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)

Sixteen patients with cervical intraepithelial neoplasia (CIN), grades 2 and 3, and vulvar intraepithelial neoplasia (VIN), grade 3, associated with human papillomavirus (HPV) infection were treated with human fibroblast interferon (HFI). Treatment consisted of 2-3 X 10(6) IU/day injected intra- and perilesionally for five days per week for two to three weeks with or without topically applied cream (1.2 X 10(6) IU/day for five days). Eight complete and two partial regressions occurred. The duration of the response ranged from 4 to 20 months. Fever, chills and fatigue with or without headache were the side effects. Our preliminary results indicate that HFI was active against CIN and VIN associated with HPV infection.
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PMID:Human fibroblast interferon in cervical and vulvar intraepithelial neoplasia associated with viral cytopathic effects. A pilot study. 298 15

This is the first report of extraneural metastasis of malignant glioma through V-P shunt tube and growth in peritoneal cavity as ascitic form. The patient was a 43-year-old man who was admitted to our hospital with occipital headache. CT scan showed enhanced cystic tumor mass at left temporal lobe. Craniotomy and partial excision of the tumor was done and the histology of tumor tissue showed a malignant astrocytoma. Following this treatment, the patient received the adjuvant therapies of radiation, chemotherapy and immunotherapy with interferon, and also recraniotomy three times. In the mean time, a ventriculo-peritoneal shunt was set up for internal hydrocephalus. One month later, abdominal bulging appeared and yellowish ascites could be obtained with peritoneal tap. In the ascite, tumor cells with glial fibrillary acidic protein were observed at the concentration of 5-10 x 10(4) cells/ml. The patient died three months after extraneural metastasis to the abdominal cavity as ascitic form. At autopsy, solid metastatic mass lesion was not found in extraneural region include abdomen.
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PMID:[Extraneural metastasis of malignant glioma through a ventriculo-peritoneal shunt: growth in peritoneal cavity as ascitic form]. 299 92

Sixty-six patients with recurrent respiratory papillomatosis of juvenile onset were treated for six months with interferon alfa-n1 (Wellferon) in a randomized crossover trial. Half received interferon alfa-n1 intramuscularly at a dosage of 5 megaunits per square meter daily for 28 days and then thrice weekly for five months, followed by six months of observation. The other half were observed for six months and then treated. Operations were performed every two months to assess disease extent by a scale developed for this purpose. The score for the patients during the first observation period was stable. There was a statistically significant lowering of score in patients receiving interferon alfa-n1 during both periods of drug administration. Eight of 57 patients with assessable airway disease achieved complete remission, as did one additional patient with disease limited to the nasopharynx. No patients achieved complete remission during six months of observation alone. This difference was statistically significant. Patients without tracheostomy were significantly more likely to achieve remission than those with a tracheostomy. The patients who were observed after discontinuation of the drug therapy showed a significant rise in score within four months. Symptoms of toxicity included transient fever, fatigue, nausea, and headache. Elevations in serum aspartate aminotransferase levels occurred in 64% of the patients. There was an inverse correlation between age and the ability to tolerate the medication. The dose studied may be close to the maximum tolerated dose. It appears that interferon alfa-n1 as an adjuvant to routine surgical management is effective in slowing the growth of respiratory papillomas.
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PMID:Randomized surgical adjuvant trial of interferon alfa-n1 in recurrent papillomatosis. 304 38

Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-gamma) (specific activity approximately 2 X 10(7) units/mg, purity greater than 99%) given by 1-hour iv infusion three times a week for 6 weeks, at fixed dose levels of 0.1, 0.5, 1.0, or 2.0 mg/m2/day. The common side effects were constitutional symptoms, including fever, chills, myalgias, and headache, but these were less severe than those observed following daily 6-hour iv infusions. Significant changes in blood cell counts and routine serum chemistries were not observed, but there was a dose-dependent increase in serum triglyceride levels. The maximum safely tolerated dose achieved was 1.0 mg/m2/day. Peak serum interferon levels occurred at the midpoint of the infusion and were dose-dependent. rIFN-gamma was rapidly cleared from serum and no detectable activity was found 2 hours after the infusion. Two patients, both with B-cell malignancies, showed objective evidence of tumor regression during the treatment. Treatment was associated with an increase in serum levels of beta 2-microglobulin and the H2O2 secretory capacity of peripheral blood monocytes. We conclude that rIFN-gamma administered by short iv infusion can induce biological activities and causes less toxicity than when given by prolonged iv infusion.
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PMID:Phase I trial of recombinant interferon gamma by 1-hour i.v. infusion. 308 30

Six patients with hairy-cell leukemia were treated with gamma-(IFN-gamma) and alpha-(IFN-alpha-2b) interferon; 3-35 months following splenectomy, treatment was started with 4 X 10(6) U/m2 IFN-gamma sc (iv) every second day for 9-35 weeks. Although the white blood cell counts decreased during therapy from 4.1-49 X 10(9)/l to 1.5-43 X 10(9)/l, no hematological or clinical improvement was obtained. Subsequently (interval 0-13 weeks), IFN-alpha-2b was given at an initial dose of 4 X 10(6) U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-gamma administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9-14 months after start of treatment; maintenance therapy, 1 X 10(6) U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-gamma is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-alpha-2b does result in improvement of hematological values and well-being in almost all patients.
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PMID:[Effectiveness of gamma interferon and alpha interferon in hairy cell leukemia]. 311 51

