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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The collared lemming, Dicrostonyx stevensoni Nelson, possesses special characteristics which make it a useful animal model for the study of hypercholesteremia, atherosclerosis, breast cancer, kidney disease, and other biomedical research problems. Hematologic values for the lemming were similar to those for the laboratory white mouse except for smaller erythrocytes and fewer leukocytes. Organ weights, when compared as a percent of total body parts, differed only slightly from those of white mice. The basal metabolic rate, measured between 25-30 degrees C, was 40% higher than the standard metabolic rate for a mammal of similar size. Litter size at birth averaged 2.8 in captivity. The mean life span of 254 colony-reared lemmings dying from natural causes was 189 da. Growth rate was rapid during the first 2 mo of life, with moderate increases thereafter to an adult weight of approximately 70 g. Husbandry requirements included the use of shavings as litter and facial tissue as nesting material, all of which was changed weekly. Oats, wheat germ, rabbit pellets, carrots, and lettuse were offered as food.
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PMID:The collared lemming (Dicrostonyx stevensoni Nelson) in biomedical research. 112 Nov 64

Estrogen replacement therapy may offer significant benefits to nearly all postmenopausal women, especially those for whom the menopause occurred at an early age. Women at high risk for atherosclerosis, or who already have cardiovascular disease, may particularly benefit from estrogen use. The increased risk for endometrial and breast cancer seen with estrogen replacement therapy is low in comparison with its protective effect against cardiovascular disease. For women who cannot or choose not to take estrogens, etidronate may be of value in preventing osteoporotic fractures. For women many years beyond menopause who consume low-calcium diets, calcium supplementation should be recommended.
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PMID:Menopause: advanced management strategies. 181 2

Current findings and controversies between oral contraceptives (OCs) and cardiovascular disease and cancers. Specifically, venous thromboembolism, stroke, myocardial infarction, (MI), atherosclerosis, breast cancer, cervical cancer, endometrial cancer, and ovarian cancer are reviewed. The concentration in the literature is on higher dose estrogen (at least 50 mg) studies which suggest that there is with current users, particularly older women who smoke, a risk of myocardial infarction, venous thrombosis, and subarachnoid hemorrhage. Of the 11 case control studies and 4 cohort studies it appears that venous thrombosis increases in risk with an increase in estrogen content and remains constant for duration of use. However, definitive studies have not been completed on 50 mg doses of ethinyl estradiol (EE) and mestranol (ME). The actual individual risk may be small, 1/1000 current users/year. Thrombotic and hemorrhagic stroke in the 1970s had a risk of 37/100,000 users per year, mostly among smokers 35 years and older with predisposing medical conditions. It is suggested that although there were mixed findings between current and past users in the 1970s low dose current or past users are not substantially at risk. The pre-mid 1970 risk of MI was 7 and 67 cases/100,000 current users ged 30-39 respectively per year. The risk group is similar to stroke. Thrombosis seems to be responsible for the increased risk, rather than atherosclerosis. More data are needed on low preparations; however limited findings suggest little if any risk. There is no available data on the risk for coronary artery atherosclerosis due to OC use, even though 50% of all women die from atherosclerosis-related processes regardless of OC use. Non human primate studies, however, suggest that there may be a reduced risk, perhaps due to the presence of estrogen receptors in arterial endothelium and smooth muscles. Data clearly indicate that the overall risk of breast cancer pre and post 1950 is the same, but age may be a factor with younger OC users at risk; parity protects. The association for lifetime risk, however, cannot be determined since most use occurred in the 1960s. For cervical cancer, 8 found no increased risk and 9 did, and the suggestion is the 5 years use is related to increased risk. Biases related to sexual behavior confound control and analysis of data. The most common cancer in developing countries is cervical, which warrants greater Pap smear screening to reduce this preventable cancer. Protection from cancer of the endometrium occurs for 15 years following 12 months of OC use at a 40% reduced risk. A protected effect is also found for epithelial ovarian cancer, with a 40% risk reduction. It is concluded that health benefits of OCs far exceed the health risks.
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PMID:Long-term health risks and benefits of oral contraceptive use. 209 41

The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.
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PMID:Contraception. 210 26

