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James L Mills

Publications and source records attributed to James L Mills.

34 records · Page 2Linked to original sources
PubMed2004

Self-concept in adult survivors of childhood acute lymphoblastic leukemia: a cooperative Children's Cancer Group and National Institutes of Health study.

BACKGROUND: Self-concept was compared between adult survivors of childhood acute lymphoblastic leukemia (ALL) and sibling controls. Adult survivor subgroups at greatest risk for negative self-concept were identified. PROCEDURE: Survivors (n = 578) aged > or =18 years, treated before age 20 years on Children's Cancer Group (CCG) ALL protocols, and 396 sibling controls completed a telephone interview and the Harter Adult Self-Perception Profile (ASPP). RESULTS: Survivors global self-worth scores were significantly lower than sibling controls (mean 3.09 vs. 3.18; P = 0.022). Unemployed survivors reported lower global self-worth scores than employed (mean 2.77 vs. 3.12; P = 0.0001), whereas employment status was not associated with self-worth in controls. Among survivors, predictors of negative self-concept included unemployment (odds ratio (OR) = 2.87; 95% CI: 1.50-5.50), and believing that cancer treatment limited employability (OR = 3.17; 95% CI: 1.79-5.62). Unemployment increased the odds for negative self-concept among survivors who received combinations of central nervous system (CNS) irradiation (CRT) and intrathecal methotrexate (IT-MTX), except high CRT with no or low dose IT-MTX. Employed survivors who perceived that treatment limited their employability showed increased odds of negative self-concept for all treatment groups compared to those who did not. Minority ethnic group membership was a borderline significant predictor of negative self-concept (OR = 1.79; 95% CI: 0.94-3.33). CONCLUSIONS: Global self-worth was significantly lower in ALL survivors than sibling controls, however, 81% of survivors had positive self-concept. Survivor subgroups most vulnerable to negative self-concept were the unemployed survivors, believing that cancer treatment affected employability, and ethnic minority group members. Targeted intervention may have greater clinical relevance for these subgroups.

Adolescent↗
PubMed2004

Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood.

Fertility impairments among men treated during childhood for cancer are known to occur after some, but not all, types of anti-cancer therapy. This is the first study to evaluate proven fertility among adult male survivors of childhood acute lymphoblastic leukemia (ALL). In a retrospective cohort study, proven fertility (ever fathered a pregnancy) was evaluated by self-report among 213 men treated for ALL before age 18 on protocols of the Children's Cancer Group (CCG). Controls (N = 145) were drawn from among male siblings. Overall, with a proportional hazards analysis, proven fertility of male survivors was not different from that of controls (relative fertility (RF) = 0.95, 95% CI 0.63-1.43). However, married men treated before age 10 with high dose (24 cGy) cranial radiotherapy (RT), without spinal RT, had only 9% of the fertility of controls (Relative risk, RR = 0.09, 95% CI 0.01-0.82). High dose cranial RT at older ages was not associated with a statistically significant fertility deficit (RR = 0.56, 95% CI 0.25-1.28). In this first study of proven fertility among men treated for childhood leukemia, the majority of survivors showed no evidence of fertility impairment compared to controls. However, men treated at a young age with high dose cranial RT may have impaired fertility. These results suggest that further investigation of men with these treatments is needed to confirm and extend these findings.

Adolescent↗
PubMed2004

Fertility in women treated with cranial radiotherapy for childhood acute lymphoblastic leukemia.

BACKGROUND: Fertility impairments among women treated during childhood for cancer are known to occur after some, but not all, types of anticancer therapy. Although leukemia is the most common cancer of childhood, until now fertility in survivors has not been comprehensively assessed. PROCEDURE: We investigated functional impairment of fertility in women who were long-term survivors of acute lymphoblastic leukemia (ALL) with a retrospective cohort study. Proven fertility (defined as ever pregnant) was evaluated by self-report among 182 females treated on protocols of the Children's Cancer Group (age at interview, 22.6 years on average) and 170 controls drawn from among the survivors' female siblings (23.4 years). The interview included psychosocial inventories designed to detect mood problems. RESULTS: Significant fertility deficits were noted in female survivors treated with cranial radiotherapy (CRT) at any dose around the time of menarche (relative fertility (RF)) = 0.27, 95% CI = 0.09, 0.82, P = 0.03). Controlling for marital status, mood at interview, and many fertility-related situations did not change the association. CONCLUSION: This study provides evidence for fertility deficits after treatment for ALL with CRT, and, in addition, for the first time, suggests that girls treated around the time of menarche are especially at risk. Clinical confirmation of these results is needed. If gonadal damage occurs in women receiving these treatments, their risk for further sequelae, such as osteoporosis and heart disease, may be significantly raised, requiring active management and intervention.

