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)

Benzamide riboside (BR), a synthetic C-nucleoside, acts as a strong growth inhibitor of cancer cells in vitro and in vivo. BR, like TR and related nucleoside prodrugs, act by anabolism to NAD analogs. These analogs selectively inhibit IMPDH, leading to depletion of cellular GTP, growth cessation, and cell differentiation. To date only preclinical studies have been carried out. However, in tiazofurin (TR), a related drug, phase I/II clinical trials have been conducted in patients with acute leukemia and shown to be a very promising agent with a response rate of 85% in 26 patients in one of the trials. Tiazofurin is now undergoing phase III clinical trials as a result. Dose limiting toxicity of tiazofurin was headache, somnolence and nausea with no myelosuppression noted. By contrast, BR showed skeletal muscle toxicity, hepatotoxicity and myelosuppression in preclinical data. Skeletal muscle toxicity was noted in the paraspinal muscles and may represent dose-limiting toxicity. Since BR does exhibit myelosuppression, the most common chemotherapy-related side effect in humans, careful judgment is warranted should BR be included in multidrug regimens, although BR's potent cytotoxicity to tumor cells in preclinical models still makes it a promising drug.
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PMID:Toxicity and efficacy of benzamide riboside in cancer chemotherapy models. 1196 43

The vast majority of community-acquired skin and soft tissue infections (SSTIs) are caused by gram-positive cocci or are polymicrobial in nature. Hospital-acquired SSTIs are caused by gram-positive cocci in more than 50% of patients. Multidrug-resistant gram-positive cocci are rarely associated with community-acquired SSTIs but are frequently found in hospital-acquired SSTIs. Linezolid is the first member of a new class of antibiotics, the oxazolidinones. These antimicrobial agents have a unique mechanism of action and exhibit excellent activity against a variety of gram-positive organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Linezolid is 100% orally absorbed, allowing for easy intravenous-to-oral continuation therapy. There is considerable clinical experience with the use of linezolid in SSTIs in phase II and III clinical trials. In comparative trials, linezolid was as effective as oxacillin-dicloxacillin or flucloxacillin in patients with complicated SSTIs caused by gram-positive organisms. Linezolid was also associated with significantly earlier hospital discharge than comparator agents among patients with SSTIs. It was equally effective as vancomycin in patients with SSTIs caused by methicillin-resistant Staphylococcus aureus and has also demonstrated efficacy in patients with SSTIs caused by vancomycin-resistant enterococci. Linezolid is well tolerated: the most common adverse events (gastrointestinal effects, headache) are reported in frequencies similar to those reported for comparator agents. Myelosuppression has been reported after prolonged administration but is reversible after discontinuation of the drug. Overall, linezolid has favorable efficacy and safety profiles and will be an increasingly useful option for the treatment of SSTIs, particularly those due to multidrug-resistant, gram-positive organisms.
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PMID:Efficacy and safety of linezolid in the treatment of skin and soft tissue infections. 1262 92

Although recombinant human interleukin-3 (rhIL-3) shortens both the duration of chemotherapy-induced neutropenia and thrombocytopenia, its effect on nadir counts is limited. Concurrent administration of rhIL-3 and chemotherapy may enhance this effect. However, simultaneous administration of other hematopoietic growth factors and chemotherapy has resulted in enhanced myelosuppression. We investigated whether concomitant administration of rhIL-3 and chemotherapy would result in enhanced myelosuppression. Twelve patients with relapsed small cell lung cancer received vincristine, ifosfamide, mesna, and carboplatin on day 1 every four weeks. RhIL-3 was administered subcutaneously on days 1-14 during cycle 1 at doses of 4 (three patients) or 8 micrograms/kg/day (nine patients). During cycle 2 patients received only chemotherapy. No significant difference in leukocyte (1.4 +/- 1.0 vs. 0.9 +/- 0.4 x 10(9)/l (mean +/- SD), neutrophil (0.5 +/- 0.6 vs. 0.2 +/- 0.2 x 10(9)/l), and platelet (64 +/- 60 vs. 38 +/- 58 x 10(9)/l) nadir counts were demonstrated. The hemoglobin nadir level was significantly higher during cycle 1 (6.5 +/- 1.1 vs. 5.5 +/- 0.9 mmol/l, P = 0.05). Both leukocyte and platelet recovery were significantly enhanced in the rhIL-3 cycle. There was no significant difference in chemotherapy postponement or platelet transfusions. As a result of severe headaches, rhIL-3 administration was discontinued in one patient at 8 micrograms. RhIL-3 during this chemotherapy regimen for relapsed small cell lung cancer did not enhance myelotoxicity but did improve bone marrow recovery. This observation may increase the application of rhIL-3, for instance in combination with other hematopoietic growth factors.
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PMID:Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer. 1241 20

