Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the synthesis of epoetins alpha and -beta, a third molecule of recombinant human erythropoietin (rHuEPO) was synthesized and was named epoetin-omega. The molecule of epoetin-omega is a sialoglycoprotein with smaller amounts of O-bound sugars, less acidic and with different hydrophylity than the other 2 epoetins. The purpose of the study was to assess the efficacy, safety and clinical tolerance of epoetin-omega for treatment of renal anemia. In an open-label, uncontrolled prospective clinical study, 22 end-stage renal disease patients (9 male and 13 female) were followed for 6 months. They all had a hemoglobin (Hb) value below 85 g/l, and were on regular hemodialysis therapy 3 times a week, 4 hours per session. The initial weekly dose of epoetin-omega was 90 units per kg of body weight (b.w.) divided in 3 equal portions and administered subcutaneously after each dialysis session. After correction of the hemoglobin, the dose of rHuEPO was individualized to keep Hb within target limits of 100-120 g/l. To follow efficacy and safety, a number of clinical and laboratory parameters were monitored. All patients responded well to the therapy with corrected hemoglobin after the 10th week of the study. The mean dose of epoetin-omega during the correction period never exceeded 100 U/kg b.w. per week. The average maintenance dose of rHuEPO was 50-60 U/kg b.w. per week. Iron was, where needed, supplied intravenously. We noted no change in serum urea. creatinine, phosphorus, and heparin dose per dialysis session. The prothrombin time improved during the study. Serum albumin increased. No change was observed in urea reduction ratio (URR), body weight and mean arterial pressure. One serious adverse event was noted: worsening of hypertension in 1 patient, with the development of hypertensive encephalopathy and severe headache. rHuEPO treatment was stopped. The blood pressure was effectively controlled by reducting her body weight by 5%. Thereafter, rHuEPO therapy was resumed with good blood pressure control. We could conclude that recombinant human erythropoietin-omega was an efficient and safe therapeutic agent for the treatment of renal anemia.
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PMID:Epoetin omega for treatment of anemia in maintenance hemodialysis patients. 1192 56

Two children, ages 2 and 4 years, envenomed by the snake Cerastes vipera are presented. Both children suffered from local pain and swelling of the hand that spread up to the shoulder in the 2-year-old and up to the elbow in the 4-year-old. A hemorrhagic blister was noted on the bitten finger in the younger patient. Urinary retention, tachycardia, and a slight prolongation of prothrombin time was noted in the 2-year-old, whereas hypertension and fever were observed in the 4-year-old. In both cases, the swelling receded gradually and the patients were discharged from the hospital after several days without any complications and in a good condition.
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PMID:Snake bite by Cerastes vipera in children: report of two cases. 1199 90

Prothrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n approximately 250 each). Population-based controls free of clinical cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical and subclinical CVD (n approximately 250) were used for comparison. The 20210 A allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.
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PMID:No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. 1200 43

DNA samples collected as part of a large population-based case-control study were genotyped to examine the associations of five prothrombotic gene polymorphisms with pre-eclampsia (PE) and gestational hypertension (GH). The polymorphisms studied were: G1691A in Factor V (Factor V Leiden; FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, plasminogen activator inhibitor-1 4G/5G and the platelet collagen receptor alpha2beta1 C807T. A group of 404 women who developed PE were retrospectively compared with 303 women with GH and 164 control women. The frequency of genotypes did not differ significantly between cases of PE or GH and controls for any of the five polymorphisms studied. We conclude that these prothrombotic genotypes are not associated with the development of PE or GH in our population. The systematic review supports our conclusion, for all but cases of severe disease. which appear to be associated with FVL and, to a lesser extent, MTHFR C677T. There is little value in antenatal screening for prothrombotic polymorphisms to predict the development of pre-eclampsia or gestational hypertension.
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PMID:Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. 1203 75

Oral contraceptive therapy (OCT) is widely used in the world. It is usually safe and effective but side effects are occasionally seen. Venous thromboembolism is one of the most feared side effects. To avoid this complication adequate guidelines are needed. These have to take into account family history, personal history, and suitable laboratory investigations. The presence of an idiopathic venous thrombosis in the family or in the personal history is of paramount importance. However it is often difficult to ascertain whether a venous thrombosis is idiopathic or not. Even when there is doubt, a coagulation study should be carried out. An adequate coagulation study in this case should include at least an evaluation of antithrombin, protein C, and protein S. A search for homozygosity of factor V Leiden appears advisable. These defects represent absolute contraindications to the use of OCT. Relative contraindications may be represented by other minor coagulation disorders such as heterozygous factor V Leiden, fibrinolysis defects, and a G-to-A 20210 prothrombin abnormality. Other noncoagulation-related conditions such as hypertension, liver damage, and obesity may represent absolute or relative contraindications to the use of OCT.
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PMID:Tentative guidelines and practical suggestions to avoid venous thromboembolism during oral contraceptive therapy. 1212 Oct 63

