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Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research. [ABSTRACT FROM AUTHOR]

Objective: Although older patients represent the most rapidly growing segment of the oncology population, clinical care is guided by very little data on patient-reported outcomes, particularly satisfaction with healthcare. Using a large cancer center registry, we sought to describe factors associated with satisfaction with care for older and younger oncology patients., Methods: Data were collected through the University of North Carolina Health Registry Cancer Survivorship Cohort. Satisfaction was measured with the Patient Satisfaction Questionnaire Short Form. Quality of life (QOL) measures included were the Promis Global short form and the Functional Assessment of Cancer Therapy General (FACT-G)., Results: A total of 2385 patients were included. 460 (20%) were aged 70 and above (older group). Older patients reported significantly higher levels of satisfaction in domains of time spent with doctor (scores 3.84 versus 3.73 p=0.03) and financial aspects (scores 4.03 versus 3.44 p<0.001) compared to younger patients. In multivariable analysis, higher QOL scores and higher self-reported ECOG performance status were associated with higher satisfaction scores. African American race was associated with lower satisfaction scores in all age groups. QOL was more closely correlated with satisfaction in older patients compared to younger patients., Conclusions: Older patients with cancer report higher levels of satisfaction with care, in part due to lesser financial burden of care. Better QOL is associated with satisfaction with care in older patients. Use of patient-reported outcomes such as patient satisfaction may help improve patient-centered geriatric oncology care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients., Methods: We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores., Results: Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16)., Conclusion: Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: : Nonmedical factors may modify the biological risk of prostate cancer (PCa) and contribute to the differential use of early detection; curative care; and, ultimately, greater racial disparities in PCa mortality. In this study, the authors examined patients' usual source of care, continuity of care, and mistrust of physicians and their association with racial differences in PCa screening., Methods: : Study nurses conducted in-home interviews of 1031 African-American men and Caucasian-American men aged > or =50 years in North Carolina and Louisiana within weeks of their PCa diagnosis. Medical records were abstracted, and the data were used to conduct bivariate and multivariate analyses., Results: : Compared with African Americans, Caucasian Americans exhibited higher physician trust scores and a greater likelihood of reporting a physician office as their usual source of care, seeing the same physician at regular medical encounters, and historically using any PCa screening. Seeing the same physician for regular care was associated with greater trust and screening use. Men who reported their usual source of care as a physician office, hospital clinic, or Veterans Administration facility were more likely to report prior PCa screening than other men. In multivariate regression analysis, seeing the same provider remained associated with prior screening use, whereas both race and trust lost their association with prior screening., Conclusions: : The current results indicated that systems factors, including those that differ among different sources of care and those associated with the continuity of care, may provide tangible targets to address disparities in the use of PCa early detection, may attenuate racial differences in PCa screening use, and may contribute to reduced racial disparities in PCa mortality. Cancer 2009. Published 2009 by the American Cancer Society.

Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor beta superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer., Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs)., Results: A statistically significant difference (P =.006) in genotype frequency was observed for the nonsynonymous change H6D (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95% CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer., Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.

Inflammation has been implicated as an etiological factor in several human cancers. Growing evidence suggests that chronic inflammation may also play a role in the etiology of prostate cancer. Considering that genetic susceptibility is a major risk factor for this disease, we hypothesize that sequence variants in genes that regulate inflammation may modify individual susceptibility to prostate cancer. The lipopolysaccharide receptor Toll-like receptor 4 (TLR4) is a central player in the signaling pathways of the innate immune response to infection by Gram-negative bacteria and is an important candidate inflammatory gene. We performed a systematic genetic analysis of TLR4 sequence variants by evaluating eight single-nucleotide polymorphisms that span the entire gene among 1383 newly diagnosed prostate cancer patients and 780 age- and residence-matched controls in Sweden. We found an association between a sequence variant (11381G/C) in the 3'-untranslated region of the TLR4 gene and prostate cancer risk. The frequency of the variant genotypes (CG or CC) was significantly higher in the patients (24.1%) than in the controls (19.7%; P = 0.02). The frequency of risk genotypes among patients diagnosed before the age of 65 years was even higher (26.3%). Compared with men who had the wild-type genotype of this single-nucleotide polymorphism (GG), those with GC or CC genotypes had a 26% increased risk for prostate cancer (odds ratio, 1.26; 95% confidence interval, 1.01-1.57) and 39% increased risk increased risk for early onset prostate cancer (before age 65 years; odds ratio, 1.39; 95% confidence interval, 1.02-1.91). The risk attributable to this variant for prostate cancer in Sweden was estimated to be 4.9%. Although the biological mechanism of the observed association remains to be elucidated, our finding supports a role for a bacteria-associated response pathway, possibly acting via inflammation, in the development of prostate cancer.

