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Query: UMLS:C0028754 (obesity)
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Known risk factors for coronary artery disease are very common in the Hopkins Lupus Cohort, in spite of the fact that the average patients age is only 38.3 years. Three or more known risk factors were found in 53% of patients. Risk factors for CAD were common even in patients not on a regimen of prednisone therapy during their cohort follow-up. Hypercholesterolemia increased significantly with greater average prednisone dose. Despite the frequency of risk factors, patients' awareness of the risk of CAD was low, with only 16.9% of patients believing they were at high risk for developing CAD within 5 years. In general, awareness of individual risk factors was lower in black than in white patients with SLE. Preventive practices were most commonly addressed towards hypertension. Preventive practices directed against obesity, hypercholesterolemia, and smoking were underutilized. Whether these known risk factors are sufficient in and of themselves to explain the high frequency of CAD in the cohort (8%) or whether they are "enabling" factors acting upon endothelium damaged by immune-complex disease cannot be addressed by this study. However, both further investigation of these risk factors and attention to lifestyle and pharmacologic approaches to risk factor reduction are indicated by this study.
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PMID:Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. 152 5

Modern contraceptive methods are discussed, with special emphasis on oral contraceptives, which are regarded as the most effective. They are also regarded as generally safe, although there are contraindications and the drugs should only be prescribed after careful examination. The need for selecting the drug most suitable for the individual patients, mainly on the basis of the characteristics of the menstrual cycle (suggesting a predominance of estrogen or progestin, within safety limits, such as 50 mcg of estrogen), is emphasized. The examinations required include a general clinical, gynecological, and breast examination, cytology tests, evaluation of the menstrual flow pattern, measurements of arterial pressure, weight, glucose, cholesterol and triglyceride levels, and urine tests. They should be repeated at 6-month intervals, or 3-month intervals in the case of high-risk patients (varicose veins, obesity, heavy smokers, high cholesterol and triglyceride levels, history of jaundice, slight heart condition, clinical or potential diabetes, porphyria or predisposition to uterine myoma). Oral contraceptives are contraindicated in cases presenting a history of thromboembolism, phlebitis, cerebral apoplexy; sickle cell anemia, which indicates a predisposition to thromboembolic accidents; serious liver disease or recent hepatitis; serious heart disease; hormone-dependent neoplasia (breast cancer); predisposition to uterine cancer; erythematous lupus; metorrhagia of unknown origin; psychic disorders, especially of a depressive type. They should also be avoided for 3-4 years after puberty, in order to avoid interfering with the development of the hypothalamus and with growth. A carcinogenic effect of the pill and an increase in the risk of giving birth to abnormal children can be ruled out, although the incidence of abortions due to chromosome anomalies after suspending treatment is rather high (due to the previous inhibition of ovulation, a situation similar to repeated pregnancies at short intervals, which involve the same risk).
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PMID:[Current clinical problems of contraception]. 502 53

The New Zealand Obese (NZO) mouse was studied as a potential model for autoimmune diabetes. NZO mice develop obesity, glucose intolerance, and insulin resistance, and have low-titer IgM antibodies to the insulin receptor. It is shown that they have circulating antibodies to both native DNA and denatured, single-stranded DNA. The antibody levels are higher in females, and, up to 6 mo of age, are comparable to those found in the related NZB X NZW F1 (NZB/W) mouse, a model for systemic lupus erythematosus. After 6 mo of age the antibody levels in NZO mice fall toward normal, in contrast to the persistently elevated levels in NZB/W mice. NZB/W mice are known to succumb to immune complex-mediated proliferative glomerulonephritis before 1 yr of age, whereas NZO mice survive. NZO kidneys exhibit light microscopic features of both diabetic and lupus nephropathies: glomerular proliferation, mesangial deposits, mild basement membrane thickening, glomerulosclerosis, eosinophilic nodules in some glomeruli, occasional hyalinization of the glomerular arterioles, and healing arteriolar inflammation. These changes are associated with glomerular deposition of immunoglobulin, especially IgM, in a granular pattern on fluorescent staining. The NZO mouse, therefore, has evidence of a generalized immune disorder and provides a model for studying the relationship between autoimmunity, obesity, and diabetes.
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PMID:Diabetes is associated with autoimmunity in the New Zealand obese (NZO) mouse. 700 65

