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Biomedical subjects

M A Caudill

Publications and source records attributed to M A Caudill.

13 recordsLinked to original sources

Folate status in women of childbearing age residing in Southern California after folic acid fortification.

OBJECTIVE: The purpose of this study was to investigate folate status in healthy, nonpregnant women (18 to 45 years) following folic acid (FA) fortification of the food supply. DESIGN: This was a cross-sectional study design in which a fasting blood sample was obtained from socio-economically advantaged (n=85) and disadvantaged (n=50) women residing in Southern California who had not consumed supplemental FA within the past 12 months. Serum folate (SF), red cell folate (RCF) and plasma homocysteine (tHcy) concentrations were measured and methylene tetrahydrofolate reductase (MTHFR) genotype (C677T) was determined. RESULTS: SF and RCF concentrations (mean+/-SD) for socio-economically advantaged (54+/-18, 1387+/-329 nmol/L, respectively) and disadvantaged women (41+/-18, 1172+/-342 nmol/L, respectively) greatly exceeded the levels deemed acceptable for SF (> or = 13.6 nmol/L) and RCF (> or = 362 nmol/L). Moreover, 95% of socio-economically advantaged women and 78% of disadvantaged women achieved RCF concentrations > or = 906 nmol/L, which are associated with very low risk of neural tube defects (NTD). Plasma tHcy concentrations for both socio-economically advantaged (5.2+/-1.6 micromol/L) and disadvantaged women (6.1+/-1.6 micromol/L) were within the lower limit of normal range and indicative of adequate folate status. For the combined groups (n=135), the frequency of the C/C, C/T and T/T genotype was 56.0, 37.3 and 6.7%, respectively. MTHFR genotype was not associated with SF, RCF or tHcy. CONCLUSIONS: These data suggest that women of childbearing age are achieving positive folate balance and RCF concentrations associated with reduced risk of NTD following FA fortification of the food supply.

Adolescent↗

Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice.

Because S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are the substrate and product of essential methyltransferase reactions; the ratio of SAM:SAH is frequently used as an indicator of cellular methylation potential. However, it is not clear from the ratio whether substrate insufficiency, product inhibition or both are required to negatively affect cellular methylation capacity. A combined genetic and dietary approach was used to modulate intracellular concentrations of SAM and SAH. Wild-type (WT) or heterozygous cystathionine beta-synthase (CBS +/-) mice consumed a control or methyl-deficient diet for 24 wk. The independent and combined effect of genotype and diet on SAM, SAH and the SAM:SAH ratio were assessed in liver, kidney, brain and testes and were correlated with relative changes in tissue-specific global DNA methylation. The combined results from the different tissues indicated that a decrease in SAM alone was not sufficient to affect DNA methylation in this model, whereas an increase in SAH, either alone or associated with a decrease in SAM, was most consistently associated with DNA hypomethylation. A decrease in SAM:SAH ratio was predictive of reduced methylation capacity only when associated with an increase in SAH; a decrease in the SAM:SAH ratio due to SAM depletion alone was not sufficient to affect DNA methylation in this model. Plasma homocysteine levels were positively correlated with intracellular SAH levels in all tissues except kidney. These results support the possibility that plasma SAH concentrations may provide a sensitive biomarker for cellular methylation status.

Analysis of Variance↗

Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable-isotopic labeling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools.

To investigate the effects of pregnancy on folate metabolism, we conducted an 84-d study in second-trimester (gestational wk 14-25) pregnant women (n = 6) and nonpregnant controls (n = 6) with stable-isotopic tracer methods. All subjects were fed a diet containing approximately 272 nmol/d (120 microg/d) folate from food, along with supplemental folic acid that contained 15% [3',5'-(2)H(2)] folic acid ([(2)H(2)]folic acid) during d 1--41 and that was unlabeled during d 42--84 to yield a constant total folate intake of 1.02 or 1.93 micromol/d (450 or 850 microg/d). Isotopic enrichment of plasma folate, urinary folate and the urinary folate catabolites para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) was determined at intervals throughout the study. The labeling of pABG and ApABG reflected that of tissue folate pools from which the catabolites originate. After the intake of labeled folic acid was terminated on d 41, labeling of urinary folate exhibited a biphasic exponential decline with distinct fast and slow components. In contrast, during d 42--84, the enrichment of urinary pABG and ApABG exhibited primarily monophasic exponential decline, and plasma folate underwent little decline of labeling during this period. Pregnant women and controls did not differ in estimates of body folate pool size and most aspects of the excretion of labeled urinary folate and catabolites, rates of decline of excretion, and areas under the curves for folate and catabolite excretion. Pregnant women, however, tended to have a slower rate of decline of pABG than ApABG and higher enrichment at d 42 of ApABG and pABG. These data support and extend our previous findings indicating that pregnancy (gestational wk 14--26) causes subtle changes in folate metabolism but does not elicit substantial increases in the rate or extent of folate turnover at these moderately high folate intakes.

