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Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study.

The familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] was investigated in families ascertained through both random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. Nonrandom proband ascertainment was based on single selection through truncation for hyperlipidemia at an earlier screening. A path model was used to investigate the nature of familial resemblance using appropriate adjustments for ascertainment and to determine whether random and hyperlipidemic samples are heterogeneous with regard to the multifactorial model. The results suggest that parameter estimates are consistent with those from previous studies in which only random families were used and that random and nonrandom samples are homogeneous with regard to the path model for CH and LDL. However, for TG and HDL the random and hyperlipidemic samples are significantly heterogeneous. This heterogeneity would be observed if familial hypertriglyceridemia and/or familial hypoalphalipoproteinemia segregates predominantly in the hyperlipidemic rather than in the random sample, as on might expect.

Chromosome Banding↗

Weekly work hours and clinical activities of Canadian family physicians: results of the 1997/98 National Family Physician Survey of the College of Family Physicians of Canada.

BACKGROUND: Health systems planning is a challenging task, exacerbated by a lack of detailed information on the role played by family physicians, as indicated by practice variations across regions and demographic characteristics. Outcome measures used in past studies of family physician practice patterns were not uniform. Furthermore, past research has generally been limited to narrowly defined geographic regions. A national study of family physician practice patterns was undertaken to allow regional-level comparisons of clinical workload and range of medical services offered. METHODS: The 1997/98 National Family Physician Survey was mailed to a sample of 5198 Canadian family physicians and general practitioners (FP/GPs); the overall response rate was 58.4% (3036 questionnaires returned, of which 3004 were analyzable). Sampling strata were based on College of Family Physicians of Canada (CFPC) membership status and regions of Canada. RESULTS: Clinical workload varied considerably across the demographic categories studied. Male physicians reported 8.9 more total weekly work hours than female physicians, but the mean number of medical and clinical services offered did not differ between the sexes. Solo practitioners reported 53.8 (95% confidence interval [CI] 52.7-55.0) total weekly work hours, whereas those practising in multidisciplinary clinics reported 45.0 (95% CI 43.2-46.8) hours. FP/GPs in the Atlantic and Prairie provinces reported 5.6 and 5.1 more weekly work hours, respectively, than the national average of 51.4 (95% CI 50.8-52.0) hours. Finally, FP/GPs who served inner-city populations reported 48.6 (95% CI 46.8-50.5) total weekly work hours, whereas those serving rural populations reported 57.0 (95% CI 54.7-59.2) hours. Mean weekly work hours were similar for all age cohorts less than 65 years. FP/GPs practising in less populated provinces and in rural areas reported the highest numbers of work hours, medical services offered and clinical procedures performed. INTERPRETATION: These data suggest significant variations in FP/GP clinical workload in relation to key demographic variables.

Adult↗

Coparental and family group-level dynamics during infancy: early family precursors of child and family functioning during preschool.

This study examines longitudinal correlates of coparental and family group-level dynamics during infancy. Thirty-seven couples observed at play with their 8-11-month-old infants (15 boys, 22 girls) rated their child's internalizing and externalizing symptoms, and their own coparenting behavior 3 years later. Teachers also rated child behavior at the 3-year follow-up. Several significant relationships emerged between observed family process (high hostility-competitiveness, low family harmony, and high parenting discrepancies in the triad) at Time 1, and subsequent reports of child and coparenting behavior at Time 2. Larger parenting discrepancies at Time 1 predicted greater child anxiety as rated by teachers; greater hostility-competitiveness and lower harmony forecast higher child aggression. Time 1 family process continued to predict Time 2 aggression even after controlling for individual and marital functioning. Several links were also found between distressed family process and later parental reports of negative coparenting behavior. These parental reports of coparenting also explained unique variance in concurrent child behavior ratings. The significance of coparenting as a distinct family construct is discussed.

Child Behavior Disorders↗

Family psychology and family law--a family court judge's perspective: comment on the special issue.

