Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds.

A newly recognized familial hyperlipoproteinemia, familial hyper-alpha-lipoproteinemia, is described in 18 kindreds. Affected probands and relatives had distinctive elevations of alpha-lipoprotein cholesterol (C-HDL), slight elevations of total cholesterol, no elevation of LDL and VLDL cholesterol, and normal triglyceride levels. The proband and at least one additional first degree relative had distinctive elevations of C-HDL in 16 of 18 kindreds. Simple segregation analysis involving 84 offspring of 22 hyper-alpha X normal-alpha matings from these 16 kindreds revealed a ratio of hyper-alpha to normal of 37:47, a ratio not significantly different from 1:1 (chi 2(1) = 1.2), the ratio consistent with autosomal dominant transmission. Despite the suggestion of a major gene effect by this analysis, evaluation of the C-HDL distribution in kindred members failed to reveal bimodality, and familial correlation analysis revealed no parent-offspring correlation. The present data suggest that an environmental cause common to sibships is possibly important in causing the disorder. Longevity analysis demonstrated elongation of life expectancy for kindred members, and there was an apparent rarity of premature cardiac events.     

Causal analysis of academic performance

Maximum likelihood methods are presented to test for the relations between causes and effects in linear path diagrams, without assuming that estimates of causes are free of error. Causal analysis is illustrated by published data of the Equal Educational Opportunity Survey, which show that American schools do not significantly modify socioeconomic differences in academic performance and that little of the observed racial difference in academic performance is causal. For two races differing by 15 IQ points, the differential if social class were randomized would be only about 3 points. The principle is stressed that a racial effect in a causal system may be environmental and that its etiology can be studied only by analysis of family resemblance in hybrid populations.PGL Paper No. 155. This work was supported by Grants GM 17173, 1-K3-GM-31, 732, GM HD16697, and HD06003 from the National Institutes of Health.     

Major gene model for the inheritance of catechol-o-methyltransferase activity in five large families

Five large families including 1,189 individuals were each ascertained through one proband with essential hypertension. Four of the probands were white and one was black. Erythrocyte catechol-o-methyltransferase (COMT) activity was measured in 551 family members. Standard statistical methods were used to investigate sex, age, and family differences in COMT activity. Maximum-likelihood methods were used to fit mixtures of normal distributions to COMT activity. COMT activity is distinctly bimodal. Pedigree segregation analyses were performed on the untransformed COMT values, their square roots, and natural logarithms in each family. In no family and under none of the three transformations was it possible to reject the hypothesis of Mendelian transmission of a major gene with two alleles in Hardy-Weinberg equilibrium. In most cases a genetic hypothesis with complete dominance or recessiveness, or a hypothesis of equal transmission probabilities was rejected. While the different transformations had a large effect on the skewness and kurtosis of the overall distribution of the data, they had little effect on the outcome of these segregation analyses. Therefore, this study strongly supports the concept that variation in COMT activity is due in large part to the effects of a major gene.     

Colorectal carcinoma screening procedure use among primary care patients

BACKGROUND: Despite evidence-based recommendations for colorectal carcinoma screening, population-based surveys report low screening rates. To the authors' knowledge, the extent to which screening procedures are used by patients seen in primary care is not as clear. The authors estimated the annual and 5-year colorectal carcinoma screening procedure use among a cohort of primary care patients and evaluated the correlation between patient characteristics and the use of screening procedures. METHODS: The authors identified a cohort of patients (n = 21,833 patients) ages 55-70 years who had a primary care visit in 2003 and who were enrolled in a health plan for the 5-year period ending December 31, 2003. Using automated data for the 5-year period ending December 31, 2003, information on patient sociodemographic characteristics, primary care and health maintenance examination (HME) visits, comorbid diagnoses, income, and screening receipt was compiled. The latter included barium enema, colonoscopy, fecal occult blood testing (FOBT), and flexible sigmoidoscopy use. RESULTS: Approximately one-half of insured, primary care patients (54%) received recommended colorectal carcinoma screening procedures over the 5-year observation period. Among individuals who received screening, colonoscopy was used most frequently (39.9%), followed by flexible sigmoidoscopy testing alone (28.3%) or in combination with FOBT (4.3%). Annual screening rates increased by 3.1% between 1999 and 2003. Among individuals who did not receive recommended colorectal carcinoma screening, 64% had at least 3 HME visits, and 41% received at least 1 FOBT. Increasing HME visits and other primary care visit frequency, along with increasing age, income, male gender, and African-American race, were associated with screening receipt. CONCLUSIONS: Significant opportunities exist to increase colorectal carcinoma screening among primary care patients.     

The malignancy of dementias

Sruvival times were determined for 982 patients admitted over a ten-year period to the Geneva Psychiatric Clinic. Patients with dementia had one-third the life expectancy of controls. Among patients classed as having Alzheimer disease, the longest survival times were in those with neurofibrillary tangles involving the neocortex, while those lacking this anatomical abnormality had the shortest survival times. Except for women with Alzheimer disease, patients with dementia had less than 10% life expectancy from the time of their admission to the clinic compared to the life expectancy of Geneva's population.