Progestins counteract the positive effect of the estrogen component in oral contraceptives (OCs) on cholesterol levels thus increasing the risk of atherosclerosis. Low androgenic potency progestins do not have a negative effect, however. Other research indicates that the lower the estrogen dose in OCs the lower the risk of deep vein and superficial thrombosis. OC users, especially low dose OC users, with no other risk factors (e.g. smoking and hypertension) are not at increased risk of cardiovascular disease. Some research demonstrates elevated risk of stroke in OC users, however. Elevated cholesterol, obesity, diabetes and other factors further increases the risk of stroke. Combined OCs protect against endometrial and ovarian cancer and this effect increases with use and continues after use. Moreover OC users are not at increased risk of pituitary adenoma. Results of some studies shows an increased risk of cervical cancer, but other only demonstrates a slight increase. So far research does not indicate the following to increase breast cancer risk among OC users: early age at 1st OC use, formulation, family history, and history of benign breast disease. There is an increased risk for liver tumors in OC users, nevertheless it is rare. OCs do not raise the risk of diabetes or gallbladder disease. High dose formulations increases the risk of high blood pressure, but not so with low dose formulations. OC use does not impair, fertility, but delayed conception often occurs. Most research demonstrates no increase in pelvic inflammatory disease in OC users. OCs do not cause congenital malformations. Combined OC use is contraindicated for breast feeding mothers, but progestin only OCs can be used with no advance effects. Results of 1 study demonstrates an increase in HIV infection in OC users, but another study has opposite results. The article concludes with recommended clinical management practices.
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PMID:Reassessment of the metabolic effects of oral contraceptives. 185 68

The successful evaluation of tamoxifen as an antiestrogenic therapy for advanced breast cancer in the early 1970's, has resulted in its availability in more than 70 countries around the world. Currently the drug development process is focusing attention upon long-term adjuvant therapy and the future prospect of chemosuppression. Progress at this stage, however, must be cautious. Trials conducted using women with stage I disease have a high proportion of women who may never have a recurrence. At this point, the risk is justified because the toxicity of tamoxifen is low and disease recurrence is invariably very difficult or impossible to control. Future studies in the general population must be carefully weighed to ensure that the hazards do not exceed the benefits. The pharmacology of tamoxifen seems to be a balance of estrogenic and antiestrogenic effects. Longer treatments with the drug must be carefully monitored. Uterine tissue should be examined to ensure that excessive stimulation does not occur. This is particularly true in the light of the recent report that a human uterine carcinoma, transplanted into athymic mice, can grow more rapidly during tamoxifen therapy (Satyaswaroop et al., 1984; Clark and Satyaswaroop, 1985). In fact, we have recently confirmed this observation in a collaborative study with Dr. Satyaswaroop. We have demonstrated that when athymic mice are transplanted in one axilla with an MCF-7 breast tumor and the human endometrial tumor in the other, tamoxifen causes the endometrial tumor to grow, but not the breast tumor. This again illustrates the target site specific effects of tamoxifen. If, in the long run, the estrogenic side effects of tamoxifen are too severe then there is a case for the development of a non-estrogenic antiestrogen. Clearly this may provide benefit for short term (1-2 years) therapy and avoid any estrogen-like stimulation of tumor growth. Similarly, the concern about antithrombin III depression will be avoided. On the negative side, however, the concerns about atherosclerosis and osteoporosis will again have to be addressed with a new generation of agents.
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PMID:Long-term tamoxifen therapy to control or to prevent breast cancer: laboratory concept to clinical trials. 328 87

Epidemiological studies of oral contraceptives pertaining to premenopausal women are briefly reviewed. Therapeutic considerations are noted. The clinical effects of aging and hormone replacement therapy are indicated in terms of metabolism, the endometrium, and bone mass. The pharmacological advantages and consequences of nonhormonal and hormonal contraception are explored. For aging women over 40, there is a need for relief of menopausal symptoms, contraception, and reduction of risks for atherosclerosis, hypertension, coronary heart disease, endometrial carcinoma, breast cancer, and osteoporosis. With the availability and use of low estrogen products, women over 40 can insure tissue support and prevent bone loss as long as the therapy is instituted within 3 years of the last menses. Over-40 women who drink and smoke should not use oral contraceptives. Sterilization does not satisfy longterm hormonal needs, and has other reported menstrual side effects. The dose and duration regimen of hormonal therapy must be carefully considered due to the effects on the endometrium., the coagulation system, the liver, lipids, and bone. Combination estrogen and progestogen is necessary, but consideration must be given to existing levels of endogenous hormones. Lipid patterns may change due to hormone replacement or as a result of aging and contribute to coronary heart disease. Hormone replacement can reverse the atherogenic pattern of increased low density lipoprotein levels and decreased high density lipoprotein levels; a chart gives the effects on lipids and coagulation from various estrogen or estrogen plus progestogen products. For the estrogen-deficient menopausal woman, high estrogen can decrease antithrombin III plasminogen and alpha-antitrypsin antigen levels. Lower dose progestogens are recommended. Studies of dose and effects on bone mass are reviewed and vaginal rings and transdermal steroid patches, triphasic formulations, and new progestational agents such as 19-nortestosterone derivatives are described. Newer low dose formulations are needed for the aging woman, as well as further research on what product best suits the variability of women aged 40-50
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PMID:Contraception for the perimenopausal patient. 330 20