The pharmacology, antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effects of linezolid are reviewed. Linezolid, the only oxazolidinone antimicrobial approved for use in the United States, has significant activity against gram-positive bacteria, including penicillin-, cephalosporin-, and vancomycin-resistant species. Linezolid inhibits bacterial protein synthesis via binding to the 50S ribosomal subunit to prevent translation. The drug lacks cross-resistance with other antimicrobials. Linezolid is primarily excreted renally as unchanged drug. The measured plasma half-life of four to five hours permits twice-daily administration for all indicated infections. Virtually complete oral bioavailability allows for 1:1 conversion between the intravenous and oral dosage forms. Controlled comparative clinical trials demonstrate that linezolid is effective in the treatment of vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) infections, nosocomial and community-acquired pneumonia, and skin and skin-structure infections due to susceptible organisms. The recommended dosage is 600 mg i.v. or p.o. twice daily for all indications except uncomplicated skin and skin-structure infections (400 mg twice daily); adjustments for mild to moderate renal or hepatic impairment are not necessary. Clinically important interactions with monoamine oxidase inhibitors have not been observed. Reversible myelosuppression has been observed in a few patients. Linezolid has gram-positive activity comparable to that of vancomycin, is effective in a variety of infections, and is well tolerated, with diarrhea, headache, and nausea being the most frequently reported adverse effects. Linezolid provides a reasonable therapeutic alternative for patients with vancomycin-resistant E. faecium infections and patients infected with MRSA who cannot tolerate vancomycin.
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PMID:Linezolid: an oxazolidinone antimicrobial agent. 1250 40

Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.
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PMID:Safety and tolerability of linezolid. 1273 Jan 42

Several disease-modifying agents (DMAs) are approved for the treatment of multiple sclerosis, including three interferon (IFN)-beta products, glatiramer acetate and mitoxantrone. This article reviews the adverse event profiles of these DMAs based on the pivotal phase III trials, and provides practical guidelines for managing adverse effects. In general, the most common adverse events associated with IFN beta therapy are flu-like symptoms, including fever, chills and myalgias, and headache. The flu-like symptoms typically resolve within 24 hours and may be mitigated by over-the-counter anti-inflammatory agents. Adverse events related to glatiramer acetate therapy include injection-site reactions and a systemic reaction consisting of flushing, chest tightness, palpitation, anxiety or dyspnoea. The systemic reaction is transient (30 seconds to 30 minutes) and self-limited. Mitoxantrone may cause nausea, vomiting, alopecia, amenorrhoea and myelosuppression; isolated cases of acute leukaemia and dose-related cardiotoxicity have been reported in the literature. Longer-term tolerability data on mitoxantrone as a treatment for multiple sclerosis are needed. It is important for physicians to counsel patients on DMA-related adverse effects, most of which are transient and of mild-to-moderate severity. Various strategies that can be employed to prevent or manage these adverse effects and lessen their impact on the patient are discussed.
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PMID:US FDA-approved disease-modifying treatments for multiple sclerosis: review of adverse effect profiles. 1574 Jan 78

The present work focuses on the therapeutic efficacy and the toxicity of alpha interferon in patients younger than age 18 years. 5 patients younger than 18 years were treated and followed up between 1990 and 1999 at the department of haematology (Aziza Othmana Hospital) Hydroxyurea was given as initial treatment to all patients. After a median period of 8 months, these patients received alpha interferon (5 millions units/m2 once). Six months after the beginning of the alpha interferon a complete hematologic response was obtained in all patients. The median overall survival was of 66 months: 3 patients are still alive (2 patients in an advanced stage and one patient in chronic phase) and 2 patients died after transformation. The most common reported side effects of alpha interferon were asthenia, weight loss, fever, myalgia, chills and headaches--these toxic manifestations were mild and were noticed in all our patients. Myelosuppression was noted in two patients. Interferon is well tolerated in patients younger than age years 18 old, with CML. It may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without histocompatible donor. The role of new agents such as STI 571 needs to be evaluated as well.
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PMID:[Alpha interferon in children with Philadelphia chromosome-positive chronic myeloid-leukaemia]. 1604 5

Sulfasalazine (salazosulfapyridine) [Azulfidine, Salazopyrin] is a well established disease-modifying antirheumatic drug (DMARD) used in the treatment of patients with rheumatoid arthritis. Clinical trials with sulfasalazine have used an array of measures of disease activity, such as the number of tender and swollen joints, Ritchie articular index (RAI) and erythrocyte sedimentation rate (ESR). In randomised, double-blind, placebo-controlled trials, sulfasalazine was associated with statistically significant benefits for various measures of disease activity, according to results of individual trials and/or meta-analysis. Sulfasalazine was associated with broadly similar efficacy to that of various other DMARDs in several randomised, double-blind, comparative trials. Promising results have also been demonstrated with sulfasalazine in combination with other DMARDs (e.g. methotrexate and hydroxychloroquine) in patients with early rheumatoid arthritis and in those with more established disease. Sulfasalazine was generally well tolerated in clinical trials, the most frequently reported adverse effects being adverse gastrointestinal effects, headache, dizziness and rash; myelosuppression can also occur. Sulfasalazine has a relatively short lag time until its onset of action and is often considered to be among the more efficacious traditional DMARDs. Based on considerations of safety, convenience and cost, many rheumatologists (particularly outside of the US) select sulfasalazine as initial therapy, although preferred first-line treatment options vary between countries.
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PMID:Sulfasalazine: a review of its use in the management of rheumatoid arthritis. 1611 81

Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years of age remains unsatisfactory, with low remission rates and poor overall survival. We have previously established the activity of clofarabine plus cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine plus cytarabine in patients aged 50 years or older with previously untreated AML. Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15 [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse events were mainly grade 2 or lower and included diarrhea, nausea, vomiting, mucositis, skin reactions, liver test abnormalities, and infusion-related facial flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation.
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PMID:Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older. 1640 5

Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylation in vitro and in vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.
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PMID:Hydralazine target: from blood vessels to the epigenome. 1650


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