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)

GR38032F is a specific 5-HT3 (serotonin) receptor antagonist with antiemetic activity in animal and early human studies. We performed a dose-ranging phase I study of GR38032F in 43 evaluable patients receiving cisplatin 60 120 mg/m2 for the first time (38 of these patients were chemotherapy-naive). Intravenous GR38032F was administered over a dose range from 0.01 to 0.48 mg/kg given three times at four-hour intervals beginning one half hour before cisplatin, and patients were observed for 24 hours. An additional five patients were treated with 0.18 mg/kg given three times at six-hour intervals. Excellent antiemetic efficacy was noted, with 44% of patients experiencing no vomiting and 26% no nausea. Major protection from vomiting (less than or equal to 2 episodes) and from nausea (less than or equal to 2 hours) was experienced by 81% and 44%, respectively. Mild to moderate headache (40%), lightheadedness (21%), and elevated transaminase (19%) were the most common adverse events reported. One patient experienced an apparent hypersensitivity reaction that responded to conventional medications. No extrapyramidal reactions or akathisia were seen. GR38032F was effective through most of the dose range. However, efficacy decreased at the 0.01 mg/kg level and number and intensity of adverse events increased at the 0.48 mg/kg level. Analysis of those patients receiving high-dose cisplatin (100 to 120 mg/m2) revealed a positive association of GR38032F dose and antiemetic activity (Fisher's exact test, two-sided; P less than .05). The 5-HT3 receptor antagonists may provide antiemetic efficacy similar to high-dose metoclopramide without antidopaminergic toxicity. The maximum recommended dose on this schedule of GR38032F is 0.36 mg/kg.
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PMID:Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting. 252 64

A series of single dose studies has been undertaken after intravenous, subcutaneous and oral administration to healthy volunteers to determine safety, tolerability and pharmacokinetics of GR43175, a novel 5-HT 1-like receptor agonist. GR43175 proved to be well tolerated using all routes of administration. Minor side effects were reported including scalp tingling, sensations of bodily warmth, lightheadedness and heavyheadedness. In addition, short-lasting vasopressor effects were encountered, although no drug-related changes were seen in heart rate and ECG or in laboratory safety screens. The drug was rapidly absorbed after oral dosing and had a mean absolute bioavailability of 14% due at least in part to first-pass metabolism. Plasma concentrations in healthy volunteers fell within the range for producing relief of headaches in migraine patients. GR43175 had a high mean plasma clearance (1313 ml/min), the majority of which was due to non-renal clearance and a large volume of distribution (2351). The mean half-lives were 1.7 h and 2.3 h after intravenous and oral doses, respectively.
Cephalalgia 1989
PMID:Early studies with the novel 5-HT 1-like agonist GR43175 in healthy volunteers. 254 85

Respiratory insufficiency of any cause has significant effects on the nervous system. Headache, mental status changes, papilledema, and numerous motor abnormalities including asterixis are commonly seen. Abnormalities in ventilation and gas exchange result in hypoxia, hypercapnia, and respiratory acidosis, and these, in turn, interfere with cerebral metabolism, increase CBF, and may raise intracranial pressure. Chronic respiratory insufficiency can persist for many months with minimal neurologic symptoms, as numerous compensatory mechanisms, particularly renal, may take effect. Treatment includes restoring adequate ventilation and improving gas exchange and may require tracheal intubation and assisted ventilation. Supplemental oxygen therapy should be carefully monitored, as high rates of flow may suppress the hypoxic drive for respiration and lead to significant carbon dioxide retention. The sleep apnea syndromes are a group of disorders in which abnormal respiratory patterns during sleep result in hypercapnia and hypoxemia. Intermittent obstruction of the upper airway and abnormalities of brainstem respiratory centers cause frequent nocturnal awakenings and apneas in these patients. Treatments vary and include weight loss in obese subjects, respiratory stimulants, tracheostomy, and diaphragmatic pacing. Rapid ascent to high altitudes may result in headache, changes in mental status, papilledema, and other neurologic symptoms in certain individuals: a syndrome known as high-altitude sickness. Hypoxia leading to cerebral edema, nocturnal periodic breathing, and hypobaria produces neurologic symptoms in these individuals. Acetazolamide and dexamethasone may be effective in minimizing symptoms of this disorder. Sustained hyperventilation produces acral and circumoral paresthesias and lightheadedness in anxious individuals and can be maintained by relatively normal ventilatory patterns once established. These symptoms are due to hypophosphatemia and respiratory alkalosis, the latter reducing CBF and causing localized tissue hypoxia. Rebreathing into a paper bag at the first awareness of symptoms is the most effective form of treatment.
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PMID:Neurologic manifestations of pulmonary disease. 267 37

