Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
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Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

A large number of drugs within the 3 currently classes of calcium antagonists are in common medical use for the treatment of hypertension and ischaemic heart disease. The reported adverse effect profile for each of these drugs varies, but tends to hold true to drug class and are typified by the adverse reactions reported for nifedipine and amlodipine (dihydropyridines), diltiazem (benzothiazepines) and verapamil (phenylalkylamines). Minor adverse effects such as flushing, headache, ankle oedema, palpitations and constipation are not uncommon and frequently require the cessation of treatment. Of greater concern affecting the wide and common first-line use of calcium antagonists is the as-yet unresolved issue of a reportedly greater risk of myocardial infarction and death following the use of short-acting nifedipine in patients with a history of hypertension, myocardial infarction or angina. Until this issue is fully resolved, it would seem prudent to limit the use of this agent in 'at-risk' patients and to await the results of further prospective studies before a final conclusion can be made.
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PMID:A comparative review of the adverse effects of calcium antagonists. 888 61

The aims of this ancillary study to the Italian Longitudinal Study of Aging were: (1) to provide reliable prevalence data on headache in an elderly population, (2) to classify the subtypes of headache according to International Headache Society criteria, and (3) to identify possible risk factors and associated pathologies in the elderly. A total of 312 subjects were examined, 148 women and 164 men, with a mean age of 73 years (SD 5.5). For 236 subjects (75.7%), 141 men (85.9%) and 95 women (64.2%), headache had never been a problem; 57 subjects (18.3%), 21 men (12.8%) and 36 women (24.3%), reported troublesome headache only in the past. Nineteen subjects (6%), 6 men (3.6%) and 13 women (8.8%), reported current headache: in this group tension-type headache was the most prevalent, accounting for 2.6%; secondary headaches ranked second, accounting for 2.2%; and only 1% had current migraine. Our data indicate female sex and younger age as risk factors for headache, and associate migraine and secondary headaches with hypertension, tension-type headaches and secondary headaches with diabetes, and tension-type headaches with myocardial ischemia.
Headache 1997 Feb
PMID:Headache in a population-based elderly cohort. An ancillary study to the Italian Longitudinal Study of Aging (ILSA). 907 91

Carvedilol competitively blocks beta 1, beta 2 and alpha 1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through alpha 1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. Recent data have confirmed the antihypertensive efficacy of carvedilol in patients with mild to moderate essential hypertension. Carvedilol has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors and hydrochlorothiazide. Carvedilol also improves exercise tolerance and ischaemic symptoms in patients with stable angina pectoris. Significant reductions in serious cardiac events after acute myocardial infarction and in frequency and severity of ischaemic events in patients with unstable angina have also been demonstrated. Interest in the use of carvedilol in patients with congestive heart failure (CHF) has culminated in the publication of a cumulative analysis of data from 1094 patients with mild to severe CHF who participated in the US Carvedilol Heart Failure Study Program (4 trials). After a median follow-up of 6.5 months, a significant overall reduction in mortality relative to placebo (3.2 vs 7.8%) was revealed in patients who had received carvedilol 6.25 to 50 mg twice daily (plus diuretics and ACE inhibitors). All-cause mortality, risk of hospitalisation for cardiovascular reasons and hospitalisation costs were also reduced significantly (by 65, 28% and 62%, respectively) in these trials. In addition, the Australia and New Zealand Heart Failure Research Collaborative Group showed a 26% reduction in the combined risk of death or hospitalisation with carvedilol 12.5 to 50 mg/day relative to placebo after a mean 19-month follow-up period in 415 patients with CHF (relative risk 0.74). Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related and are usually seen early in therapy. Events most commonly reported are related to the vasodilating (postural hypotension, dizziness and headaches) and the beta-blocking (dyspnoea, bronchospasm, bradycardia, malaise and asthenia) properties of the drug. Carvedilol appears to date to have little effect on the incidence of worsening heart failure. Concomitant administration of carvedilol with some medications requires monitoring. Carvedilol is therefore likely to have a beneficial role in the management of controlled CHF, but further clinical studies are required to show the place of beta-adrenoceptor blocking therapy in general in this indication, and the position of carvedilol relative to other similar agents. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
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PMID:Carvedilol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders. 921 Oct 87

Electrocardiographic changes, left ventricular wall motion abnormalities, myocardial ischemia, myocytolysis and arrhythmias have been well documented in patients with cerebral bleed. These complications may be related to stimulation of autonomic nervous system and central nervous system. We report a case of a 38-year-old back woman without previous heart disease, taken to emergency unit with headache and subarachnoid Haemorrhage. One day after, she complained of retroesternal pain. An electrocardiographic tracing showed significant and diffuse ST-T wave abnormalities. The patient remained stable with no neurologic or cardiac deficits. She was treated with bed rest, nimodipine, isossorbide propranolol and is symptomless six months of follow-up.
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PMID:[Signs of myocardial ischemia associated with subarachnoid hemorrhage]. 924 29

We report two patients with exertional headaches beginning with vigorous exercise and relieved by rest. Neurologic evaluation and neuroimaging were normal in both. During exercise stress testing, the onset of the patients' typical headaches correlated with ECG changes indicative of myocardial ischemia. In both patients coronary angiography revealed three-vessel disease, and myocardial revascularization procedures were followed by complete resolution of headaches. Based on these patients, and a review of prior similar reports, we conclude that myocardial ischemia is a rare and treatable cause of exertional headache. Accurate diagnosis is critical to controlling headaches and preventing myocardial infarction.
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PMID:Cardiac cephalgia: a treatable form of exertional headache. 952 6