This comment presents the responses of an experienced family court judge to the eight articles published in this special issue. The value of these scholarly articles to family court judges is enormous. Judges have little, if any, formal training in family dynamics and child development, yet are called upon to make rulings in complex cases that have life-long ramifications for all family members. The changing demographics and current realities of traditional and nontraditional family structures in our society as well as the increasing divorce rates have widened the gap between legal precedence and current social science research. It is essential that the material covered in this issue can be accessible to family law personnel in language that they can understand and learn from.

Family↗

Working with families in Tower Hamlets: an evaluation of the Family Welfare Association's Family Support Services.

This paper describes an evaluation carried out by South Bank University of the work of the Family Welfare Association's (FWA's) Family Support Services (FSSs) in Tower Hamlets, London. Tower Hamlets is a multi-racial area in east London that, according to the 1991 census, has high levels of poverty, overcrowding and unemployment. Increasing poverty and social exclusion, which further entrench inequalities in health, are reported by sources such as government, health and social services and research as requiring innovative local responses to meet pressing welfare needs. The evaluation reported here examined three projects: Family Support, Building Bridges and Quality Protects - these are referred to collectively as FSSs. The evaluation shows that FSSs are innovative services that demonstrate effective ways of working with vulnerable families affected by experiences of racism, bullying, mental health difficulties, domestic violence or child abuse. In common with other successful initiatives in the UK and abroad, FSSs are aimed to be non-stigmatising, non-intrusive and responsive to the ethnicity, views and specific needs of families. This paper focuses on the participatory work of FSSs with families to illustrate effective methods of quality support, detail outcomes, and draw lessons for policy and practice.

Adolescent↗

Family function in families with children of normal height and in families with short children.

UNLABELLED: The purpose of this study was to examine any differences regarding cohesion and adaptability between Swedish families with children of normal stature (group A) and those with children of short stature (group B). Cohesion and adaptability were measured using a Swedish translation of the third version of the self-report questionnaire FACES (Family Adaptability and Cohesion, Evaluation Scales). Most of the 55 families in group A and most of the 49 families in group B appeared to be well balanced with regard to cohesion and adaptability. There was no statistically significant difference between the two groups concerning the variable cohesion. Significant differences were found in adaptability: fathers in group A had higher values than mothers in group A and than mothers and fathers in group B. CONCLUSION: There are no major differences between families with children of normal stature and those with short children. However, it was found that fathers with children of normal stature perceived a greater adaptation within their families compared with mothers with children of normal stature and mothers and fathers with children of short stature.

Body Height↗

Familial aggregation of blood pressure and weight in adoptive families. I. Comparisons of blood pressure and weight statistics among families with adopted, natural, or both natural and adopted children.

Tests of homogeneity of means, variances and correlations for systolic blood pressure (BP), diastolic BP and weight among subdivisions of a smple of adoptive families are presented. The means and variances of either type of BP, but not weight, were not significantly heterogeneous among families grouped according to the number of parents and children, natural and/or adopted, in the family unit. Estimates of correlation between family members wree not heterogeneous among subdivisions for each of the three variables. Our results indicate that these data are suitable for a genetic analysis of familial aggregation. Pooled correlations suggest that the degree of resemblance of BP and of weight between family members varies within and across generations. Correlations involving the adoptees were significantly different from zero only for diastolic BP.

Adolescent↗

Clinical practice in academic medical center departments of family medicine. The Association of Departments of Family Medicine Task Force on Clinical Practice in US family medicine departments in academic medical centers.

