Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathophysiology, outcome and some therapeutic problems of hypertension were described. Frequency of secondary hypertension and its underlying diseases in a hypertensive population greatly varied by study population. In the adult general population (Hisayama study) it was estimated to be 3.8%. Significance of various tests was evaluated in the diagnosis of renovascular hypertension and primary aldosteronism. Consideration of sodium balance in the evaluation was very necessary. The usefulness of captopril test was emphasized. Blood pressure was tended to decrease in upright posture and ambulation in cases with essential hypertension responding to acute sodium depletion by a significant reduction in blood pressure. In the observation of diurnal rhythm of urinary sodium excretion, the peak phase appeared about 3 hours earlier in essential hypertension than in normal control and 5 to 6 hours later in primary aldosteronism and Cushing syndrome. Sympathoadrenal function was activated in young borderline hypertensives but not in middle-aged ones. Outcome of hypertension accompanying diabetes mellitus was poor. Cardiovascular disease and renal failure occurred much frequently. Significance of hypertension as a risk factor of cardiovascular disease was described based on the data obtained through prospective epidemiological study (Hisayama Study). Hypertension was significantly correlated with stroke but not with myocardial infarction. Serum cholesterol level did not significantly correlate with both stroke and myocardial infarction. Reduction in stroke incidence in recent years was described in relation to the changes in risk factors of cardiovascular diseases. Pathophysiology and outcome of malignant hypertension (KW III-IV) were described in relation to underlying disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiology and outcome of hypertensive subjects. 389 32

Enalapril maleate is a prodrug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. Enalapril maleate is 60% absorbed and 40% bioavailable as enalaprilat. Both compounds undergo renal excretion without further metabolism. The functional half-life for accumulation of enalaprilat is 11 h, and this is increased in the presence of a reduction in renal function. Inhibition of converting enzyme inhibition is associated with reductions in plasma angiotensin II and plasma aldosterone, and with increases in plasma renin activity and plasma angiotensin I. Acute and chronic effects have been reviewed. When given with hydrochlorothiazide, enalapril attenuates the secondary aldosteronism and ameliorates the hypokalaemia from diuretics. Both acutely and chronically in patients with essential hypertension, enalapril reduced blood pressure with a rather flat dose-response curve. No evidence of a triphasic response such as seen with captopril has been demonstrated with enalapril, and blood pressure returns smoothly to pretreatment levels when the drug is abruptly discontinued. Once- or twice-daily dosing gives similar results. The antihypertensive effects of enalapril are potentiated by hydrochlorothiazide. Haemodynamically, blood pressure reduction is associated with a reduced peripheral vascular resistance and an increase in cardiac output and stroke volume with little change in heart rate. Renal vascular resistance decreases, and renal blood flow may increase without an increase in glomerular filtration in patients with normal renal function. In patients with essential hypertension and glomerular filtration rates below 80 ml/min/m2, both renal blood flow and glomerular filtration rates may increase.
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PMID:An overview of the clinical pharmacology of enalapril. 609 37

Hypertension is a common trait of multifactorial determination imparting an increased risk of myocardial infarction, stroke, and end-stage renal disease. The primary determinants of hypertension, as well as the factors which determine specific morbid sequelae, remain unknown in the vast majority of subjects. Knowledge that a large fraction of the interindividual variation in this trait is genetically determined motivates the application of genetic approaches to the identification of these primary determinants. Success in this effort will afford insights into pathophysiology, permit preclinical identification of subjects with specific inherited susceptibility, and provide opportunities to tailor therapy to specific underlying abnormalities. To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain. These early findings demonstrate the feasibility and utility of the application of genetic analysis to dissection of this trait.
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PMID:Genetic determinants of human hypertension. 756 73

19-Noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, possesses potent mineralocorticoid and hypertensinogenic activities. 18,19-Dihydroxycorticosterone (18,19-(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), a possible precursor of 19-noraldosterone, have been identified in human urine. These mineralocorticoid hormones are regulated by the renin-angiotensin system and synthesized in adrenal glomerulosa cells. Urinary 19-noraldosterone correlated with urinary 18,19-(OH)2-B, 18-OH-19-nor-B, 18-hydroxycorticosterone (18-OH-B), and aldosterone. Urinary excretion of 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B were increased in patients with aldosterone-producing adenoma (APA) and in those with idiopathic hyperaldosteronism (IHA), but the two did not differ significantly. Urinary 18-OH-B and 18-hydroxycortisol (18-OH-F) were significantly higher in APA compared with IHA. Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, urinary 19-noraldosterone, 18,19-(OH)2-B, and 18-OH-19-nor-B could not be used to distinguish the two subsets of primary aldosteronism. Urinary 19-noraldosterone did not differ in hypertensive and normotensive patients. However, urinary 19-noraldosterone was increased in some hypertensive patients. In spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), urinary 19-noraldosterone was increased at the prehypertensive stage compared with Wistar-Kyoto (WKY) rats. Urinary 19-noraldosterone was decreased in 9-week-old SHR and SHRSP compared with WKY rats. However urinary 19-noraldosterone was higher in SHRSP than in SHR. These elevated levels of 19-noraldosterone may contribute to hypertension in some individuals and in experimental hypertensive rats.
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PMID:Significance of 19-noraldosterone, a new mineralocorticoid, in clinical and experimental hypertension. 779 99

Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition.
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PMID:Rapid diagnosis of glucocorticoid suppressible hyperaldosteronism in infants and adolescents. 791

Renovascular hypertension and high renin hypertension were found to be associated with an excess prevalence of carotid artery atherosclerotic lesions and to a higher risk of stroke, respectively, as compared to low-to-normal renin hypertension. Primary aldosteronism, being characterized by hypertension and a chronically suppressed plasma renin activity, should be accompanied by a low prevalence of carotid artery lesions. To verify this hypothesis we investigated prospectively, by a high resolution duplex ultrasound technique, the prevalence of extracranial carotid artery lesions in a case-controlled study of 34 (22 women and 12 men, aged 22 to 76 years) patients with no history or symptoms of cerebrovascular disease. Primary aldosteronism was diagnosed in 17 patients; 12 had a surgically confirmed unilateral aldosterone-secreting adenoma; and 5 had idiopathic hyperaldosteronism. Each primary aldosteronism patient was individually matched with a control with primary hypertension for sex, race, age, body mass index, casual blood pressure levels, duration of hypertension, smoking, diabetes mellitus, total serum cholesterol, and triglycerides. After the matching, the two groups were similar in terms of demographic features and overall cardiovascular risk profile (all P = NS). However, plasma renin activity and aldosterone levels were significantly lower and higher, respectively, in primary aldosteronism than in primary hypertensive patients. In primary aldosteronism the overall prevalence of carotid artery lesions at duplex was 59%, not significantly different from that (53%) found in primary hypertensives. Thus, at variance with renovascular hypertension, primary aldosteronism is not associated with an excess prevalence of carotid artery lesions.
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PMID:Prevalence of extracranial carotid artery lesions at duplex in primary aldosteronism. 842 67

1. Early diagnosis of Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-suppressible hyperaldosteronism) in asymptomatic, affected individuals is essential if death from stroke is to be prevented. 2. In 21 patients with FH-I (presence of the causative hybrid 11 beta-hydroxylase/aldosterone synthase gene confirmed by Southern blot testing), various biochemical parameters were compared as possible screening tests. Hypokalaemia and elevated plasma aldosterone each detected only two (10%) of the affected individuals. 3. Plasma renin activity 19 (90%) and aldosterone/renin ratio 18 (86%) were more reliable but not free from false negatives. 4. Levels of the urinary 'hybrid' steroid, 18-oxocortisol, were elevated (P < 0.01) in all 15 patients tested (138.2 +/- 17.4 micrograms/g creatinine, range 41.6 +/- 281.0 micrograms/g) with no overlap when compared with 11 normals (9.7 +/- 1.3 micrograms/g, range 2.8-17.4 micrograms/g). 5. We conclude that measurement of urinary 'hybrid' steroids is probably the most rapid and reliable biochemical screening test currently available for FH-I, with confirmation dependent on demonstration of the hybrid gene by genetic techniques.
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PMID:Hybrid gene or hybrid steroids in the detection and screening for familial hyperaldosteronism type I. 858 97

Glucocorticoid remediable aldosteronism (GRA), an autosomal dominant cause of primary aldosteronism, has been described as resulting in severe hypertension with premature death from stroke. We describe two new large pedigrees which include subjects who have the abnormal chimaeric gene strongly linked to GRA. The majority of affected members, who have only mild hypertension and normal biochemistry, are clinically indistinguishable from patients with essential hypertension. It is therefore likely that this condition is underdiagnosed.
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PMID:Variation of phenotype in patients with glucocorticoid remediable aldosteronism. 882 44