Genes in the interleukin-1 (IL-1) gene cluster on human chromosome 2 play an important role in mediating inflammatory responses and are associated with numerous diseases. We have identified a novel IL-1-like gene, IL-1F10, on human chromosome 2q13-14.1 near the IL-1 receptor antagonist gene (IL-1RN). The IL1F10 gene is encoded by 5 exons spanning over 7.8 kb of genomic DNA. The 1008-bp IL-1F10 cDNA encodes a 152-amino acid protein that shares between 41% and 43% amino acid identity with human IL-1 receptor antagonist (IL-1Ra) and FIL-1delta, respectively. IL-1F10 shares characteristics of the IL-1Ra family, including key amino acid consensus sequences and a similar genomic structure. By multitissue first-strand cDNA PCR analysis, IL-1F10 mRNA is expressed in heart, placenta, fetal liver, spleen, thymus, and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-1F10 in the inflammatory response.

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 ( approximately 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region.

Family history of coronary heart disease (CHD) has been found to be a risk factor for CHD in numerous studies. Few studies have addressed whether a quantitative measure of family history of CHD (family risk score, FRS) predicts CHD in African Americans. This study assessed the association between FRS and incident CHD of participants, and the variation of the association by gender and race. Participants in the study were a biracial population-based cohort with 3,958 African Americans and 10,580 Whites aged 45-64 years old in the ARIC baseline survey (1987-1989). They were randomly selected from four U. S. communities. During follow-up (1987-1993), 352 participants experienced the onset of CHD. Incidence density of CHD (per 1,000 person-years) was 7.8 and 3.6 among African-American men (AAM) and women (AAW), and 7.2 and 2.2 among White men (WM) and women (WW). The hazard rate ratio (HRR) of CHD associated with one standard deviation increase of FRS was 1.52 in AAW, 1.46 in AAM, 1.41 in WW, and 1.68 in WM. The HRRs decreased 4.6% in AAW, 1.4% in WW, 5.7% in AAM, and 3.0% in WM, but increased 2.1% in AAM after adjustment for selected covariates. FRS predicts incident CHD in African Americans and Whites, men and women. The relation of FRS to incident CHD can be only partially explained by the selected risk factors in the biological causal pathways: IMT, T-G, LDL, HDL, Lp(a), fibrinogen and hypertension. No significant difference by race has been found in this study., (Copyright 2000 Wiley-Liss, Inc.)

Proband-reported family histories are widely used in research and counseling, yet little is known about the validity of family history reporting. The Family Heart Study (FHS), a population-based study of familial cardiovascular disease, gathered family history information from 3,020 middle-aged probands in four U.S. communities. Probands reported on the history of coronary heart disease (CHD), diabetes, hypertension, and asthma among a total of 10,316 living relatives (9,186 siblings, 1,130 parents) and 2,685 spouses. Questionnaires were returned by 6,672 siblings, 901 parents, and 2,347 spouses, yielding response rates of 73, 79, and 87%, respectively. Utilizing the relatives' self-report as the standard, sensitivity of the proband report on their spouse, parent, and sibling was 87, 85, and 81% for CHD, 83, 87, and 72% for diabetes, 77, 76, and 56% for hypertension, and 66, 53, and 39% for asthma, respectively. Most specificity values were above 90%. Analyses using generalized estimating equations (GEE) were performed to evaluate differences in proband accuracy based on the proband's age, gender, disease state, center, and ethnicity. In multivariate models, age, gender, and disease status were significantly associated with the accuracy of proband's report of sibling disease history, but had little effect on the accuracy of their report on spouses or parents. In general, older probands were significantly less accurate reporters of disease than younger probands. These results demonstrate that CHD family history can be captured effectively based on proband reports, but suggest that additional family contacts may be helpful when working with older probands or with chronic diseases that have few recognized medical events or procedures.

