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Neurological symptoms in Hypophosphatasia.
Colazo JM, Hu JR, Dahir KM, Simmons JH
(2019) Osteoporos Int 30: 469-480
MeSH Terms: Adolescent, Adult, Aged, Alkaline Phosphatase, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Hypophosphatasia, Male, Mental Disorders, Middle Aged, Nervous System Diseases, Prevalence, Retrospective Studies, United States, Vitamin B 6, Young Adult
Show Abstract · Added April 6, 2019
Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options.
INTRODUCTION - Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP.
METHODS - A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms.
RESULTS - Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%.
CONCLUSIONS - The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.
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19 MeSH Terms
Impaired functional vitamin B6 status is associated with increased risk of lung cancer.
Theofylaktopoulou D, Midttun Ø, Ueland PM, Meyer K, Fanidi A, Zheng W, Shu XO, Xiang YB, Prentice R, Pettinger M, Thomson CA, Giles GG, Hodge A, Cai Q, Blot WJ, Wu J, Johansson M, Hultdin J, Grankvist K, Stevens VL, McCullough MM, Weinstein SJ, Albanes D, Ziegler R, Freedman ND, Langhammer A, Hveem K, Naess M, Sesso HD, Gaziano JM, Buring JE, Lee IM, Severi G, Zhang X, Stampfer MJ, Han J, Smith-Warner SA, Zeleniuch-Jacquotte A, Le Marchand L, Yuan JM, Wang R, Butler LM, Koh WP, Gao YT, Rothman N, Ericson U, Sonestedt E, Visvanathan K, Jones MR, Relton C, Brennan P, Johansson M, Ulvik A
(2018) Int J Cancer 142: 2425-2434
MeSH Terms: Aged, Biomarkers, Carcinoma, Squamous Cell, Case-Control Studies, Cohort Studies, Female, Humans, Lung Neoplasms, Male, Middle Aged, Odds Ratio, Risk Factors, Vitamin B 6
Show Abstract · Added April 3, 2018
Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
© 2017 UICC.
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13 MeSH Terms
Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3).
Fanidi A, Muller DC, Yuan JM, Stevens VL, Weinstein SJ, Albanes D, Prentice R, Thomsen CA, Pettinger M, Cai Q, Blot WJ, Wu J, Arslan AA, Zeleniuch-Jacquotte A, McCullough ML, Le Marchand L, Wilkens LR, Haiman CA, Zhang X, Han J, Stampfer MJ, Smith-Warner SA, Giovannucci E, Giles GG, Hodge AM, Severi G, Johansson M, Grankvist K, Langhammer A, Krokstad S, Næss M, Wang R, Gao YT, Butler LM, Koh WP, Shu XO, Xiang YB, Li H, Zheng W, Lan Q, Visvanathan K, Bolton JH, Ueland PM, Midttun Ø, Ulvik A, Caporaso NE, Purdue M, Ziegler RG, Freedman ND, Buring JE, Lee IM, Sesso HD, Gaziano JM, Manjer J, Ericson U, Relton C, Brennan P, Johansson M
(2018) J Natl Cancer Inst 110:
MeSH Terms: Adult, Aged, Aged, 80 and over, Asia, Australia, Case-Control Studies, Cotinine, Europe, Female, Folic Acid, Humans, Incidence, Lung Neoplasms, Male, Methionine, Middle Aged, Prospective Studies, Protective Factors, Risk Factors, Sex Factors, Smoking, United States, Vitamin B 6
Show Abstract · Added April 3, 2018
Background - Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.
Methods - Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.
Results - Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.
Conclusions - Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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MeSH Terms
Preparation and investigation of vitamin B6-derived aminopyridinol antioxidants.
Serwa R, Nam TG, Valgimigli L, Culbertson S, Rector CL, Jeong BS, Pratt DA, Porter NA
(2010) Chemistry 16: 14106-14
MeSH Terms: Amino Alcohols, Aminopyridines, Antioxidants, Free Radical Scavengers, Humans, Lipid Peroxidation, Molecular Structure, Oxidation-Reduction, Vitamin B 6, alpha-Tocopherol
Show Abstract · Added May 29, 2014
3-Pyridinols bearing amine substitution para to the hydroxylic moiety have previously been shown to inhibit lipid peroxidation more effectively than typical phenolic antioxidants, for example, α-tocopherol. We report here high-yielding, large-scale syntheses of mono- and bicyclic aminopyridinols from pyridoxine hydrochloride (i.e., vitamin B(6)). This approach provides straightforward, scaleable access to novel, potent, molecular scaffolds whose antioxidant properties have been investigated in homogeneous solutions and in liposomal vesicles. These molecular aggregates mimic cell membranes that are the targets of oxidative damage in vivo.
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10 MeSH Terms
Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women.
Shrubsole MJ, Yang G, Gao YT, Chow WH, Shu XO, Cai Q, Rothman N, Gao J, Wagner C, Zheng W
(2009) Cancer Epidemiol Biomarkers Prev 18: 1003-6
MeSH Terms: Adult, Aged, Case-Control Studies, China, Colorectal Neoplasms, Diet, Female, Folic Acid, Humans, Logistic Models, Methionine, Middle Aged, Niacinamide, Proportional Hazards Models, Prospective Studies, Registries, Riboflavin, Risk, Surveys and Questionnaires, Vitamin B 12, Vitamin B 6
Added March 18, 2014
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21 MeSH Terms
The type of oil used for cooking is associated with the risk of nonfatal acute myocardial infarction in costa rica.
