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)

Recombinant interferon beta (IFN-beta ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 x 10(6) IU to 14 patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-beta ser appears to have activity in human glioma and is well tolerated at this dosage and schedule.
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PMID:A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma. 208 58

A phase I trial involving continuous infusion of both beta- and gamma-interferon (IFN-beta and IFN-gamma) was conducted in 20 patients in order to determine whether combinations of high doses of IFN-beta and IFN-gamma were tolerable when administered under conditions which mimic conditions of in vitro antiproliferative studies. Patients received a 5-day continuous infusion of IFN-beta/IFN-gamma, followed by a 9-day rest period. Two cycles were administered. Doses of IFN-beta/IFN-gamma were escalated between 4 dose levels, with 5 patients per dose level. Dose-dependent side effects, consisting primarily of constitutional symptoms typical of those experienced with IFN, were observed. The maximally tolerated dose of continuous IFN-beta/IFN-gamma infusion was 3 x 10(6) units of IFN-beta and 200 micrograms of IFN-gamma. Dose-limiting side effects consisted of severe headache, fatigue, fever, and hepatic toxicity. No clinical responses were observed. Serum IFN was measurable only at the highest 3 dose levels. Only 5 patients (4 at the highest dose level) had total serum levels which exceeded 50 laboratory units/ml (55, 63, 800, 800, and 550 laboratory units/ml, respectively). In order to confirm the biological effectiveness of this schedule, we measured IFN-inducible proteins prior to therapy, 24 h after the initiation of the infusion, and at the completion of the 5-day infusion. 2'-5'-Oligoadenylate synthetase, serum beta 2-microglobulin, neopterin, and p78 levels all increased significantly, and serum tryptophan decreased significantly within 24 h after the initiation of treatment (P less than 0.0001). A dose-response effect was observed for serum beta 2-microglobulin, neopterin, and p78 (P less than 0.02). We retrospectively compared the results of this trial with those of another IFN-beta/IFN-gamma trial in which IFN-beta and IFN-gamma were administered by i.v. bolus. Within the limitations of a retrospective comparison, continuous infusion was less well tolerated than our previous schedule of bolus administration 3 times/week. However, the continuous infusion schedule appeared to be more effective in enhancing 2'-5'-oligoadenylate synthetase levels in mononuclear cells. We conclude that tolerable doses of IFN-beta and IFN-gamma do not result in serum IFN levels which produce significant synergistic antiproliferative responses in vitro. This study and other findings suggest that, unless higher doses can be achieved, combinations of IFN-beta and IFN-gamma are unlikely to have significant therapeutic activity.
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PMID:Biological and clinical effects of the combination of beta- and gamma-interferons administered as a 5-day continuous infusion. 211 42

Human fibroblast interferon (IFN-beta) was administered by serial lumbar puncture to ten patients with multiple sclerosis (MS). Their clinical courses were compared with those of ten MS control patients who did not receive IFN-beta. As of this writing, the recipients have been followed up for 1.8 to 2.0 years (mean, 1.9 years), and the controls for 1.5 to 1.7 years (mean, 1.6 years). During the study, two recipients suffered four exacerbations, and six controls suffered 11 exacerbations. The recipients' rates of exacerbation during the study were significantly less than their rates both for the entire prestudy duration of the disease and for the 1.8 to 2.0 years immediately preceding entry into the study. The controls' rates of exacerbation before the study and during the study period did not differ significantly. Clinically, the conditions of five recipients and two controls improved, those of three recipients and four controls were unchanged, and those of two recipients and four controls worsened. Headaches, sometimes accompanied by fever and rarely by nausea and vomiting, occurred after injections of IFN-beta. Toxic symptoms usually disappeared within 24, hours; rarely, they persisted for seven to ten days. Each recipient had transient CSF pleocytosis and elevated levels to total protein (the latter remaining elevated in seven). These findings show that intrathecal administration of IFN-beta is feasible in patients with MS, warrant cautious optimism that intrathecal IFN-beta may be effective in altering the course of the disease, and support concepts of a viral or dysimmune cause of MS.
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PMID:Intrathecal interferon in multiple sclerosis. 675 2

Interferon-gamma (IFN-gamma) is produced by activated T cells and probably by NK cells. Its production can be induced by mitogens, antigens and other molecules. IFN-gamma interacts with cells by binding to specific membrane receptors. IFN-gamma--1b is an Escherichia coli--derived recombinant DNA product, which has biological activity identical to natural human IFN-gamma. This IFN type is a more potent immunomodulator than IFN-alpha and IFN-beta. Long term treatment with a therapeutic dosage of IFN-gamma--1b produces a significant reduction in the incidence of serious infections in patients with chronic granulomatous disease. This cytokine can be also useful in the treatment of patients with visceral leishmaniasis, Epstein-Barr virus infections, lepromatous leprosy and other infectious diseases. Phase I and II studies have demonstrated it to be capable of producing antitumor effects, especially in metastatic renal cell carcinoma and some hematologic malignancies. Clinical trials have suggested efficacy of IFN-gamma in the treatment of severe atopic dermatitis and rheumatoid arthritis. The most common adverse reactions are fever, headaches and erythema at the injection site.
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PMID:[Biological properties and clinical applications of interferon gamma (IFN-gamma)]. 820 10

Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts. Subjects were randomized to receive subcutaneous injections of either 2 x 10(6) or 4 x 10(6) IU/m2 of IFN-beta (Biogen) three times a week for a total of 6 weeks. Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals. Systemic side- effects were modest in intensity and included fever, chills, myalgia, and headaches (flu-like symptoms). During the first 2 weeks of therapy, they were more common in the high dose group than in the low dose group (P = 0.02). Using survival analysis, there was no significant difference between the two groups in rates of resolution of warts present at baseline (P = 0.62). However, the rate of new lesion formation during the study was significantly lower in the high dose group (P = 0.04).
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PMID:A randomized, double-blind trial of parenteral low dose versus high dose interferon-beta in combination with cryotherapy for treatment of condyloma acuminatum. 922 60

The number of clinic consultations for condylomata acuminata (genital warts) has increased substantially during the last 30 years. Most infections produce benign lesions but a few types may be associated with cervical and penile cancers. Interferons (IFN) have shown antiviral properties to these infections and IFN-beta in particular has demonstrated a specific cytopathic effect in humans. A total of 124 patients with condylomata acuminata, the majority of whom had failed previous therapy, were treated intralesionally with either recombinant human interferon-beta la (r-hIFN-beta-1a) or placebo. Up to 6 lesions were treated in each patient, and injections were made 3 times per week for a total of 9 injections. The patients were then followed up for 3 months. Efficacy assessments at all time points (day 19, week 6 and month 3) showed a clear advantage for the r-hIFN-beta-1a interferon-beta treatment. Patients receiving r-hIFN-beta-1a showed a greater proportion of treatment success in terms of the complete or partial reduction (at least 50%) of the total area of the treated lesions. The treatment was also well tolerated. Headache, flu-like symptoms and asthenia were more common in patients receiving r-hIFN-beta-1a, but these adverse events were generally mild in severity and rarely led to patient withdrawal. It was concluded that r-hIFN-beta-1a has good efficacy in condylomata acuminata, and therefore presents a useful therapeutic alternative in this hard-to-treat condition.
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PMID:Recombinant human interferon-beta in the treatment of condylomata acuminata. 931 Feb 21

A 57-year-old woman who had severe opticospinal multiple sclerosis (OSMS) was admitted to our hospital. She had presented with visual loss and gait disturbance at the age of 48, and had since experienced more than 10 relapses and been hospitalized 9 times. Interferon beta-lb treatment (8,000,000 units on alternate days) had been started at her last admission. Prior to the present admission, she had developed left visual loss and gait difficulty after headache lasting a few days. Cerebrospinal fluid showed elevation of cell count (322/mm3), protein (130 mg/dl), and myelin basic protein (462 pg/ml; normal, <102 pg/ml). On examination, she exhibited decreased left visual acuity, paraplegia, ataxia of the right upper extremity, and sensory disturbance, particularly in the lower extremities. Bowel and bladder disturbances were also evident Laboratory testing showed lymphocytopenia (420/microl), compared to a white cell count of 1700/microl just before initiation of interferon beta-lb1therapy. MRI revealed a new lesion in the cerebellum in addition to small T2-hyperintense lesions in the white matter of the brain;these had been noted previously. Interferon beta-1b therapy was ceased and she was treated using methylprednisolone pulse therapy. After the abnormal findings resolved, however, interferon beta-lb1therapy was restarted. Three months after, she exhibited right hemiparesis without facial palsy concurrent with lymphocytopenia. MRI showed T2-hyperintense lesions in the periventricular white matter, left cerebral peduncle, bilateral middle cerebellar peduncles, and right cerebellar hemisphere. We reduced the doses of interferon beta-lb1immediately. Thereafter, she did not have relapse for 29 months, but her EDSS (expanded disability status scale) has not recovered. Although interferon beta-lb1has been recognized as an effective drug for decreasing the relapse rate and severity of both secondary progressive MS and relapsing-remitting MS, the present case showed the possibility of interferon beta-1b being associated with phenotype change from OSMS to conventional MS (CMS).
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PMID:[Case of opticospinal multiple sclerosis showing phenotype change to conventional type induced by interferon beta-1b]. 1751 Dec 77