Serum proteins and lipoproteins were determined in 23 menopausal females after surgery for early forms of breast cancer and the results compared with data from a matched group of randomly selected healthy females. The patients were randomly divided into 2 groups, one serving as a control group, the other receiving 40 mg tamoxifen daily for 2 months. Breast cancer patients were found to have significantly higher concentrations of serum cholesterol than controls (7.90 +/- 1.15 vs. 6.87 +/- 1.18 mmol/l, P less than 0.001), which was the result of a 16% higher concentration in LDL cholesterol (P less than 0.05) and a 13% higher concentration in HDL cholesterol (P less than 0.05). During tamoxifen therapy total TG tended to increase, whereas total cholesterol fell. Significant lipoprotein changes were found in the LDL fraction where LDL-TG increased from 0.46 to 0.56 (P less than 0.01) and LDL cholesterol fell from 5.11 to 4.10 mmol/l (P less than 0.001). During tamoxifen therapy haptoglobin and orosomucoid concentrations fell significantly (P less than 0.01), whereas those of alpha-antitrypsin and ceruloplasmin increased (P less than 0.001). Factors such as diet and weight may explain the differences between breast cancer patients and controls. The tamoxifen-induced changes indicate that this anti-oestrogen exerted a mild oestrogen-like effect with regard to protein and lipoprotein metabolism.
Atherosclerosis 1984 Sep
PMID:Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. 649 36

The study included 191 patients with obesity, atherosclerosis, diabetes mellitus, endometrial cancer, breast cancer and healthy subjects of various age. Somatomedin activity was determined by incorporation of radioactive natrium sulfate in vitro into the cartilage of female rats. The results of the study showed that somatomedin activity was not changed in subjects with normal metabolic parameters and ranged from 0.47 to 0.69 U/ml. In patients with diabetes mellitus, atherosclerosis and obesity accompanied by increased blood concentration of cholesterol and triglycerides, somatomedin activity rose up to 1.36- 1.62 U/ml. In patients with breast and endometrial cancer somatomedin activity was also increased, particularly in those with hypercholesterolemia and hypertriglyceridemia (3.04 U/ml for breast cancer patients and 2.20 U/ml for endometrial cancer patients). Theoretically, this may promote proliferation of somatic cells and thus contribute to tumor processes in oncological patients whose pool of cells is extremely sensitive to mitogenic agents.
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PMID:Interrelation between lipidemia and somatomedin activity in cancer and age-associated pathology. 713 38

Cardiovascular diseases remain the leading cause of death in American women. Evidence from epidemiological studies indicates that estrogen replacement therapy in postmenopausal women can reduce their risk of coronary heart disease. Current users, in particular, appear to enjoy the most substantial cardiac benefits. It remains possible that the protective effect of estrogen observed in these studies may be due, in part, to bias. Women who use estrogen see a physician regularly, and compliance with estrogen therapy may identify a low-risk group of women. Furthermore, women who choose to use estrogen may lead generally healthier lifestyles than those who do not take such medication. However, adjustment for known cardiac risk factors in many of the large studies had little impact on the results, implying an equivalent risk status for users and nonusers. In addition, both animal and human studies show that estrogen use lowers low-density lipoprotein cholesterol levels, increases high-density lipoprotein cholesterol levels, improves blood flow, and reduces atherosclerosis. The effect of progestin added to estrogen therapy has not been adequately assessed, but initial evidence suggests that it may somewhat attenuate, although not completely eliminate, the benefits of estrogen on cardiovascular disease. Finally, each individual woman differs in her particular risks and benefits, and careful consideration of each woman's unique situation is required; the fear of breast cancer should be considered, together with the knowledge that many interventions are available to reduce the risk of cardiovascular disease.
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PMID:The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. 749 82


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