Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large pituitary prolactinoma was found in a mentally deficient 45 year old woman presenting with amenorrhoea, galactorrhoea, headache, anaemia and hypertension, and removed surgically. She was subsequently found to have multiple adrenal aldosterone-producing adenomas, a gastric schwannoma and colonic polyadenomas. All these tumors were also removed surgically. Despite the absence of parathyroid and islet-cell hyperplasia, this case seems to be a variant of multiple endocrine neoplasia (MEN) type I.
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PMID:Pituitary prolactinoma, adrenal aldosterone-producing adenomas, gastric schwannoma and colonic polyadenomas: a possible variant of multiple endocrine neoplasia (MEN) type I. 711 90

Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acting vasodilator that should cause relatively less reflex tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients with moderate to severe hypertension. Flosequinan caused a fall in blood pressure (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS) from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS). Forearm venous distensibility remained stable around 0.03% mm Hg (NS). Neurohormonal parameters showed the consequences of systemic vasodilation: noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0.34 nmol/l (P < 0.01), adrenaline from 0.16 +/- 0.03 to 0.35 +/- 0.10 nmol/l (NS), plasma renin activity from 2.33 +/- 0.46 to 3.27 +/- 0.73 ng/ml/h (P < 0.05) and aldosterone from 14.31 +/- 2.47 to 26.3 +/- 8.02 ng/ml (P < 0.05). The serum concentrations of flosequinan and its major metabolite were within the therapeutic limits. Nine patients experienced minor side-effects such as headache, nausea and palpitations. We conclude that flosequinan has hypotensive efficacy with signs of systemic counter-regulatory mechanisms but without a clear forearm vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute effects of flosequinan (BTS 49465) in untreated moderate to severe hypertension. 762 74

Primary aldosteronism caused by an aldosterone-producing adrenal adenoma was documented in an 11-year-old girl who presented with persistent hypertension, headache, tinnitus and hypokalemia. Elevated plasma aldosterone concentration (PAC) (45.5 ng/dl) and suppressed plasma renin activity (PRA) (< 0.3 ng/ml/hrs) were detected. Saline infusion test and postural test helped to confirm the diagnosis. The tumor site was localized by magnetic resonance imaging (MRI). Surgical removal of the tumor yielded dramatic improvement in blood pressure; PAC and PRA returned to normal range. This rare case illustrates the feasibility of recognition and localization of adrenal adenoma in children. The high cure rate by surgical excision warrants careful screening of hypertensive patients with this entity.
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PMID:Adrenal adenoma with primary aldosteronism in a child: a case report. 798 40

Acute altitude illnesses include acute mountain sickness (AMS), a benign condition involving headache, nausea, vomiting, irritability, insomnia, dizziness, lethargy, and peripheral edema, and potentially lethal high-altitude cerebral edema and pulmonary edema (HAPE). Recent evidence is summarized that AMS is related to cerebral edema secondary at least in part to hypoxic cerebral vasodilation and elevated cerebral capillary hydrostatic pressure. This results in reduced brain compliance with compression of intracranial structures in the absence of altered global brain metabolism. It is postulated that these primary intracranial events elevate peripheral sympathetic activity that acts neurogenically in the lung possibly in concert with pulmonary capillary stress failure to cause HAPE and in the kidney to promote salt and water retention. The adrenergic responses are likely modulated by striking increases of aldosterone, vasopressin and atrial natriuretic peptide. The effects of exercise on altitude-induced illness and various therapeutic regimens (acetazolamide, CO2 breathing, dexamethasone, and alpha adrenergic inhibitors) are discussed in light of this hypothesis.
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PMID:A neurogenic basis for acute altitude illness. 816 37

We report a case of renovascular hypertension associated with neurofibromatosis complicated by moderate proteinuria. A 16-year-old female was admitted to Kensei General Hospital with a complaint of headache and a blood pressure of 230/120 mm Hg. She was referred to us for further evaluation of the hypertension. On examination, cafe-au-lait spots were seen over her extremities and flank, and a bruit was heard in the right upper abdomen. The urinary protein excretion was 2.1 g/day. The plasma renin activity (PRA) and plasma aldosterone concentration were high, but the levels of catecholamines were normal. The renogram was asymmetric and on venous sampling, the PRA in the right renal vein was 58.3 ng/ml/h and that in the left was 22.1 ng/ml/h. CT scan detected an approximately 10-mm mass in the proximal right renal artery. Arteriography disclosed severe stenosis in the right renal artery and the superior mesenteric artery. Therefore, we concluded that her hypertension resulted from stenosis of the right renal artery due to neurofibromatosis. Accordingly, she underwent an operation to reconstruct that artery. After the operation, her blood pressure and PRA normalized without administration of any anti-hypertensive drug and urinary protein disappeared.
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PMID:A case of renovascular hypertension associated with neurofibromatosis. 873 Apr 48

