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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

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

Venous thromboembolism is a common and potentially fatal disease. If properly used, anticoagulation therapy is effective in preventing recurrence of venous thromboembolism and in improving survival. Symptomatic patients with an objective diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should receive immediate systemic heparin anticoagulation at dosages sufficient to rapidly prolong the activated partial thromboplastin time into the laboratory-specific therapeutic range; this range corresponds to a plasma heparin concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration), or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should be started within 24 hours after starting heparin; the starting dose should be the estimated patient-specific daily dose with no loading dose. Heparin and warfarin anticoagulation should be overlapped for at least 4 to 5 days and until the international normalized ratio (INR) is within the therapeutic range (2.0 to 3.0) on 2 measurements made at least 24 hours apart. The duration of warfarin anticoagulation should be individualized based on the respective risks of venous thromboembolism recurrence and anticoagulant-related bleeding. In general, warfarin should be continued for at least 3 months, and longer for patients with recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic disease with extremity paresis, obesity, or laboratory evidence of a lupus anticoagulant/anticardiolipin antibody, homozygous carrier or combined heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A mutations, and possibly deficiency of either antithrombin, protein C, or protein S. Low molecular weight heparin (LMWH) is effective and well tolerated as acute therapy for patients with DVT or stable PE, and does not require laboratory monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and cost effective for most patients with DVT, and possibly for selected patients with PE.
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PMID:Current management of acute symptomatic deep vein thrombosis. 1472 51

The vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk factors. The risk factors of VPP classified as moderate include age (> or = 35 years), increased blood pressure during the second trimester of pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic diseases. Risk is significantly elevated among obese (BMI > or = 25), primiparous women, women with a past familial history (first degree) of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria, hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia (antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous thromboembolism or vascular placental pathology remains controversial.
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PMID:[Vascular placental pathology in high-risk groups: definition and synopsis]. 1502 87

Paraguay is a landlocked country located in South America with a total population of 5,884,491. Most of the population (95%) is mestizo, a mixture of Spanish and American/Indian races. The total number of indigenous people in the country has increased from 38,703 in 1981 to 85,674 in 2002. The gross domestic product per capita was US $932.00 annually per person in the year 2002. Between 1992 and 1997, there were 380 patients on chronic dialysis in Paraguay and 75 patients received renal transplants, mostly living-related. The prevalence of renal replacement therapy was 87 patients per million, and the incidence of renal disease continues to rise. Seventy percent of cases of ESRD are of unknown etiology and 15% have diabetes-related renal disease. Only citizens covered by the employee's national health insurance have complete coverage for dialysis and transplantation. The remainder of the population has to apply to public hospitals when the need for hemodialysis arises. At such hospitals, they can receive hemodialysis coverage from the National Institute of Nephrology or from other medical foundations to obtain entrance to these programs. They must otherwise use their own resources to pay for treatment. Seventy percent of patients on chronic dialysis turn to public hospitals for treatment. Hospital hemodialysis is the method most widely used. Home dialysis is rarely performed and there are very few programs for ambulatory peritoneal dialysis. Thus, a large number of patients are not able to enter chronic dialysis programs. In a recent survey of 4655 ill children registered, the distribution of main renal disease was acute glomerulonephritis in 42 cases (9 per 1000), nephrotic syndrome in 40 cases (8.5 per 1000), systemic lupus erythematosis in 28 cases (6 per 1000), and hematuria alone in 11 cases (2.3 per 1000). In ambulatory pediatric practice, urinary tract infection is the leading reason for seeking medical advice. Two thirds of such cases are associated with urinary tract anomalies. Children with ESRD are able to enter hemodialysis programs, but there are not sufficient resources to transplant them. Over 60% of the children with ESRD are hospitalized with terminal renal failure; malformations of the urinary tract are the usual cause. One study of 9880 adults aged 18 to 74 years reported that 39.1% of the women and 26.8% of the men examined were found to have hypertension. Almost half who were found to have raised blood pressure in this study were not previously known to have hypertension. In another cross-sectional study of the urban and suburban mestizo population of Asuncion among patients between 20 and 74 years of age, the overall prevalence of diabetes mellitus was 6.5%, impaired glucose tolerance 13.5%, hypertension 17%, and obesity 31.6%. Extrapolating from this data, we can assume that 178,000 patients with hypertension in Paraguay need medical treatment. To face the problem of growing numbers of patients with end-stage renal failure, it is necessary to carry out basic epidemiologic research to detect and quantify cases early in the course of disease, and thus propose treatments designed to slow the progress of the disease. Without this type of data, it would be difficult to establish an efficient action plan for improving the development of the treatment of renal disease. Thus, we are recommending the establishment of early detection and treatment campaigns for chronic renal disease, especially in individuals at risk. It is also desirable to promote renal transplantation using related live donors. We need to cooperate with government authorities to increase the insurance coverage of patients on chronic dialysis and find the most practical ways to establish long-term dialysis programs. A major question that is hard to answer in practice is whether there should be universal insurance for dialysis and transplantation for all who need it from the outset, as opposed to implementation in successive stages, which gives priority to only a minority of the population; which could be better adapted to our financial possibilities.
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PMID:Kidney disease in Paraguay. 1601 89

Not only antiphospholipid antibodies (aPLs) but also other factors should be considered in assessing the risk of thrombosis development in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPLs). The kinds of risk factors, including past history of thrombotic event (PHTE), hypertension, hypercholesterolemia, diabetes mellitus (DM), obesity, and smoking, in conjunction with aPLs, that contribute to the development of new thrombotic events in patients with SLE and aPLs were studied prospectively over a 5-year observation period. One-hundred and sixty-six Japanese patients with SLE (55 patients with aPLs and 111 patients without aPLs) were examined and followed up for 5 years. Five major risk factors for ischemic coronary disease and stroke according to the Framingham heart cohort study were evaluated objectively in these patients. A significant difference was seen for 4 factors: past history of thrombotic event (PHTE; odds ratio: 101.93; 95% confidence interval: 12.29-845.22; p < 0.0001), hypertension (odds ratio: 8.87; 95% CI: 2.58-30.53; p < 0.001), DM (odds ratio: 5.42; 95% CI: 1.44-20.46; p < 0.05), and lupus anticoagulant (LAC; odds ratio: 47.41; 95% CI: 5.88-382.03, p < 0.0001) as aPLs, when the incidence of these risk factors was compared between patients with and without new thrombotic events. Furthermore, PHTE (odds ratio: 30.19, 95% CI: 1.33-683.13), hypertension (odds ratio: 15.44; 95% CI: 1.77-134.80), and LAC (odds ratio: 14.11; 95% CI: 0.48-412.42) showed higher odds ratios than DM (odds ratio: 11.53; 95% CI: 0.83-159.94) on multivariate logistic analysis as well as analysis of the combination of risk factors, suggesting that these are important risk factors for the development of new thrombotic events in patients with SLE and aPLs.
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PMID:Risk factors for recurrent thrombosis: prospective study of a cohort of Japanese systemic lupus erythematosus. 1619


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