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

A 62-year-old African-American man with a history of hypertension, asthma, and prostate cancer, but no prior history of haemophilia presented with gross haematuria following a motor vehicle accident. Coagulation studies revealed a prolonged partial thromboplastin time. Subsequent mixing study and factor analysis confirmed factor VIII (FVIII) deficiency. The patient subsequently developed a knee haemarthrosis associated with persistent haematuria and a profoundly elevated FVIII inhibitor titre. Fresh frozen plasma was initiated upon presentation. Once FVIII inhibitor was discovered, immunosuppressive agents were started. Concurrent treatment with acute bypass agents including porcine FVIII, and recombinant human factor VIIa (rFVIIa;NovoSeven), was also given. Ultimately, anti-inhibitor coagulant complex (Autoplex T) was administered, stabilizing the haematuria and haemarthrosis. There was no additional bleeding 6 months after the last dose of anti-inhibitor coagulant complex. This case is consistent with others in which anti-inhibitor coagulant complex therapy was used successfully to manage patients with serious acute bleeding problems who are found to have acquired inhibitors to factor VIII.
 ...
PMID:Anti-inhibitor coagulant complex for the rescue therapy of acquired inhibitors to factor VIII: case report and review of the literature. 1219 81

This case-control study was designed to identify risk factors for cryptogenic brain infarction. We assessed the frequency of prothrombotic states, homocysteine, lipoprotein (a) [Lp(a)] and other lipids and the apolipoprotein E phenotype together with conventional risk factors in 46 patients (19 women and 27 men) with cryptogenic brain infarction aged from 15 to 60 years and in 104 community-based controls. Multivariate odds ratios (ORs) for risk factors and 95% CIs were calculated by logistic regression. Hypertension (OR 4.5; 95% CI, 1.5-13.2; P = 0.006), current smoking (OR 2.9; 95% CI, 1.2-6.8; P = 0.012), low HDL cholesterol (HDL-C) (OR 5.4; 95% CI, 1.1-25.5; P = 0.035) and high clotting factor VIII activity (OR 3.6; 95% CI, 1.1-12.2; P = 0.041) were variables associated with cryptogenic brain infarction. These risk factors were not equally frequent in women and men. Low HDL-C and high factor VIII activity in the women, and hypertension, current smoking and a low level of plasma folate in the men were risk factors for cryptogenic stroke. Several of the observed risk factors for cryptogenic brain infarction were lifestyle-associated, which emphasizes the role of health education in addition to pharmacological treatment in the prevention of stroke.
 ...
PMID:Risk factors for cryptogenic ischaemic stroke. 1245 78

To determine the incidence rate of cardiovascular disease (CVD) and its association with conventional and less well-established risk factors in African Americans with diabetes, we studied 741 African Americans aged 45 to 64 years with diabetes, in the Atherosclerosis Risk in Communities (ARIC) study. Risk factors were measured from 1987 to 1989, and incident CVD (n = 143 coronary heart disease (CHD) or stroke events) was ascertained through 1998. The crude incidence rate (per 1000 person-years) of CVD was 22.5 (11.9 for CHD and 12.0 for stroke). After multivariate adjustments, total cholesterol, prevalent hypertension and current smoking were significantly and positively associated with incident CVD among these African Americans with diabetes. Among the non-conventional risk factors, serum creatinine, factor VIII, von Willebrand factor, and white blood cell count were positively and serum albumin negatively and independently associated with CVD incidence. Adjusted relative risks for highest versus lowest tertiles of these risk factors ranged from 1.77 to 2.13. This study confirms that the major risk factors (hypercholesterolemia, hypertension and smoking) are important determinants of CVD in African Americans with diabetes. In addition, several blood markers of hemostasis or inflammatory response and elevated serum creatinine also proved to be CVD risk factors in African Americans with diabetes.
 ...
PMID:Incidence and risk factors for cardiovascular disease in African Americans with diabetes: the Atherosclerosis Risk in Communities (ARIC) study. 1251 Jul 2

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.
 ...
PMID:[Myocardial infarction and thromboembolism during pregnancy]. 1275 75

