Treating dermatitis artefacta.
Explore the source record for details and available documents.
Dermatitis↗
Biomedical subjects
C MacLean
Publications and source records attributed to C MacLean.
Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome.
We used segregation analysis to investigate the genetic basis of variation in dystopia canthorum, one of the key diagnostic features of Waardenburg syndrome type 1 (WS1). We sought to determine whether the W-index, a quantitative measure of this craniofacial feature, is influenced primarily either by allelic variation in the PAX3 disease gene or other major loci, by polygenic background effects, or by all of these potential sources of genetic variation. We studied both WS1-affected individuals and their WS1-unaffected relatives. After adjustment of the W-index for WS1 disease status, segregation analyses by the regression approach indicated major-locus control of this variation, although residual parent-offspring and sib-sib correlations are consistent with additional (possibly polygenic) effects. Separate analyses of WS1-affected and WS1-unaffected individuals suggest that epistatic interactions between disease alleles at the PAX3 WS1 locus and a second major locus influence variation in dystopia canthorum. Our approach should be applicable for assessing the genetic architecture of variation associated with other genetic diseases.
Alleles↗
Stressful life events, genetic liability, and onset of an episode of major depression in women.
OBJECTIVE: This study was undertaken to clarify how genetic liability and stressful life events interact in the etiology of major depression. METHOD: Information about stressful life events and onset of major depressive episodes in the past year was collected in a population-based sample of female-female twin pairs including 2,164 individuals, 53,215 person-months of observation, and 492 onsets of depression. RESULTS: Nine "personal" and three aggregate "network" stressful events significantly predicted onset of major depression in the month of occurrence, four of which predicted onset with an odds ratio of > 10 and were termed "severe": death of a close relative, assault, serious marital problems, and divorce/breakup. Genetic liability also had a significant impact on risk of onset of depression. For severe stressful events, as well as for 10 of the 12 individual stressful events, the best-fitting model for the joint effect of stressful events and genetic liability on onset of major depression suggested genetic control of sensitivity to the depression-inducing effects of stressful life events. In individuals at lowest genetic risk (monozygotic twin, co-twin unaffected), the probability of onset of major depression per month was predicted to be 0.5% and 6.2%, respectively, for those unexposed and exposed to a severe event. In those at highest genetic risk (monozygotic twin, co-twin affected), these probabilities were 1.1% and 14.6%, respectively. Linear regression analysis indicated significant Genotype by Environment interaction in the prediction of onset of major depression. CONCLUSIONS: Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.
Adult↗
Systemic lupus erythematosus: calciphylaxis induced cardiomyopathy.
A 31-year-old woman with systemic lupus erythematosus (SLE), diabetes mellitus, and chronic renal failure developed digital ischemia, myocardial dysfunction, abnormal ECG, and elevated CPK levels. Radiographic studies revealed calcification of the peripheral vasculature although coronary angiography was unremarkable. An endomyocardial biopsy demonstrated intra and extracellular myocardial calcification without evidence of vasculitis or primary myocarditis. A diagnosis of calciphylaxis, as a result of secondary hyperparathyroidism, was made. This case demonstrates that calciphylaxis can mimic the cardiovascular manifestations of SLE. Early differentiation of these disparate diseases is important because treatment strategies employed in SLE may exacerbate calciphylaxis.
Adult↗
Transcranial assessment of maternal cerebral blood flow velocity in normal VS pre-eclamptic women (variation with maternal posture). A preliminary study.
To compare the effect of a change in maternal posture on maternal cerebral blood flow velocity assessed transcranially in a normal vs a pre-eclamptic group 5 normotensive and 5 pre-eclamptic patients had maternal middle cerebral artery (MCA) blood flow velocity assessed in 2 positions supine and sitting upright using a 2 mHz transcranial doppler ultrasound. Comparison was then made of the effect of a change in posture on cerebral blood flow velocity in both groups using paired student-t test. Normotensive women showed minimal change in MCA blood flow velocity while pre-eclamptic women showed a 20% rise in all aspects of MCA blood flow velocity from supine to sitting. In pre-eclamptic patients MCA blood flow velocity which showed a significant rise with change in posture is not accompanied by significant changes in blood pressure and so is not a secondary response to a change in cardiac output by may be a primary effect related to local circulatory changes. Transcranial assessment of maternal cerebral blood flow velocity performed in normotensive and various hypertensive groups showed significant variation with change in posture in the pre-eclamptic group.
Blood Flow Velocity↗
Transcranial assessment of maternal cerebral blood flow velocity in normal vs. hypertensive states. Variations with maternal posture.