The association between family history of coronary heart disease (CHD) and morbidity and mortality due to atherosclerotic sequelae, although well documented in population-based samples of whites, has been little studied in African Americans. Less is known about the relationship between a family history of CHD and pre-clinical atherosclerosis. We report the relation between family history of CHD, summarized in a family risk score (FRS), and asymptomatic atherosclerosis at the extracranial carotid arteries, measured by B-mode ultrasound. The FRS was assessed in relatives of 3,034 African Americans and 9,048 white probands aged 45 to 64 years, in the four community-based cohorts of the ARIC Study. The analyses were restricted to individuals free of clinically manifest CHD. The distribution of CHD FRS by ethnic-gender groups was right skewed, with slightly higher mean values for white than African-American males, and for African-American than white females. In a series of multivariate linear regression models with mean carotid artery intima-media wall thickness (IMT) as the dependent variable, FRS was associated positively with IMT in white and African-American women and white men. In a multiple regression model, approximately one-half of the quantitative statistical relationship of the CHD FRS with IMT in whites was statistically explained by the major risk factors considered as intervening, explanatory variables in this analysis. This association in African-American women was fully explained by the major risk factors. The FRS was not, however, associated with atherosclerosis or major risk factors in African-American males, in the ARIC Study.

Two pregnancies in a 25-year-old woman with hereditary orotic aciduria who was managed prenatally on uridine therapy are described. The first pregnancy resulted in an infant with multiple congenital anomalies and a 47,xx,inv(4)(p12q25), +der(22)t(11;22)(p23;q11) karyotype. The proposita was found to be a carrier of a de novo 11;22 translocation and a pericentric inversion of chromosome 4. Subsequently, several carriers of orotic aciduria in this family were identified with the inverted chromosome 4. The second pregnancy resulted in a normal male with an inverted chromosome 4.

In a study group of 166 patients with unusually high maternal serum alpha-fetoprotein values greater than or equal to 5 multiples of the median, 110 (66%) patients had a condition affecting obstetric care compared with 14% in the 2.5 to 2.9 range, 26% in the 3.0 to 3.9 range, and 30% in the 4 to 4.9 range of multiples of median. Fetal anomalies composed a significantly greater proportion (p less than 0.0001) of positive findings in the study group than the group with maternal serum alpha-fetoprotein values of greater than or equal to 2.5 to 4.9 multiples of the median. Fetal death either before 20 weeks or of one twin occurred significantly more often in the study group (p less than 0.0001). Neural tube defects (21%) and fetal death before 20 weeks (19%) were the most common findings in the study group. There was not a statistically significant difference (p less than 0.53) in pregnancy complications or in late complications between the two groups although oligohydramnios and abdominal pregnancies occurred more often in the study group (p less than 0.029 and less than 0.011). Diagnosticians evaluating patients with unusually elevated maternal serum alpha-fetoprotein values must be aware of the usual differential diagnosis as well as rarer causes. One must recognize that finding an unaffected fetus does not preclude the subsequent development of a pregnancy complication.

A derivative of ergosterol, ergosta-5,7,9,22-tetraen-3 beta-ol, was synthesized and characterized. Its properties in membranes are similar to those of cholesterol as measured by glucose-permeability and by order parameters derived from electron spin resonance of spin-labels. Thus, because of the three conjugated double bonds, this molecule can be used as an optical probe of sterol behavior in membranes. Circular dichroism (CD) spectra of sonicated egg phosphatidylcholine vesicles containing the probe exhibited CD transitions whose intensity was dependent on sterol content. CD spectra from this probe in human low-density and high-density lipoproteins indicated distinctly different environments for the sterol in the two lipoproteins.

Records were reviewed retrospectively on 72 infants with open spina bifida followed from birth through one year of age. Thirty-two infants were born by cesarean section and 40 vaginally. The following variables were compared between the two groups: 1) mortality in the nursery and between nursery discharge and one year of age, 2) incidence of meningitis in the neonatal period, 3) length of initial hospital stay, and 4) neurologic and developmental status at one year. No significant differences were noted between the two groups. Although it has been suggested that cesarean section may improve the prognosis for infants with open spina bifida, our data do not support that conclusion.

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.

Trisomic codominant expression of the HLA antigens was observed in an infant with duplication of a part of 6p occurring as a result of crossing over within a paternally transmitted pericentric inversion. The HLA-A and B loci were linked absolutely with the inversion chromosome in a four generation pedigree.

We describe a newborn infant with 9p- syndrome and nonketotic hyperglycinemia. This unusual occurrence may not have been coincidental and suggests that there may be a gene for nonketotic hyperglycinemia located on the short arm of chromosome 9.