Diane C. Tucker

Blood pressure reactivity to psychological stress and coronary calcification in the Coronary Artery Risk Development in Young Adults Study.

A longstanding hypothesis is that individuals who exhibit large increases in blood pressure during psychological stress are at risk for atherosclerosis. We tested whether blood pressure changes during psychological stress predict subsequent coronary calcification (CaC) in young healthy adults. We evaluated 2816 healthy black and white women, 20 to 35 years of age, from the Coronary Artery Risk Development in Young Adults Study, who were not using medication for hypertension or diabetes in 1987–1988. Participants completed video game and star tracing tasks while their blood pressure was recorded. Thirteen years later (2000–2001), they completed computed tomography measures of CaC. Overall 9.3% (261 of 2816) had CaC present at follow-up. Each 10 mm Hg change in systolic blood pressure during the video game was associated with a 24% increased odds of having CaC at follow-up (unadjusted odds ratio, 1.24; 95% CI, 1.06 to 1.46; P=0.008). This association persisted after adjustment for age, race, sex, education, smoking, alcohol, family history of myocardial infarction, smoking, daily alcohol consumption, body mass index, and resting or baseline blood pressure (odds ratio, 1.31; 95% CI, 1.08 to 1.58; P=0.006). Blood pressure changes during the star tracing task were not associated with subsequent CaC. Blood pressure changes during a video game predicted the presence of CaC 13 years later. To our knowledge, this is the first study that reports blood pressure reactivity to a stressor being related to calcification in the coronary arteries. Blood pressure reactivity may provide useful prognostic information about future risk beyond standard risk factors.

Knowledge About Genetic Risk for Breast Cancer and Perceptions of Genetic Testing in a Sociodemographically Diverse Sample

Informed consent for genetic testing for breast–ovarian cancer susceptibility requires that women understand basic concepts about the inheritance of cancer susceptibility and the benefits and risks associated with genetic testing. Women awaiting routine medical services (N = 220) were surveyed about their knowledge of breast cancer and cancer genetics and their perceptions of genetic testing and personal risk. There were no racial differences in median income or mean level of education. Compared to Caucasian women, African American women knew significantly less about breast cancer and about genetic risk for breast cancer. African American women had different psychological, social, and economic concerns as evidenced by how they weighted the benefits and risks of genetic testing. This study is the first to assess several dimensions of informed consent for genetic testing among a sociodemographically diverse group. The findings should enable health professionals to target the African American and lower-income populations with the appropriate education and counseling.

Use of the Internet for Information and Support: Disclosure Among Persons With Breast and Prostate Cancer

The present study examined the feasibility of evaluating online communication of cancer patients using an automated content analysis program modified for application to cancer-related communication. Public messages posted to the Breast Cancer Discussion List and the Prostate Problems Mailing List were content analyzed using an augmented version of Linguistic Inquiry and Word Count to evaluate communication styles within these two cancer types. Breast cancer patients were more likely to submit multiple messages to the list and made greater use of words related to emotional disclosure and cognitive processing compared with prostate cancer patients. Prostate cancer patients were less likely to seek emotional support or repeated interaction with other patients, and more of their communication focused on cancer-related information. Use of cancer-specific word libraries significantly increased word identification within these samples. Content analysis of online communication appears to be a promising method for detecting communication differences among subgroups of cancer patients.

Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis

OBJECTIVE:The aim of this study was to evaluate patient compliance with phlebotomy therapy of hemochromatosis-associated iron overload.METHODS:We reviewed medical records of white adults with hemochromatosis and iron overload diagnosed during medical care. We defined three elements of compliance: 1) achieving iron depletion (serum ferritin ≤ 20 ng/ml); 2) timeliness of phlebotomies on a weekly or biweekly schedule to achieve iron depletion; and 3) participation in therapy to maintain serum ferritin ≤ 50 ng/ml. We evaluated associations of timeliness of phlebotomy and participation in maintenance therapy with these variables: age at diagnosis, sex, pretreatment serum ferritin concentration, HFE genotype, units of blood removed to achieve iron depletion, and presence or absence of cirrhosis at diagnosis.RESULTS:A total of 118 patients were evaluable for iron depletion and 142 for maintenance therapy; 96.6% achieved iron depletion, and 33.1% and 43.2% followed weekly and biweekly schedules, respectively. Timeliness was not significantly associated with the variables we evaluated. In the first year of maintenance therapy, 84.0% of patients complied; the percentage of C282Y homozygotes complying was significantly greater than that of other patients. Average compliance with maintenance therapy decreased 6.8% annually; the mean follow-up after achieving iron depletion was 4.1 ± 2.8 yr (range 0.6–9.7 yr).CONCLUSION:Most patients with hemochromatosis diagnosed in medical care achieve iron depletion with phlebotomy; one-third tolerate and adhere to weekly phlebotomy. There is a constant rate of decline in the percentage of patients who comply with maintenance therapy.

Neovascularization of Embryonic Rat Hearts Cultured in oculo Closely Mimics in utero Coronary Vessel Development

Coronary neovascularization was studied following grafting of avascular hearts from gestation day-12 (E-12) rat embryos to the anterior eye chambers of adult rats. Volume densities (Vv) of vessels, myocytes, and the extracellular matrix (ECM) after 3-7, 14, 21, and 35 days in oculo were compared to Vv in hearts developing in utero at E-15, E-18, and E-20. The myocardium in both models exhibited similar vessel Vv and capillary developmental stages: (1) clustering of endothelial cells and red blood cells; (2) endothelial cell migration, and (3) tube formation/maturation. The Vv of myocytes increased while that of the ECM remained constant over time. Cross-species grafting utilizing species-specific antibodies determined that the majority, but not all, of the 10-day graft vasculature was of graft origin. Therefore, both de novo growth (vasculogenesis) and sprouting (angiogenesis) were occurring in oculo. Tracer molecules infused into host rats reached the outermost graft vessels only after 10 days in oculo, suggesting a functional link with the host circulation after this time. Thus, we have shown that both models exhibit similar: (1) vascular Vv; (2) shifts in Vv of nonvascular components; (3) stages of neovascularization, and (4) mechanisms of neovascularization. In conclusion, coronary neovascularization occurring in oculo closely mimics normal coronary vessel development.

Quantification and localisation of angiotensin II receptors and angiotensin converting enzyme in the developing rat heart

OBJECTIVE The aim was to determine the quantification and localisation of angiotensin II receptors and angiotensin converting enzyme (ACE) in the developing rat heart. METHODS Quantitative autoradiography was used to determine the density of [125I]Sar1-angiotensin II binding to angiotensin II receptors and the density of [125I]351A binding to ACE. RESULTS Angiotensin II receptors were first detected in the myocardium on embryonic day 14, and reached a maximum density within the first postnatal week. During the perinatal period, the density of angiotensin II receptors was twofold higher in atrial than in ventricular myocardium [27(SEM 7) v 11(1) fmol.mg-1 protein]. By adulthood, however, the density of angiotensin II receptors did not differ between atria and ventricles. A high density of angiotensin II receptors was first detected in the cardiac vasculature on embryonic day 19, with binding density decreasing during development. During the embryonic and early postnatal periods, most of the binding in the cardiac vasculature was to AT2 receptors. ACE was first detected in the myocardium on the day of birth, with the density of binding to ACE increasing during development. On postnatal day 56, the density of binding to ACE was fourfold higher in atrial than in ventricular myocardium [99(22) v 22(4) fmol.mg-1 protein]. A moderate density of binding to ACE was first detected in the cardiac vasculature and heart valves on embryonic day 19, with binding density increasing during development. By adulthood, the density of binding to ACE was 10- to 25-fold higher in the cardiac vasculature and heart valves than in the myocardium. CONCLUSIONS The density of angiotensin II receptors and the density of binding to ACE are developmentally regulated in the heart. Both AT1 and AT2 receptors were present in the rat heart by late gestation and could, therefore, mediate the effects of angiotensin II on early cardiac growth and development.