4-Aminobenzoic Acid↗

Predicting completion of a cognitive-behavioral pain management program by initial measures of a chronic pain patient' s readiness for change.

OBJECTIVE: There is a need to identify pretreatment patient indicators, which are predictive of the successful enrollment and completion of chronic pain treatment programs. Recent evidence suggests the Pain Stages of Change Questionnaire can predict enrollment and completion of a 10-session cognitive-behavioral pain management program. The purpose of this study is to determine whether the pretreatment Stages of Change Questionnaire can predict patients who would complete a cognitive-behavioral pain treatment program. DESIGN: Prospective cohort study using logistic regression analyses. SETTINGS: Patients referred for a 10-session cognitive-behavioral treatment program at a tertiary care multidisciplinary pain clinic or a community-based specialty clinic. SUBJECTS: Three hundred chronic pain patients (151 in the tertiary setting and 149 in the community-based setting) participated, with 147 of the patients (49%) completing and 153 (51%) patients not completing the 10-session program. INTERVENTION: Ten-visit cognitive-behavioral program for chronic pain patients. OUTCOME MEASURE: Completion of program. RESULTS: The Stages of Change Questionnaire scores could predict completion status chi2 (N = 300, 2 df) = 39.7, p <0.001, (goodness-of-fit test chi2 = 5.69, p = 0.68). Those patients completing the program were slightly older and reported higher levels of pain, depression, and disability than did those patients who did not complete. Low "Precontemplation" score remained the best single predictor, as it identified correctly 61% of the cases patients who completed the program and predicted who would drop out in 65% of the cases. CONCLUSION: The Stages of Change Questionnaire is a potentially useful tool; however, the current scoring method is insufficient to recommend its use as an inclusion or exclusion criterion for enrollment in a cognitive-behavioral program.

Adult↗

Plasma homocyst(e)ine concentrations in pregnant and nonpregnant women with controlled folate intake.

OBJECTIVE: To assess the effects of folate intake and pregnancy on plasma total homocyst(e)ine concentrations in women during the second trimester of pregnancy compared with young, healthy nonpregnant women. METHODS: The diet provided either 450 or 850 microg of folate per day. These levels are approximately the current (400 microg/day) and previous (800 microg/day) Recommended Dietary Allowances for folate in pregnant women. Folate was provided as both food folate (120 microg/day) and supplemental folic acid (either 330 or 730 microg/day) for a period of 12 weeks. Plasma homocyst(e)ine (sum of free and protein-bound homocysteine), serum folate, and erythrocyte folate concentrations were determined weekly. RESULTS: Homocyst(e)ine concentrations were lower in pregnant women during the second trimester of normal pregnancy than in nonpregnant controls, independent of dietary folate intake. The overall mean (+/- standard deviation) homocyst(e)ine concentration of the pregnant subjects (5.4 +/- 1.4 micromol/L) was significantly lower than that observed in the nonpregnant control group (8.7 +/- 1.7 micromol/L) (P < .0001). This difference in homocyst(e)ine concentrations remained constant throughout the 12 weeks of the investigation. CONCLUSION: The folate intakes in this investigation were adequate to maintain constant homocyst(e)ine concentrations in pregnant and nonpregnant women. The lower homocyst(e)ine concentrations observed in pregnant subjects compared with nonpregnant controls may be a physiologic response to pregnancy.

Adolescent↗

Folate catabolism in pregnant and nonpregnant women with controlled folate intakes.