The authors define pro-thrombotic states as conditions associated with a high frequency of thrombosis; this association is based on pathogenetic or simply clinical and epidemiological relationships. Thrombophilic states have well-defined, specific causes: antithrombin III, protein C and S and similar deficiencies for inherited thrombophilias, and lupus anticoagulant, antiphospholipid antibodies for the acquired forms. Another identifiable group is made up of several conditions predisposing to thrombosis (CPT) characterized by less specific and multiple mechanisms (e.g. malignancy, inflammatory bowel disease, nephrotic syndrome, diabetes, obesity, etc.). These conditions may induce thrombosis by themselves or contribute to its clinical onset in patients with true thrombophilic states. This is especially the case for patients who are taking contraceptive drugs, are pregnant, have undergone surgery or trauma. The term hypercoagulability states is by no means equivalent to either thrombophilia or CPT. In fact, hypercoagulability may be defined as "activation of blood coagulation" in the presence of specific markers such as fibrinopeptide A and prothrombin fragment F1 + 2. Hypercoagulability is therefore a laboratory rather than a clinical condition and can be a transient feature appearing during certain phases of thrombophilia or CPT. Lastly, conditions involving the presence of hemostatic risk factors for atherothrombosis are simply terms used to describe a statistical-epidemiological relationship between certain hemostatic variables (fibrinogen, factor VII, PAI, etc.) involving the risk of cardiovascular morbidity and mortality but not necessarily indicating a hypercoagulability state.
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PMID:Pro-thrombotic states and their diagnosis. 800 87

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
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PMID:Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. 962 86

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
Lupus 2000
PMID:Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. 1080 83

We encountered 16 cases of venous thromboembolism (VTE) in women during pregnancy and/or puerperium over the past 15 years at our perinatal center, representing 0.14% of all patients who delivered babies. The present study was undertaken to analyze the risk factors, clinical course and outcomes in these 16 cases. The ages of the patients varied from 29 to 39 years. Four women had pulmonary embolism (PE), 3 of which after caesarean section (C/S) at 35 to 40 weeks, and one case after ovarian cystectomy at 13 weeks of gestation. Twelve cases had deep venous thrombosis (DVT), 4 of which during pregnancy, and the remaining 8 cases after C/S. Four patients who had DVT during a normal course of pregnancy had severe thrombophilia: antiphospholipid antibody syndrome, a history of thrombosis and antithrombin (AT) deficiency. They were treated with heparin with or without AT and had healthy babies via successful vaginal deliveries. The common risk factors in 3 cases of PE with C/S was prolonged bed rest due to threatened premature delivery with total placenta previa, uterine myoma and Ehlers-Danlos syndrome. Other risk factors were massive bleeding, and positive lupus anticoagulant. However, the case of the ovarian cystectomy had only one risk factor, which was obesity. This patient died but the remaining patients recovered with treatment. Because of the low incidence of thrombosis in the Japanese population, prophylactic anticoagulant therapy has not routinely been given to patients undergoing obstetrical operations. However, proper management including prophylactic anticoagulant therapy might be considered for risk patients, depending on the risk factors.
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PMID:Clinical study of venous thromboembolism during pregnancy and puerperium. 1137 69

Deficiency of the weak androgen dehydroepiandrosterone (DHEA) and its sulfoconjugated metabolite DHEA-S has been associated with a number of serious illnesses, including lupus, diabetes, Alzheimer's disease and some cancers. Accordingly, supplementation with DHEA has been proposed for a variety of illnesses. Observational clinical studies and in vitro experiments have suggested that DHEA treatment might have a significant impact on immunological function, bone density, cognition, atherosclerotic disease, some malignancies, insulin resistance and obesity. Endogenous circulating DHEA levels, however, may vary widely by gender, age and ethnicity and can be affected by acute changes in corticosteroid production, alcohol intake, smoking, body mass index, medications and thyroid function [1-3]. Clearly, these variables complicate the interpretation of clinical data. DHEA also gives rise to a number of as yet poorly characterised metabolites, further confusing the assessment of its net effects when considered as treatment in heterogenous populations. Given the complexity of potential effects of DHEA and its metabolites, coupled to the diversity of clinical conditions that they might, at least in theory, affect, it is not surprising that clinical confirmation of efficacy in several clinical contexts has been inconsistent and controversial, hampering drug development in what might potentially be an important and widespread market. The current review will consider recent work suggesting efficacy of DHEA (GL-701, prasterone, Prestara( trade mark ) [US], Anastar( trade mark ) [Europe]; Genelabs) in systemic lupus erythematosus.
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PMID:Dehydroepiandrosterone, a sex steroid metabolite in development for systemic lupus erythematosus. 1278 5

CERTAIN OF THE ACUTE PHASE REACTANT TESTS WERE PERFORMED ON THE SAME SPECIMEN OF BLOOD FROM PERSONS WITH THE FOLLOWING STATES: Normal, acute respiratory disease, streptococcosis, acute rheumatic fever, acute glomerulonephritis, acute rheumatoid arthritis, inactive rheumatic fever, lupus erythematosus, malignant disease, obesity, asthma, and allergic rhinitis. Of the tests performed, the mucoprotein-tyrosine and the antistreptolysin-0 titer when done together appeared to be the most discriminating. It is suggested that the performance of such tests on the same sample of blood might aid in differentiating mild acute rheumatic fever and acute rheumatoid arthritis from each other and also from other disease states.
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PMID:Diagnosis of rheumatic fever and like conditions; evaluation of certain of the acute phase reactants in a single specimen of blood. 1334 8


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