Possible hepatic effects of oral contraceptives (OCs) include tumors, intrahepatic cholestasis, and less well known vascular lesions such as Budd-Chiari syndrome and peliosis, a disseminated pseudocystic dilatation of the sinusoid capillaries of the liver. A 29-year-old woman with a history of 4 pregnancies, hypertension and diabetes both requiring daily medication, and use since April 1983 of an oral contraceptive (OC) containing .15 mg levonorgestrel and .03 mg of ethinyl estradiol complained in March 1984 of epigastric pain and increased abdominal volume. Ascitis was diagnosed and the patient was hospitalized. She had experienced a generalized pruritus for several months and had lost weight. The bilirubin, alcaline phosphatase, and Gamma GT levels were slightly elevated. Sonography showed a hypertrophied liver. Incipient esophageal varices were seen with gastric fibroscopy. The small subhepatic venous branches had a cloudy aspect. The peliosis hepatis was diagnosed by a transjugular puncture biopsy of the liver. With discontinuation of the OCs, the ascites did not reappear after puncture and the perturbations of the liver functioning normalized. On follow-up in April 1985, slight hepatomagaly persisted but the patient reported no further symptoms. She continued her medication for hypertension and diabetes. Peliosis hepatis was 1st described in 1964 and several cases related to OC use have been reported since 1972. Peliosis has the aspect of multiple small congestive cavities of 1-3 mm in diameter in the parenchyma. The lesions consist of areas of hepatocellular necrosis secondarily filled with blood. The cysts may be voluminous and subcortical, creating a risk of hemoperitoneum. The lesions may also be associated with a benign or malignant liver tumor. Regression of the lesions is possible with termination of the etiologic agent. Clinically, hepatomegaly, painful or not, sometimes associated with splenomegaly, is often found with peliosis. Moderate jaundice is very frequent. Ascites or edema of the legs are observed. Hyperbilirubinemia and augmentation of phosphatases and Gamma GT are the main laboratory findings. Transaminases may be slightly elevated, and the rate of prothrombin may be diminished. The condition is sometimes diagnosed with laparoscopy, celiomesenteric arteriography, or phlebography, but hepatic puncture biopsy usually establishes the diagnosis. The contition may improve if the etiologic agent is removed or it may worsen because of liver failure or a complication such as hemoperitoneum or an associated tumor.
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PMID:[Peliosis hepatis and oral contraceptives: a case report]. 1228 Oct 5

First-degree relatives of type 2 diabetic patients with or without a family history of hypertension are at increased risk for cardiovascular diseases. The aim of this study was to verify some possible hemostatic alterations in first-degree relatives of type 2 diabetic, normotensive and hypertensive patients. In 78 non-diabetic, normotensive first-degree relatives of type 2 diabetic patients (47 without a family history of hypertension and 31 with a family history of hypertension) and in 36 normoglycemic, normotensive subjects with no family history of hypertension, we evaluated plasma levels of fasting glucose and insulin, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1 + 2 (F1+2). Insulin resistance, calculated by the HOMA model, and plasma levels of t-PA and PAI-1 were significantly higher in relatives of diabetics compared to controls. As far as the thrombin activation indexes are concerned, we detected a significant increase in DD and F1+2 in relatives of diabetics with hypertension compared to other study subjects. In conclusion, our data indicate that familial predisposition may influence the hemostatic system in first-degree relatives of diabetic and/or hypertensive patients.
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PMID:Hemostasis and fibrinolysis factors in first-degree relatives of patients with Type 2 diabetes without hypertension. 1237 26

Mutations such as factor V Leiden G1691A (FVL), prothrombin G20210A (FIIM), methylenetetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthase (CBS) 844ins68 and endothelial cell protein C receptor (EPCR) 4031ins23 are risk factors for thromboembolism. To assess the role of these mutations in young adults with cerebral ischemia of otherwise undetermined etiology, 93 patients younger than 50 years old with thromboembolic strokes or transient ischemic attacks were studied. One hundred and eighty-six healthy age-matched and sex-matched blood donors served as controls. The FVL mutation was detected in 15/93 patients and 13/186 controls. After adjustment for smoking, arterial hypertension, and hyperlipidemia, the association of the FVL mutation with cerebral ischemia [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.38-7.39] remained significant. One of 93 patients and 6/186 controls were carriers of FIIM (OR, 0.33; 95% CI, 0.04-2.75). We detected the MTHFR TT677 genotype in 9/93 patients and 26/186 controls (OR, 0.66; 95% CI, 0.30-1.47), a CBS 844ins68 mutation in 12/93 patients and 19/186 controls (OR, 1.30; 95% CI, 0.60-2.81), and an EPCR 4031ins23 mutation in 1/93 patients and in no control individual (P = 0.33). In conclusion, in younger adults the FVL mutation is a risk factor for cerebrovascular disease. FIIM, the MTHFR TT677 genotype and the CBS 844ins68 mutation did not contribute to the risk in this group of patients. The EPCR 4031ins23 mutation is very rare, its possible role needs further investigation.
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PMID:Genetic risk factors in young adults with 'cryptogenic' ischemic cerebrovascular disease. 1243 43