BACKGROUND AND OBJECTIVES: Conducted by a task force of the Association of Departments of Family Medicine, this study defines current issues in the clinical practice of academic departments of family medicine in US medical schools. METHODS: A survey instrument on departmental demographics, funding, teaching, and governance in regard to clinical practice was sent to 130 family medicine department chairs or other key contacts in US medical schools. A total of 106 usable responses were obtained, for an 81.5% response rate. RESULTS: Results indicate that, in response to a need to increase clinical practice income, academic medical centers (AMCs) and departments are increasingly hiring physician faculty for positions that mainly involve patient care, although at salaries less than the community level. In spite of increasing departmental responsibilities in predoctoral and resident education and clinical practice, much teaching is done by community physicians. There is significant purchasing of community practices and growing involvement of the AMCs in the practice activities of departments. Two thirds of clinical chairs reported "pretty good" to "great" satisfaction on a five-point scale. CONCLUSIONS: Departments of family medicine are increasing their practice activities, perhaps to the detriment of teaching and research. The clinical practice autonomy of departments of family medicine is being diluted by increased institutional control and by mergers with the practices of other primary care disciplines. These changes give rise to a reasonable concern that academic departments of family medicine and their faculty may give up control of their clinical practice and lose their identity through conversion to "generic" primary care departments and providers.

Academic Medical Centers↗

A multivariate analysis of familial associations of lipoprotein levels in the Lipid Research Clinics Collaborative Family Study: I. Familial correlation and regression analyses.

In view of the complex, intraindividual relationships among different lipoprotein levels (LDL-C, HDL-C, and VLDL-C), multivariate methods aimed at assessing joint familial associations and their possible determinants were performed in the white, random sample component of the Collaborative Lipid Research Clinics Family Study data (1,336 families with 5,097 subjects). After appropriate transformations and covariate adjustments of the data, several kinds of correlation and regression analyses were performed, taking into consideration variable family size and possible age and clinic differences. The association patterns across clinics and age strata were found to be homogeneous for the vast majority of comparisons. The results of multivariate analyses (especially the significant association of each lipoprotein among biological relatives), the persistence of parental levels as the best predictors for the same lipoprotein levels among the offspring, and the essentially unchanged partial correlation estimates as compared to ordinary correlations suggest strong influence of factors specific to each lipoprotein in the familial associations. But the highly significant intraindividual correlations and the nonnegligible cross-correlations among relatives also suggest the additional presence of common underlying factors for the familial associations, especially between HDL-C and VLDL-C and to a lesser extent between LDL-C and VLDL-C. The issues stemming from these analyses and the directions for further analyses are discussed.

Cholesterol↗

Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype.

Small, dense LDL particles consistently have been associated with hypertriglyceridemia, premature coronary artery disease (CAD), and familial combined hyperlipidemia (FCH). Previously, we have observed linkage of LDL particle size with four separate candidate-gene loci in a study of families enriched for CAD. These loci contain the genes for manganese superoxide dismutase (MnSOD), on chromosome 6q; for apolipoprotein AI-CIII-AIV, on chromosome 11q; for cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT), on chromosome 16q; and for the LDL receptor (LDLR), on chromosome 19p. We have now tested whether these loci also contribute to LDL particle size in families ascertained for FCH. The members of 18 families (481 individuals) were typed for genetic markers at the four loci, and linkage to LDL particle size was assessed by nonparametric sib-pair linkage analysis. The presence of small, dense LDL (pattern B) was much more frequent in the FCH probands (39%) than in the spouse controls (4%). Evidence for linkage was observed at the MnSOD (P=.02), CETP/LCAT (P=.03), and apolipoprotein AI-CIII-AIV loci (P=.005) but not at the LDLR locus. We conclude that there is a genetically based association between FCH and small, dense LDL and that the genetic determinants for LDL particle size are shared, at least in part, among FCH families and the more general population at risk for CAD.

Adult↗

BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases.

Ovarian cancer is a clinically important cancer in Turkey. The contribution of BRCA1 and BRCA2 to ovarian cancer in Turkish patients has not previously been described. In this study we investigated the presence of BRCA1 and BRCA2 mutations in 102 consecutively ascertained, hospital-based, ovarian cancer cases. Four out of 15 (26.7%, 95% confidence interval (CI), 7.8%-55.1%) familial cases were found to carry mutations in BRCA1. Thirteen of the 87 (14.9%, 95% CI, 7.5%-22.4%) non-familial cases had BRCA1 and BRCA2 mutations, six in BRCA1, and seven in BRCA2. We have further studied the non-familial ovarian cancer cases to determine which subgroups have a likelihood of carrying clinically important mutations. Our study shows that those Turkish ovarian cancer patients with serous histopathology harbor a high proportion of mutations (12/58, 20.7%, 95% CI, 10.3%-31.1%) compared to all non-familial cases (14.9%) regardless of pathology. Within the serous sub-group, those that were also diagnosed below age 50 have an even greater percentage of mutations (8/28, 28.6%, 95% CI, 11.8%-45.3%). Our findings demonstrate that a substantial proportion of Turkish ovarian cancer patients, both with and without a family history, carry BRCA1 and BRCA2 mutations, demonstrating the importance of BRCA1 and BRCA2 in the development of ovarian cancer in this population.