The basic clinical pathophysiology of primary aldosteronism (PAL) was described by Conn in terms of autonomous production of aldosterone, secondary suppression of renin and development of hypertension with hypokalaemic alkalosis. Conn recognised a normokalaemic form of the syndrome and suggested that it might masquerade as essential hypertension and be not uncommon. This was hotly disputed at the time, and normokalaemic PAL considered rare until recently, and, as a consequence, overlooked. The advent of a simple screening test, the aldosterone-renin ratio, led to recognition that normokalaemic forms are not uncommon. In fact, PAL may be the commonest specifically treatable and potentially curable form of hypertension so far identified. In all patients with PAL confirmed by lack of suppressibility ("autonomy") of aldosterone production, Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-remediable hyperaldosteronism, reviewed elsewhere in this issue) should first be excluded by dexamethasone suppression or genetic testing. Capable of causing fatal stroke in young people affected by this dominantly inherited disorder, it can be reversed by doses of glucocorticoids such as dexamethasone which partially suppress endogenous ACTH without producing "steroid" side-effects. The remaining varieties of PAL may eventually also be shown to have a genetic basis, but are currently treated either by excision of a solitary aldosterone-secreting tumour or by antagonism of aldosterone's action in the renal tubule. It is possible that both adrenal cortices are genetically predisposed to overproduction of aldosterone in all varieties of PAL, whether because of anomalous regulation of aldosterone secretion or because of a tendency towards hyperplasia and neoplasia. Aldosterone-producing adenomas (APA's) can be divided into two main subtypes based on morphology and biochemical behaviour. The first subtype to be morphologically and biochemically characterised is composed predominantly of fasciculata-like cells and is unresponsive to angiotensin II (ALL-U-APA). The more recently characterised subtype is composed predominantly of glomerulosa-like cells, is responsive to angiotensin II (AII-R-APA) and could previously have been misdiagnosed as bilateral hyperplasia. The renin gene is often overexpressed in the second variety of adenoma, and in surrounding non-tumorous cortex, and the two subgroups show different allelic frequencies for RFLP's of the constitutive renin gene and the constitutive ANP gene locus. Unilateral, solitary, benign adrenal cortical adenomas producing aldosterone (APA's) represent a potentially surgically curable form of hypertension. Adrenal venous sampling (AVS) should always be performed because APA's are biochemically recognisable by adrenal venous steroid measurement before they are identifiable by computerised tomography or scintigraphy, and adrenal masses seen on CT may not be responsible for PAL. The secretory activity of adrenal masses must therefore be established by AVS before surgical removal. Discovery of an adrenal mass on CT requires formulation of a plan, whether or not it is found to be secreting hormones in excess. Independently of the treatment of the patient's hypertension, an apparently nonfunctioning adrenal mass ("incidentaloma") should be removed if 2.5 cm or more in diameter, because of the risk of cancer. Smaller masses require long-term follow-up. Primary aldosteronism not lateralising on AVS should be treated with low dose spironolactone, or with amiloride. For any such patients intolerant of medical treatment, laparoscopic removal of the adrenal showing higher production of aldosterone on AVS is an option worthy of consideration.The resultant reduction in mass of tissue autonomously secreting aldosterone should improve hypertension, as aldosterone productions falls below a critical level, and may even be curative in the short, medium or long term, depending on the rate of growth and activity of au
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PMID:Primary aldosteronism. 922 Dec 68

There are anecdotal reports of early cerebrovascular complications occurring in patients with glucocorticoid-remediable aldosteronism (GRA). The issue has never been systematically evaluated. In this study, we retrospectively reviewed the International Registry for GRA to see if there was an association between cerebrovascular complications and GRA. We searched the records of 376 patients from 27 genetically proven GRA pedigrees for premature death or cerebrovascular complications. Each case was subsequently verified through the referring physician, or autopsy reports. The number of complications occurring in patients with proven GRA were compared to GRA negative subjects from the same pedigrees. There were 18 cerebrovascular events in 15 patients with proven GRA (n=167) and none in the GRA negative group (n=194; P<.001). There were an additional 15 events in 15 subjects that were suspected of having GRA based on clinical history. Seventy percent of events were hemorrhagic strokes; the overall case fatality rate was 61%. The mean (+/- SD) age at the time of the initial event was 31.7+/-11.3 years. In total, 48% of all GRA pedigrees and 18% of all GRA patients had cerebrovascular complications, which is similar to the frequency of aneurysm in adult polycystic kidney disease. GRA is associated with high morbidity and mortality from early onset of hemorrhagic stroke and ruptured intracranial aneurysms. Screening for intracranial aneurysm with magnetic resonance angiography is advised for patients with genetically proven GRA.
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PMID:Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. 945 43


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