A 68-year-old man with coronary artery disease was admitted for chest pain and ventricular tachycardia. After electric cardioversion, therapeutic heparinization was started for myocardial ischemia and nontransmural infarction. On day 3, headache and fever developed, followed by an altered sensorium and hyponatremia. Infectious etiology for the fever was excluded, and results of computed tomography of the brain were normal. Later magnetic resonance imaging (Day 10) demonstrated a pituitary macroadenoma with hemorrhage. Treatment for panhypopituitarism with stress-dose steroids stabilized the patient, and the fever and hyponatremia resolved. Transsphenoidal resection of the pituitary adenoma was performed without incident. This is the first reported case of pituitary apoplexy after heparin anticoagulation for acute myocardial infarction, although chronic anticoagulation in other settings has been reported as a precipitant of apoplexy. The uncommon presentation of a "central" fever and confusion in a patient with previously undiagnosed adenoma posed a diagnostic challenge. Subtle presentations of panhypopituitarism, knowledge of which should lead to suspicion and early diagnosis of pituitary apoplexy, will prevent anticoagulant-induced central nervous system catastrophes and potential fatalities.
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PMID:Heparin therapy for myocardial infarction: an unusual trigger for pituitary apoplexy. 936 41

The authors report two cases where headaches was the only manifestation of severe myocardial ischemia. They had high degree coronaria sclerosis which was demonstrated by angiocardiography in one patient and at autopsy in the second patient. These findings suggest that in the mechanism of headache angina rather the pain perception than generalized vasospasm plays an important role.
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PMID:[Headache as a symptom of angina]. 943 43

Nitrates, which have been used for more than a century, are the second oldest drug (after digitalis alkaloids) in the cardiological pharmacological arsenal. However, several facets of their mode of use still remain controversial. Their vasodilator and arteriolodilator action (especially in coronary vessels) and their platelet aggregation inhibitory effect make them useful drugs, particularly in all clinical forms of ischaemic heart disease (unstable or stable angina and acute myocardial infarction), for the prevention or treatment of ischaemic episodes (silent or not) and also in heart failure where nitrates are useful not only as symptomatic treatment (alone or associated with diuretics), but also in view of their positive effect on survival (associated with hydralazine: V-Heft I trial). At the present time, nitrates can be administered via the sublingual, oral, intravenous of transdermal routes in the form of nitroglycerin and isosorbide dinitrate or mononitrate (short-acting and sustained-effect forms). Their rare contraindications concern patients suffering from severe hypotension (< 70 mmHg), severe anaemia, glaucoma or intracranial hypertension. The most serious adverse effects are pulsatile headache (which usually disappear after several days), postural hypotension (possibly causing fainting), facial erythema, vertigo, palpitations or nausea and vomiting. Most of these adverse effects can be controlled by dosage adaptation and it is rarely necessary to stop treatment. However, the major problem raised by the use of nitrates concerns the development of a tolerance. The pathophysiology of this multifactorial phenomenon is still unclear. The protagonist role played by loss of SH groups or activation of humoral feedback mechanisms, with an increase of circulating catecholamine levels, activation of the R-A-A system and increased plasma volume, has been postulated. This complication can be avoided by prescribing intermittent treatment, with a drug-free interval of 10-12 hours per day. A single dose of a sustained-release preparation (60 mg of isosorbide dinitrate or 40 to 60 mg of isosorbide mononitrate), or 2 or 3 doses of a short-acting preparation (20-40 mg of isosorbide mononitrate) can be prescribed via the oral route. When the transdermal route is used, the patch should be left in place for 12 hours. Treatment should be started at low doses, which are then gradually increased. The free period is usually at night, which can be covered, when necessary, by other antiischaemic drugs (for example, beta-blockers and/or calcium channel blockers), already usually used in combination with nitrates. This interruption is not accompanied by a rebound phenomenon. It must be remembered that nitrates potentiate the action of other vasodilators and calcium channel blockers and that, in some patients, intravenous nitroglycerin reduces the anticoagulant effect of heparin, while indomethacin can inhibit their vasodilator effect. Nitrates are therefore in very good health despite their advanced age and, when used correctly, they continue to be very useful in the pharmacological treatment of cardiovascular diseases.
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PMID:[Principles and rules of the use of nitrates]. 945 73

The purpose of the study was to study admission delay in patients with stroke, and to analyze the influence of demographic, medical, and pathophysiological factors on admission delay. The study was prospective and consecutive and included 1197 unselected patients admitted with acute stroke from a well-defined catchment area in Copenhagen. Only 35% were admitted within the first six hours from stroke onset, and 50% of the patients were admitted later than 14 hours from stroke onset. Living alone (OR 1.75, 95% CI 1.3 to 2.3) and retired working status (OR 1.6, 95% CI 1.01 to 1.54) delayed admission. A well-functioning social network thus seems important to early admission. The milder the stroke, the higher was the risk of delayed admission (OR 1.25 per 10 points increase in stroke severity (Scandinavian Neurological Stroke Scale on admission), 95% CI 1.06 to 2.54. Other factors such as age, sex, diabetes, hypertension, ischaemic heart disease, other comorbidity, previous stroke, headache, aphasia, apraxia, anosognosia, neglect, lowered consciousness, mental status, and type of stroke had no independent influence on admission time. However, a history of TIA increased the chance of early admission by odds 1.64 (95% CI 1.01 to 2.54), indicating that an increase in public awareness and knowledge may reduce delay and save precious time.
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PMID:[Pattern of admissions of patients with apoplexy. Time connection between symptom onset and admission and relation to medical and social factors. The Copenhagen Stroke Study]. 946 80


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