Symptomatic common carotid artery occlusion (CCAO) is rare. We studied 17 patients with ischemic cerebrovascular symptoms and unilateral CCAO on angiography to help clarify clinical and radiologic features. Mean age was 62 years; 65% were women. Predominant symptoms and signs included visual-ipsilateral monocular or retrochiasmal symptoms (88%), motor weakness (88%), sensory disturbance (59%), dizziness/lightheadedness (53%), and syncope (24%). Dysarthria, headache, or involuntary limb shaking occurred less frequently. Positionally related symptoms occurred in approximately two-thirds of the patients. TIAs were often multiple and preceded a stroke or occurred without subsequent stroke in 82%. Hemispheric TIAs contralateral to the CCAO occurred in 41%. Ten patients (59%) suffered stroke, seven (70%) of which were ipsilateral to the CCAO. Vascular risk factors included cigarette use (76%), hypertension (71%), diabetes mellitus (41%), and hyperlipidemia (41%); 82% had two or more risk factors. Known cardiac disease was present in 59%. CCAO was present at the origin of the vessel in most patients. Most had atherosclerotic narrowing of multiple extracranial large vessels. During follow-up, none of the patients had a spontaneous second infarct; five had TIAs, including two with amaurosis fugax, all in the CCAO territory. More restricted external carotid collaterals may, in part, explain the higher frequency of ipsilateral stroke and contralateral TIAs than reported for internal carotid occlusion.
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PMID:Common carotid artery occlusion. 279 68

Recently, calcium antagonists have been reported to have a clinically beneficial effect in patients with asthma. Felodipine is a new calcium antagonist of the dihydropyridine group with a high selectivity for arteriolar smooth muscle; it is under clinical investigation for the treatment of hypertension. In this double-blind, randomized crossover trial in 9 patients, the effect of 10 mg felodipine in oral solution on exercise-induced asthma was compared with a placebo on separate days. The FEV1 was at least 80% of the predicted normal value, with variation between study days of less than 10%. Heart rate, blood pressure, and FEV1 were measured before and at 15 and 30 min after each treatment. The exercise test consisted of steady state running at submaximal work loads for 6 to 8 min and started at 30 min after treatments. FEV1 was measured at 1, 2, 5, 10, 15, and 30 min after the end of exercise. The predrug baseline FEV1 values were comparable on the 2 days of the study, and felodipine had no effect on the resting lung function. The mean percentage fall in FEV1 (SEM) after exercise with placebo was 27.0 (4.5)%, and with felodipine it was 13.5 (3.7)%. The difference between felodipine and placebo was statistically significant. While receiving felodipine, the resting heart rate was increased by 15%, with a tendency to lower systolic and diastolic blood pressures. The heart rate after exercise was higher during felodipine treatment than during placebo treatment. One patient receiving placebo and 7 receiving felodipine noted a transient headache. Two patients receiving felodipine also noticed lightheadedness after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Felodipine, a new calcium antagonist, modifies exercise-induced asthma. 320

Zindotrine, a new bronchodilator, may be an alternative to theophylline in treating reversible airflow obstruction. Efficacy and cardiovascular effects of a single 300 mg oral dose of zindotrine were compared with placebo in a two-period, double-blind, crossover trial. Twelve subjects with airflow obstruction reversible after isoproterenol and theophylline completed the trial. Improvement in pulmonary function (forced vital capacity [FVC], forced expiratory volume in one second, and forced expiratory flow rate from 25 to 75 percent of FVC) was greater after zindotrine than with placebo. Pulmonary function tests increased 15 percent or more over baseline in 30 minutes after active drug, lasting up to 6 hours. Mild decreases in heart rate and mean blood pressure occurred after both treatments, with changes equal in both treatment groups. Six subjects had mild subjective side effects after zindotrine (headache, dizziness, vertigo, flushing, and heartburn) compared with one report of lightheadedness after placebo. A single dose of zindotrine 300 mg provides effective bronchodilator action with a relatively prolonged response and tolerable side effects.
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PMID:Single-dose efficacy and safety of zindotrine, a new oral bronchodilator. 322 40