To better understand potentially reversible causes of idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, and an apparent association of IIH with polycystic-ovary syndrome (PCOS), we assessed associations of IIH with coagulation disorders and with PCOS in 38 women with well-documented IIH. Fifteen women were found to have PCOS; 14 of them were obese, with a body-mass index (BMI) greater than 30 kg/m(2), and 10 were extremely obese (BMI > or = 40). Factor VIII concentration was high (>150%) in 9 of 38 (24%) IIH cases, compared with 0 of 40 healthy adults controls (P(f) =.0009). Familial aggregation of high concentrations of factor VIII, associated with thrombophilia, was documented in all 5 of the 9 high-level factor VIII probands' families who were sampled. Activated partial thromboplastin time (APTT) was prolonged (> or =31.5 seconds) in 10 of 38 (26%) IIH cases, compared with 1 of 32 (3%) controls (P(f) =.009) and, in 4 of these cases, was accompanied by the lupus anticoagulant. Plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 9 of 38 cases (24%), compared with 1 of 40 controls (3%) (P(f) =.006). Lipoprotein A was high (> or =35 mg/dL) in 13 of 37 cases (35%), compared with 5 of 40 controls (13%) (P(f) =.03). IIH cases did not differ (P >.05) from controls for homocysteine, proteins C and S, free S, antithrombin III, ACLAs IgG and IgM, dilute Russell's viper venom time, Factor XI, factor V Leiden G1691A, G20210A prothrombin, C677T MTHFR, plasminogen activator inhibitor 4G/5G, or platelet glycoprotein PL A1A2 mutations. Exogenous estrogens (n = 23), clomiphene (n = 1), or pregnancy (n = 4) accompanied the first appearance of IIH in 28 women. PCOS and coagulation disorders, often augmented by exogenous estrogens or pregnancy, are associated with IIH.
 ...
PMID:Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome. 1287 84

As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.
 ...
PMID:Traditional and novel risk factors in older adults: cardiovascular risk assessment late in life. 1501 Jun 53

We studied thrombophilia, hypofibrinolysis, and polycystic-ovary syndrome (PCOS) in 65 women consecutively referred because of idiopathic intracranial hypertension (IIH) as a means of better understanding the origin of IIH, with the ultimate goal of developing novel medical therapies for IIH. Our hypothesis: IIH results in part from inadequate drainage of cerebrospinal fluid (CSF) resulting from thrombotic obstruction to CSF resorption-outflow, favored by thrombophilia-hypofibrinolysis. We conducted the polymerase chain reaction (PCR) and assessed serologic coagulation measures in 65 women (64 of them white) with IIH, PCR in 102 healthy white female controls (72 children, 30 age-matched adults), and serologic measures in the 30 adults. Of the 65 patients, 37 (57%) were found to have PCOS; 16 (43%) were obese (BMI > or = 30 to < 40), and 19 (51%) were extremely obese (BMI > or = 40). Of the 65 women with IIH, 25 (38%) were homozygous for the thrombophilic C677T MTHFR mutation, compared with 14% of controls (14/102) ( P = .0002). Thrombophilic high concentrations of factor VIII (>150%) were present in 9 of 65 (14%) IIH cases, compared with 0 of 30 controls (0%) (Fisher's p [p f ] = .053). An increased concentration of lipoprotein A (> or = 35 mg/dL), associated with hypofibrinolysis, was present in 19 of 65 IIH cases (29%), compared with 3 of 30 controls (10%) (p f = .039). IIH occurred in 18 of 65 IIH patients taking estrogen-progestin contraceptives (28%), in 6 patients taking hormone-replacement therapy (9%), and in 5 pregnant subjects (8%). We speculate that PCOS, associated with obesity and extreme obesity, is a treatable promoter of IIH. We also speculate that if thrombophilia-hypofibrinolysis and subsequent thrombosis are associated with reduced CSF resorption in the arachnoid villi of the brain, thrombophilia and hypofibrinolysis-often exacerbated by thrombophilic exogenous estrogens, pregnancy, or the paradoxical hyperestrogenemia of PCOS-are treatable promoters of IIH.
 ...
PMID:Idiopathic intracranial hypertension, polycystic-ovary syndrome, and thrombophilia. 1574 49

The existence of an association between idiopathic intracranial hypertension (IIH) and coagulation disorders in men was assessed prospectively. Microthrombi, associated with thrombophilia-hypofibrinolysis, occlude arachnoid sinus villi, thus reducing resorption of cerebrospinal fluid, leading to IIH. Ten consecutively referred men with IIH, nine whites, one African American, median age 36 years, were 2 to 1 matched by age and race by healthy male controls. Polymerase chain reaction assays were done for four thrombophilic and one hypofibrinolytic gene mutations: G1691A factor V Leiden, G20210A prothrombin, C677T MTHFR, platelet glycoprotein IIb/IIIa (PL A1/A2), and 4G/5G polymorphism of the plasminogen activator inhibitor (PAI-1) gene promoter. Coagulation measures in plasma included dilute Russel's viper venom time (dRVVT), activated partial thromboplastin time (aPTT), the lupus anticoagulant, factor VIII, factor XI, plasminogen activator inhibitor activity (PAI-Fx), protein C antigenic, protein S total (antigenic), protein S free (antigenic), antithrombin III (functional), and resistance to activated protein C (RAPC). Tests performed on serum included anticardiolipin antibodies, homocysteine, and Lp(a). The body mass index was 40 kg/m(2) or greater (extremely obese) in two men, 30 to 40 kg/m(2) (obese) in three, and was 25 to 30 kg/m(2) in five (overweight). Cases differed from controls for inherited 4G4G homozygosity of the PAI-1 gene, four of 10 (40%) vs. one of 20 (5%), Fisher's p [p(f)]= .031, and for high levels (>21.1 U/mL) of the hypofibrinolytic PAI-1 gene product, PAI-Fx, 5 of 10 (50%) vs. one of 18 (6%), p(f) = .013. Thrombophilic factor VIII was high (> or = 150%) in three of 10 (30%) cases vs. zero of 16 (0%) controls, p(f)=. 046. The thrombophilic lupus anticoagulant was present in two of 10 (20%) cases vs. zero of 32 (0%) controls, p(f) = .052. Heritable hypofibrinolysis and heritable and acquired thrombophilia appear, speculatively, to be treatable etiologies of IIH in men. Understanding contributions of hypofibrinolysis and thrombophilia to the development of IIH should facilitate development of novel new approaches to treat this often-disabling neurologic disorder.
 ...
PMID:Idiopathic intracranial hypertension: associations with thrombophilia and hypofibrinolysis in men. 1624 70

Prophylaxis with von Willebrand factor (VWF)-containing concentrates is considered to be a potential approach for patients with von Willebrand disease (VWD) and severe bleeding tendency. We report the case of a 57-year-old man with type 3 VWD and a history of recurrent melaena. Bleeding frequency and severity had progressively increased and the patient showed chronic anaemia and persistent haemoglobin in the stools. Endoscopic examinations revealed multiple vascular mucosal abnormalities (MVA) of the stomach and large bowel. Photocoagulation of some actively bleeding lesions and octreotide did not significantly affect his clinical conditions: six red cell transfusions and >400 000 IU of intermediate-purity factor VIII (FVIII) concentrate (Haemate P) on-demand were needed during 2002. Prophylaxis with Haemate P 40 IU kg(-1) (102 IU kg(-1) VWF:RCo) thrice weekly was associated with improvement of his mean haemoglobin levels, cessation of clear-cut melaena and red cell transfusions and reduction of total Haemate P requirements (-20% over 2003-04). Prophylaxis with Haemate P is still ongoing without any adverse event over a 30-month period. Clinical course and pharmacokinetic evaluations led to administer Haemate P each 72-96 h. Possible vascular complications were excluded by a careful clinical follow up, as the patient suffered from arterial hypertension and diabetes mellitus; thrombophilic abnormalities were previously excluded and no signs of abnormal coagulation activation or FVIII:C levels >150% were detected thereafter. Long-term prophylaxis with Haemate P has been shown to be safe, effective (also in terms of quality of life) and cost saving in this patient with severe gastrointestinal bleeding due to MVA and VWD.
 ...
PMID:Long-term prophylaxis with intermediate-purity factor VIII concentrate (Haemate P) in a patient with type 3 von Willebrand disease and recurrent gastrointestinal bleeding. 1640 82

The present study was designed to explore whether there are any effects on neurogenic responses in penile small arteries during the development of hypertension in a one-kidney, one-clip (1K1C) model, a non-renin-dependent model of renovascular hypertension. Five weeks after surgery, male Sprague-Dawley rats were given vehicle, bendroflumethiazide (7.5 mg/kg/day), or L-arginine (2 g/kg/day) in their drinking water for five weeks. Experiments were performed on penile small artery rings (150-200 microm) mounted on microvascular myographs for electrical field stimulation (EFS), and erectile tissue was processed for immunohistochemistry. Maximal neurogenic contractions were unmodified in penile preparations. Relaxations induced by EFS were reduced in the presence of ADMA. In 1K1C rats, neurogenic vasorelaxation mediated by nitric oxide (NO) was unaltered, while relaxation resistant to NO synthase inhibition was blunted. L-arginine and bendroflumethiazide lowered blood pressure in 1K1C rats, but vasodilation was still blunted in the penile arteries. Immunoreactivity for factor VIII and neuronal NO synthase was unaltered in penile arteries from 1K1C animals. Endothelium-dependent vasorelaxation evoked by acetylcholine was also blunted in preparations from 1K1C rats, while exogenous NO relaxation was unaffected. Plasma concentrations and urinary excretion of ADMA did not differ among the experimental animals. Our findings indicate that the reduced release of a non-NO vasodilatory neurotransmitter accounts for the impaired neurogenic vasodilation of the penile arteries. Although ADMA inhibits penile vasorelaxation, it is unlikely to affect erectile function in 1K1C rats.
 ...
PMID:Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats. 1657 96


<< Previous 1 2 3 4 5 6 7 8 Next >>