Adult↗

Familial aggregation of blood pressure and weight in adoptive families. III. Analysis of the role of shared genes and shared household environment in explaining family resemblance for height, weight and selected weight/height indices.

This study presents an analysis of the role of genetic and household environment in explaining the familial aggregation of height (HT), weight (WT), and body mass indices (WT/HT1.2 and WT/HT2.0). The biologic model used for the analysis partitions the covariances between family members into the contributions of genetic and environmental variability shared within and across generations, including a variance component shared only by a mother and her natural children. Tests of hypotheses suggest that shared genes and shared household environmental factors make significant contributions to the familial aggregation of WT (adjusted for age and sex) and of HT (adjusted for age and sex), whereas family resemblance of WT adjusted for age and HT can be attributed mostly to the effects of shared genes. The familial aggregation of selected WT/HT indices is attributed to the effects of shared household environment only, suggesting that these variables measure a characteristic of stature that is independent of height and weight.

Adolescent↗

A family study of familial positive vs. familial negative alcoholics.

Of 259 alcoholics studied, 173 were primary alcoholics. Familial positive primary alcoholics tended to have earlier onset of alcoholism and males seemed to have more complications from drinking. Family study data indicated that the familial positive group had family pedigrees more likely to contain relatives with antisocial personality disorder. This relationship to antisocial personality may help in explaining previous research findings in familial positive alcoholics.

Adult↗

Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study.

In an attempt to better understand the genetic basis of the metabolic syndrome, we have undertaken a series of studies on the familial aggregation in the clustering of the coronary heart disease risk factors which characterize this syndrome. In the present study, the hypothesis of shared genetic (pleiotropy) and/or environmental factors between body fat and blood lipids is investigated by examining cross-trait (eg, father's body fat with his son's blood lipid) familial resemblance between 4 indicators of body fat (body mass index [BMI], sum of 6 skin folds [SF6]) and fat distribution (the ratio of the trunk to extremity skin folds adjusted [TER-sf] and unadjusted [TER] for SF6), and 5 blood lipid variables (total cholesterol [CH], triglycerides [TG], cholesterol associated with high-density lipoproteins [HDL], the CH/ HDL ratio and the difference between CH and HDL [CH-HDL]) measured in 1239 individuals from 309 families participating in the Quebec Family Study. A bivariate correlation model was used to obtain maximum likelihood estimates of cross-trait spouse, parent-offspring, and sibling correlations after adjustment of body fat and lipid data for the effects of age, separately in the four sex-by-generation groups. Likelihood ratio tests revealed the presence of significant (P < .05) cross-trait resemblance between body fat (BMI and SF6) and all lipid traits except CH and also between fat distribution (TER and TER-sf) and CH/HDL and CH-HDL. Only sibling cross-trait correlations were significant for all body fat-lipid pairs of measures, with bivariate familiality estimates (i.e., shared genetic and/or environmental factors) ranging from 8% to 40%. Although the hypothesis of genetic pleiotropy cannot be ruled out from the pattern of cross-trait correlations found in the present study, we conclude that environmental factors shared within sibships are probably more important than common genes in determining the covariation between body fat and blood lipids.

Adolescent↗

Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database.

