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)

Twenty volunteers were inoculated with various doses of human serum containing Phlebotomus fever virus (Sicilian type) to determine their clinical and serologic responses as well as the human infectious dose50 of the virus. All infected subjects developed fever which varied in duration from 6 to 74 hours. The most common symptoms during sandfly fever were headache, anorexia, myalgia, photophobia, low back and retro-orbital pain. Infected individuals developed a marked leukopenia characterized by an initial lymphopenia followed by protracted neutropenia. Little complement fixing antibody was detected in convalescent sera but most subjects developed significant rises in hemagglutination inhibiting antibodies. All infected subjects developed specific neutralizing antibodies with titers ranging from 1:40 to 1:2,560. Of the three serologic tests performed, the plaque reduction neutralization method appears to be the most sensitive test for detecting antibodies to Phlebotomus fever viruses.
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PMID:Clinical and serologic responses of volunteers infected with phlebotomus fever virus (Sicilian type). 18 Aug 44

Twenty-three difficult to control patients with 1 or more seizures per week despite diphenylhydantoin (DPH), phenobarbital and/or primidone in near and toxic doses and blood levels were entered in the study. 3 had grand mal. 8 psychomotor seizures and 12 had both. During a 6 1/2 month study period the patient received active drug and placebo for 3 months each; randomized, double-blind. The dose was to be increased within 4 weeks up to 6 capsules per day equal to 1,200 mg of carbamazepine (C), while the doses or previously taken (basis) anticonvulsants were to remain unchanged. Hematopoetic system and heptic functions were monitored. Complete seizure control attributable to C was not achieved in any, but up to 50% improvement occurred in 12 patients. Questionable improvement was thought to take place in 3 patients, no change occurred in 7, and psychomotor seizures became more frequent in 1 patient. A clear-cut psychotropic effect was not observed. Adverse effects attributable to C were a decline of WBC below 4,000 with relative neutropenia in 3 patients followed by at return to the previous after discontinuation of C. Nystagmus and unsteadiness were seen in about half of the patients, and some headache and drowsiness occurred in one quarter. The highest C blood level was 11.8 mug/ml, the lowest 3.8 mug/ml (average 5.6 mug/ml) during 1,200 mg intake. It seemed, generally, that intoxication occurred with lower blood levels of carbamazepine in those patients whose basis anticonvulsant blood levels were highest.
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PMID:Carbamazepine in difficult to control epileptic out-patients. 81 Oct 74

To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin-cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose-limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.
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PMID:Effects of interleukin-3 after chemotherapy for advanced ovarian cancer. 151 36

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. 152

Angiotensin-converting enzyme (ACE) inhibitors are useful first-line drugs in the therapy of mild and moderate hypertension. Adverse reactions to this drug class are rarely serious. Hypotension, cough, rash, and taste disturbance are uncommon; reduced glomerular filtration and hyperkalemia occur infrequently; angioedema is rare and neutropenia is extremely rare. Quinapril is a new ACE inhibitor that is converted to biologically active quinaprilat in the liver. This ACE inhibitor has a rapid onset of action and inhibits local tissue converting enzyme systems in kidney, heart, and brain, as well as in the circulating renin-angiotensin system. Clinically significant adverse effects of quinapril occur at low rates. In 1,771 patients receiving quinapril, the reported incidence of the first occurrence of orthostatic hypotension was comparable to that seen in patients receiving placebo. In other studies, headache was reported by up to 4.7% of patients receiving quinapril, which is comparable to reported incidences of headache in patients receiving other ACE inhibitors. Other adverse events reported at rates greater than 1% include cough with associated rhinitis and bronchitis, dizziness, and somnolence. Such adverse events have only rarely led to the withdrawal of patients from clinical studies of quinapril.
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PMID:Adverse effects of angiotensin-converting enzyme inhibitors in antihypertensive therapy with focus on quinapril. 154 39

Enalapril is an effective agent in the treatment of mild to severe hypertension. It is equally effective in elderly and young adult patients but appears to be more effective in white than in black hypertensive patients. Following treatment with enalapril, an assessment of maximum exercise performance found a decrease in total peripheral resistance without significant changes in cardiac output, heart rate, or stroke volume compared with pretreatment values. In addition, there have been reports of reversal of left ventricular hypertrophy in enalapril-treated hypertensive patients. Enalapril is also effective and well tolerated in hypertensive patients with renal impairment of varying etiology. The most common adverse experiences reported in controlled clinical trials were headache (5.2%), dizziness (4.3%), and fatigue (3.0%). In high-risk hypertensive patients, no enalapril-treated neutropenia, proteinuria, dysgeusia, or ageusia were reported. It may be concluded that the benefit-to-risk ratio of enalapril is among the best of the antihypertensive therapies currently available.
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PMID:Enalapril: benefit-to-risk ratio in hypertensive patients. 169 15

The natural history of HIV infection continues to change with improved diagnostic and therapeutic modalities available to manage opportunistic infections and malignancies. Antiretroviral therapy with zidovudine and other investigational agents has improved the median survival of AIDS patients from 11 months in 1985 to 18-25 months at present. Most importantly, early intervention with zidovudine can delay onset of clinical illness in asymptomatic patients and progression to AIDS in symptomatic patients. A 500 mg/d dose has been found as effective as previously recommended doses of 1200-1500 mg/day. Lower doses decrease the incidence and severity of adverse effects and therapeutic benefit appears to be greatest in asymptomatic patients with CD4 lymphocyte counts less than 500/ul. Indications for zidovudine, therefore, have been expanded to include asymptomatic adults with CD4 lymphocyte counts less than 500/ul. Concerning early intervention with zidovudine, studies were not designed to measure survival or define the optimal timing of intervention based on immunologic status. In addition, long-term benefits are not clearly defined, particularly since the drug seems to lose clinical effectiveness after approximately two years, probably due to emergence of resistant HIV strains. Adverse effects continue to occur even at low doses including headaches, nausea, anemia and neutropenia, myopathy and possible hepatitis. Nevertheless, the overall clinical benefit seems to be greatest, albeit temporary, in asymptomatic patients. The optimal dosage appears to be 500-600 mg/d; however, this may not be sufficient for infection in the central nervous system.
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PMID:Management of HIV infection in adults. 175 30

We studied escalating doses of recombinant human interleukin-1 beta (IL-1 beta) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P less than .00001) on the days of IL-1 beta administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1 beta administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 micrograms/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1 beta than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1 beta has stimulatory effects in human hematopoiesis.
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PMID:A phase I trial of recombinant human interleukin-1 beta alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer. 188 14

Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril-treated patients and in 18% of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizziness, and fatigue. The incidence of side effects was not affected by the degree of hypertension, age, gender, race, dosage, or the degree of renal impairment. Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension, which occurred at a relatively low rate with benazepril, and hyperkalemia and elevation of serum creatinine, which occurred to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor side effect is unknown; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertensive patients treated with benazepril has not been reported. Overall, benazepril is generally well tolerated by hypertensive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.
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PMID:Safety profile of benazepril in essential hypertension. 189 40

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.
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PMID:Zidovudine update: 1990. 219 18


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