Candesartan cilexetil is rapidly and completely hydrolysed to the active compound candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, long-acting, selective angiotensin II AT1 receptor blocker. The pharmacokinetics of candesartan were investigated after single and repeated once-daily doses of candesartan cilexetil in the dose range 2-16 mg in both younger (19-40 years) and elderly (65-78 years) healthy volunteers in five studies. Blood pressure, heart rate, and hormones associated with the renin-angiotensin system, and safety of candesartan cilexetil administration were also assessed. Placebo comparisons were made in four studies. Frequent blood samples were collected after the first single dose of candesartan cilexetil, and during the last dosing interval after 1 week repeated once-daily administration. Serum and plasma were analysed for candesartan cilexetil, candesartan and its inactive metabolite, CV-15959, as well as angiotensin I and II, aldosterone, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity. The AUC and Cmax of candesartan showed dose-proportional increases in the dose range of 2-16 mg candesartan cilexetil after both single and repeated once-daily tablet intake, indicating linear pharmacokinetics in both younger and elderly healthy subjects. The pharmacokinetics did not change on repeated dosing and, as expected from the half-life of candesartan of approximately 9 h in younger subjects, there was almost no accumulation after repeated once-daily dosing. The time to peak candesartan concentrations after tablet intake was consistently approximately 4 h at all dose levels. Both Cmax and AUC of candesartan were increased after single and repeated once-daily dosing in the elderly compared to younger subjects by approximately 50%. However, no accumulation after repeated once-daily dosing were seen in the elderly. The half-life of candesartan in the elderly (9-12 h) was somewhat longer than in the younger healthy adult volunteers (approximately 9 h) and no gender-related differences in the disposition of candesartan were observed. Serum concentrations of CV-15959 were much lower than candesartan, and reached peak serum concentrations later, about 4-9 h after dose intake. The elimination of CV-15959 was somewhat slower than that of candesartan. Candesartan cilexetil, the prodrug to candesartan, was not measurable in serum. No differences in ACE activity or serum aldosterone concentrations were observed between subjects receiving candesartan cilexetil and placebo tablets. Plasma angiotensin I and II concentrations and PRA were augmented after single doses and further increased after 1 week repeated candesartan cilexetil dosing. Single and repeated doses of candesartan cilexetil were well tolerated in the younger and elderly volunteers. Only mild adverse events were recorded, with 'headache' as the most commonly reported event, and no increase in the number of reported adverse events was observed with higher doses of candesartan cilexetil. No clinically significant changes in respect to vital signs, physical examination, ECG, and clinical laboratory tests were observed.
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PMID:Pharmacokinetics of candesartan after single and repeated doses of candesartan cilexetil in young and elderly healthy volunteers. 933 Oct

We review the role of several biochemical and hormonal factors in menstrual migraine pathogenesis: ovarian hormones, aldosterone circadian rhythm, nocturnal urinary melatonin excretion, sympathetic autonomic system, prolactin levels and dopaminergic function, endogenous opioid tonus, platelet activity and arachidonic acid metabolites. In particular, we focus on certain aspects of platelet function and prostaglandin metabolism, taking into consideration the different behavior of platelet sensitivity to prostacyclin, intraplatelet 5HT, peripheral plasma concentrations of 6-keto-PGF1alpha and PGE2 in menstrual migraine sufferers and in control subjects during the menstrual cycle. A comprehensive view of the data suggests that a complex impairment of PG and 5HT metabolism, and of platelet function, may play a significant role in the pathogenesis of menstrual migraine. However, it is not yet clear whether these alterations are primary or secondary to neuroendocrine disorders.
Cephalalgia 1997 Dec
PMID:Pathophysiological aspects of menstrual migraine. 949 76