Adolescent↗
PubMed2004

Peripheral nerve conduction abnormalities in children exposed to alcohol in utero.

OBJECTIVE: We performed a longitudinal study of nerve conduction velocity to determine the effect of prenatal alcohol exposure on the peripheral nervous system. Study design We studied 17 children exposed to >2 oz of absolute alcohol/day prenatally and 13 unexposed children, identified prospectively from a cohort of pregnant women screened during prenatal care. Nerve conduction assessment was done on the median, ulnar, peroneal and tibial nerves during the newborn period and between 12 and 14 months of age. RESULTS: At both assessments the alcohol-exposed subjects had significantly slower ulnar motor nerve velocity (P=.007), smaller proximal (P=.018) and distal amplitude (P=.051). They also showed reduced tibial nerve velocity (P=.06) and a decrease in distal amplitude. CONCLUSIONS: This study demonstrates that prenatal alcohol exposure is associated with abnormalities in nerve electrical properties, and that the pattern is different from that seen in adults. Electrophysiologic abnormalities in peripheral nerves should be added to the problems found in children of alcohol abusing mothers.

Action Potentials↗
PubMed2004

Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients.

OBJECTIVE: Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. STUDY DESIGN: A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. RESULTS: There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. CONCLUSIONS: The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.

Adrenal Insufficiency↗
PubMed2003

Impact of CNS treatment on mood in adult survivors of childhood leukemia: a report from the Children's Cancer Group.

PURPOSE: This study assessed the relationship between CNS treatment and psychologic mood using the Profile of Moods State (POMS), a standardized measure of affect, among a large sample of young adult survivors of childhood acute lymphoblastic leukemia (ALL; N = 555). PATIENTS AND METHODS: Survivors of childhood ALL (ages 18 to 33 years at study entry) participated in a structured telephone interview eliciting demographic, health, and behavioral data and the POMS. Treatment data included total dose of CNS irradiation (CRT) and intrathecal methotrexate (MTX) obtained from medical records. RESULTS: Mood disturbance was reported by 24% of survivors. High-dose CRT and MTX predicted disturbance rates modestly and primarily in combination with education variables. Interactions between educational achievement, a history of attendance in special education classes, and sex were better predictors than treatment type or dose. Nonwhite males, those younger than 12.5 years of age at diagnosis, and those with negative perceptions of current health and cancer's impact on employment were also at greater risk for mood disturbance (P <.01 to.001). CONCLUSION: Although most survivors are doing well psychologically, a subset of long-term survivors show potentially serious mood disturbance. Mood disturbance seems to be a function of interactions between preexisting individual difference variables (eg, sex, race/ethnicity), treatment factors, and posttreatment educational experiences. Prevention strategies aimed at childhood cancer survivors at greatest risk for mood disturbance may be improved by focus on posttreatment psychosocial and educational supports.

Adolescent↗
PubMed2003

Analysis of the MTHFR 1298A-->C and 677C-->T polymorphisms as risk factors for neural tube defects.

The thermolabile variant (677TT) of methylenetetrahydrofolate reductase (MTHFR) is a known risk factor for neural tube defects (NTDs). The relationship between a second MTHFR polymorphism (1298A-->C) and NTD risk has been inconsistent between studies. We genotyped 276 complete NTD triads (mother, father and child affected with an NTD) and 256 controls for MTHFR 1298A-->C. Our findings do not support a role for the 1298A-->C polymorphism in NTDs (OR 0.85 (95% CI 0.49-1.47), p= 0.55), nor do we observe a combined effect with the 677C-->T polymorphism.

Case-Control Studies↗
PubMed2003

Polymorphisms within the vitamin B12 dependent methylmalonyl-coA mutase are not risk factors for neural tube defects.

Methionine synthase and methylmalonyl-CoA mutase (mutase) are the only two known vitamin B(12) (B(12)) dependent enzymes in humans. A lower level of B(12) has been shown to be an independent maternal risk factor for neural tube defects (NTDs) prompting an investigation of common genetic variants within B(12) dependent enzymes. To investigate the role of methylmalonyl-CoA mutase variants we studied 279 complete NTD triads (NTD affected case and both parents) and 256 controls. Based on case-control and family based (transmission disequilibrium test) analyses we did not find an association between the mutase single nucleotide polymorphisms (SNPs) K212K (636A-->G), H532R (1595A-->G) and V671I (2011G-->A) and NTDs. However, there was a significant difference in the frequencies of these polymorphisms between a group of African Americans and American Caucasians (K212K, P=0.002; H532R, P</=0.001; V671I, P=0.006). In conclusion, common variants in the mutase gene do not appear to be risk factors for NTDs but their allele frequencies are significantly different between ethnic groups.