Acute myocardial infarction is a very rare event during pregnancy and bears the problem of misdiagnosis. However, about 150 cases have been published worldwide with a preponderance of anterior wall infarcts. With more women delaying childbearing until an older age and increasing prevalence of smoking in young women, it can be expected that all forms of coronary artery disease--including acute myocardial infarction--will be seen more often in the future. Among the causes of coronary artery occlusion in pregnancy are (1) rupture of very small coronary artery plaques triggered by different events, e.g., hypertension; (2) plain coronary artery disease; (3) dissection of coronary arteries; (4) coronary artery spasms with/without arterial thrombosis. Prompt diagnosis and immediate therapy are necessary to lower the high mortality of mother and fetus. The gold standard in the therapy of acute myocardial infarction during pregnancy is immediate coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation. Application of thrombolytics (recombinant tissue plasminogen activator [rt-PA], r-PA, streptokinase [SK], urokinase [UK]) has been reported in single patients but should be limited to cases where acute PTCA is not available and where the infarct occurs before the 14th week of pregnancy because of possible embryopathy. If the patient is in the last 10 weeks of pregnancy, anticipation of delivery should be part of the medical planning. Consultation with an obstetrician must be obtained as soon as the patient enters the hospital. Besides bleeding complications, venous thrombosis with pulmonary embolism is among the most common causes of death during pregnancy. Pregnancy-related changes in physiology - increase in the resistance to flow from the lower extremities to the heart - and congenital coagulation abnormalities are most important to be recognized. This leads to the fact that superficial and deep venous thromboses occur more often in pregnancy than in the nonpregnant state. Among the coagulation abnormalities found in pregnancy are hypercoagulability (increased levels of fibrinogen, factor VII, factor VIII, factor X), decreased fibrinolytic activity due to an increased level of plasminogen activator inhibitor, increased adhesion and aggregation of platelets, decreased level of protein C and of the APC (activated protein C) ratio. Individual risks factors justifying diagnostic screening include contraception, smoking, immobilization, infection, adiposity, placental insufficiency, and a family history of thrombosis. It is even more important to establish/rule out the diagnosis of thrombosis in pregnancy than in the nonpregnant state, because the use of anticoagulants carries certain risks during pregnancy. Doppler vein studies should be used for diagnosis. If necessary, venography may be used with shielding of the maternal abdomen. Therapy consists of subcutaneous application of heparin, compression, and early mobilization. Alternatively, especially for long-term management, treatment with low molecular weight heparins is feasible. Thrombolytic treatment is contraindicated in most cases due to the high risk of bleeding complications. However, the application of thrombolytics can be contemplated in single cases after careful consideration of the pros and cons. Most cases of pulmonary embolism should also be handled conservatively with heparin. Only in massive pulmonary embolism with severe hemodynamic compromise, thrombolytic treatment is indicated. To guide future therapy in the patients, it is necessary to establish the lifetime risk of recurrent events by determining: APC resistance, prothrombin mutation 20210 A, homocysteine, AT III, protein C and S, antiphospholipid antibodies, and anticardiolipin antibodies.
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PMID:[Myocardial infarction and thromboembolism during pregnancy]. 1275 75

The aim of this study was to assess, comprehensively, medical and genetic attributes of venous thromboembolism (VTE) in a multiracial American population. The Genetic Attributes and Thrombosis Epidemiology (GATE) study is an ongoing case-control study in Atlanta, Georgia, designed to examine racial differences in VTE etiology and pathogenesis. Between 1998 and 2001, 370 inpatients with confirmed VTE, and 250 control subjects were enrolled. Data collected included blood specimens for DNA and plasma analysis and a medical lifestyle history questionnaire. Comparing VTE cases, cancer, recent surgery, and immobilization were more common in caucasian cases, while hypertension, diabetes, and kidney disease were more prevalent in African-American cases. Family history of VTE was reported with equal frequency by cases of both races (28-29%). Race-adjusted odds ratios for the associations of factor V Leiden and prothrombin G20210A mutations were 3.1 (1.5, 6.7) and 1.9 (0.8, 4.4), respectively. Using a larger external comparison group, the odds ratio for the prothrombin mutation among Caucasians was a statistically significant 2.5 (1.4, 4.3). A case-only analysis revealed a near significant interaction between the two mutations among Caucasians. We found that clinical characteristics of VTE patients differed across race groups. Family history of VTE was common in white and black patients, yet known genetic risk factors for VTE are rare in African-American populations. Our findings underscore the need to determine gene polymorphisms associated with VTE in African-Americans.
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PMID:The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study. 1287 43


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