably be required to produce significant breathing deficits in the awake state. copyright 2008 The Author. Journal compilation copyright 2008 The Physiological Society.

Takeda, S., Y. Fujii, et al. (1996). "Central alveolar hypoventilation syndrome (Ondine's curse) with gastroesophageal reflux." CHEST 110(3): 850-2.

Congenital central hypoventilation syndrome (Ondine's curse) is a rare disorder with lack of automatic control of ventilation during sleep. We have reported a case of Ondine's curse in a patient who underwent Nissen's fundoplication for gastroesophageal reflux (GER) at age 5 months. Ventilatory challenge test during sleep was done to confirm central alveolar hypoventilation. This female patient, without cor pulmonale, was a good candidate for diaphragm pacing. Thus, the patient underwent implantation of a diaphragm pacer at age 3 years; she had required mechanical ventilation since birth. Diagnosis, pathogenesis, and problems in the setting of diaphragm pacing for an infant are discussed.

Takken, T., M. Van Brussel, et al. (2008) Exercise therapy in juvenile idiopathic arthritis. Cochrane Database of Systematic Reviews Volume, DOI: 10.1002/14651858.CD005954.pub2

BACKGROUND: Exercise therapy is considered an important component of the treatment of arthritis. The efficacy of exercise therapy has been reviewed in adults with rheumatoid arthritis but not in children with juvenile idiopathic arthritis (JIA). OBJECTIVES: To assess the effects of exercise therapy on functional ability, quality of life and aerobic capacity in children with JIA. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE (January 1966 to April 2007), CINAHL (January 1982 to April 2007), EMBASE (January 1966 to October 2007), PEDro (January 1966 to October 2007), SportDiscus (January 1966 to October 2007), Google Scholar (to October 2007), AMED (Allied and Alternative Medicine) (January 1985 to October 2007), Health Technologies Assessment database (January 1988 to October 2007), ISI Web Science Index to Scientific and Technical Proceedings (January 1966 to October 2007) and the Chartered Society of Physiotherapy website (http://www.cps.uk.org) were searched and references tracked. SELECTION CRITERIA: Randomised controlled trials (RCTs) of exercise treatment in JIA. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data were extracted by two review authors working independently. MAIN RESULTS: Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (n = 198; WMD -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: n = 115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (n = 124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. AUTHORS' CONCLUSIONS: Overall, based on 'silver-level' evidence (www.cochranemsk.org) there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The low number of available RCTs limits the generalisability. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. The large heterogeneity in outcome measures, as seen in this review, emphasises the need for a standardised assessment or a core set of functional and physical outcome measurements suited for health research to generate evidence about the possible benefits of exercise therapy for patients with JIA. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear. EXERCISE THERAPY IN JUVENILE IDIOPATHIC ARTHRITIS (JIA): This summary presents what we know from research about the effect of exercise therapy in JIA. The review shows that in children with JIA, exercise may not lead to any difference in a child's ability to function or move their joints fully, the number of joints with swelling, quality of life, overall wellbeing, pain or aerobic capacity. Aerobic capacity is the amount of oxygen the body consumes during exercise. If a person has low aerobic capacity, it generally means he or she is able to do less physical activity and may tire easily. The number of joints with pain was not measured in these studies. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. No short-term adverse effects of exercise therapy were found in the studies that make up this review.What is exercise therapy and what is JIA?Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is an important cause of short-term and long-ter disability. In JIA the cause of the arthritis is unknown. It generally begins in children younger than age 16 years. It always lasts for at least six weeks. A physician will rule out other conditions that may be causing the symptoms before diagnosing JIA.Several types of exercise therapy are described in this review, for example, physical training programs such as strength training for improving muscle strength and endurance exercise for improving overall fitness (either land based or in a pool).Best estimate of what happens to children with JIA and exerciseAbility to function: a child's ability to function changed less than 1 more point on a scale of 0 to 3. Other studies state that a change of 0.13 on the score of the Childhood Health Assessment Questionnaire (CHAQ) is a clinically important improvement from the perspective of children and their parents. This level of change has not been found in this reviewQuality of life: a child's quality of life changed between 2.5 and 4 more points on a scale of 1 to 50.There may be little or no difference with exercise. It is possible that these differences are the result of chance.Adverse effects: no short-term effects have been reported after exercise therapy for children with JIA.
Talikka, M., G. Stefani, et al. (2004). "Characterization of Xenopus Phox2a and Phox2b defines expression domains within the embryonic nervous system and early heart field." Gene Expression Patterns 4(5): 601-607.

The closely related homeodomain containing genes, Phox2a and Phox2b, are essential for neuronal specification and differentiation within discrete subsets of neurons during vertebrate embryogenesis. We have isolated Xenopus Phox2 homologs, termed Xphox2a and Xphox2b, and characterized their expression during early development. In addition, we have characterized a Phox2a splice variant, termed Xphox2a.2, which lacks homeo- and C-terminal protein coding domains. Xphox2a, Xphox2a.2 and Xphox2b transcripts are expressed in dynamic temporal and regional patterns during nervous system development. The expression of Xphox2a and Xphox2b is only partially overlapping and includes cranial motor and interneuron populations as well as peripheral sympathetic and cranial ganglion neurons, sites linked to Phox2 expression in other species. In addition, we have identified an early domain of Xphox2a and subsequent Xphox2b expression in ventral regions of the embryo, within the developing heart field. XPhox2 expression within this domain is preceded by the gastrula-stage expression of the proneural basic helix-loop-helix transcription factor, Xash1, pointing to a new region of action for this group transcription factors during vertebrate development. copyright 2004 Elsevier B.V. All rights reserved.