Case-Control Studies↗
PubMed2003

Analysis of the human folate receptor beta gene for an association with neural tube defects.

The folate receptor beta (FRbeta) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FRbeta polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FRbeta polymorphisms we studied NTD-affected children and their parents (254 triads) recruited throughout Ireland and a control population of 296 pregnant women who did not give birth to an NTD-affected child. Five potential single nucleotide polymorphisms (SNPs) were examined. These were located within the coding, intronic and 3(')-untranslated regions of the FRbeta gene. Four of these SNPs were not found to be variable within our Irish cohort. SNP rs651646 (A-->T), located upstream of exon 2 within an intronic region, is polymorphic and is thus a marker for an FRbeta NTD association study. The frequency of the SNP rs651646 "A" allele was not significantly different in cases (odds ratio [OR] 1.07, 95% CI. 0.84-1.36; P=0.60), their mothers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.51) or fathers (odds ratio [OR] 1.09, 95% CI. 0.86-1.38; P=0.50) when compared to controls. Comparisons of allele transmission from 255 informative heterozygous parents of NTD cases showed no preferential transmission of either the A or T alleles (A: 50.2%, n=128; T: 49.8%, n=127; P=1.00, McNemar chi(2) 0.0). We also measured allele frequencies in a sample of American-Caucasians and African-Americans. Highly significant allele frequency differences were observed between populations. In conclusion, SNP rs651646 within the FRbeta gene is polymorphic but is not associated with neural tube defects within the Irish population.

3' Untranslated Regions↗
PubMed2003

Adverse pregnancy outcomes in snuff users.

OBJECTIVE: The purpose of the study was to evaluate the effects of smokeless tobacco use during pregnancy. STUDY DESIGN: We examined birth weight, preterm delivery, and preeclampsia in women who were delivered of singleton, live-born infants in Sweden from 1999 through 2000. For each snuff user, 10 cigarette smokers and 10 tobacco nonusers were selected randomly. RESULTS: After exclusions, 789 snuff users, 11,240 smokers, and 11,495 nonusers remained. Compared with nonusers, adjusted mean birth weight was reduced in snuff users by 39 g (95% CI, 6-72 g) and in smokers by 190 g (95% CI, 178-202 g). Preterm delivery was increased in snuff users and smokers (adjusted odds ratios, 1.98 [95% CI, 1.46-2.68] and 1.57 [95% CI, 1.38-1.80], respectively). Preeclampsia was reduced in smokers (adjusted odds ratio, 0.63; 95% CI, 0.53-0.75) but increased in snuff users (adjusted odds ratio, 1.58; 95% CI, 1.09-2.27). CONCLUSION: Snuff use was associated with increased risk of preterm delivery and preeclampsia. Snuff does not appear to be a safe alternative to cigarettes during pregnancy.

Birth Weight↗
PubMed2003

Low vitamin B-12 concentrations in patients without anemia: the effect of folic acid fortification of grain.

BACKGROUND: In some patients with vitamin B-12 deficiency mistakenly treated with folic acid, anemia resolved but neurologic complications became worse (masking). Fortification of enriched cereal grains with folic acid has raised concerns that people who consume large quantities of cereal grains, particularly the elderly, may be at increased risk of masking. It is unclear, however, what proportion of people with low vitamin B-12 concentrations do not have anemia and whether the proportion is increasing. OBJECTIVE: We investigated whether fortification has increased the proportion of patients with low vitamin B-12 but without anemia. DESIGN: We reviewed the laboratory results of every patient for whom a vitamin B-12 concentration was measured at the Veterans Affairs Medical Center in Washington, DC, between 1992 and 2000. Those with a low vitamin B-12 concentration (< 258 pmol/L) had their hematocrits and mean cell volumes checked. The proportion without anemia was examined by year before, during, and after folic acid fortification began. RESULTS: There were 1573 subjects with a low vitamin B-12 concentration. The proportion without anemia did not increase significantly from the prefortification period (39.2%) to the period of optional fortification (45.5%) and the postfortification period (37.6%). These findings did not change when the analysis was limited to patients aged > 60 y or when a more conservative definition of low vitamin B-12 (< 150 pmol/L) was used. CONCLUSIONS: Despite evidence that folic acid exposure has increased dramatically since food fortification began, this population showed no evidence of an increase in low vitamin B-12 concentrations without anemia. If confirmed, these results would indicate that food fortification has not caused a major increase in masking of vitamin B-12 deficiency.