Measurement of the urinary folate catabolites, para-aminobenzoylglutamate (pABG) and the more predominant acetylated form, acetamidobenzoylglutamate (apABG), has been used to assess folate requirements in both pregnant and nonpregnant women. Folate catabolite excretion has been reported to be significantly higher in pregnant women (second trimester) compared with nonpregnant controls. The primary goals of this study were to determine if pregnant women in a controlled metabolic study excreted higher quantities of urinary folate catabolites than nonpregnant controls and if catabolite excretion was influenced by folate intake. We evaluated the effect of gestation and folate intake on the urinary excretion of apABG and pABG in pregnant women (n = 12; wk 14-26 gestation) and nonpregnant controls (n = 12) assigned to consume folate levels approximating the current (400 microg/d) and previous (800 microg/d) RDA. Subjects were fed a controlled diet containing 120 microg folate/d and either 330 or 730 microg synthetic folic acid/d. In contrast to previously reported data, no differences in mean folate catabolite excretion were detected between pregnant and nonpregnant subjects. Catabolite excretion (pABG + apABG) decreased significantly relative to initial values in pregnant women consuming 450 microg folate/d (-40 +/- 20%; mean +/- SD) and final mean excretion was significantly lower in the pregnant women consuming 450 microg folate/d (86 +/- 32 nmol/d) compared with 850 microg folate/d (148 +/- 20 nmol/d). Data from this study indicate that second trimester pregnant women do not excrete more folate catabolites than nonpregnant controls and that consumption of 450 vs. 850 microg folate/d results in a significant reduction in the quantity of folate catabolites excreted.

Adult↗

Readiness to adopt a self-management approach to chronic pain: the Pain Stages of Change Questionnaire (PSOCQ).

This manuscript describes the development and initial validation of a self-report questionnaire designed to assess an individual's readiness to adopt a self-management approach to their chronic pain condition. Theory and preliminary empirical work informed the development of a pool of items that were administered to a sample of individuals reporting chronic pain. Analyses of the data support a four factor measure that is consistent with the transtheoretical model of change and associated stages of change model. Each of the four factors, precontemplation, contemplation, action, and maintenance, was found to be internally consistent and stable over time. There was also substantial support for each factor's discriminant and criterion-related validity.

Adaptation, Psychological↗

Folate status response to controlled folate intake in pregnant women.

A metabolic study (84-d) was conducted to investigate the folate status response of pregnant subjects (n = 12) during their second trimester and nonpregnant controls (n = 12) to folate intakes approximating the current (400 microg/d) and former (800 microg/d) recommended dietary allowance (RDA). The overall goal of the study was to provide metabolic data to assist in the interpretation of the current RDA for folate. Subjects were fed a controlled diet containing 120 +/- 15 microg/d (mean +/- SD) folate and either 330 or 730 microg/d synthetic folic acid. Outcome variables between and within supplementation groups were compared at steady state. Serum folate was higher (P </= 0.05) in pregnant women consuming 850 compared with 450 microg/d (44.6 +/- 13.4, 26.3 +/- 11.3 nmol/L, respectively, mean +/- SD). No differences (P > 0.05) were detected in serum folate between pregnant and nonpregnant women within the same supplementation group. Urinary 5-methyl-tetrahydrofolate excretion was greater (P </= 0.05) in pregnant women consuming 850 compared with 450 microg/d (198.0 +/- 100.4, 9.5 +/- 3.2 nmol/d, respectively). No differences (P > 0.05) in 5-methyl-tetrahydrofolate excretion were detected between pregnant and nonpregnant women within supplementation groups. Differences (P </= 0.05) were not detected in red cell folate between pregnant women consuming either 450 or 850 microg/d (1452.5 +/- 251.8, 1733.5 +/- 208.5 nmol/L, respectively) or between pregnant and nonpregnant women consuming 450 microg/d. Our data suggest that 450 microg/d (dietary folate + synthetic folic acid) is sufficient to maintain folate status in pregnant women. This level of intake equates to approximately 600 microg/d dietary equivalents, assuming 50 and 75% availability of dietary folate and synthetic folic acid consumed with meals, respectively.

Adolescent↗

Assessment of autonomic function in humans by heart rate spectral analysis.

Spectral analysis of spontaneous heart rate fluctuations were assessed by use of autonomic blocking agents and changes in posture. Low-frequency fluctuations (below 0.12 Hz) in the supine position are mediated entirely by the parasympathetic nervous system. On standing, the low-frequency fluctuations increase and are jointly mediated by the sympathetic and parasympathetic nervous systems. High-frequency fluctuations, at the respiratory frequency, are decreased by standing and are mediated solely by the parasympathetic system. Heart rate spectral analysis is a powerful noninvasive tool for quantifying autonomic nervous system activity.

Adult↗

Legionnaires' disease associated with rhabdomyolysis and myoglobinuria.

We report a fatal case of Legionnaires' disease associated with myopathy, myoglobinuria, elevated creatine phosphokinase (CPK) level, and pneumonitis. The precise cause of skeletal muscle damage in this patient remains obscure. The association with Legionnaires' disease in this case supports the observation that the Legionnaires' organism has the potential for affecting multiple organ systems, including skeletal muscle. Elevated CPK levels and myoglobinuria in a patient with pneumonitis should suggest the diagnosis of Legionnaires' disease.

Humans↗