Tanino, M., T. Tachi, et al. (1984). "[A case of malignant clear cell hidradenoma of the skin presumably arising from adenoma]." Gan No Rinsho - Japanese Journal of Cancer Clinics 30(14): 1845-8.

A left parietal skin tumor showing rapid enlargement in a 33-year-old woman was excised. The cut surface of the skin revealed a whitish tumor 4 cm in diameter associated with a cyst formation. Histologically, the whitish tumor was mucinous carcinoma in which large clear cells were conspicuous. Because nests of clear cell hidradenoma (CCH) were seen in the cyst wall, this carcinoma was diagnosed as malignant CCH presumably arising from a part of benign CCH. Malignant CCHs are thought to be malignant from their onset. Those proved to have developed from benign CCHs like the present case are extremely rare.

Tanuseputro, P., D. G. Manuel, et al. (2003). "Risk factors for cardiovascular disease in Canada." CANADIAN JOURNAL OF CARDIOLOGY 19(11): 1249-59.

BACKGROUND: This paper provides an update of the prevalence of important cardiovascular disease (CVD) risk factors in subgroups of the Canadian population. To improve awareness of the impact of CVD risk factor variations on disease burden, smoking-attributable mortality (SAM) has been estimated for the first time for each health region in Canada. METHODS: The 2000/01 Canadian Community Health Survey (CCHS) was used to estimate the prevalence of current smoking, obesity, physical inactivity, low income, diabetes and hypertension. Combining smoking prevalence data from the 2000/01 CCHS, mortality data from the 1995 to 1997 Canadian Mortality Database, and relative risk estimates (relating smoking and smoking-associated deaths) from the American Cancer Society's Cancer Prevention Study II, SAM values were generated using population-attributable risk techniques. RESULTS: Based on self-reported data, the 2000/01 CCHS shows that 26.0% of Canadians currently smoke, 14.9% are obese, 53.5% are physically inactive, 11.3% have low income, 13.0% have hypertension and 4.2% have diabetes. Cardiovascular and all-cause SAM were estimated at 18,209 and 44,271 annual deaths, and contributed to 23% and 22% of total CVD and all-cause mortality in Canada, respectively. There are large variations in the prevalence of CVD risk factors and in SAM estimates between sexes and across age groups and geographic regions. CONCLUSIONS: The high prevalence of potentially modifiable CVD risk factors and the large variation that exists between subgroups of the Canadian population suggest that the burden of CVD could be reduced through risk factor modification. While prevalence data for risk factors in a population give an initial understanding of some of the contributing causes of a disease, the actual burden of disease caused by a risk factor is also modified by the magnitude of the increased risk to mortality and morbidity, and is best represented by its estimated attributable mortality and morbidity.

Tassinari, C. A. (1976). "[Nosology and boundaries of syndromes with periodic respiration during sleep (Pickwickian syndrome, Undine's syndrome, obstruction of the superior airway, microsleep syndrome, insomnia, and narcolepsy)]." Revue d Electroencephalographie et de Neurophysiologie Clinique 6(1): 53-61.

Tellez-Zenteno, J. F., S. B. Patten, et al. (2007). "Psychiatric comorbidity in epilepsy: a population-based analysis." EPILEPSIA 48(12): 2336-44.

PURPOSE: The estimated prevalence of mental health disorders in those with epilepsy in the general population varies owing to differences in study methods and heterogeneity of epilepsy syndromes. We assessed the population-based prevalence of various psychiatric conditions associated with epilepsy using a large Canadian national population health survey. METHODS: The Canadian Community Health Survey (CCHS 1.2) was used to explore numerous aspects of mental health in persons with epilepsy in the community compared with those without epilepsy. The CCHS includes administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Age-specific prevalence of mental health conditions in epilepsy was assessed using logistic regression. RESULTS: The prevalence of epilepsy was 0.6%. Individuals with epilepsy were more likely than individuals without epilepsy to report lifetime anxiety disorders or suicidal thoughts with odds ratio of 2.4 (95% CI = 1.5-3.8) and 2.2 (1.4-3.3), respectively. In the crude analysis, the odds of lifetime major depression or panic disorder/agoraphobia were not greater in those with epilepsy than those without epilepsy, but the association with lifetime major depression became significant after adjustment for covariates. CONCLUSIONS: In the community, epilepsy is associated with an increased prevalence of mental health disorders compared with the general population. Epilepsy is also associated with a higher prevalence of suicidal ideation. Understanding the psychiatric correlates of epilepsy is important to adequately manage this patient population.
Terao, S.-i., N. Miura, et al. (2004). "Rapidly progressive fatal respiratory failure (Ondine's curse) in the lateral medullary syndrome." Journal of Stroke & Cerebrovascular Diseases 13(1): 41-4.

A 70-year-old man presented with unilateral lateral medullary infarction, and then died of rapidly progressive respiratory failure within a day. The clinical manifestations were hiccups, hoarseness, dysarthria, nystagmus, left central facial paralysis, paralysis of the left soft palate, dysphagia, decreased superficial sensation over the right face and upper limb, and cerebellar ataxia in the left upper and lower limbs. The arterial blood gas analysis revealed mild hypoventilation. Soon thereafter, an apneic episode occurred during a sleep and advanced to ataxic respiration, and the patient died. Pathologically, there were fresh ischemic infarction localized to the left dorsolateral area of the upper medulla, caused by atherothrombotic occlusion of the left vertebral artery. These foci were in the areas including the medullary reticular formation, the solitary nucleus, the intramedullary fibers of the vagus nerve, and the nucleus ambiguus on the left side. We attributed the fatal acute progressive respiratory impairment in the present case to impairment of the automatic respiratory system (Ondine's curse) rather than the voluntary respiratory system.