Aged↗
PubMed2002

Plasma folate levels and risk of spontaneous abortion.

CONTEXT: Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. OBJECTIVE: To study the association between plasma folate levels and the risk of spontaneous abortion. DESIGN, SETTING, AND POPULATION: Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. MAIN OUTCOME MEASURE: Risk of spontaneous abortion vs maternal plasma folate level. RESULTS: Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33). CONCLUSION: Low plasma folate levels were associated with an increased risk of early spontaneous abortion.

Abortion, Spontaneous↗
PubMed2002

A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.

Women who take folic acid periconceptionally reduce their risk of having a child with a neural tube defect (NTD) by >50%. A variant form of methylenetetrahydrofolate reductase (MTHFR) (677C-->T) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid. This has prompted the search for additional NTD-associated variants in folate-metabolism enzymes. We have analyzed five potential single-nucleotide polymorphisms (SNPs) in the cytoplasmic, nicotinamide adenine dinucleotide phosphate-dependent, trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) for an association with NTDs in the Irish population. One SNP, R653Q, in this gene appears to be associated with NTD risk. We observed an excess of the MTHFD1 "Q" allele in the mothers of children with NTD, compared with control individuals. This excess was driven by the overrepresentation of QQ homozygotes in the mothers of children with NTD compared with control individuals (odds ratio 1.52 [95% confidence interval 1.16-1.99], P=.003). We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.

Aminohydrolases↗
PubMed2002

MTRR and MTHFR polymorphism: link to Down syndrome?

Polymorphisms in genes encoding the folate metabolizing enzymes methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase reductase (MTRR A66G) have been linked to the etiology of Down syndrome. We examined the prevalence of these variant genotypes in mothers who had given birth to a child with Down syndrome (n = 48) and in control mothers (n = 192), and investigated the biochemical factors influenced by the presence of MTRR A66G and MTHFR C677T. The frequency of the MTRR variant genotypes (AG, GG) was significantly higher in mothers of children with Down syndrome compared to controls (P = 0.0028). MTHFR C677T genotype frequencies were not significantly altered in mothers of children with Down syndrome (P = 0.74). However, mothers who had a MTHFR CT or TT genotype and a MTRR GG genotype had a 2.98-fold increased risk of having a child with Down syndrome (P = 0.02). The MTRR polymorphism did not increase plasma homocysteine. Higher homocysteine was found with the presence of the MTHFR T allele. In conclusion, MTRR A66G is significantly more common in mothers of children with Down syndrome but does not appear to increase the risk for Down syndrome by changing homocysteine metabolism. Women who have both the MTRR and MTHFR variant genotypes are also at increased risk of producing offspring with Down syndrome.

Alleles↗
PubMed2002

Maternal and fetal plasma homocysteine concentrations at birth: the influence of folate, vitamin B12, and the 5,10-methylenetetrahydrofolate reductase 677C-->T variant.

OBJECTIVE: The purpose of this study was to determine the nutritional and genetic factors that influence fetal plasma homocysteine concentrations. STUDY DESIGN: Maternal and umbilical cord venous blood was taken from 201 women who were delivered after uncomplicated pregnancies of 37 to 41 gestational weeks. Red blood cell folate, plasma folate, plasma vitamin B12, and plasma homocysteine concentrations were measured in all samples. Cord and maternal bloods were also genotyped for the 677C-->T variant. RESULTS: The fetal circulation had lower homocysteine concentrations (7.87 +/- 2.87 micromol/L; mean +/- SD) than the maternal circulation (8.34 +/- 2.94 micromol/L; P =.003), but there was a strong linear association between the levels in these 2 compartments (r = 0.72; P <.0001). Overall, the maternal homocysteine level had the strongest influence on the fetal homocysteine concentration (P <.0001), with the fetal and maternal vitamin B12 having important additional effects (P =.016 and P =.0045, respectively). Fetal plasma folate and 5,10-methylenetetrahydrofolate reductase 677C-->T genotype had no significant effects (P =.23 and P =.54, respectively), probably because of folic acid supplement use. CONCLUSION: The maternal homocysteine level is the primary predictor of blood homocysteine in the developing fetus. If lowering maternal blood homocysteine proves critical to preventing pregnancy complications, it will be important to maintain optimal vitamin B12 status in addition to optimal tissue folate status.

Female↗