Kabagambe EK, Baylin A, Ascherio A, Campos H
(2005) J Nutr 135: 2674-9
MeSH Terms: Adipose Tissue, Aged, Alcohol Drinking, Cooking, Costa Rica, Developing Countries, Diet Records, Dietary Fats, Unsaturated, Fatty Acids, Essential, Female, Folic Acid, Humans, Linoleic Acid, Male, Middle Aged, Myocardial Infarction, Palm Oil, Plant Oils, Risk Factors, Smoking, Soybean Oil, Vitamin B 6, alpha-Linolenic Acid
Show Abstract · Added March 7, 2014
Palm oil and soybean oil are the 2 most widely used cooking oils in the world. Palm oil is consumed mainly in developing countries, where morbidity and mortality due to cardiovascular disease (CVD) are on the rise. Although claims about adverse or protective effects of these oils are commonly made, there are no epidemiologic studies assessing the association between these oils and cardiovascular disease endpoints. We examined whether consumption of palm oil relative to soybean oil and other unsaturated oils (predominantly sunflower) is associated with myocardial infarction (MI) in Costa Rica. The cases (n = 2111) were survivors of a first acute MI and were matched to randomly selected population controls (n = 2111). Dietary intake was assessed with a validated semiquantitative FFQ. Adipose tissue profiles of essential fatty acids were assessed to validate cooking oil intake and found to be consistent with self-reported major oils used for cooking. The data were analyzed using conditional logistic regression. Palm oil users were more likely to have an MI than users of soybean oil [odds ratio (OR) = 1.33; 95% CI: 1.08-1.63] or other cooking oils (OR = 1.23; CI: 0.99-1.52), but they did not differ from users of soybean oil with a high trans-fatty acid content (OR = 1.14; CI: 0.84-1.56). These data suggest that as currently used in Costa Rica, and most likely in many other developing countries, the replacement of palm oil with a polyunsaturated nonhydrogenated vegetable oil would reduce the risk of MI.
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23 MeSH Terms
Modeling short (7 hour)- and long (6 week)-term kinetics of vitamin B-6 metabolism with stable isotopes in humans.
Coburn SP, Townsend DW, Ericson KL, Reynolds RD, Ziegler PJ, Costill DL, Mahuren JD, Schaltenbrand WE, Pauly TA, Wang Y, Fink WJ, Pearson DR, Hachey DL
(2003) Adv Exp Med Biol 537: 173-92
MeSH Terms: Biological Transport, Biotransformation, Humans, Kinetics, Liver, Models, Biological, Organ Specificity, Vitamin B 6
Added March 20, 2014
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8 MeSH Terms
Vitamin B6 deficiency in uremia.
Stone WJ, Warnock LG, Wagner C
(1975) Am J Clin Nutr 28: 950-7
MeSH Terms: Adult, Aged, Apoenzymes, Aspartate Aminotransferases, Erythrocytes, Humans, Male, Middle Aged, Pyridoxal Phosphate, Renal Dialysis, Uremia, Vitamin B 6 Deficiency
Show Abstract · Added January 20, 2015
Significant decreases in plasma pyridoxal-5-phosphate (PLP), plasma glutamic-oxaloacetic transaminase (PGOT) and erythrocyte glutamic-oxaloacetic transaminase (EGOT) were found in 29 uremic patients including 14 who had been on hemodialysis an average of 15.8 months. The mean PLP values of the uremic patients (5.39 +/- 0.37 ng/ml) were clearly lower than the values obtained for the normal group (9.30 +/- 0.80 mg/ml). The mean PGOT values of the uremic patients (dialyzed 4.07 +/- 0.29 U/liter, undialyzed 5.31 +/- 0.49 U/liter) were significantly lower than the normal group (6.57 +/- 0.39 U/liter). The mean EGOT value of the uremic patients (325 +/- 17 U/liter) was also lower than normal subjects (416 +/-21 U/liter). Stimulation of the EGOT by exogenous PLP (EGOT index) was less in dialyzed patients (1.60) than normal subjects (1.80) while the undialyzed uremic subjects had a greater than normal stimulation (2.12). All of these results indicate that uremic patients are vitamin B6 deficient and that those undergoing hemodialysis may have decreased amounts of the EGOT apoenzyme.
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12 MeSH Terms
Increased plasma clearance of pyridoxal 5'-phosphate in vitamin B6-deficient uremic man.
Spannuth CL, Warnock LG, Wagner C, Stone WJ
(1977) J Lab Clin Med 90: 632-7
MeSH Terms: Adult, Humans, Kidney Failure, Chronic, Metabolic Clearance Rate, Middle Aged, Pyridoxal Phosphate, Renal Dialysis, Uremia, Vitamin B 6 Deficiency
Added January 20, 2015
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9 MeSH Terms