The importance of genetic factors in etiology of chronic lymphocytic leukemia (CLL) is suggested by family and population studies. However, the spectrum of malignancies sharing common genetic factors with CLL and the effects of sex and age on familial risk are unknown. We used the Swedish Family-Cancer Database to test for increased familial risks of CLL and other lymphoproliferative tumors. Cancer diagnoses from 1958 to 1998 were assessed in 14 336 first-degree relatives of 5918 CLL cases and in 28 876 first-degree relatives of 11 778 controls. Cancer risks in relatives of cases were compared with those in relatives of controls using marginal survival models. Relatives of cases were at significantly increased risk for CLL (relative risk [RR] = 7.52; 95% confidence interval [CI], 3.63-15.56), for non-Hodgkin lymphoma (RR = 1.45; 95% CI, 0.98-2.16), and for Hodgkin lymphoma (RR = 2.35; 95% CI, 1.08-5.08). CLL risks were similar in parents, siblings, and offspring of cases, in male and female relatives, and were not affected by the case's age at diagnosis. Anticipation was not significant when analyzed using life table methods. We conclude that the familial component of CLL is shared with other lymphoproliferative malignances, suggesting common genetic pathways. However, because clinically diagnosed CLL is uncommon, absolute excess risk to relatives is small.

Age of Onset↗

Familial amyloidosis, Finnish type: G654----a mutation of the gelsolin gene in Finnish families and an unrelated American family.

The Finnish type of familial amyloid polyneuropathy (FAF) is an autosomal dominant form of systemic amyloidosis caused by a mutation in the gelsolin gene. The mutation leads to the expression of amyloidogenic mutant Asp187----Asn gelsolin, an actin-modulating protein. We previously developed a DNA test based on amplification by the polymerase chain reaction followed by allele-specific oligonucleotide hybridization that identifies the base substitution adenine for guanine at nucleotide 654 in the gelsolin gene causing the disease. We show here that the same mutation is present in members of six apparently unrelated Finnish families and in a member of an unrelated American family. These results, taken together with previously published findings in nine additional Finnish families and another unrelated American family, indicate that most, perhaps all, FAF patients in Finland and possibly worldwide carry the same mutation. We suggest two alternative explanations: (i) the mutation arose in a very early common ancestor or (ii) the Asn187 mutation is particularly, perhaps uniquely, amyloidogenic.

Amino Acid Sequence↗

Cross-trait familial resemblance for body fat and blood pressure: familial correlations in the Québec Family Study.

Cross-trait resemblance between body fat and blood pressure (BP) was examined among families in the Québec Family Study by using a bivariate familial correlation model assessing both intraindividual (e.g., comparison of father's body fat with his own BP) and interindividual (e.g., comparison of father's body fat with son's BP) cross-trait correlations. Each of six body-fat measures-(i) percent body fat, (ii) body-mass index, (iii) the sum of six skinfolds, (iv) the ratio of the sum of six skinfolds to total fat mass, (v) the ratio of the trunk skinfold sum to the extremity skinfold sum, and (vi) the regression of the trunk-extremity skinfold ratio on the sum of six skinfolds--was analyzed separately with systolic BP and with diastolic BP. Results showed that (1) upper-body fat was the strongest interindividual correlate of BP (especially the correlation of trunk-extremity ratio with diastolic BP), suggesting shared pleiotropic genetic and/or common familial environmental effects; (2) summary body-fat measures either were inconsistent (in the case of both percent body fat and sum of six skinfolds) or gave no evidence of interindividual cross-trait resemblance with BP (in the case of body-mass index); and (3) intraindividual resemblance between the sum of six skinfolds and BP largely vanished once the skinfold sum was adjusted for fat mass, suggesting that the intraindividual association may be mediated largely by the absolute amount of subcutaneous fat rather than by the subcutaneous proportion. Finally, the magnitude of the spouse resemblance for the trunk-extremity ratio with diastolic BP suggests that a significant proportion of the resemblance may be due to environmental influences. In summary, our investigation confirms a heritable link between BP and truncal-abdominal fat as predicted by the metabolic-syndrome hypothesis. That this result is obtained in primarily normotensive, nonobese families, suggests the connection involves normal metabolic paths.

Adipose Tissue↗