Although adrenal tumors detected during pregnancy are extraordinarily rare, the pathophysiologic repercussions of untreated adrenal neoplasms are enormous to both mother and fetus. From our computer-based registry of pregnant patients from 1975 through 1996 (n = 30,246), four cases of adrenal neoplasms associated with pregnancy were identified (0.013%), analyzed, and compared with the current medical literature. Four women ages 36, 29, 22, and 21 years had adrenal neoplasms diagnosed with pregnancy. Patient 1 had an unsuspected pheochromocytoma identified at autopsy. At 27 weeks into her pregnancy the patient suffered a myocardial infarction, and both she and the fetus died. Patient 2 was incidentally found to have adrenal and pancreatic neoplasms on screening abdominal computed tomography for von Hippel-Lindau disease. The study identified a pregnancy. She elected to terminate the pregnancy and underwent resection of both tumors. She died 3 years later of metastatic islet cell cancer. Both of these patients had previously delivered healthy babies, but both pregnancies were complicated by hypertension. Patient 3 had a functional adrenal tumor identified initially by urinary aldosterone studies because of symptoms of severe hypertension, and patient 4 had an adrenal mass diagnosed via ultrasonography at 30 weeks' gestation because of concerns for right-sided pyelonephritis. These two women underwent careful monitoring throughout the remainder of their pregnancies with eventual delivery of healthy babies. Both women later underwent successful operative resection of benign adrenal adenomas. Adrenal neoplasms discovered during pregnancy are rare. The onus, however, is on physicians to consider this diagnosis in pregnant women with hypertension, headaches, or other manifestations of adrenal disorders. Surgical management of identified adrenal lesions is thereafter straightforward. Missing the diagnosis has grave implications for these young women and their fetuses.
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PMID:Adrenal tumors and pregnancy. 988 Apr 29

To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a novel K+ channel opener, a single blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 28 healthy volunteers. The volunteers were randomly allocated to dosage groups of 50 micrograms, 100 micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were administered orally, after overnight fasting, and serial blood sampling and pharmacodynamic measurements were performed up to 48 hours after the drug was administered. The 200 micrograms group was further studied for food interactions in a crossover fashion. Drug concentrations in plasma were determined by HPLC. Hemodynamic changes after drug administration were evaluated by serial measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and total peripheral resistance (TPR), using computerized impedance cardiography. Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an active metabolite, showed linear pharmacokinetic characteristics, and food intake did not significantly affect the pharmacokinetic characteristics of either compound. Dose-related pharmacological effects were obvious for both the 200 micrograms and 300 micrograms groups. Hemodynamic parameters related to vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR, CI, and TPR, showed significant dose-dependent changes. The area under the time-effect curve (AUEC) of the parameters also showed a similar dose-dependent pattern. The PRA and PAC exhibited significant changes 4 hours after drug administration in the 300 micrograms group. Adverse effects, such as headaches, were more frequently observed at the higher dose levels. SKP-450 was generally well tolerated by these normotensive subjects. The antihypertensive efficacy of SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.
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PMID:Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers. 1088 17

Although the biological effects of adrenomedullin (AM) and PAMP have been reported extensively in animal studies and from in-vitro experiments, relatively little information is available on responses to the hormone administered to man. This review summarizes data from the few studies carried out in man. In healthy volunteers, i.v. infusion of AM reduces arterial pressure, probably at a lower rate of administration than is required to elicit other responses. AM stimulates heart rate, cardiac output, plasma levels of cAMP, prolactin, norepinephrine and renin whilst inhibiting any concomitant response in plasma aldosterone. Little or no increase in urine volume or sodium excretion has been observed. Patients with essential hypertension differ only in showing a greater fall in arterial pressure and in the development of facial flushing and headache. In patients with heart failure or chronic renal failure, i.v. AM has similar effects to those seen in normal subjects but also induces a diuresis and natriuresis, depending on the dose administered. Infusion of AM into the brachial artery results in a dose-related increase in forearm and skin blood flow, more prominent and more dependent on endogenous nitric oxide in healthy volunteers than in patients with cardiac failure. When infused into a dorsal hand vein, AM partially reversed the venoconstrictor action of norepinephrine. Although much more information is required to clarify the role of AM under physiological and pathophysiological circumstances, it is clear that it has prominent hemodynamic and neurohormonal effects, though generally lesser urinary effects when administered short-term in doses sufficient to raise its levels in plasma to those seen in a number of clinical disorders. The only study of PAMP in man showed that its skeletal muscle vasodilator potency, when infused into the brachial artery of healthy volunteers, was less than one hundredth that of AM, and it was without effect on skin blood flow.
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PMID:Bioactivity of adrenomedullin and proadrenomedullin N-terminal 20 peptide in man. 1175 60


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