Patient acceptability of genotypic testing for hemochromatosis in primary care

Purpose: Genetic screening can enable timely detection and treatment of hereditary hemochromatosis (HH). Little is known about patient acceptability of DNA testing as compared to conventional phenotypic testing.Methods: Within the HEIRS Study, a large primary-care screening study of HH and iron overload, we randomly assigned participants to receive brief information on either HH genotypic or phenotypic testing, and assessed the willingness to accept this test. The study was designed to recruit an equal number of African Americans and Caucasians.Results: A total of 2500 participants were recruited from waiting rooms of primary care practices; 2165 participants who self-identified as African Americans and Caucasians were included in the analyses. Overall, 56% had accepted a genotypic test versus 58% for a phenotypic test. Adjusting for Field Center (FC), age, gender, race, educational attainment, global health rating, and knowledge of the test, the odds ratio of accepting a genotypic versus phenotypic test was 0.85 (95% CI: 0.71, 1.02; P = 0.078). Characteristics associated with test acceptance were age 45–64 years, female gender, Caucasian race, self-rated health less than “very good”, and knowledge of the test. Test acceptance was associated with interest in knowing more about health (81%) and in helping family members (71%). Refusal reasons included a need to talk with a doctor (44%), concern about privacy (32%), and dislike of blood drawing (29%).Conclusion: In this diverse sample of primary care patients, stated acceptance of genotypic testing for HH mutations was similar to phenotypic testing for blood iron. Patient education regarding the nature of test, importance of disease detection, and privacy protection appear to be essential for achieving high rates of screening participation.

Investigation of the effects of gender and preparation on quality of communication in Internet support groups

Abstract The present study examined communication among males and females participating in Internet support groups. Previous qualitative research on Internet support groups has suggested that female cancer patients exhibit higher levels of emotional expression than males, and male cancer patients use Internet support groups for information exchange. We developed a laboratory-based protocol for investigating gender differences in online communication, testing the hypothesis that preparation for the online groups would increase levels of disclosure. One hundred and sixty-seven undergraduates were enrolled in same-gender support groups to discuss the shared experience of having a loved one with cancer. Participants were randomized to one of three preparation groups: minimal instruction, detailed instruction with social modeling, and detailed instruction with social modeling and practice. Linguistic Inquiry and Word Count was used to measure levels of emotional and cognitive expression in messages sent to the group. Participants used increasing levels of emotional and cognitive expression over time; this pattern was not altered by preparation and did not differ between males and females. The levels of emotional and cognitive expression during Internet communication suggest that the Internet may be a viable medium for the provision of psychosocial services to people in need of supportive care, such as cancer patients.

Indicators of Delayed Maturation of Rat Heart Treated Prenatally with Dexamethasone

We investigated the effects of prenatal dexamethasone treatment on indicators of cardiac maturation: heart weight/body weight ratios, myosin heavy chain (MHC) expression, cell proliferation, and extracellular matirix. We administered dexamethasone, a synthetic glucocorticoid (approximately 48μg/d, 3-wk slow release pellets), to pregnant rats (n = 8) beginning at 17 d postconception. Control dams were unmanipulated (n= 8). After approximately 4-5 d of dexamethasone exposure, hearts were collected from neonatal rats (12-24 h after birth). The prenatal dexamethasone treatment produced smaller pups with larger heart/body weight ratios, accompanied by a higher proliferative index and a reduction in extracellular matrix in the ventricles (with lowest values in the septal region) compared with control pups. We also report that, although there were no sex differences in body mass or heart and heart/body weight ratios, females had a greater proportion of cells synthesizing DNA in the heart. In addition, ventricles of male pups treated with dexamethasone contained lower levels of α-MHC mRNA, as reflected in a sex by treatment interaction. The changes in each parameter are consistent with delayed maturation. Our findings suggest that exposure to excess glucocorticoids in utero can affect cardiac development in potentially detrimental ways and that assessment of cardiac function should be closely monitored when such circumstances arise.

Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation.