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)

A 73-year-old man was admitted with gait disturbance and dysarthria. He showed right-side cerebellar ataxia. Computed tomography of brain showed left thalamic bleeding. Nine months later, he was admitted again because of seizure and consciousness disturbance. He had a history of diabetes mellitus and gout for five years, but no hypertension. On physical examination the lungs and heart were normal. On neurological examination, he showed stupor,pupils and eye position were normal. He showed right hemiparesis and urinary incontinence. The deep tendon reflexes were (+) at the upper limbs and (2+) at the right knee and ankle. Blood pressure was 162/88 mmHg and glucose was 275 mg/dl. Other laboratory data were normal. Brain CT showed hemorrhage of the left frontal lobe. The cystatin C level in cerebrospinal fluid was 68 ng/ml. Therefore we suspected cystatin C deposit amyloid angiopathy. In this case, thalamic hemorrhage was initially thought to be amyloid angiopathy. In cases of cerebral hemorrhage in the elderly without hypertension, we must be considered amyloid angiopathy.
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PMID:[A case of recurrent cerebral hemorrhage considered to be cerebral amyloid angiopathy by cerebrospinal fluid examination]. 143 57

CAA is the infiltration of leptomeningeal and penetrating cortical vessels with amyloid, sparing the subcortical regions and the systemic vasculature. It occurs with increasing frequency after the sixth decade. The major clinical manifestation of CAA is lobar intracerebral hemorrhage, which can be sporadic or hereditary. CAA has also been associated with normal aging, Alzheimer's disease, cerebral infarction, and periventricular demyelination. Biochemical studies have shown that the amyloid deposits in the brains of patients with normal aging, sporadic CAA-associated hemorrhage, hereditary cerebral hemorrhage, and Alzheimer's disease are identical. The exact mechanism by which CAA produces lobar hemorrhages and the role of CAA in the development of dementia are unclear. Biopsy of the involved cerebral cortex and leptomeninges is the only definitive way to diagnose CAA. Acute management of CAA-associated lobar hemorrhage consists of aggressive control of associated hypertension and supportive care. Surgical removal of the hemorrhage has not been shown to improve survival. Antiplatelet and anticoagulant therapy should be avoided in elderly patients with known CAA.
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PMID:Diagnosis and treatment of cerebral amyloid angiopathy. 186 14

The goals in the treatment of hypertension have been outlined previously. The antihypertensive drugs should achieve as many of these criteria as possible. 1. Efficacious as monotherapy in more than 50% of all patients (demographics) 2. 24-hour blood pressure control during all activities 3. Once per day dosing 4. Hemodynamically logical and effective: reduces SVR, improves arterial compliance, preserves CO and maintains perfusion to all vital organs 5. Lack of tolerance or pseudotolerance: no reflex volume retention or stimulations of neurohumoral mechanisms 6. Favorable biochemical and metabolic effects 7. Reverses the structural, vascular smooth muscle, cardiac hypertrophy, LVH, and improves systemic and diastolic compliance, LV contractility and function, and reduces ventricular ectopy if present 8. Reduces all end-organ damage: cardiac, cerebrovascular, renal, retinal and large artery 9. Maintains normal hemodynamic response to aerobic and anerobic exercise 10. Low incidence of side effects and good quality of life 11. Good compliance with drug regimen 12. Good profile in concomitant diseases or problems The drugs that come closest to these characteristics include CCB, ACEI, CAA, and alpha blockers. All of these agents are effective as monotherapy and should be given as initial therapy to the maximum dose shown in Table 10 or until the advent of side effects, whichever occurs first. Combination therapy should be the next step, using the principal of go low, go slow, using additive or synergistic drug combinations. Therapy should be individualized using the subsets of hypertension approach: Diuretics in particular, especially high-dose diuretics, and BB to a lesser extent, should be reserved as second- or third-line drugs and used for specific indications and in the lowest dose possible to achieve clinical results. For example, diuretics would be reserved for volume overload states, systolic CHF, and volume-resistant hypertension. Beta blockers would be reserved for patients after a Q-wave myocardial infarction, those with obstructive angina, specific cardiac arrhythmias, and other like conditions. Long-term, prospective, clinical trials will be needed to confirm that CCB, ACEI, CAA, and alpha blockers reduce end-organ damage more effectively than diuretics, BB, direct vasodilators, and older antihypertensive drugs. Until then, one must rely on scientific evidence, discussed here, that strongly suggests that reduction in risk factors for end-organ damage will reduce the end-organ damage in heart, brain, kidney, and large arteries.
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PMID:Hypertension strategies for therapeutic intervention and prevention of end-organ damage. 194 95

Patients with bioptically ascertained glomerulonephritis of the years 1969-1981 were examined. At the time of the kidney biopsy etiology, onset of the disease and data of the findings were evaluated. Moreover, in 160 out of 300 patients after-examinations were performed. Especially also the examination of patients with erythrocyturia was carried out with the help of the phase contrast microscopy. In a second part of the examinations which we report on 2 therapy studies were performed. In the first therapy study the effectiveness of the therapy with prednisolone (n = 33), prednisolone + cytostatic drug (n = 43) as well as the indomethacin treatment (n = 52) in patients with and without nephrotic syndrome was examined. We found that an initial prednisolone dose of more than 50 mg/die for at least over 1 month is more successful than a low prednisolone dose. Indomethacin has no clinically provable therapeutic effect in the nephrotic syndrome. In normal renal function the duration of the disease has no ascertained influence on the results of the therapy. In the second therapy study the effectiveness of the CAA- (n = 27) and the CAAP-therapy, respectively, (n = 98) (cytostatic drugs, anticoagulant drugs, thrombocyte aggregation inhibitors and prednisolone) was investigated. The results of the therapy depending upon the clinical course and the morphological findings revealed that there is an indication to the CAA-CAAP-therapy in nephrotic syndromes in glomerulonephritis with and without sclerosation as well as in glomerulonephritis with relapsing exacerbations with and without sclerosations. No indication for this therapy is given in chronic courses of glomerulonephritis with slight proteinuria and in nephrotic syndromes with hypertension.
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PMID:[Diagnosis and therapy of chronic glomerulonephritis in long-term follow-up]. 370 78

Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.
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PMID:Resistance to activated protein C and Legg-Perthes disease. 1037 32

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer's disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.
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PMID:Epidemiology of vascular dementia. 1042 61

Amyloid-beta (A beta) deposition in cerebral vessels (cerebral amyloid angiopathy, CAA) is accompanied by degeneration of vascular cells, including pericytes and smooth muscle cells. Previous studies indicated that specific A beta protein isoforms are toxic for cultured human brain pericytes and smooth muscle cells. In particular, A beta 1-40 carrying the E22Q mutation, as in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), is toxic. We investigated the effects of the A beta-binding protein apolipoprotein E (ApoE) on the toxicity of A beta for cultured human brain pericytes. We compared the toxicity of HCHWA-D A beta 1-40 for pericyte cultures with different ApoE genotypes, studied the accumulation of A beta and ApoE in these different cell cultures, and investigated the effects of exogenous ApoE. Pericyte cultures with an ApoE epsilon 2/epsilon 3 genotype were more resistant to HCHWA-D A beta 1-40 treatment than cultures with a epsilon 3/epsilon 3 or epsilon 3/epsilon 4 genotype. Cell death was highest in cultures homozygous for ApoE epsilon 4. The extent to which both A beta ApoE accumulated at the cell surface was parallel to the degree of toxicity. The addition of purified ApoE resulted in a decrease in cell death. These data suggest that ApoE4 may direct A beta more efficiently than other ApoE isoforms into a pathological interaction with the HBP cell surface. The results of this study are in line with the observations that inheritance of the ApoE epsilon 4 allele increases the risk of developing Alzheimer's disease, and that the ApoE epsilon 2 allele has a relatively protective effect.
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PMID:Amyloid-beta-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype. 1081 7

In this follow-up study, 526 persons were followed for almost 5 years to assess the reversibility and predictive value of four kidney biomarkers in a field epidemiology setting. This study examined (a) whether elevations in urinary albumin, N-acetyl-beta-D-glucosaminidase, retinol-binding protein, and alanine aminopeptidase remained elevated at follow-up and (b) whether these initial elevations were predictive of kidney disease (as measured by markers of kidney dysfunction: serum creatinine, serum cystatin C, creatinine clearance, and urine osmolality) at follow-up. Study participants were 8-76 years of age at baseline and were followed for an average of 4.5 years. Approximately 50% of adults who had an elevated biomarker did not have an elevation at followup. Youths with elevated biomarkers at baseline, but who completed adolescence by the time of the follow-up, no longer had any elevations in biomarkers at follow-up. Adult participants who had elevated biomarkers and selected health conditions at baseline (diabetes and, to a lesser extent, heart disease, hypertension, gout, and urinary tract disease) were more likely to show early indicators of kidney impairment at follow-up. Participants with these health conditions and normal kidney biomarker values at baseline had kidney test results at follow-up that were similar to results of study participants who did not have these health conditions at baseline. The presence or absence of elevated biomarkers at baseline among generally healthy participants was not associated with the development of early indicators of kidney impairment at follow-up. This longitudinal study confirmed the utility of these four kidney biomarker tests as markers of preclinical organ dysfunction among adults with certain preexisting medical conditions.
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PMID:Confirming the utility of four kidney biomarker tests in a longitudinal follow-up study. 1457 88

The pathogenesis of ischemic coronary events involves degradation of the extracellular matrix in atherosclerotic lesions. The cysteine protease inhibitor cystatin-C may be involved in this phenomenon. The association of plasma cystatin-C with the incidence of myocardial infarction-coronary death and angina, was examined in a nested case-control (two controls per case) design within the prospective cohort study (Prospective Epidemiological Study of Myocardial Infarction (PRIME Study)) which included 9,758 men aged 50-59 years who were free of coronary heart disease (CHD) on entry and followed for a 5-year period. Three hundred and thirteen participants suffered myocardial infarction or coronary death (n = 159) or angina pectoris (n = 154) during follow-up. Cystatin-C was positively correlated with body mass index (BMI), low-density lipoprotein (LDL)-cholesterol, triglycerides and several inflammatory markers such as fibrinogen (r = 0.18), C-reactive protein (CRP) (r = 0.24), interleukin-6 (= 0.20), tumor necrosis factor-alpha (TNFalpha) (r = 0.27) and two TNFalpha receptors: TNFR1A (r = 0.43) and TNFR1B (r = 0.41); and negatively with high-density lipoprotein (HDL)-cholesterol (r = -0.25). After adjustment for traditional risk factors (age, diabetes, smoking, hypertension, BMI, triglycerides, LDL- and HDL-cholesterol), cystatin-C was significantly associated with the occurrence of the first ischemic coronary event. However, this association was no longer significant when CRP was included in the analysis. A decrease in glomerular filtration rate did not explain higher cystatin-C in cases than in controls. Cystatin-C appears to participate in the inflammatory phenomenon observed in the atherosclerotic process. Cystatin-C is not a more predictive risk marker of CHD than CRP or interleukin-6, but could be useful in detecting moderate chronic renal disease.
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PMID:Plasma cystatin-C and development of coronary heart disease: The PRIME Study. 1604 22

We determined the sensitivity, specificity, receiver operating characteristics and correlation between cystatin C (cysC) and two widely used markers of renal function, creatinine clearance and serum creatinine, in 244 patients (84 diabetics, 84 hypertensive and 76 healthy subjects). Renal failure was defined as creatinine clearance of less than either 80 or 60 mL/min. Variables were evaluated for two definitions of renal failure and compared between patient groups. Correlation coefficients with cysC were -0.87 for creatinine clearance and 0.92 for creatinine in patients with hypertension; -0.90 for creatinine clearance and 0.97 for creatinine in diabetics; and -0.61 for creatinine clearance and 0.94 for creatinine in the control group. The receiver operating characteristic curves with a cut-off value of 60 mL/min were similar for creatinine and cysC, while at 80 mL/min they were 0.626 for creatinine and 0.813 for cysC levels. We classified the patients into three groups with respect to creatinine clearance (1, >80 mL/min; 2, 60-80 mL/min; 3, <60 mL/min). Mean creatinine (p<0.0001) and cysC (p<0.0001) levels were significantly different between all the groups. Sensitivity, specificity and predictive values were higher for cysC levels, particularly in diabetics and hypertensive patients. The current study suggests that cysC is preferable for detecting temporal changes in renal function in the early stages of renal insufficiency.
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PMID:The efficacy of cystatin C assay in the prediction of glomerular filtration rate. Is it a more reliable marker for renal failure? 1620 97


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