This study compared the effect of a change in maternal posture on maternal cerebral blood flow velocity assessed transcranially in normal vs. various hypertensive groups. Ten normotensive, 10 preeclamptic and 10 chronically hypertensive patients had maternal middle cerebral artery (MCA) blood flow velocity assessed in three positions--left lateral decubitus, supine and sitting upright--using 2-mHz transcranial Doppler ultrasound. Comparison was then made of the effect of a change in posture on cerebral blood flow velocity in each group using analysis of variance with Student's t test for statistical significance. Normotensive and chronically hypertensive women showed minimal changes in MCA blood flow velocity, while preeclamptic women showed a 30% rise in all aspects of MCA blood flow velocity from the left lateral decubitus to sitting up. In preeclamptic women, MCA blood flow velocity, which showed a significant rise with changes in posture, was not accompanied by significant changes in blood pressure and so is not a secondary response to a change in cardiac output but may be a primary effect of local circulatory changes.
Adult↗
Detection of hepatitis C virus infection with recombinant immunoblot assay, synthetic immunoblot assay, and polymerase chain reaction.
The newly developed immunoblot assay, RIBA SIA (recombinant and synthetic polypeptide immunoblot assay), Chiron, Calif., was compared with the commercially available second generation recombinant immunoblot assay (RIBA-2) for the detection of antibody to hepatitis C virus (anti-HCV). The two immunoblot tests were also compared with the polymerase chain reaction (PCR) for the detection of HCV RNA. Ninety-one percent of samples reactive by RIBA-2 were positive for anti-HCV by RIBA SIA. A total of 31% of RIBA-2 indeterminate samples became reactive by RIBA SIA, 24% became non-reactive, and 45% remained the same. Samples reactive by RIBA-2 or SIA from different risk groups, were mostly positive (67-100%) by PCR for HCV RNA. All indeterminate samples from hemophiliacs and intravenous drug users were PCR positive. RIBA SIA is more sensitive and specific than RIBA-2 and correlates well with PCR results.
Female↗
Hepatitis B and C infection in an institution for the developmentally handicapped.
Explore the source record for details and available documents.
Down Syndrome↗
Evaluation of first- and second-generation RIBA kits for detection of antibody to hepatitis C virus.
Samples reactive by first-generation recombinant immunoblot assay (RIBA) to detect antibody to hepatitis C virus (anti-HCV) (RIBA-1 [Chiron, Calif.]) remained reactive by a second-generation test (RIBA-2) for HCV antibodies. A total of 75% of specimens indeterminate by RIBA-1 became reactive, 12.5% were nonreactive, and 12.5% remained indeterminate by RIBA-2. Among RIBA-1-nonreactive specimens, 12.0% became positive and 5.1% became indeterminate by RIBA-2. The antigens c33c and c22-3 have increased the sensitivity of RIBA-2.
Diagnostic Errors↗
The genetic epidemiology of bulimia nervosa.
OBJECTIVE: The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD: Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS: Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS: The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.
Adolescent↗
Smoking, pulmonary function, and mortality.
The association of pulmonary function (as percent of predicted forced expiratory volume in 1 second [FEV1]) with total and cause-specific mortality over 15 to 18 years was investigated in a large cohort (5924) of prospectively followed Japanese-American men. Among those who never smoked, pulmonary function was found not to be significantly predictive of total mortality in a multivariate model in which adjustment for variables that might confound the results was made. Among past and current smokers, highly significant associations were found (P < 0.0001). The positive relationship of pulmonary function to mortality in smokers was so strong that it overshadowed these differences in nonsmokers in a model including all smoking groups combined, even after adjusting for smoking. A smoking-pulmonary function interaction term added to this model was statistically significant (P < 0.003). This illustrates the need for attention to the potential for complex interactions between biologic variables when carrying out multivariate statistical analysis. Findings for cardiovascular and noncardiovascular mortality were similar. This analysis indicates that while pulmonary function is associated with subsequent mortality, the relationship is significantly associated with smoking history.
Asian↗
Orthostatic hypotension, catecholamines, and alpha-adrenergic receptors in mitral valve prolapse.
The reported association of mitral valve prolapse with autonomic dysfunction and neuroendocrine abnormalities is derived from studies of patients selected because of symptoms or specifically referred for investigation. To determine whether such associations occur in nonreferred and unselected women with mitral valve prolapse, we measured blood pressure, heart rate, and norepinephrine response to standing in 13 volunteers with mitral valve prolapse and in 11 control subjects. Platelet alpha-adrenergic receptor quantity and affinity on standing also were determined in all persons. No significant differences were found between the groups in any of these measurements. Although small subsets of women with mitral valve prolapse may indeed have associated neuroendocrine epiphenomena and autonomic dysfunction, it is probably incorrect to generalize these findings to the vast spectrum of those with mitral valve prolapse.
Adolescent↗
Response bias in the Honolulu Heart Program.