Thirty patients with documented metastatic melanoma were randomly assigned to receive recombinant DNA-produced gamma-interferon (specific activity approximately, 20 MU/mg) intravenously (IV) over either two or 24 hours at dosages of 3, 30, 300, 1,000, or 3,000 micrograms/m2. Objective toxicity resembled that of alpha-interferon and included fever, chills, myalgias, headache, and fatigue. Neutropenia, elevations in liver enzymes, tachyarrhythmias, and CNS changes also were noted. Dose-limiting toxicity included neutropenia, liver enzyme abnormality, constitutional symptoms, and a change in mental status. The incidence of toxicity was qualitatively similar in both two- and 24-hour treatment arms, but was quantitatively more severe in the 24-hour continuous infusion arm. Maximum tolerated dose was 1,000 micrograms/m2 in both schedules. Pharmacokinetic studies showed a half-life of six to nine hours. One patient had a complete response after two cycles of therapy and an additional patient entered partial remission after three cycles. Recombinant gamma-interferon (rIRN-gamma) is tolerated at dosages of 1,000 micrograms/m2 administered daily either by two or 24 hour infusion for 14 days in patients with metastatic melanoma. The responses documented in this early trial warrant further evaluation for the treatment of metastatic melanoma.
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PMID:A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma. 311 86

In the clinical trial of reaferon, introduced intramuscularly and intravenously in different doses (2 X 10(6), 6 X 10(6) and 9 X 10(6) I. U. daily) for 3 days, various side effects were observed. Their intensity depended on the dose of the preparation and the route of administration. The most regular reaction was a rise in temperature, accompanied by slight weakness, headache, loss of appetite, slight dizziness, euphoria. All side effects were transient. No toxic or allergic reactions involving the organs and systems of the body were observed. Low doses of the preparation (2 X 10(6) I. U. daily) promoted an increase in the amount of lymphocytes in the peripheral blood, stimulated cellular immunity factors and contributed to the optimal functioning of the interferon systems. High doses (6 X 10(6) to 9 X 10(6) I. U. daily) had a pronounced immunosuppressing effect. On the whole, reaferon proved to be fairly tolerable.
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PMID:[Reactogenicity, toxicity and tolerance of reaferon in healthy volunteers]. 336 74

Consensus interferon (r-metHuIFN-Con1) is the product of a gene constructed to code for the most frequent amino acid residues known to occur in subspecies of alpha interferons. Twenty-one patients with advanced malignancy entered this phase I trial with dosing levels of 3, 7.5, 15, 30, and 45 mcg/m2/day given intramuscularly on days 1-5 and 8-10 of each 28-day cycle. The initial dose was randomly given by intravenous, intramuscular, or subcutaneous injection to facilitate pharmacokinetic studies. Vomiting and diarrhea were dose-limiting at 45 mcg/m2/day, preventing completion of therapy. Malaise, flu-like symptoms, nausea, and headache were frequent but tolerable at a dose of 30 mcg/m2/day. Patients were able to escalate to 45 mg/m2/day, suggesting tachyphlaxis to these toxicities. The initial distribution phase (T1/2 alpha) was 4.9-9.0 minutes with a T1/2 beta of 34-415 minutes in three patients for whom sequential values could be determined. r-MetHuIFN-Con1 was absorbed after both subcutaneous and intramuscular administration. 2'5'-Synthetase levels increased following treatment, although no consistent pattern was noted. One partial response was seen in a patient with gastrointestinal carcinoma. The recommended phase II starting dose of r-metHuIFN-Con1 is 30 mg/m2/day using this schedule by any of these routes of administration.
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PMID:Phase I study of recombinant methionyl human consensus interferon (r-metHuIFN-Con1). 339 52

Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.
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PMID:Interferon therapy for condylomata acuminata. 353 60

Patients with nodular lymphoma initially respond to a number of therapies but relapse is common and inexorable with time, and despite further therapy, most patients will ultimately die of their lymphoma. The recent demonstration of their sensitivity to alpha-interferon is promising. The importance of this human antitumor effect is that it is presumably based on mechanisms different from conventional agents. Phase I trials of various doses and schedules of recombinant alpha-interferon have shown that effective serum levels can be obtained by intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes. Virtually all patients experienced some degree of acute toxicity manifested by fever, chills, myalgia, and headache. Tolerance usually developed to acute adverse effects within the first few weeks of therapy, regardless of dose or schedule. Fatigue and anorexia were the most important adverse reactions, occurring during the first two weeks of treatment and generally persisting for the duration of therapy. Occasional adverse effects relating to the central nervous and cardiovascular systems have been reported. Primary laboratory abnormalities observed during treatment include decreases in hematologic parameters and elevations of liver function tests. The clinical efficacy of alpha-interferon, both natural and recombinant, has been demonstrated in both untreated and heavily pretreated patients with nodular lymphoma. The response rate has approached 50% in recent studies; however, less than half were complete responders. Future directions include combination of interferon with cytotoxic agents or other biological response modifiers and use as adjuvant therapy.
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PMID:Alpha-interferon in the treatment of nodular lymphomas. 354 Dec 18


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