A retrospective chart review was conducted at two regional poison centers to determine the clinical outcome of boric acid ingestions and to assess the relationship between serum boric acid levels and clinical presentation. A total of 784 cases were studied; all but 2 were acute ingestions. No patients developed severe manifestations of toxicity, and 88.3% were entirely asymptomatic. The most common symptoms were vomiting, abdominal pain, and diarrhea. Lethargy, headache, lightheadedness, and atypical rash were seen less frequently. Boric acid levels were obtained in 51 patients and ranged from 0 to 340 micrograms/mL. Blood levels were 70 micrograms/mL or more in 7 patients; 4 remained asymptomatic, whereas the other 3 had nausea or vomiting. Dialysis was performed in 4 of these 7 patients, only 1 of whom had symptoms (vomiting). On the basis of data from 9 patients, the mean half-life of boric acid was determined to be 13.4 hours (range, 4.0 to 27.8). Hemodialysis in 3 patients significantly shortened the half-life compared with pre- and postdialysis half-lives. Our results suggest that acute boric acid ingestions produce minimal or no toxicity and that aggressive treatment is not necessary in most patients.
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PMID:Clinical manifestations of toxicity in a series of 784 boric acid ingestions. 337 93

Nineteen Sewage Treatment Workers (STWs) exposed to industrial sewage that contained benzene, toluene, and other organic solvents at a primary sewage treatment plant in New York City (Plant A) were examined for evidence of solvent toxicity. Fourteen (74%) complained of central nervous system (CNS) symptoms consistent with solvent exposure, including lightheadedness, fatigue, increased sleep requirement, and headache. The majority of these symptoms resolved with transfer from the plant. Men working less than 1 yr at Plant A were more likely to complain of two or more CNS symptoms than men who were working there longer than 1 yr (p = .055). Objective abnormalities in neurobehavioral testing were found in all 4 men working longer than 9 yr at this plant, but in only 5 of 15 employed there for a shorter period (p = .03). These results are consistent with the known effects of solvent exposure. Occupational health personnel must be aware that STWs can be exposed to solvents and other industrial wastes.
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PMID:Neurotoxic effects of solvent exposure on sewage treatment workers. 341 51

Isobutyl nitrite is a volatile liquid sold without a prescription as a "room odorizer" but is widely used as an inhalant to produce feelings of euphoria. Of the 173 13-22-year-olds (mean age, 16 years) clients of a long-term drug treatment facility who completed a questionnaire related to drug use, 74 (43%) admitted to having used isobutyl nitrite at least once, 22 (13%) had used the substance ten or more times, and eight (4%) used the substance 50 or more times. Inhalation of this malodorous substance leads almost universally to dizziness and lightheadedness and usually to severe symptoms of vasodilatation such as "pounding of the heart," blurred vision, and a "warm feeling." The feeling was unpleasant to 44 percent of the users in this study, and most also experienced pulsatile headache. In addition, contact dermatitis and irritation of the tracheobronchial tree and eyes occurred in some users. The primary use of this substance as an euphoric agent warrants consideration of banning its sale altogether.
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PMID:Abuse of isobutyl nitrite inhalation (Rush) by adolescents. 369 54

Embolic and thrombotic infarction in the territory of the posterior cerebral artery (PCA) is described with emphasis on the stroke and cerebrovascular features rather than special neurological syndromes. Of 47 cases of obstruction at the distal bifurcation of the basilar artery, 43 (95%) were consistent with embolism. The clinical categories and pathological findings are presented. Local embolism, vertebral distal-stump embolism, the dynamics of hemorrhagic infarction and embolus-in-transit are briefly described. The prodromal manifestations of PCA thrombotic occlusion include photopsias, hemianopic blackouts, headache, transient episodes of numbness, episodic lightheadedness, spells of bewilderment and rarely tinnitus. Recognition of these may allow prevention of a stroke. Prodromal photopsias did not closely resemble the scintillating displays of migraineurs. When the stroke occurred, visual complaints usually predominated. A sensory deficit occurred in one-third of cases. In 25 cases of memory impairment the dominant hemisphere was involved in 24. The kinds of visual hallucinations, simple and formed, are described.
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PMID:The posterior cerebral artery syndrome. 374 39


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