The 14-year incidence rates (1969-1982) for coronary heart disease, cerebrovascular disease (stroke), total mortality, and cause-specific mortality were compared between 8,006 examined and 3,130 nonexamined men of the Honolulu Heart Program using identical surveillance procedures. There was a significant decrease in examination participation with increasing age. Examined men smoked less, weighed more, had a higher level of education, and had a lower percentage of never-married status than did nonexamined men. Total mortality rates, cancer mortality rates, and coronary heart disease incidence rates were higher in nonexamined men, while there were no differences in stroke rates. The average annual response error for total mortality and coronary heart disease rates was underestimated at 8.7% and 5.4%, respectively. The differences in rates were greatest during the first half of the follow-up period and converged during the second half. By the end of 10 years, there were no differences between nonexamined and examined men for any of the endpoints studied. The pattern of convergence of rates suggests a diminishing healthy participant advantage over time. In conclusion, a response bias did occur in this study, but the effect was small and did not alter any of the earlier findings concerning the relative incidence of cardiovascular disease. Because the degree of response bias can vary widely depending on when during follow-up a particular analysis is undertaken, it is recommended that prospective studies monitor, insofar as possible, a sample of nonparticipants in order to ensure valid results.
Aged↗
A prospective study of cerebral artery atherosclerosis.
Atherosclerosis in the circle of Willis and its major branches was studied prospectively in 198 men in the Honolulu Heart Program who were free of cardiovascular disease at the entry examination. The level of atherosclerosis was greater in the large arteries of the circle of Willis than in the small arteries, and autopsy-verified cerebral infarction was strongly associated with increasing severity of atherosclerosis in both. Analyses of the association of atherosclerosis scores with biologic and lifestyle characteristics measured at entry into the study indicated that atherosclerosis in the large arteries was consistently related to age, diastolic blood pressure, serum cholesterol, and height (inversely). Weak trends of association were also found with increasing serum glucose concentration, increasing cigarette use, and decreasing alcohol intake. Atherosclerosis scores in the small arteries were associated with diastolic blood pressure and serum triglyceride concentration. Analysis of dietary intake indicated that atherosclerosis scores were higher for men who reported low intakes of fat and animal protein and high intakes of vegetable protein and total carbohydrates. These patterns were consistent with similar findings on the incidence of clinical stroke in this cohort. Age-adjusted and -specific atherosclerosis scores from both the large and small arteries declined significantly during the period 1965-1983.
Age Factors↗
"Substance M", a serotonin modulator candidate from human urine?
Explore the source record for details and available documents.
Carrier Proteins↗
Does obesity protect hypertensives against cardiovascular diseases?
Recent studies suggest that obesity may protect hypertensives against cardiovascular disease (CVD). This concept was investigated by the Honolulu Heart Program, a prospective epidemiologic study of CVD in a cohort of Japanese-American men aged 45 to 65 years who have been followed up for 12 years. The combined effect of body mass index (BMI), as a measure of obesity, and blood pressure on coronary heart disease and CVD incidence was examined in 7554 men who were free of CVD and cancer at baseline. Rates of coronary heart disease and CVD were higher in the most obese than in the nonobese men for both normotensives and hypertensives. Blood pressure-BMI interaction was not significant for any CVD end point. Hypertension was associated with higher rates of coronary heart disease and CVD at all levels of BMI. This study supports the conclusion that hypertension is associated with an increased risk of CVD in both obese and nonobese men and that the relationship of blood pressure to CVD incidence does not vary with level of BMI. The inclusion of prevalent cases of CVD and the collapsing of continuous data into two categories may explain the results of earlier studies.
Aged↗
The product of gene US11 of herpes simplex virus type 1 is expressed as a true late gene.
The genes of herpes simplex virus type 1 (HSV-1) can be divided into at least three temporally regulated groups termed immediate early (IE), early and late. We have studied in detail the expression of a member of the late class of genes, US11, which encodes a polypeptide of apparent molecular weight 21K. Highly specific and sensitive probes were used to monitor US11 RNA and protein synthesis during HSV-1 infection of tissue culture cells in the presence and absence of phosphonoacetic acid, an inhibitor of viral DNA replication. The results were compared with a similar study of the products of a delayed early gene, US6, encoding glycoprotein D (gD). It was found that the patterns of RNA and protein synthesis from US11 were significantly different to those of gD. US11 products appeared later and accumulated until late in infection, while gD RNA was significantly reduced at late times. In the presence of the inhibitor of DNA synthesis, US11 gene expression was reduced 50- to 100-fold while gD expression was reduced five- to tenfold. We conclude that US11 behaves as a true late gene during HSV-1 infection. However, the use of sensitive assays, which allowed the detection of very low levels of US11 gene products under conditions designed to eliminate DNA replication, brings into question the absolute requirement for DNA replication for the expression of a true late HSV-1 gene. These results are discussed in terms of current models for the regulation of late gene expression.
Animals↗